Pharmaceutical Glossary GMP GEEK

A
Abuse of Medicinal Products Lạm dụng thuốc

Persistent or sporadic, intentional excessive use of medicinal products which is accompanied by
harmful physical or psychological effects. [Directive 2001/83/EC]
Accelerated Testing Thử nghiệm khắc nghiệt - Lão hóa cấp tốc
Studies designed to increase the rate of chemical degradation or physical change of a drug
substance or drug product by using exaggerated storage conditions as part of the formal stability
studies. Data from these studies, in addition to long term stability studies, can be used to assess
longer term chemical effects at non accelerated conditions and to evaluate the effect of short
term excursions outside the label storage conditions such as might occur during shipping. Results
from accelerated testing studies are not always predictive of physical changes. [ICH Q1A]
Accelerator Máy gia tốc

A device to accelerate energetic charged particles linearly or in circular paths by means of a
radiofrequency field and an electromagnetic field in case of cyclotrons. The accelerated particles
cause nuclear reactions in the atoms of targets placed in their path. [Canadian GMP Guidelines
2009, Annex 5]
Acceptance Criteria Tiêu chí chấp nhận

Numerical limits, ranges, or other suitable measures for acceptance of test results. [EU GMP
Guide, Part II]
Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical
procedures. [ICH Q6A]
Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical
procedures which the drug substance or drug product or materials at other stages of their
manufacture should meet. [ICH Q6B]
Measurable terms under which a test result will be considered acceptable. [Main Principles for
Pharmaceutical Products, WHO]
The criteria assigned, before undertaking testing, to allow evaluation of test results to
demonstrate compliance with a test phase of delivery requirement (Pre-Determined Acceptance
Criteria). [PIC/S PI 006-3]
Product specifications and acceptance/rejection criteria, such as acceptable quality level and
unacceptable quality level, with an associated sampling plan, that are necessary for making a
decision to accept or reject a lot or batch (or any other convenient subgroups of manufactured
units). [21 CFR Part 210, FDA]
Numerical limits, ranges, or other suitable measures of test results necessary to determine
acceptance of the drug substance, drug products, or materials at stages of their manufacture.
[Guidance for Industry cGMP for Phase 1 Investigational Drugs, FDA]
Accuracy Sự chính xác

The accuracy of an analytical procedure expresses the closeness of agreement between the value
which is accepted either as a conventional true value or an accepted reference value and the
value found. This is sometimes termed trueness. [ICH Q2]
Action Level / Action Limit Giới hạn hành động

An internal (in-house) value used to assess the consistency of the process at less critical steps.
[ICH Q6B]
Established criteria, e.g. microbial or particulate levels, requiring immediate follow-up and
corrective action if exceeded. [PIC/S PI 007-6]
The action limit is reached when the acceptance criteria of a critical parameter have been
exceeded. Results outside these limits will require specified action and investigation. [Main
Principles for Pharmaceutical Products, WHO]
An established microbial or airborne particle level that, when exceeded, should trigger
appropriate investigation and corrective action based on the investigation. [Guidance for
Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Active Pharmaceutical Ingredient (API) / Drug Substance Hoạt chất dược dụng
Any substance or mixture of substances intended to be used in the manufacture of a drug
(medicinal) product and that, when used in the production of a drug, becomes an active
ingredient of the drug product. Such substances are intended to furnish pharmacological activity
or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to
affect the structure and function of the body. [EU GMP Guide Part II, FDA Guidance for
Industry cGMP for Phase 1 Investigational Drugs, ICH Q7, Canadian GMP Guidelines 2009]
The unformulated drug substance that may subsequently be formulated with excipients to
produce the dosage form. [ICH Q1A]
Any substance or mixture of substances intended to be used in the manufacture of a

pharmaceutical dosage form and that, when so used, becomes an active ingredient of that
pharmaceutical dosage form. Such substances are intended to furnish pharmacological activity or
other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to
affect the structure and function of the body. [Guide to Good Storage Practices for
Pharmaceuticals, WHO]
Any substance or mixture of substances to which the effect of a finished medicinal product is
adjudged, or which acts as such. [PIC/S PE 010-4]
Any component that is intended to furnish pharmacological activity or other direct effect in the
diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any
function of the body of man or other animals. The term includes those components that may
undergo chemical change in the manufacture of the drug product and be present in the drug
product in a modified form intended to furnish the specified activity or effect. [21 CFR Part 210,
FDA]
Active Substance Hoạt chất dược dụng

Any substance or mixture of substances intended to be used in the manufacture of a medicinal
product and that, when used in its production, becomes an active ingredient of that product
intended to exert a pharmacological, immunological or metabolic action with a view to restoring,
correcting or modifying physiological functions or to make a medical diagnosis. [Directive
2001/83/EC]
Active Substance Gas Khí dược dụng

Any gas intended to be an active substance for a medicinal product. [EU GMP Guide, Annex 6]
Adjuvant
A chemical or biological substance that enhances the immune response against an antigen. [EU
GMP Guide, Annex 2]
Advanced Electronic Signature Chữ ký điện tử/Chữ ký số

(see also Electronic Signature)
An electronic signature, which meets the following requirements:
(a) it is uniquely linked to the signatory,
(b) it is capable of identifying the signatory,
(c) it is created using means that the signatory can maintain under his control, and
(d) it is linked to the data to which it relates in such a manner that any change of the data is
detectable.
[PIC/S PI 011-3]
Adventitious Virus
Unintentionally introduced contaminant virus. [ICH Q5A, Canadian GMP Guidelines 2009,
Annex 2]
Adverse Event Yếu tố bất lợi

(see also Serious Adverse Event)
Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal
product and which does not necessarily have a causal relationship with this treatment. [Directive
2001/20/EC]
Adverse Reaction Phản ứng bất lợi

(see also Serious Adverse Reaction (SAR))
A response to a medicinal product which is noxious and unintended. [Directive 2001/83/EC]
Agitated Immersion
A system of cleaning in which the manufacturing equipment is filled with cleaning solution, and
the cleaning solution is agitated, usually with the existing agitation equipment in that equipment.
Agitation
The mixing or movement of a cleaning solution in the equipment. Agitation may occur from
flow of the cleaning solution, or it may be due to mixers or impellers. Agitation continually
supplies fresh cleaning solution to the surfaces.
Air Lock Chốt gió

An enclosed space with two or more doors, and which is interposed between two or more rooms,
e.g. of differing class of cleanliness, for the purpose of controlling the air-flow between those
rooms when they need to be entered. An air-lock is designed for and used by either people or
goods. [EU GMP Guide, Glossary]
A small room with interlocked doors, constructed to maintain air pressure control between
adjoining rooms (generally with different air cleanliness standards). The intent of an aseptic
processing air lock is to preclude ingress of particulate matter and microorganism contamination
from a lesser controlled area. [Guidance for Industry: Sterile Drug Products Produced by Aseptic
Processing – cGMP, FDA]
An enclosed space with two or more doors, that is interposed between two or more rooms,
usually of differing classes of cleanliness, for the purpose of controlling the airflow between
those rooms when either people or goods need to enter or leave them. [Canadian GMP
Guidelines 2009]
Air Separation
Separation of atmospheric air into its constituent gases using fractional distillation at cryogenic
temperatures. [EU GMP Guide, Annex 6]
Air Separation Plant

Air separation plants take atmospheric air and through processes of purification, cleaning,
compression, cooling, liquefaction and distillation separate the air into the gases oxygen,
nitrogen and argon. [EU GMP Guide, Annex 6]
Alert Level Mức độ cảnh báo

An established microbial or airborne particle level giving early warning of potential drift from
normal operating conditions and triggers appropriate scrutiny and follow-up to address the
potential problem. Alert levels are always lower than action levels. [Guidance for Industry:
Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Alert Limit Giới hạn cảnh báo

The alert limit is reached when the normal operating range of a critical parameter has been
exceeded, indicating that corrective measures may need to be taken to prevent the action limit
being reached. [Main Principles for Pharmaceutical Products, WHO]
(media fill) Established levels or numbers of positive media filled units, the cause of which
should be investigated, but which are not necessarily grounds for definitive corrective action.
[PIC/S PI 007-6]
(environmental monitoring) Established microbial or particulate levels giving early warning of

potential drift from normal operating conditions which are not necessarily grounds for definitive
corrective action but which require follow-up investigation. [PIC/S PI 007-6]
Allergoid
Allergens which are chemically modified to reduce IgE reactivity. [EU GMP Guide, Annex 2]
Allogeneic Donation
Blood collected from an individual and placed in the general blood supply for the purpose of
transfusion to another person. [Canadian GMP Guidelines, Annex 14]
Analytical Procedure Quy trình phân tích

The analytical procedure refers to the way of performing the analysis. It should describe in detail
the steps necessary to perform each analytical test. This may include but is not limited to: the
sample, the reference standard and the reagents preparations, use of the apparatus, generation of
the calibration curve, use of the formulae for the calculation, etc. [ICH Q2]
Annual Review Đánh giá hàng năm

An evaluation, conducted at least annually, that assesses the quality standards of each drug
product to determine the need for changes in drug product specifications or manufacturing or
control procedures. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP
Regulations, FDA]
Antibody
Proteins produced by the B-lymphocytes that bind to specific antigens. Antibodies may divided
into 2 main types based on key differences in their method of manufacture. [EU GMP Guide,
Annex 2]
Antibody Screen
Serological test by which donor serum/plasma is tested with reagent red cells of known antigenic
profile to determine if unexpected clinically significant antibodies are present. "clinically
significant" refers to antibodies that may cause adverse reactions in the recipient due to
incompatibility. [Canadian GMP Guidelines, Annex 14]
Antibody, monoclonal (MAb)

Homogenous antibody population obtained from a single clone of lymphocytes or by
recombinant technology and which bind to a single epitope. [EU GMP Guide, Annex 2]
Antibody, polyclonal
Derived from a range of lymphocyte clones, produced in human and animals in response to the
epitopes on most 'non-self' molecules. [EU GMP Guide, Annex 2]
Antigen
Substances (e.g. toxins, foreign proteins, bacteria, tissue cells) capable of inducing specific
immune responses. [EU GMP Guide, Annex 2]
API
see Active Pharmaceutical Ingredient
API Starting Material Nguyên liệu đầu vào

A raw material, intermediate, or an API that is used in the production of an API and that is
incorporated as a significant structural fragment into the structure of the API. An API Starting
Material can be an article of commerce, a material purchased from one or more suppliers under
contract or commercial agreement, or produced in-house. API Starting Materials are normally of
defined chemical properties and structure. [EU GMP Guide, Part II, ICH Q7]
Application-Specific Software
A software program developed or adapted to the specific requirements of the application. [PIC/S
PI 011-3]
Area Khu vực

A specific set of rooms within a building associated with the manufacturing of any one product
or multiple products that has a common air handling unit. [EU GMP Guide, Annex 2]
Asepsis Vô trùng
A state of control attained by using an aseptic work area and performing activities in a manner
that precludes microbiological contamination of the exposed sterile product. [Guidance for
Aseptic Area Khu vực vô trùng

A zone or zones within a clean area where Grade A or B conditions are maintained (see table in
Section C.02.029 of these guidelines). [Canadian GMP Guidelines 2009]
The place, among the work areas, where the aseptic drug substances or sterilized containers are
exposed to the air in the work areas, where the filling operations for the drug substances are
conducted, where the sealing operations for the containers are conducted, or where the aseptic
operations including sterility tests are conducted. [Japan MHLW Ministerial Ordinance No. 179,
2004]
Aseptic Filling Đóng vô trùng

Operation whereby the product is sterilized separately, then filled and packaged using sterilized
containers and closures in critical processing zones. [PIC/S PI 007-6]
Aseptic Manufacturing Area Khu vực sản xuất vô trùng

The classified part of a facility that includes the aseptic processing room and ancillary
cleanrooms. For purposes of this document, this term is synonymous with “aseptic processing
facility” as used in the segregated segment context. [Guidance for Industry: Sterile Drug
Products Produced by Aseptic Processing – cGMP, FDA]
Aseptic Process Quy trình vô trùng

A method of producing a sterile product in which sterile bulk drug or sterile raw materials are
compounded and assembled with sterile packaging components under Grade A or B conditions
(see table in Section C.02.029 of these guidelines). [Canadian GMP Guidelines 2009]
Aseptic Processing Facility Nhà xưởng sản xuất vô trùng

A building, or segregated segment of it, containing cleanrooms in which air supply, materials,
and equipment are regulated to control microbial and particle contamination. [Guidance for
Aseptic Processing Room Phòng thao tác vô trùng

A room in which one or more aseptic activities or processes is performed. [Guidance for
Aseptic Technique and Manipulation

The manipulation of sterile materials in such a way as to minimize the risk of microbiological
contamination from the environment. These techniques usually involve eliminating surface to
surface contacts (except between sterile surfaces) minimizing the area exposed and the duration
of exposure. [PIC/S PI 014-3]
At-Line
Measurement where the sample is removed, isolated from, and analyzed in close proximity to the
process stream. [Guideline on process validation for finished products, EMA]
At-Rest
Condition where the installation is complete with equipment installed and operating in a manner
agreed upon by the customer and supplier, but with no personnel present. [Main Principles for
Condition where the installation is installed, complete with production equipment but with no
operating personnel present and no production activities. [Chinese GMP Guidelines, Annex1]
Auditing / Inspection
One-site assessment of the compliance with the Community GMP principles performed by
officials of Community Competent Authorities. [Compilation of Community Procedures on
Inspections and Exchange of Information, EMA]
An independent and objective activity designed to add value and improve an organization’s
operations by helping the organization to accomplish its objectives by using a systematic,
disciplined approach to evaluate and improve the effectiveness of risk management, control and
governance processes. [Good Distribution Practices for Pharmaceutical Products, WHO]
Autologous Donation
Blood collected from an individual for the purpose of transfusion back to the same individual.
[Canadian GMP Guidelines, Annex 14]
Automated System
Term used to cover a broad range of systems, including automated manufacturing equipment,
control systems, automated laboratory systems manufacturing execution systems and computers
running laboratory or manufacturing database systems. The automated system consists of the
hardware, software and network components, together with the controlled functions and
associated documentation. Automated systems are sometimes referred to as computerised
systems, in this Guide the two terms are synonymous. [PIC/S PI 011-3]
B
Barrier
A physical partition that affords aseptic processing area (ISO 5) protection by partially
separating it from the surrounding area. [Guidance for Industry: Sterile Drug Products Produced
by Aseptic Processing – cGMP, FDA]
Batch / Lot Lô
A defined quantity of starting material, packaging material or product processed in one process
or series of processes so that it could be expected to be homogeneous. Note: To complete certain
stages of manufacture, it may be necessary to divide a batch into a number of sub batches, which
are later brought together to form a final homogeneous batch. In the case of continuous
manufacture, the batch must correspond to a defined fraction of the production, characterized by
its intended homogeneity. For control of the finished product, the following definition has been
given in Annex 1 of Directive 2001/83/EC as amended by Directive 2003/63/EC: 'For the control
of the finished product, a batch of a proprietary medicinal product comprises all the units of a
pharmaceutical form which are made from the same initial mass of material and have undergone
a single series of manufacturing operations or a single sterilization operation or, in the case of a
continuous production process, all the units manufactured in a given period of time'. [EU GMP
Guide, Glossary]
A specific quantity of material produced in a process or series of processes so that it is expected

to be homogeneous within specified limits. In the case of continuous production, a batch may
correspond to a defined fraction of the production. The batch size can be defined either by a
fixed quantity or by the amount produced in a fixed time interval. [EU GMP Guide, Part II, ICH
Q7]
A defined quantity of pharmaceutical products processed in a single process or series of

processes so that it is expected to be homogeneous. [Good Distribution Practices for
Pharmaceutical Products, WHO, PIC/S PE 010-4]
A specific quantity of a drug or other material that is intended to have uniform character and
quality, within specified limits, and is produced according to a single manufacturing order during
the same cycle of manufacture. [21 CFR Part 210, FDA, Guidance for Industry cGMP for Phase
1 Investigational Drugs, FDA]
One or more components or finished [medical] devices that consist of a single type, model, class,
size, composition, or software version that are manufactured under essentially the same
conditions and that are intended to have uniform characteristics and quality within specified
limits. [21 CFR Part 820, FDA]
A quantity of drug in dosage form, a raw material, or a packaging material, homogeneous within
specified limits, produced according to a single production order and as attested by the
signatories to the order. In the case of continuous manufacture, a batch corresponds to a defined
fraction of the production, that is characterized by its intended homogeneity. It may sometimes
be necessary to divide a batch into a number of sub-batches, which are later brought together to
form a final homogeneous batch. [Canadian GMP Guidelines 2009]
Batch Certificate
A certificate issued by the fabricator of a lot or batch of a drug that is exported within the
framework of a mutual recognition agreement and in which the fabricator
 identifies the master production document for the drug and certifies that the lot or batch
has been fabricated, packaged/labelled and tested in accordance with the procedures
described in that document,
 provides a detailed description of the drug, including
1. a statement of all properties and qualities of the drug, including the identity,
potency and purity of the drug, and
2. a statement of tolerances for the properties and qualities of the drug,
 identifies the analytical methods used in testing the lot or batch and provides details of
the analytical results obtained,
 sets out the addresses of the buildings at which the lot or batch was fabricated,
packaged/labelled and tested, and
 certifies that the lot or batch was fabricated, packaged/labelled and tested in accordance
with the Good Manufacturing Practices of the regulatory authority that has recognized
those buildings as meeting its Good Manufacturing Practices standard.” (C.01A.001)
(The certificate’s content is also described in Appendix A).
[Canadian GMP Guidelines 2009]
Batch Number / Lot Number / Control Number Số lô - Số kiểm soát

A unique combination of numbers, letters, and/or symbols that identifies a batch (or lot) and
from which the production and distribution history can be determined. [EU GMP Guide, Part II,
ICH Q7]
A distinctive combination of numbers and/or letters that specifically identifies a batch. The batch
number appears on the batch records, certificates of analysis, etc. [PIC/S PE 010-4, Canadian
GMP Guidelines 2009]
A distinctive combination of numbers and/or letters which uniquely identifies a batch, for
example, on the labels, its batch records and corresponding certificates of analysis. [Good
Distribution Practices for Pharmaceutical Products, WHO]
Any distinctive combination of letters, numbers, or symbols, or any combination of them, from
which the complete history of the manufacture, processing, packing, holding, and distribution of
a batch or lot of drug product or other material can be determined. [21 CFR Part 210, FDA]
Any distinctive symbols, such as a distinctive combination of letters or numbers, or both, from
which the history of the manufacturing, packaging, labeling, and distribution of a unit, lot, or
batch of finished [medical] devices can be determined. [21 CFR Part 820, FDA]
Batch Record Hồ sơ lô
All documents associated with the manufacture of a batch of bulk product or finished product.
They provide a history of each batch of product and of all circumstances pertinent to the quality
of the final product. [Main Principles for Pharmaceutical Products, WHO]
Bespoke
A system produced for a customer, specifically to order, to meet a defined set of user
requirements. [PIC/S PI 011-3]
Bioburden
The level and type (e.g. objectionable or not) of micro-organisms that can be present in raw
materials, API starting materials, intermediates or APIs. Bioburden should not be considered
contamination unless the levels have been exceeded or defined objectionable organisms have
been detected. [EU GMP Guide Part II, ICH Q7]
The level and type (i.e. objectionable or not) of micro-organism present in raw materials, media,
biological substances, intermediates or products. Regarded as contamination when the level
and/or type exceed specifications. [EU GMP Guide, Annex 2]
Total number of viable microorganisms on or in a pharmaceutical product prior to sterilization.

[PIC/S PI 007-6]
The total number of microorganisms associated with a specific item prior to sterilization.
[Guidance for Industry Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Biogenerator
A contained system, such as a fermenter, into which biological agents are introduced along with
other materials so as to effect their multiplication or their production of other substances by
reaction with the other materials. Biogenerators are generally fitted with devices for regulation,
control, connection, material addition and material withdrawal. [EU GMP Guide, Glossary]
Biological Activity Hoạt tính sinh học

The specific ability or capacity of the product to achieve a defined biological effect. Potency is
the quantitative measure of the biological activity. [ICH Q6B]
Biological Agent Tác nhân sinh học

Microorganisms, including genetically engineered microorganisms, cell cultures and
endoparasites, whether pathogenic or not. [EU GMP Guide, Glossary]
Biological Indicator (BI) Chỉ thị sinh học

A population of microorganisms inoculated onto a suitable medium (e.g., solution, container or
closure) and placed within appropriate sterilizer load locations to determine the sterilization
cycle efficacy of a physical or chemical process. The challenge microorganism is selected based
upon its resistance to the given process. Incoming lot D-value and microbiological count define
the quality of the BI. [Guidance for Industry: Sterile Drug Products Produced by Aseptic
Biometrics Sinh trắc học

A method of verifying an individual’s identity based on measurement of the individual’s
physical feature(s) or repeatable action(s) where those features and/or actions are both unique to
that individual and measurable. [21 CFR Part 11, FDA]
Biosafety Level (BSL) Mức độ an toàn sinh học

The containment conditions required to safely handle organisms of different hazards ranging
from BSL1 (lowest risk, unlikely to cause human disease) to BSL4 (highest risk, cause severe
disease, likely to spread and no effective prophylaxis or treatment available). [EU GMP Guide,
Annex 2]
Blending Trộn
Blending is the process of combining materials or different batches to produce a homogeneous
intermediate or finished product. [Specific Pharmaceutical Products, WHO]
Blinding Giả dược

A procedure in which one or more parties to the trial are kept unaware of the treatment
assignment(s). Single-blinding usually refers to the subject(s) being unaware, and double-
blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data
analyst(s) being unaware of the treatment assignment(s). In relation to an investigational
medicinal product, blinding shall mean the deliberate disguising of the identity of the product in
accordance with the instructions of the sponsor. Unblinding shall mean the disclosure of the
identity of blinded products. [EU GMP Guide, Annex 13, Canadian GMP Guidelines 2009,
Annex 13]
The lowest amount of analyte in a sample which can be quantitatively determined with defined
precision and accuracy under the stated experimental conditions. [PIC/S PI 006-3]
Blood Máu
Whole blood collected from a single donor and processed either for transfusion or further
manufacturing. [EU GMP Guide, Annex 14]
Whole blood collected from a single donor and processed either for transfusion or further
manufacturing. The term is often used to describe blood components in general. [Canadian GMP
Guidelines 2009, Annex 14]
Blood Component Thành phần máu

A therapeutic constituent of blood (red cells, white cells, platelets and plasma) that can be
prepared by various methods. [EU GMP Guide, Annex 14]
A therapeutic agent produced by physical or mechanical separation of the constituents of whole
blood. Components include, but are not limited to, red blood cells, platelets, plasma and
cryoprecipitated Anti-Haemophiliac Factor (AHF). [Canadian GMP Guidelines 2009, Annex 14]
Blow / Fill / Seal Unit Máy thổi-đóng-hàn kín

Purpose built machines in which, in one continuous operation, containers are formed from a
thermoplastic granulate, filled and then sealed, all by the one automatic machine. [Chinese GMP
Guide, Annex1]
Bracketing Lấy mẫu phân tầng

The design of a stability schedule such that only samples on the extremes of certain design
factors (e.g., strength, package size) are tested at all time points as in a full design. The design
assumes that the stability of any intermediate levels is represented by the stability of the
extremes tested. Where a range of strengths is to be tested, bracketing is applicable if the
strengths are identical or very closely related in composition (e.g., for a tablet range made with
different compression weights of a similar basic granulation, or a capsule range made by filling
different plug fill weights of the same basic composition into different sized capsule shells).
Bracketing can be applied to different container sizes or to different fills in the same container
closure system. [ICH Q1A, Canadian GMP Guidelines 2009]
Bracketing Approach
A validation scheme/protocol designed such that only batches on the extremes of certain
predetermined and justified design factors, e.g., strength, batch size, pack size are tested during
process validation. This approach assumes that validation of any intermediate levels is
represented by the extremes validated. Where a range of strengths is to be validated, bracketing
could be applicable if the strengths are identical or very closely related in composition (e.g., for a
tablet range made with different compression weights of a similar basic granulation, or a capsule
range made by filling different plug fill weights of the same basic composition into different size
capsule shells). Bracketing can be applied to different container sizes or different fills in the
same container closure system. [Guideline on Process Validation for Finished Products, EMA]
Brokering of Medicinal Products

All activities in relation to the sale or purchase of medicinal products, except for wholesale
distribution, that do not include physical handling and that consist of negotiating independently
and on behalf of another legal or natural person. [Directive 2001/83/EC]
Bug Lỗi phần mềm

A manifestation of an error in software (a fault). [PIC/S PI 011-3]
Bulk Drug Thuốc bán thành phẩm

A drug in dosage form that is not in its final packaging, usually in quantities larger than the
largest commercially available package size. [Canadian GMP Guidelines 2009]
Bulk Product Bán thành phẩm

Any product that has completed all processing stages up to, but not including, final packaging.
[EU GMP Guide, Glossary, PIC/S PE 010-4]
Bulk Production Batch
A batch of product, of a size described in the application for a marketing authorization, either
ready for assembly into final containers or in individual containers ready for assembly to final
packs. (A bulk production batch may, for example, consist of a bulk quantity of liquid product,
of solid dosage forms such as tablets or capsules, or of filled ampoules). [EU GMP Guide,
Annex 16]
C
Calibration Hiệu chuẩn
The set of operations which establish, under specified conditions, the relationship between values
indicated by a measuring instrument or measuring system, or values represented by a material
measure, and the corresponding known values of a reference standard.
The demonstration that a particular instrument or device produces results within specified limits
by comparison with those produced by a reference or traceable standard over an appropriate
range of measurements. [EU GMP Guide, Part II, ICH Q7]
Set of tests that confirms under desired conditions, the relationship between values indicated by a
measuring instrument or measuring system, or values represented by a material measure, and the
corresponding values of a reference standard. [Canadian GMP Guidelines 2009, Annex 5]
Campaigned Manufacture Sản xuất chiến dịch

The manufacture of a series of batches of the same product in sequence in a given period of time
followed by strict adherence to accepted control measures before transfer to another product. The
products are not run at the same time but may be run on the same equipment. [EU GMP Guide,
Annex 2]
CAPA (Corrective and Preventive Action) Hành động khắc phục & phòng ngừa
A systematic approach that includes actions needed to correct (“correction”), prevent recurrence
(“corrective action”), and eliminate the cause of potential nonconforming product and other
quality problems (preventive action). [21 CFR 820, FDA, Guidance for Industry: Quality
Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Capability of a Process Hiệu năng quy trình

Ability of a process to realise a product that will fulfil the requirements of that product. The
concept of process capability can also be defined in statistical terms. [ISO 9000:2005, ICH Q10]
Carrier Chất mang

A stable element present with a radionuclide of the same element. [Canadian GMP Guidelines,
Annex 5]
A stable element that is added, in detectable quantities, to a radionuclide of the same element,
usually to facilitate processing of the radionuclide. [Canadian GMP Guidelines, Annex 3]
Catalyst Chất xúc tác
A substance usually used in small amounts relative to the reactants that modifies and increases
the rate of a reaction without being consumed in the process. [Canadian GMP Guidelines, Annex
5]
Cell Bank
(see also Working Cell Bank)
Cell bank system: A cell bank system is a system whereby successive batches of a product are
manufactured by culture in cells derived from the same master cell bank. A number of containers
from the master cell bank are used to prepare a working cell bank. The cell bank system is
validated for a passage level or number of population doublings beyond that achieved during
routine production. Master cell bank: A culture of [fully characterized] cells distributed into
containers in a single operation, processed together in such a manner as to ensure uniformity and
stored in such a manner as to ensure stability. A master cell bank is usually stored at -70 °C or
lower. Working cell bank: A culture of cells derived from the master cell bank and intended for
use in the preparation of production cell cultures. The working cell bank is usually stored at -
70°C or lower. [EU GMP Guide, Glossary]
A collection of appropriate containers, whose contents are of uniform composition, stored under
defined conditions. Each container represents an aliquot of a single pool of cells. [EU GMP
Guide, Annex 2]
A cell bank is a collection of appropriate containers, whose contents are of uniform composition,
stored under defined conditions. Each container represents an aliquot of a single pool of cells.
[ICH Q5D, Canadian GMP Guidelines 2009, Annex 2]
Cell Culture
The result from the in-vitro growth of cells isolated from multicellular organisms. [EU GMP
Guide, Glossary]
Maintenance or propagation of cells in vitro. Cell culture is performed according to good
aseptic/sterile techniques to ensure the absence of microbial contamination. [Canadian GMP
Cell Line
Type of cell population which originates by serial subculture of a primary cell population, which
can be banked. [ICH Q5D]
Cell Stock
Primary cells expanded to a given number of cells to be aliquoted and used as starting material
for production of a limited number of lots of a cell based medicinal product. [EU GMP Guide,
Annex 2]
Cell Substrate
Cells used to manufacture product. [ICH Q5A]
Certificate of Analysis (COA)

A document containing the name and address of the laboratory performing the test(s), name and
specifications of the material(s), test(s) performed, test method(s) used, actual numerical results,
approval date(s), signature of approver, and any other technical information deemed necessary
for its proper use. [Canadian GMP Guidelines 2009]
Certificate of Compliance (CoC)

A certificate issued by a Regulatory Authority attesting to the GMP compliance of a recognized
building in that country. In Canada, the CoC is issued by the HPFB Inspectorate. [Canadian
Certificate of Manufacture
A document issued by a vendor to a distributor or importer that attests that a specific lot or batch
of drug has been produced in accordance with its master production documents. Such certificates
include a detailed summary of current batch documentation, with reference to respective dates of
revision, manufacture, and packaging, and are signed and dated by the vendor’s quality control
department. For drugs that are fabricated, packaged/labelled and tested in MRA countries, the
batch certificate is considered to be equivalent. [Canadian GMP Guidelines 2009]
Certificate of Pharmaceutical Product (CPP)

A certificate issued by the Inspectorate establishing the regulatory status of the pharmaceutical,
biological, radiopharmaceutical or veterinary product listed and the GMP status of the fabricator
of the product. This certificate is in the format recommended by the WHO. [Canadian GMP
Guidelines 2009]
Certification of the Finished Product Batch

The certification in a register or equivalent document by a Qualified Person (QP), as defined in
Article 51 of Directive 2001/83/EC and Article 55 of Directive 2001/82/EC, before a batch is
released for sale or distribution. [EU GMP Guide, Annex 16]
Change Control
A formal system by which qualified representatives of appropriate disciplines review proposed
or actual changes that might affect a validated status of facilities, systems, equipment or
processes. The intent is to determine the need for action that would ensure that the system is
maintained in a validated state. [EU GMP Guide, Annex15, PIC/S PI 011-3]
A formal system by which qualified representatives of appropriate disciplines review proposed

or actual changes that might affect a validated status. The intent is to determine the need for
action that would ensure and document that the system is maintained in a validated state. [Main
Principles for Pharmaceutical Products, WHO, PIC/S PI 006-3]
A written procedure that describes the action to be taken if a change is proposed

(a) to facilities, materials, equipment, and/or processes used in the fabrication, packaging, and
testing of drugs, or
(b) that may affect the operation of the quality or support system.
[Canadian GMP Guidelines 2009]
Change Management
A systematic approach to proposing, evaluating, approving, implementing and reviewing
changes. [ICH Q10]
A less formal approach to change control that is generally utilised during the preliminary
planning and design stage of a project. (Many companies will elect to move straight to a change
control system in a design stage of a complex project. This has the advantage of formality, more
accurate records and documentation as well as a strong traceability and accountability feature).
[PIC/S PI 006-3]
Changeover Procedure
A logical series of validated steps that ensures the proper cleaning of suites and equipment
before the processing of a different product begins. [Canadian GMP Guidelines 2009]
Chemical Development Studies

Studies conducted to scale-up, optimize, and validate the manufacturing process for a new drug
substance. [ICH Q3A]
Chemical Transformation Step

For Chemical Entities, a step involved in the synthesis of the chemical structure of the drug
substance from precursor molecular fragments. Typically it involves C-X or C-C bond formation
or breaking. [ICH Q11]
Chiral
Not super imposable with its mirror image, as applied to molecules, conformations, and
macroscopic objects, such as crystals. The term has been extended to samples of substances
whose molecules are chiral, even if the macroscopic assembly of such molecules is racemic.
[ICH Q6A]
Classical Fermentation
The term "classical fermentation" refers to processes that use microorganisms existing in nature
and/or modified by conventional methods (e.g. irradiation or chemical mutagenesis) to produce
APIs. APIs produced by "classical fermentation" are normally low molecular weight products
such as antibiotics, amino acids, vitamins, and carbohydrates. [Chinese GMP Guidelines, Annex
2]
Clean Area
An area with defined environmental control of particulate and microbial contamination,
constructed and used in such a way as to reduce the introduction, generation and retention of
contaminants within the area. Note: The different degrees of environmental control are defined in
the Supplementary Guidelines for the Manufacture of sterile medicinal products. [EU GMP
Guide, Glossary]
An area (or room) with defined environmental control of particulate and microbial
contamination, constructed and used in such a way as to reduce the introduction, generation and
retention of contaminants within the area. [Main Principles for Pharmaceutical Products, WHO]
An area with defined environmental control of particulate and microbial contamination
constructed and used in such a way as to reduce the introduction, generation and retention of
contaminants within the area. [PIC/S PE 010-4]
An area with defined particle and microbiological cleanliness standards. [Guidance for Industry:
A room or suite of rooms where Grade C or D conditions (see table in Section C.02.029 of these
guidelines) are required. The rooms have a defined environmental control of particulate and
microbial contamination and are constructed, maintained, and used in such a way as to minimize
the introduction, generation, and retention of contaminants. [Canadian GMP Guidelines 2009]
Throughout this Ministerial Ordinance means the place, among those areas where the
manufacturing operations are conducted (hereinafter referred to as “work areas”), where the
weighing operations for the raw materials or the formulating operations for the drug substances
are conducted or where the cleaned containers are exposed to the air in the work areas. [Japan
MHLW Ministerial Ordinance No. 179, 2004]
Cleaning Validation
Cleaning validation is documented evidence that an approved cleaning procedure will provide
equipment which is suitable for processing medicinal products. [EU GMP Guide, Annex 15]
Documented evidence to establish that cleaning procedures are removing residues to

predetermined levels of acceptability, taking into consideration factors such as batch size,
dosing, toxicology and equipment size. [Main Principles for Pharmaceutical Products, WHO]
Documented evidence that an approved cleaning procedure will provide equipment which is
suitable for processing of pharmaceutical products or active pharmaceutical ingredients (APIs).
[PIC/S PI 006-3]
Cleanroom
A room designed, maintained, and controlled to prevent particle and microbiological
contamination of drug products. Such a room is assigned and reproducibly meets an appropriate
air cleanliness classification. [Guidance for Industry: Sterile Drug Products Produced by Aseptic
Clinical Trial
Any investigation in human subjects intended to discover or verify the clinical, pharmacological
and/or other pharmacodynamic effects of an investigational product(s) and/or to identify any
adverse reactions to an investigational product(s), and/or to study absorption, distribution,
metabolism, and excretion of one or more investigational medicinal product(s) with the object of
ascertaining its/their safety and/or efficacy. [EU GMP Guide, Annex 13]
Closed Isolator System

Exclude external contamination from the isolator’s interior by accomplishing material transfer
via aseptic connection to auxiliary equipment, rather than use of openings to the surrounding
environment. Closed systems remain sealed throughout operations. [Guidance for Industry:
Closed Procedure
A procedure whereby a sterile pharmaceutical product is prepared by transferring sterile
ingredients or solutions to a pre-sterilized sealed container, either directly or using a sterile
transfer device, without exposing the solution to the external environment. [PIC/S PE 010-4]
Closed System
Where a drug substance or product is not exposed to the immediate room environment during
manufacture. [EU GMP Guide, Annex 2]
A system for collecting and/or processing blood in containers that have been connected together
before sterilization, so that there is no possibility of microbial contamination from outside after
collection of blood from the donor. [Canadian GMP Guidelines, Annex 14]
Cold Chain
Maintenance of a designated temperature throughout the manufacturing process and during
storage, until the product is used. [Canadian GMP Guidelines, Annex 2]
Colony Forming Units (CFU)

Visible outcome of growth of micro-organisms arising from a single or multiple cells. [PIC/S PI
012-3]
A microbiological term that describes the formation of a single macroscopic colony after the
introduction of one or more microorganisms to microbiological growth media. One colony
forming unit is expressed as 1 CFU. [Guidance for Industry: Sterile Drug Products Produced by
Aseptic Processing – cGMP, FDA]
Combination Product
A drug product which contains more than one drug substance [ICH Q6A]
Commercial Off-the-Shelf (COTS)

Configurable programs – stock programs that can be configured to specific user applications by
“filling in the blanks”, without (COTS) altering the basic program. [PIC/S PI 011-3]
Commissioning
An engineering term that covers all aspects of bringing a system or sub-system to a position
where it is regarded as being ready for use in pharmaceutical manufacture. Commissioning
involves all the basis requirements of Installation Qualification (IQ) and Operational
Qualification (OQ). [PIC/S PI 006-3]
The setting up, adjustment and testing of equipment or a system to ensure that it meets all the
requirements, as specified in the user requirement specification, and capacities as specified by
the designer or developer. Commissioning is carried out before qualification and validation.
[TRS 961 Annex 7, WHO]
Commitment Batch
Production batches of a drug substance or drug product for which the stability studies are
initiated or completed post approval through a commitment made in the registration application.
[ICH Q1A, Canadian GMP Guidelines 2009]
Common Name
The international non-proprietary name recommended by the World Health Organization, or, if
one does not exist, the usual common name. [Directive 2001/83/EC]
Comparability Bridging Study

A study performed to provide nonclinical or clinical data that allows extrapolation of the existing
data from the drug product produced by the current process to the drug product from the changed
process. [ICH Q5E]
Comparability Exercise
The activities, including study design, conduct of studies, and evaluation of data, that are
designed to investigate whether the products are comparable. [ICH Q5E]
Comparable
A conclusion that products have highly similar quality attributes before and after manufacturing
process changes and that no adverse impact on the safety or efficacy, including immunogenicity,
of the drug product occurred. This conclusion can be based on an analysis of product quality
attributes. In some cases, nonclinical or clinical data might contribute to the conclusion. [ICH
Q5E]
Comparator Product
An investigational or marketed product (i.e. active control), or placebo, used as a reference in a
clinical trial. [EU GMP Guide, Annex 13, Canadian GMP Guidelines 2009, Annex 13]
Complaint
Any written, electronic, or oral communication that alleges deficiencies related to the identity,
quality, durability, reliability, safety, effectiveness, or performance of a [medical] device after it
is released for distribution. [21 CFR Part 820, FDA]
Component
Any ingredient intended for use in the manufacture of a drug product, including those that may
not appear in the final drug product.
[Guidance for Industry Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA,
Guidance for Industry cGMP for Phase 1 Investigational Drugs, FDA, 21 CFR Part 210, FDA]
Any raw material, substance, piece, part, software, firmware, labeling, or assembly which is
intended to be included as part of the finished, packaged, and labeled [medical] device. [21 CFR
Part 820, FDA]
A unit of a drug, other than a radionuclide, separately packaged in a kit for use in the preparation
of a radiopharmaceutical, or an empty vial or other accessory item in a kit. [Canadian GMP
Compounding
A process wherein bulk drug substance is combined with another bulk drug substance and/or one
or more excipients to produce a drug product. [PIC/S PI 007-6]
Compressed Gas
Gas which, when packaged under pressure for transport, is entirely gaseous at all temperatures
above –50 °C. [EU GMP Guide, Annex 6]
Computer Hardware
Various pieces of equipment in the computer system, including the central processing unit, the
printer, the modem, the cathode ray tube (CRT), and other related apparatus. [PIC/S PI 011-3]
Computer System
A group of hardware components and associated software, designed and assembled to perform a
specific function or group of functions. [EU GMP Guide, Part II, ICH Q7]
Computer hardware components assembled to perform in conjunction with a set of software

programs, which are collectively designed to perform a specific function or group of functions.
[PIC/S PI 011-3]
Computerised System
A system including the input of data, electronic processing and the output of information to be
used either for reporting or automatic control. [EU GMP Guide, Glossary]
A process or operation integrated with a computer system. [EU GMP Guide, Part II, ICH Q7]
A computer system plus the controlled function that it operates. [Authors note: Today this may
be considered to be rather a narrow definition, especially in the context of integrated computers.
The definition should therefore include all outside influences that interface with the computer
system in its operating environment. These may typically include monitoring and network links,
(to/from other systems or instruments), manual (keypad inputs), links to different media, manual
procedures and automation. The term also covers automated instruments and systems. See also
the definition for ‘automated systems’ in this section and Section 26, Reference 11, the GLP
OECD consensus document. PIC/S GMP Annex 11(4) is relevant here regarding documenting
the scope and interaction of systems.] [PIC/S PI 011-3]
Concurrent Production
Simultaneous processing of more than one product in the same room/suite of a multi-product
facility, or simultaneous processing of more than one lot of a product in a dedicated facility.
Concurrent Release
Releasing for distribution a lot of finished product, manufactured following a qualification
protocol, that meets the lot release criteria established in the protocol, but before the entire study
protocol has been executed [Guidance for Industry: Process Validation: General Principles and
Practices, FDA]
Concurrent Validation
Validation carried out in exceptional circumstances, justified on the basis of significant patient
benefit, where the validation protocol is executed concurrently with commercialisation of the
validation batches. [EU GMP Guide, Annex 15]
Validation carried out during routine production of products intended for sale. [PIC/S PI 006-3]
Confidential Unit Exclusion (CUE)

A system that allows the donor, in private, to indicate that his/her collected blood should, or
should not, be used for transfusion to another individual.
[Canadian GMP Guide, Annex 14]
Configuration
The documented physical and functional characteristics of a particular item, or system, e.g.
software, computerised system, hardware, firmware and operating system. A change converts
one configuration into a new one. [PIC/S PI 011-3]
Configuration Management
The process of identifying and defining the configuration items in a system, controlling the
release and change of these items throughout the system life cycle, recording and reporting the
status of configuration items and change requests, and verifying the completeness and
correctness of configuration items. [PIC/S PI 011-3]
Confirmation
A signed statement that a process or test has been conducted in accordance with GMP and the
relevant marketing authorization, as agreed in writing with the Qualified Person responsible for
certifying the finished product batch before release. Confirm and confirmed have equivalent
meanings.
[EU GMP Guide, Annex 16]
Confirmatory Studies
Studies undertaken to establish photostability characteristics under standardized conditions.
These studies are used to identify precautionary measures needed in manufacturing or
formulation and whether light resistant packaging and/or special labeling is needed to mitigate
exposure to light. For the confirmatory studies, the batch(es) should be selected according to
batch selection for long-term and accelerated testings which is described in the Parent Guideline.
[ICH Q1B]
Conjugated Product
A conjugated product is made up of an active ingredient (for example, peptide, carbohydrate)
bound covalently or noncovalently to a carrier (for example, protein, peptide, inorganic mineral)
with the objective of improving the efficacy or stability of the product. [ICH Q5C]
Consignment
The quantity of a pharmaceutical(s), made by one manufacturer and supplied at one time in
response to a particular request or order. A consignment may comprise one or more packages or
containers and may include material belonging to more than one batch. [Main Principles for
The quantity of pharmaceutical products supplied at one time in response to a particular request
or order. A consignment may comprise one or more packages or containers and may include
pharmaceutical products belonging to more than one batch. [Good Distribution Practices for
The quantity of a bulk starting material, or of a drug product, made by one manufacturer or
supplied by an agent, and supplied at one time in response to a particular request or order. A
consignment may comprise one or more lot-identified packages or containers and may include
material belonging to more than one lot-identified batch. [Sampling Operations, WHO]
Constituent with Known Therapeutic Activity

Substances or groups of substances which are chemically defined and known to contribute to the
therapeutic activity of a herbal material or of a preparation. [Good Manufacturing Practices:
Specific Pharmaceutical Products, WHO]
Contained Area
An area constructed and operated in such a manner (and equipped with appropriate air handling
and filtration) so as to prevent contamination of the external environment by biological agents
from within the area. [EU GMP Guide, Glossary]
Container
A container is a cryogenic vessel (tank, tanker or other type of mobile cryogenic vessel) a
cylinder, a cylinder bundle or any other package that is in direct contact with the gas. [EU GMP
Guide, Annex 6]
The material employed in the packaging of a pharmaceutical product. Containers include

primary, secondary and transportation containers. Containers are referred to as primary if they
are intended to be in direct contact with the product. Secondary containers are not intended to be
in direct contact with the product. [Good Distribution Practices for Pharmaceutical Products,
WHO]
Container Closure System

The sum of packaging components that together contain and protect the dosage form. This
includes primary packaging components and secondary packaging components, if the latter are
intended to provide additional protection to the drug product. A packaging system is equivalent
to a container closure system. [ICH Q1A]
Containment
The action of confining a biological agent or other entity within a defined space. [EU GMP
Guide, Glossary]
A process or device to contain product, dust or contaminants in one zone, preventing it from
escaping to another zone. [TRS 957 Annex 5, WHO]
(confinement) Total isolation of one or more steps of a manufacturing process to prevent cross-
contamination of the product, or staff, from all other steps of the process. [Canadian GMP
(primary)
EA system of containment which prevents the escape of a biological agent into the immediate
working environment. It involves the use of closed containers or safety biological cabinets along
with secure operating procedures. [EU GMP Guide, Glossary]
(secondary)
A system of containment which prevents the escape of a biological agent into the external
environment or into other working areas. It involves the use of rooms with specially designed air
handling, the existence of airlocks and/or sterilisers for the exit of materials and secure operating
procedures. In many cases it may add to the effectiveness of primary containment. [EU GMP
Guide, Glossary]
Contaminant
Any adventitiously introduced materials (e.g., chemical, biochemical, or microbial species) not
intended to be part of the manufacturing process of the drug substance or drug product. [ICH
Q6B]
Contamination
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign
matter, into or onto a raw material, inter mediate, or API during production, sampling, packaging
or repackaging, storage or transport. [EU GMP Guide, Part II, ICH Q7]

matter, into or onto a starting material, or intermediate or finished product during production,
sampling, packaging or repackaging, storage or transport. [Guide to good storage practices for
pharmaceuticals, WHO]
matter, into or onto a raw material, in-process material, or phase 1 investigational drug during
manufacturing, sampling, packaging or repackaging, storage, or transport. [Guidance for
Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Continuous Cell Line

A cell line having an infinite capacity for growth. Often referred to as "“immortal”" and
previously referred to as “established”. [ICH Q5D]
Continuous Culture
Process by which growth of cells is maintained by periodically replacing a portion of the cells
and medium such that there is no lag or saturation phase. [Canadian GMP Guidelines, Annex 2]
Continuous Process Verification

An alternative approach to process validation in which manufacturing process performance is
continuously monitored and evaluated. [ICH Q8]
Continual Improvement
Recurring activity to increase the ability to fulfil requirements. (ISO 9000:2005). [ICH Q10]
Ongoing activities to evaluate and positively change products, processes, and the quality system
to increase effectiveness. [Guidance for Industry: Quality Systems Approach to Pharmaceutical
cGMP Regulations, FDA]
Contract Facility
Organization performing work associated with the manufacturing process for the manufacturer.
[Canadian GMP Guide, Annex 14]
Contract Manufacturer
A manufacturer performing some aspect of manufacturing on behalf of the original
manufacturer. [EU GMP Guide, Part II, ICH Q7]
Control Measure
Any action and activity that can be used to prevent or eliminate a pharmaceutical quality hazard
or reduce it to an acceptable level. [Hazard and Risk Analysis, WHO]
Control Number
see Batch Number
Control Strategy
A planned set of controls, derived from current product and process understanding, that assures
process performance and product quality. The controls can include
parameters and attributes related to drug substance and drug product materials and components,
facility and equipment operating conditions, in-process controls, finished product specifications,
and the associated methods and frequency of monitoring and control. [ICH Q10]
Controlled Area
An area constructed and operated in such a manner that some attempt is made to control the
introduction of potential contamination (an air supply approximating to grade D may be
appropriate), and the consequences of accidental release of living organisms. The level of control
exercised should reflect the nature of the organism employed in the process. At a minimum, the
area should be maintained at a pressure negative to the immediate external environment and
allow for the efficient removal of small quantities of airborne contaminants. [EU GMP Guide,
Glossary]
Controlled Work Area

An enclosed work area constructed and operated in such a manner and equipped with appropriate
air handling and filtration systems to reduce to a pre-defined level the introduction, generation
and retention of contaminants. A controlled work area may also be used to protect the external
environment from the materials being handled in it e.g. vaccines or cytotoxics. [PIC/S PE 010-4]
Correction
Repair, rework, or adjustment relating to the disposition of an existing discrepancy. [Guidance
for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Action to eliminate a detected non-conformity. Note 1: There is a distinction between correction

and corrective action. A correction can be made in conjunction with a corrective action. Note 2:
A correction can be, for example, rework or reclassification. [ISO 9000:2005]
Corrective Action (CA)

Action to eliminate the cause of a detected non-conformity or other undesirable situation. NOTE:
Corrective action is taken to prevent recurrence whereas preventive action is taken to prevent
occurrence. [ISO 9000:2005, ICH Q10]
Action taken to eliminate the causes of an existing discrepancy or other undesirable situation to
prevent recurrence. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP
Regulations, FDA]
Corrective Action and Preventive Action

see CAPA
COTS
see Commercial Off-the-Shelf
Counterfeit Pharmaceutical Product

A pharmaceutical product which is deliberately and fraudulently mislabelled with respect to
identity and/or source. Counterfeiting can apply to both branded and generic products, and
counterfeit pharmaceutical products may include products with the correct ingredients, with the
wrong ingredients, without active ingredients, with an incorrect quantity of active ingredient or
with fake packaging. [Good Distribution Practices for Pharmaceutical Products, WHO,
Inspection, WHO]
Critical
Describes a process step, process condition, test requirement, or other relevant parameter or item
that must be controlled within predetermined criteria to ensure that the API meets its
specification. [EU GMP Guide, Part II, ICH Q7]
Critical Area / Critical Zone

That part of the controlled work area where containers are opened and the product is exposed.
Particulate and microbiological contamination should be reduced to levels appropriate to the
intended use. [PIC/S PE 010-4]
Zone within the Aseptic Processing Area where sterile product, product components or product
contact surfaces are exposed to the environment. [PIC/S PE 014-4]
An area designed to maintain sterility of sterile materials. Sterilized product, containers, closures,
and equipment may be exposed in critical areas. [FDA Guidance for Industry Sterile Drug
Products Produced by Aseptic Processing – cGMP]
Area in which the sterilized drug product, containers, and closures are exposed to environmental
conditions that must be designed to maintain product sterility. Activities conducted in this area
include manipulations, such as aseptic connections, sterile ingredient additions, filling and
closing operations. [Canadian GMP Guidelines 2009]
Critical Control Point (CCP)

A step at which control can be applied and is essential to prevent or eliminate a pharmaceutical
quality hazard or to reduce it to an acceptable level. [TRS 961 Annex 7, WHO]
Critical Labelling
Labeling which identifies a product or status, such as a quarantine label or blood group label, if it
is used to control release for inventory. [Canadian GMP Guidelines, Annex 14]
Critical Operation
An operation in the manufacturing process that may cause variation in the quality of the
pharmaceutical product. [Main Principles for Pharmaceutical Products, WHO]
Critical Process Parameter (CPP)

A process parameter whose variability has an impact on a critical quality attribute and therefore
should be monitored or controlled to ensure the process produces the desired quality. [ICH Q8]
Critical Quality Attribute (CQA)

A physical, chemical, biological or microbiological property or characteristic that should be
within an appropriate limit, range, or distribution to ensure the desired product quality. [ICH Q8]
This refers to attributes of physical, chemical, biological or microorganism, should be of certain

limits, scope or distribution, so as to meet expectant product quality. [Chinese GMP Guidelines,
Annex 2]
Critical Surface
Surfaces that may come into contact with or directly affect a sterilized product or its containers
or closures. Critical surfaces are rendered sterile prior to the start of the manufacturing operation,
and sterility is maintained throughout processing. [Guidance for Industry: Sterile Drug Products
Produced by Aseptic Processing – cGMP, FDA]
Critical Variable Study

A study that serves to measure variables (parameters) critical to the satisfactory operation of a
piece of equipment or plant and to assure their operation within monitored and controlled limits.
Examples of variables would be pressure, temperature, flow rates, time etc. [PIC/S PI 006-3]
Cross-Contamination
Contamination of a material or of a product with another material or product. [EU GMP Guide
Part I, Glossary, ICH Q7, PIC/S PE 010-4]
Contamination of a starting material, intermediate product or finished product with another
starting material or product during production. [Guide to Good Storage Practices for
Contamination of a material or phase 1 investigational drug with another material or product.

[Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Contamination of a drug or biological starting material or in-process intermediate with another

drug or biological starting material or in-process intermediate. In multi-product facilities, cross-
contamination can occur throughout the manufacturing process, from generation of the MCB and
WCB through finishing. [Canadian GMP Guidelines 2009, Annex 2]
Crude Plant/Vegetable Drug

Fresh or dried medicinal plant or parts thereof. [EU GMP Guide, Glossary]
Customer
A person or organization (internal or external) that receives a product or service anywhere along
the product’s life cycle.
[Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Cylinder
A container designed to contain gas at a high pressure. [EU GMP Guide, Glossary]
Container usually cylindrical suited for compressed, liquefied or dissolved gas, fitted with a
device to regulate the spontaneous outflow of gas at atmospheric pressure and room temperature.
[EU GMP Guide, Annex 6]
Cylinder Bundle
An assembly of cylinders that are fastened together, interconnected by a manifold and
transported and used as a unit. [EU GMP Guide, Annex 6]
Cyrogenic Gas
A gas which liquefies at 1.013 bar at temperatures below -150 °C. [EU GMP Guide, Annex 6]
Cyrogenic Vessel
A container designed to contain liquefied gas at extremely low temperature. [EU GMP Guide,
Glossary]
D
D Value
The time (in minutes) of exposure at a given temperature that causes a one-log or 90 percent
reduction in the population of a specific microorganism. [Guidance for Industry: Sterile Drug
Debugging
The process of locating, analysing, and correcting suspected faults. [PIC/S PI 011-3]
Decision Maker
Person(s) with the competence and authority to make appropriate and timely quality risk
management decisions. [ICH Q9]
Decontamination
A process that eliminates viable bioburden via use of sporicidal chemical agents. [Guidance for
Dedicated
Facility or piece of equipment used only in the fabrication of a particular product. [Canadian
GMP Guidelines, Annex 2]
Facility or piece of equipment used only in the fabrication of a particular product or a closely
related group of products. [Canadian GMP Guidelines, Annex 3, Annex 5]
Degradation Product
An impurity resulting from a chemical change in the drug substance brought about during
manufacture and/or storage of the new drug product by the effect of, for example, light,
temperature, pH, water, or by reaction with an excipient and/or the immediate container closure
system. [ICH Q3B]
A molecule resulting from a change in the drug substance (bulk material) brought about over
time. For the purpose of stability testing of the products described in this guideline, such changes
could occur as a result of processing or storage (e.g., by deamidation, oxidation, aggregation,
proteolysis). For biotechnological/biological products some degradation products may be active.
[ICH Q5C]
A molecule resulting from a chemical change in the drug molecule brought about over time
and/or by the action of e.g., light, temperature, pH, water, or by reaction with an excipient and/or
the immediate container/closure system. Also called decomposition product. [ICH Q6A]
Molecular variants resulting from changes in the desired product or product-related substances
brought about over time and/or by the action of, e.g., light, temperature, pH, water, or by reaction
with an excipient and/or the immediate container/closure system. Such changes may occur as a
result of manufacture and/or storage (e.g., deamidation, oxidation, aggregation, proteolysis).
Degradation products may be either product-related substances, or product-related impurities.
[ICH Q6B]
Degradation Profile
A description of the degradation products observed in the drug substance or drug product. [ICH
Q3B]
Delayed Release
Release of a drug (or drugs) at a time other than immediately following oral administration. [ICH
Q6A]
Depyrogenation
A process used to destroy or remove pyrogens (e.g., endotoxin). [Guidance for Industry: Sterile
Drug Products Produced by Aseptic Processing – cGMP, FDA]
Design Condition
Design condition relates to the specified range or accuracy of a controlled variable used by the
designer as a basis for determining the performance requirements of an engineered system.
[Main Principles for Pharmaceutical Products, WHO]
Design History File

Compilation of records which describes the design history of a finished [medical] device. [21
CFR Part 820, FDA]
Design Input
The physical and performance requirements of a [medical] device that are used as a basis for
device design. [21 CFR Part 820, FDA]
Design Output
The results of a design effort at each design phase and at the end of the total design effort. The
finished design output is the basis for the device master record. The total finished design output
consists of the [medical] device, its packaging and labeling, and the device master record. [21
CFR Part 820, FDA]
Design Qualification (DQ)

The documented verification that the proposed design of the facilities, systems and equipment is
suitable for the intended purpose. [EU GMP Guide, Annex 15]
Documented evidence that the premises, supporting systems, utilities, equipment and processes
have been designed in accordance with the requirements of good manufacturing practices
(GMP). [TRS 961 Annex 7, WHO]
Design Review
A documented, comprehensive, systematic examination of a design to evaluate the adequacy of
the design requirements, to evaluate the capability of the design to meet these requirements, and
to identify problems. [21 CFR Part 820, FDA]
Design Space
The multidimensional combination and interaction of input variables (e.g., material attributes)
and process parameters that have been demonstrated to provide assurance of quality. Working
within the design space is not considered as a change. Movement out of the design space is
considered to be a change and would normally initiate a regulatory post approval change process.
Design space is proposed by the applicant and is subject to regulatory assessment and approval.
[ICH Q8]
Design Validation
Establishing by objective evidence that device specifications conform with user needs and
intended use(s). [21 CFR Part 820, FDA]
Desired Product
 The protein which has the expected structure, or

 the protein which is expected from the DNA sequence and anticipated post-translational
modification (including glycoforms), and from the intended downstream modification to
produce an active biological molecule. [ICH Q6B]
Detectability
The ability to discover or determine the existence, presence, or fact of a hazard. [ICH Q9]
Detection Limit
The detection limit of an individual analytical procedure is the lowest amount of analyte in a
sample which can be detected but not necessarily quantitated as an exact value. [ICH Q2]
Detoxification
Conversion of bacterial toxins to toxoids (non-toxic but immunogenic derivatives of toxins) by
chemical treatment. [Canadian GMP Guidelines, Annex 2]
Development Study
Studies conducted to scale-up, optimise, and validate the manufacturing process for a drug
product. [ICH Q3B]
Deviation / Discrepancy
Departure from an approved instruction or established standard. [EU GMP Guide Part II, ICH
Q7]
Failure to meet a critical limit. [Hazard and Risk Analysis, WHO]
Datum or result outside of the expected range, an unfulfilled requirement, may be called non-
conformity, defect, deviation, out-of-specification, out-of-limit, out-of-trend. [Guidance for
Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Deviation Report
A deviation report is a report of any deviation from standard procedures and documentation that
occurs during the preparation process, and consequent remedial action. [PIC/S PE 010-4]
Device History Record

A compilation of records containing the production history of a finished [medical] device. [21
CFR Part 820, FDA]
Device Master Record (DMR)

A compilation of records containing the procedures and specifications for a finished [medical]
device. [21 CFR Part 820, FDA]
Dilute Drug Premix

A drug for veterinary use that results from mixing a drug premix with a feed as defined in section
2 of the Feeds Act, to such a level that at least 10 kg of the resulting mixture is required to
medicate one tonne of complete feed, as defined in section 2 of the Feeds Regulations, 1983,
with the lowest approved dosage level of the drug. [Canadian GMP Guidelines 2009, Annex 4]
Diploid Cell Line

A cell line having a finite in vitro lifespan in which the chromosomes are paired (euploid) and
are structurally identical to those of the species from which they were derived. [ICH Q5D]
Direct Donation
Blood collected from an individual for the purpose of transfusion to a different individual, named
by the donor, who has been identified in advance to be compatible. [Canadian GMP Guidelines,
Annex 14]
Direct Impact System

A system that is expected to have a direct impact on product quality. These systems are designed
and commissioned in line with good engineering practice (GEP) and, in addition, are subject to
qualification practices. [Main Principles for Pharmaceutical Products, WHO]
Discrepancy
see Deviation
Disinfection
Process by which surface bioburden is reduced to a safe level or eliminated. Some disinfection
agents are effective only against vegetative microbes, while others possess additional capability
to effectively kill bacterial and fungal spores. [Guidance for Industry: Sterile Drug Products
Distribution
The procuring, purchasing, holding, storing, selling, supplying, importing, exporting, or
movement of pharmaceutical products, with the exception of the dispensing or providing
pharmaceutical products directly to a patient or his or her agent. [Good Distribution Practices for
Document Submission
The working documents received from the PDG or one or more pharmacopoeia sources (USP,
Ph. Eur., or JP) that contain the proposed pharmacopoeia text and any other support documents
provided for Q4B evaluation. [ICH Q4B]
Donor
The person who donates the cells or tissue that serves as the raw materials for the cell/tissue-
based drugs (excluding those concerned with the body of a brain-dead person specified in
Paragraph 2 of Article 6 of Law on Organ Transplantation (Law No. 104, 1997)). [Japan MHLW
Ministerial Ordinance No. 179, 2004]
Donor Animal
The animal which provides the cells or tissue that serves as the raw materials for the cell/tissue-
based drugs. [Japan MHLW Ministerial Ordinance No. 179, 2004]
Dosage Form
A pharmaceutical product type (e.g., tablet, capsule, solution, cream) that contains a drug
substance generally, but not necessarily, in association with excipients. [ICH Q1A]
Drug Identification Number

(drogue: identification numérique) A number assigned to each drug in dosage form under the
Food and Drug Regulations with the exception of blood and blood components and
radiopharmaceuticals. [Canadian GMP Guidelines 2009]
Drug Master File (DMF)

Detailed information concerning a specific facility, process or product submitted to the
medicines regulatory authority, intended for incorporation into the application for marketing
authorization. [TRS 961 Annex 7, WHO]
Drug Premix / Medicated Premix

A drug for veterinary use to which a drug identification number has been assigned, where the
directions on its label specify that it is to be mixed with feed as defined in section 2 of the Feeds
Act. (C.01A.001 of the Food and Drugs Regulations). It is a veterinary drug product prepared in
advance with a view to the subsequent manufacture of medicated feeds. [Canadian GMP
Guidelines, Annex 4]
Drug Product
The dosage form in the final immediate packaging intended for marketing. [ICH Q1A]
A pharmaceutical product type that contains a drug substance, generally, in association with
excipients. [ICH Q6B]
A finished dosage form (e.g., tablet, capsule, solution) that contains an active drug ingredient
generally, but not necessarily, in association with inactive ingredients. The term also includes a
finished dosage form that does not contain an active ingredient, but is intended to be used as a
placebo. [FDA Guidance for Industry cGMP for Phase 1 Investigational Drugs, 21 CFR 210,
FDA]
A pharmaceutical product type that contains a biological drug substance, generally in association
with excipients. It corresponds to the dosage form in the immediate packaging intended for
marketing (also called dosage form, finished product, final container product). [Canadian GMP
Drug Substance (bulk material)

(see also Active Pharmaceutical Ingredient) The material which is subsequently formulated with
excipients to produce the drug product. It can be composed of the desired product, product-
related substances, and product- and process-related impurities. It may also contain excipients
including other components such as buffers. [ICH Q6B]
Dynamic
Conditions relating to clean area classification under conditions of normal production. [Guidance
for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
E
Electrodeionisation (EDI)
(CDI = Continuous Deionisation, EDI = Electrodeionisation) A desalination process based on
electrodialysis and mixed bed technology.
Electronic Signature
(see also Advanced Electronic Signature)
An electronic measure that can be substituted for a handwritten signature or initials for the
purpose of signifying approval, authorization or verification of specific data entries. [PIC/S PI
011-3]
A computer data compilation of any symbol or series of symbols executed, adopted, or

authorized by an individual to be the legally binding equivalent of the individual's handwritten
signature. [21 CFR Part 11, FDA]
Embedded System
A system, usually microprocessor or PLC based, whose sole purpose is to control a particular
piece of automated equipment. This is contrasted with a standalone computer system. [PIC/S PI
011-3]
Enabler
A tool or process which provides the means to achieve an objective. [ICH Q10]
Enantiomer
Compounds with the same molecular formula as the drug substance, which differ in the spatial
arrangement of atoms within the molecule and are non-superimposable mirror images. [ICH
Q6A]
Enantiomeric Impurity
A compound with the same molecular formula as the drug substance that differs in the spatial
arrangement of atoms within the molecule and is a non-superimposable mirror image. [ICH
Q3A]
Endogenous Virus
Viral entity whose genome is part of the germ line of the species of origin of the cell line and is
covalently integrated into the genome of animal from which the parental cell line was derived.
For the purposes of this document, intentionally introduced, non-integrated viruses such as EBV
used to immortalise cell substrates or Bovine Papilloma Virus fit in this category. [ICH Q5A]
Endotoxin
A pyrogenic product (e.g., lipopolysaccharide) present in the bacterial cell wall. Endotoxin can
lead to reactions in patients receiving injections ranging from fever to death. [Guidance for
Enhanced Approach
A development approach where risk management and scientific knowledge ist used to identify
and understand the material attributes and process parameters which influence the critical quality
attributes of a product. [Guideline on Process Validation for Finished Products, EMA]
Enterprise Resource Planning System (ERPS)

ERP systems belong to the company management levels with strategic, commercial tasks with a
longer-term time frame. The most widely used ERP system is SAP.
Environmental Monitoring Programme

Defined documented programme which describes the routine particulate and microbiological
monitoring of processing and manufacturing areas, and includes a corrective action plan when
action levels are exceeded. [PIC/S PI 007-6]
Ethics Committee
An independent body in a Member State, consisting of healthcare professionals and nonmedical
members, whose responsibility it is to protect the rights, safety and wellbeing of human subjects
involved in a trial and to provide public assurance of that protection, by, among other things,
expressing an opinion on the trial protocol, the suitability of the investigators and the adequacy
of facilities, and on the methods and documents to be used to inform trial subjects and obtain
their informed consent. [Directive 2001/20/EC]
Evacuate
To remove the residual gas from a container/system to a pressure less than 1.013 bar, using a
vacuum system. [EU GMP Guide, Annex 6]
Ex-Vivo
Where procedures are conducted on tissues or cells outside the living body and returned to the
living body. [EU GMP Guide, Annex 2]
Excipient
Any constituent if a medicinal product other than the active substance and the packaging
material. [Directive 2011/62/EU]
Anything other than the drug substance in the dosage form. [ICH Q1A]
An ingredient added intentionally to the drug substance which should not have pharmacological
properties in the quantity used. [ICH Q6B]
Auxiliary materials used in the preparation of biological medicinal products, e.g., adjuvants,
stabilisers, excipients. [Chinese GMP Guidelines, Annex 3]
Executive Program
A computer program, usually part of the operating system, that controls the execution of other
computer programs and regulates the flow of work in a data processing system. [PIC/S PI 011-3]
Exotic Organism
A biological agent where either the corresponding disease does not exist in a given country or
geographical area, or where the disease is the subject of prophylactic measures or an eradication
programme undertaken in the given country or geographical area. [EU GMP Guide, Glossary]
 A substance, other than the active ingredient, which has been appropriately evaluated for
safety and is included in a drug delivery system to:
 aid in the processing of the drug delivery system during its manufacture,
 protect, support or enhance stability, bioavailability, or patient acceptability,
 assist in product identification, or
 enhance any other attribute of the overall safety and effectiveness of the drug during
storage or use. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Expiry Date / Expiration Date

(see also Shelf-Life)
The date placed on the container/labels of an API designating the time during which the API is
expected to remain within established shelf life specifications if stored under defined conditions,
and after which it should not be used. [EU GMP Guide Part II, ICH Q7]
The date placed on the container label of a drug product designating the time prior to which a
batch of the product is expected to remain within the approved shelf life specification if stored
under defined conditions, and after which it must not be used. [ICH Q1A]
The date given on the individual container (usually on the label) of a pharmaceutical
product/drug product up to and including the date on which the product is expected to remain
within specifications, if stored correctly. It is established for each batch by adding the shelf-life
to the date of manufacture. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
The end of the shelf life period, in non-coded form, after which the medicinal product should not
be used. Also called the use before date. [PIC/S PE 010-4]
Means the earlier of (a) the date, expressed at minimum as a year and month, up to and including
which a drug maintains its labelled potency, purity and physical characteristics, and (b) the date,
expressed at minimum as a year and month, after which the manufacturer recommends that the
drug not be used.” C.01.001) [Canadian GMP Guidelines 2009]
Export Procedure
Allow Community goods to leave the customs territory of the Union. For the purpose of these
guidelines, the supply of medicines from EU Member State to a contracting State of the
European Economic Area is not considered as export. [EU GDP Guidelines]
Expression Construct
The expression vector which contains the coding sequence of the recombinant protein and the
elements necessary for its expression. [ICH Q5B]
Extemporaneous Preparation
A product, which is dispensed immediately after preparation and not kept in stock. [PIC/S PE
010-4]
Extended Release
Products which are formulated to make the drug available over an extended period after
administration. [ICH Q6A]
Extraneous Contaminant
An impurity arising from any source extraneous to the manufacturing process. [ICH Q3A]
F
Facility
Any area, including mobile clinic sites, used for the collection, testing, component production,
storage (including records) or distribution of blood and blood components. [Canadian GMP
Factory Acceptance Test (FAT)

The partial commissioning and qualification of equipment and/or systems prior to their shipment
from the fabricators site (ISPE).
Failure Mode and Effects Analysis (FMEA)

Provides for an evaluation of potential failure modes for processes and their likely effect on
outcomes and / or product performance. Once failure modes are established, risk reduction can
be used to eliminate, contain, reduce or control the potential failures. [ICH Q9]
Failure Mode, Effects and Criticality Analysis (FMECA)

A systematic method of identifying and preventing product and process problems. [TRS 981
Annex 2, WHO]
Falsified Medicinal Product

Any medicinal product with a false representation of:
 Its identity, including its packaging and labelling, its name or its composition as regards
any of the ingredients including excipients and the strength of those ingredients,
 its source, including its manufacturer, its country of manufacturing, its country of origin
or its marketing authorization holder, or
 its history, including the records and documents relating to the distribution channels used.
[EU GDP Guidelines, Directive 2001/83/EC]
Feedback/Feedforward
Feedback: The modification or control of a process or system by its results or effects.
Feedforward: The modification or control of a process using its anticipated results or
effects. (Oxford Dictionary of English. Oxford University Press, 2003)
Feedback/ feedforward can be applied technically in process control strategies and conceptually
in quality management. [ICH Q10]
Feeder Cells
Cells used in co-culture to maintain pluripotent stem cells. For human embryonic stem cell
culture, typical feeder layers include mouse embryonic fibroblasts (MEFs) or human embryonic
fibroblasts that have been treated to prevent them from dividing. [EU GMP Guide, Annex 2]
Fermentation
A process in which cells or microorganisms are cultured in a container (bioreactor or fermenter),
in liquid or solid medium, for experimental or commercial processes. [Canadian GMP
Fiber
Any particulate contaminant with a length at least three times greater than its width. [21 CFR
Part 210, FDA]
Filling
Transferring a bulk drug into its final container and enclosing it in the container. [Canadian GMP
Guidelines 2009]
Finished Device
Any [medical] device or accessory to any device that is suitable for use or capable of
functioning, whether or not it is packaged, labeled, or sterilized. [21 CFR Part 820, FDA]
Finished Product
A medicinal product which has undergone all stages of production, including packaging in its
final container. [EU GMP Guide, Part I, Glossary, PIC/S PE 010-4]
A finished dosage form that has undergone all stages of manufacture, including packaging in its
final container and labelling. [TRS 908 Annex 4, WHO]
A product that has undergone all stages of production, including packaging in its final container
and labelling. [Canadian GMP Guidelines 2009]
Finished Product Batch

With reference to the control of the finished product, a finished product batch is defined in Part 1
Module 3 point 3.2.2.5 of Directive 2001/83/EC2 and in Part 2 section F 1 of Directive
2001/82/EC. In the context of this annex the term in particular denotes the batch of product in its
final pack for release to the market. [EU GMP Guide, Annex 16]
Firmware
A software program permanently recorded in a hardware device, such as an EPROM. (Note:
EPROM stands for ‘Erasable Programmable Read Only Memory’). [PIC/S PI 011-3]
First Expiry, First Out (FEFO)

A distribution procedure that ensures that the stock with the earliest expiry date is distributed
and/or used before an identical stock item with a later expiry date is distributed and/or used.
[Good Distribution Practices for Pharmaceutical Pro-ducts, WHO]
Flanking Control Region

Non-coding nucleotide sequences that are adjacent to the 5' and 3' end of the coding sequence of
the product which contain important elements that affect the transcription, translation, or stability
of the coding sequence. These regions include, e.g., promoter, enhancer, and splicing sequences
and do not include origins of replication and antibiotic resistance genes. [ICH Q5B]
FMEA
see Failure Mode and Effects Analysis
FMECA
see Failure Mode, Effects and Criticality Analysis
Forced Degradation Testing Study

Studies undertaken to degrade the sample deliberately. These studies, which may be undertaken
in the development phase normally on the drug substances, are used to evaluate the overall
photosensitivity of the material for method development purposes and/or degradation pathway
elucidation. [ICH Q1B]
Formal Experimental Design

A structured, organized method for determining the relationship between factors affecting a
process and the output of that process. Also known as “Design of Experiments”. [ICH Q8]
Formal Stability Study

Long term and accelerated (and intermediate) studies undertaken on primary and/or commitment
batches according to a prescribed stability protocol to establish or confirm the re-test period of a
drug substance or the shelf life of a drug product. [ICH Q1A]
Formulating
(transformation) Preparing components and combining raw materials into a bulk drug. [Canadian
Free Zone and Free Warehouse

Parts of the customs territory of the Community or premises situated in that territory and
separated from the rest of it which:
 Community goods are considered, for the purpose of import duties and commercial
policy import measures, as not being on Community customs territory, provided they are
not released for free circulation or placed under another customs procedure or used or
consumed under conditions other than those provided for in customs regulations,
 Community goods for which such provision is made under Community legislation
governing specific fields qualify, by virtue of being placed in a free zone or free
warehouse, for measures normally attaching to the export of goods. [EU GDP
Guidelines]
Functional Requirement
Statements that describe functions a computer-related system must be capable of performing.
[PIC/S PI 011-3]
Functional Specification
Statements of how the computerised system will satisfy functional requirements of the computer-
related system. [PIC/S PI 011-3]
Functional Testing
A process for verifying that software, a system, or a system component performs its intended
functions. [PIC/S PI 011-3]
G
Gap Analysis
Identification of critical elements of a process which are available at the SU but are missing from
the RU. [TRS 961 Annex 7, WHO]
Gas
Any substance that is completely gaseous at 1.013 bar and +20 °C or has a vapour pressure
exceeding 3 bar at +50 °C. [EU GMP Guide, Annex 6]
Gene
A sequence of DNA that codes for one (or more) protein(s). [EU GMP Guide, Annex 2]
Gene Therapy Medicinal Product
A biological medicinal product which has the following characteristics:

 it contains an active substance which contains or consists of a recombinant nucleic acid
used in or administered to human beings with a view to regulating, repairing, replacing,
adding or deleting a genetic sequence,
 its therapeutic, prophylactic or diagnostic effect relates directly to the recombinant
nucleic acid sequence it contains, or to the product of genetic expression of this sequence.
Gene therapy medicinal products shall not include vaccines against infectious diseases.
[Directive 2001/83/EC]
Gene Transfer
A process to transfer a gene in cells, involving an expression system contained in a delivery
system known as a vector, which can be of viral, as well as non-viral origin. After gene transfer,
genetically modified cells are also termed transduced cells. [EU GMP Guide, Annex 2]
Genotoxic Carcinogen
Carcinogens which produce cancer by affecting genes or chromosomes. [ICH Q3C]
Good Clinical Practice (GCP)

A standard for the design, conduct, performance, monitoring, auditing, recording, analysis and
reporting of clinical trials, that provides assurance that the data and reported results are
credible and accurate, and that the rights, integrity and confidentiality of trial subjects are
protected.
Good Distribution Practice (GDP)

GDP is that part of quality assurance which ensures that the quality of medicinal products is
maintained throughout all stages of the supply chain from the site of manufacturer to the
pharmacy or person authorized or entitled to supply medicinal products to the public. [EU GDP
Guidelines]
That part of quality assurance that ensures that the quality of a pharmaceutical product is
maintained by means of adequate control of the numerous activities which occur during the
distribution process as well as providing a tool to secure the distribution system from
counterfeits, unapproved, illegally imported, stolen, counterfeit, substandard, adulterated, and/or
misbranded pharmaceutical products. [Good Distribution Practices for Pharmaceutical Products,
WHO]
Good Engineering Practice (GEP)

Established engineering methods and standards that are applied throughout the project life-cycle
to deliver appropriate, cost-effective solutions. [Main Principles for Pharmaceutical Products,
WHO]
Good Laboratory Practice (GLP)

A quality assurance system based on national legal requirements (e.g. §19 of the German
Chemicals Act or 21 CFR 211) and which is subject to governmental inspection. GLP guidelines
regulate the organization, the workflow and the conditions under which non-clinical health and
environmental safety studies are planned, performed, monitored, recorded, reported, and
archived. The aim of GLP is to improve the quality and reliability of test data.
Good Manufacturing Practice (GMP)

The part of quality assurance which ensures that products are consistently produced and
controlled in accordance with the quality standards appropriate to their intended use. [Directive
2003/94/EC]
That part of quality assurance which ensures that pharmaceutical products are consistently
produced and controlled to the quality standards appropriate to their intended use and as required
by the marketing authorization. [Good Distribution Practices for Pharmaceutical Products,
WHO, Inspection, WHO]
Good Pharmacy Practice (GPP)

The practice of pharmacy aimed at providing and promoting the best use of medicines and other
health care services and products, by patients and members of the public. It requires that the
welfare of the patient is the pharmacist’s prime concern at all times. [Good Distribution Practices
for Pharmaceutical Products, WHO, Inspection, WHO]
Good Storage Practice (GSP)

That part of quality assurance that ensures that the quality of pharmaceutical products is
maintained by means of adequate control throughout the storage thereof. [Good Distribution
Practices for Pharmaceutical Products, WHO]
Good Trade and Distribution Practice (GTDP)

That part of quality assurance that ensures that the quality of pharmaceutical products is
maintained by means of adequate control throughout the numerous activities which occur during
the trade and the distribution process. [Good Distribution Practices for Pharmaceutical Products,
WHO]
Gowning Qualification
A program that establishes, both initially and on a periodic basis, the capability of an individual
to don the complete sterile gown in an aseptic manner. [Guidance for Industry: Sterile Drug
Growth Promotion Test

Test performed to demonstrate that media will support microbial growth. [PIC/S PI 007-6]
Also referred to as fertility or nutritive properties test, which is performed on the media used
during the sterility test to demonstrate that it is capable of supporting the growth of micro-
organisms. [PIC/S PI 012-3]
H
HACCP Plan
A document prepared in accordance with the principles of HACCP to ensure the control of
hazards which are significant for pharmaceutical quality in the production and supply chain.
[Hazard and Risk Analysis, WHO]
Hapten
A low molecular weight molecule that is not in itself antigenic unless conjugated to a 'carrier'
molecule. [EU GMP Guide, Annex 2]
Hardware Acceptance Test Specification

Statements for the testing of all key aspects of hardware installation to assure adherence to
appropriate codes and approved design intentions and that the recommendations of the regulated
user have been suitably considered. [PIC/S PI 011-3]
Hardware Design Specification

Description of the hardware on which the software resides and how it is to be connected to any
system or equipment. [PIC/S PI 011-3]
Harm
Damage to health, including the damage that can occur from loss of product quality or
availability. [ICH Q9, Guidance for Industry: Quality Systems Approach to Pharmaceutical
Harvesting
Procedure by which the cells, inclusion bodies or crude supernatants containing the unpurified
active ingredient are recovered. [Canadian GMP Guidelines, Annex 2]
Hazard
The potential source of harm (ISO/IEC Guide 51). [ICH Q9]
Any circumstance in the production, control and distribution of a pharmaceutical which can
cause an adverse health effect. [Hazard and Risk Analysis in Pharmaceutical Products, WHO]
Hazard Analysis
The process of collecting and evaluating information on hazards which should be addressed in
the HACCP plan. [Hazard and Risk Analysis in Pharmaceutical Products, WHO]
Healthcare Establishment
Establishments supplying medicinal products to their own patients in line with national
legislation. [PIC/S PE 010-4]
HEPA Filter
Retentive matrix designed to remove a defined percentage of particulate matter of a defined size.
[PIC/S PI 007-6]
High efficiency particulate air filter with minimum 0.3 µm particle retaining efficiency of 99.97
percent. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP,
FDA]
Herbal Material
Herbal Materials include, in addition to herbs, fresh juices, gums, fixed oils, essential oils, resins
and dry powders of herbs. In some countries, these materials may be processed by various local
procedures, such as steaming, roasting or stir-baking with honey, alcoholic beverages or other
materials. [Specific Pharmaceutical Products, WHO]
Herbal Medicinal Product

Medicinal product containing, as active ingredients, exclusively plant material and/or vegetable
drug preparations. [EU GMP Guide, Glossary]
Any medicinal product, exclusively containing as active ingredients one or more herbal
substances or one or more herbal preparations, or one or more such herbal substances in
combination with one or more such herbal preparations. [Directive 2001/83/EC]
Herbal Medicine
Herbal medicines include herbs, herbal materials, herbal preparations and finished herbal
products. [Specific Pharmaceutical Products, WHO]
Herbal Preparation
Preparations obtained by subjecting herbal substances to treatments such as extraction,
distillation, expression, fractionation, purification, concentration or fermentation. These include
comminuted or powdered herbal substances, tinctures, extracts, essential oils, expressed juices
and processed exudates. [Directive 2001/83/EC]
Herbal Product
Medicinal products containing, exclusively, plant material and/or vegetable drug preparations as
active ingredients. In some traditions, materials of inorganic or animal origin can also be present.
[ICH Q3A]
Herbal Substance
All mainly whole, fragmented or cut plants, plant parts, algae, fungi, lichen in an unprocessed,
usually dried, form, but sometimes fresh. Certain exudates that have not been subjected to a
specific treatment are also considered to be herbal substances. Herbal substances are precisely
defined by the plant part used and the botanical name according to the binomial system (genus,
species, variety and author). [Directive 2001/83/EC]
Highly Purified Water

Low endotoxin water, reverse osmosis water. [Pharmacopoeia Europaea]
Highly Water Soluble Drug

Drugs with a dose/solubility volume of less than or equal to 250 ml over a pH range of 1.2 to 6.8.
(Example: Compound A has as its lowest solubility at 37 +/–0.5 °C, 1.0 mg/ml at pH 6.8, and is
available in 100 mg, 200 mg, and 400 mg strengths. This drug would be considered a low
solubility drug as its dose/solubility volume is greater than 250 ml (400 mg/1.0 mg/ml = 400 ml).
[ICH Q6A]
Holding
Storing medicinal products. [EU GDP Guidelines]
Home Cryogenic Vessel

Mobile cryogenic vessel designed to hold liquid oxygen and dispense gaseous oxygen at patients'
home. [EU GMP Guide, Annex 6]
Homeopathic Medicinal Product

Any medicinal product prepared from substances called homeopathic stocks in accordance with a
homeopathic manufacturing procedure described by the European Pharmacopoeia or, in the
absence thereof, by the pharmacopoeias currently used officially in the Member States. A
homeopathic medicinal product may contain a number of principles. [Directive 2001/83/EC]
Homogeneity
A material is regarded as homogeneous when it is all of the same origin (e.g. from the same
batch) and as non-homogeneous when it is of differing origins. [Sampling Operations, WHO]
Hot-Cell
Shielded workstation for manufacture and handling of radioactive materials. Hot-cells are not
necessarily designed as an isolator. [EU GMP Guide, Annex 3]
A total containment cabinet shielded with lead. [Canadian GMP Guidelines 2009, Annex 3]
An aseptic total containment cabinet providing a Class A (with Laminar flow), or Class B (with
Turbulent flow) environment, and is shielded with lead of various thickness. [Canada GMP
Hybridoma
An immortalised cell line that secrete desired (monoclonal) antibodies and are typically derived
by fusing B-lymphocytes with tumour cells. [EU GMP Guide, Annex 2]
Hydrostatic Pressure Test

Test performed as required by national or international regulations, in order to ensure that
pressure containers are able to withstand pressures up to the container's design pressure. [EU
GMP Guide, Annex 6]
I
Identification Threshold
A limit above (>) which a degradation product should be identified. [ICH Q3A, Q3B]
Identified Degradation Product

A degradation product for which a structural characterization has been achieved. [ICH Q3B]
Identified Impurity
An impurity for which a structural characterization has been achieved. [ICH Q3A, Q6A]
Immediate (Primary) Pack

That constituent of the packaging that is in direct contact with the drug substance or drug
product, and includes any appropriate label. [ICH Q1B]
Immediate Packaging
The container or other form of packaging immediately in contact with the medicinal product.
Immediate Release
Allows the drug to dissolve in the gastrointestinal contents, with no intention of delaying or
prolonging the dissolution or absorption of the drug [ICH Q6A]
Immunological Medicinal Product

Any medicinal product consisting of vaccines, toxins, serums or allergen products:
 vaccines, toxins and serums shall cover in particular:
 agents used to produce active immunity, such as cholera vaccine, BCG, polio
vaccines, smallpox vaccine,
 agents used to diagnose the state of immunity, including in particular tuberculin
and tuberculin PPD, toxins for the Schick and Dick Tests, brucellin,
 agents used to produce passive immunity, such as diphtheria antitoxin, anti-
smallpox globulin, antilymphocytic globulin,
 'allergen product' shall mean any medicinal product which is intended to identify or
induce a specific aquired alteration in the immunological response to an allergizing agent.
Impermeable Container
Containers that provide a permanent barrier to the passage of gases or solvents, e.g., sealed
aluminum tubes for semi-solids, sealed glass ampoules for solutions. [ICH Q1A]
Importer
The holder of the authorization required by Article 40.3 of Directive 2001/83/EC and Article
44.3 of Directive 2001/82/EC for importing medicinal products from third countries. [EU GMP
Guide, Annex 16]
Impurity
Any component present in the intermediate or API that is not the desired entity. [EU GMP Guide
Part II, ICH Q7]
Any component of the drug substance (bulk material) or drug product (final container product)
which is not the chemical entity defined as the drug substance, an excipient, or other additives to
the drug product. [ICH Q5C, see also: Q3A, Q3B, Q6A, Q6B]
Impurity Profile
A description of the identified and unidentified impurities present in an API. [EU GMP Guide
Part II, ICH Q3A, Q3B, Q7]
In Operation State
The "in operation" state is the condition where the installation is functioning in the defined
operating mode with the specified number of personnel working. [EU GMP Guide, Annex 1]
In-house Primary Reference Material

An appropriately characterized material prepared by the manufacturer from (a) representative
lot(s) for the purpose of biological assay and physicochemical testing of subsequent lots, and
against which in-house working reference material is calibrated. [ICH Q6B]
In-house Working Reference Material

A material prepared similarly to the primary reference material that is established solely to assess
and control subsequent lots for the individual attribute in question. It is always calibrated against
the in-house primary reference material. [ICH Q6B]
In-line
Measurement where the sample is analyzed within the process stream and not removed from it.
[Guideline on Process Validation for Finished Products, EMA]
In-process Control
Checks performed during production in order to monitor and if necessary to adjust the process to
ensure that the product conforms its specification. The control of the environment or equipment
may also be regarded as a part of in-process control. [EU GMP Guide, Glossary]
Checks performed during production in order to monitor and, if necessary, to adjust the process
to ensure that the finished product conforms to its specifications. The control of the production
environment or equipment may also be regarded as a part of in-process control. [ICH Q7,
Canadian GMP Guidelines 2009]
In-process Drug
Any material or mixture of materials that must, to become a drug in dosage form, undergo
further processing. [Canadian GMP Guidelines 2009]
In-process Material
Any material fabricated, compounded, blended, or derived by chemical reaction that is produced
for, and used in, the preparation of the drug product. [21 CFR Part 210, FDA]
Any material fabricated, compounded, blended, or derived by chemical reaction (e.g.,

intermediate) that is manufactured for, and used in, the preparation of the phase 1 investigational
drug. [Guidance for Industry cGMP for Phase 1 Investigational Drugs, FDA]
In-process Test
Tests which may be performed during the manufacture of either the drug substance or drug
product, rather than as part of the formal battery of tests which are conducted prior to release.
[ICH Q6A]
In-use Expiry Date

The end of the application period, in which a medicinal product may be taken or applied after the
package has been opened, respectively after a first dose of the medicinal product has been taken
from the package. [PICS/S PE 010-4]
In-vitro Cell Age

A measure of the period between thawing of the MCB vial(s) and harvest of the production
vessel measured by elapsed chronological time in culture, population doubling level of the cells
or passage level of the cells when subcultivated by a defined procedure for dilution of the culture
[ICH Q5B, Q5A, Q5D]
In-vivo
Procedures conducted in living organisms. [EU GMP Guide, Annex 2]
Inactivation
Removal of infectivity of microorganisms by chemical or physical modification. [ICH Q5A]
Indirect Impact System

This is a system that is not expected to have a direct impact on product quality, but typically will
support a direct impact system. These systems are designed and commissioned according to GEP
only. [Main Principles for Pharmaceutical Products, WHO]
Industrial Isolator used for Aseptic Processing

Industrial isolators used for aseptic processing are isolators in which the internal space and
exposed surfaces are microbiologically controlled. Control is achieved by the use of
microbiologically retentive filters, sterilization processes, sporicidal processes (usually by
gassing) and prevention of recontamination from the external environment. [PIC/S PI 014-3]
Infiltration
The ingress of contaminated air from an external zone into a clean area. [Main Principles for
Informed Consent (IC)

Decision, which must be written, dated and signed, to take part in a clinical trial, taken freely
after being duly informed of its nature, significance, implications and risks and appropriately
documented, by any person capable of giving consent or, where the person is not capable of
giving consent, by his or her legal representative. If the person concerned is unable to write, oral
consent in the presence of at least one witness may be given in exceptional cases, as provided for
in national legislation. [Directive 2001/20/EC]
Innovation
The introduction of new technologies or methodologies. [ICH Q10]
Inspection
see Auditing
Installation Qualification (IQ)

The documented verification that the facilities, systems and equipment, as installed or modified,
comply with the approved design and the manufacturer’s recommendations. [EU GMP Guide,
Annex 15]
The performance and documentation of tests to ensure that equipment (such as machines,
measuring equipment) used in a manufacturing process, are appropriately selected, correctly
installed and work in accordance with established specifications. [PIC/S PI 006-3]
The documented act of demonstrating that process equipment and ancillary systems are
appropriately selected and correctly installed. [Canadian GMP Guidelines 2009]
Integration Site
The site where one or more copies of the expression construct is integrated into the host cell
genome. [ICH Q5B]
Integration Testing
An orderly progression of testing in which software elements, hardware elements, or both are
combined and tested until the entire system has been integrated. [PIC/S PI 011-3]
Integrity Test
Test to determine the functional performance of a filter system. [PIC/S PI 007-6]
Interchangeable
Where such status is indicated, any of the official texts from JP, EP, or USP can be substituted
one for the other (appropriately referenced) in the ICH regions for purposes of the
pharmaceutical registration/approval process. Using any of the interchangeable methods, an
analyst will reach the same accept or reject decisions irrespective of which PDG pharmacopeia is
used. [ICH Q4B]
Intermediate
Partly processed material which must undergo further manufacturing steps before it becomes a
bulk product. [EU GMP Guide, Glossary]
A material produced during steps of the processing of an API that undergoes further molecular
change or purification before it becomes an API. Intermediates may or may not be isolated.
(Note: this Guide only addresses those intermediates produced after the point that the company
has defined as the point at which the production of the API begins.) [EU GMP Guide, Part II, see
also ICH Q3A]
For biotechnological/biological products, a material produced during a manufacturing process

which is not the drug substance or the drug product but whose manufacture is critical to the
successful production of the drug substance or the drug product. Generally, an intermediate will
be quantifiable and specifications will be established to determine the successful completion of
the manufacturing step prior to continuation of the manufacturing process. This includes material
which may undergo further molecular modification or be held for an extended period of time
prior to further processing. [ICH Q5C]
Intermediate Precision
Intermediate precision expresses within-laboratories variations: different days, different analysts,
different equipment, etc. [ICH Q2]
Intermediate Product
A partly processed material, which should undergo further preparation steps before it becomes a
bulk product. [EU GMP Guide, Glossary, PIC/S PE 010-4, Good Distribution Practices for
Pharmaceutical Products, WHO, Main Principles for Pharmaceutical Products, WHO]
Intermediate Testing
Studies conducted at 30 °C / 65% RH and designed to moderately increase the rate of chemical
degradation or physical changes for a drug substance or drug product intended to be stored long
term at 25 °C. [ICH Q1A]
Intervention
An aseptic manipulation or activity that occurs at the critical area. [Guidance for Industry: Sterile
Drug Products Produced by Aseptic Processing – cGMP, FDA]
Investigational Medicinal Product
A pharmaceutical form of an active substance or placebo being tested or used as a reference in a
clinical trial, including products already with a marketing authorization but used or assembled
(formulated or packaged) in a way different from the authorized form, or when used for an
unauthorized indication, or when used to gain further information about the authorized form.
A pharmaceutical form of an active substance or placebo being tested or used as a reference in a

clinical trial, including a product with a marketing authorization when used or assembled
(formulated or packaged) in a way different from the authorized form, or when used for an
unauthorized indication, or when used to gain further information about the authorized form.
[EU GMP Guide, Annex 13; Canadian GMP Guidelines 2009, Annex 13]
Investigator
A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a
team of individuals at a trial site, the investigator is the responsible leader of the team and may
be called the principal investigator. [EU GMP Guide, Annex 13]
A doctor or a person following a profession agreed in the Member State for investigations
because of the scientific background and the experience in patient care it requires. The
investigator is responsible for conducting a clinical trial at a trial site. If a trial is conducted by a
team of individuals at a trial site, the investigator is the leader responsible for the team and may
be called the principal investigator. [Directive 2001/20/EC]
The person responsible for the trial and for protecting the rights, health and welfare of the
subjects in the trial. The investigator must be an appropriately qualified person legally allowed to
practice medicine/dentistry. [Good Manufacturing Practices: Specific Pharmaceutical Products,
WHO]
The person responsible to the sponsor for the conduct of the clinical trial at a clinical trial site,
who is entitled to provide health care under the laws of the province where that clinical trial site
is located, and who is in the case of a clinical trial respecting a drug to be used for dental
purposes only, a physician or dentist and a member in good standing of a professional medical or
dental association, and in any other case, a physician and a member in good standing of a
professional medical association. [Canadian GMP-Guidelines, Annex 13]
Investigators Brochure
A compilation of the clinical and non-clinical data on the investigational medicinal product or
products which are relevant to the study of the product or products in human subjects. [Directive
2001/20/EC]
Isolator
A decontaminated unit, supplied with Class 100 (ISO 5) or higher air quality, that provides
uncompromised, continuous isolation of its interior from the external environment (e.g.,
surrounding cleanroom air and personnel). [Guidance for Industry: Sterile Drug Products
Produced by Aseptic Processing – cGMP, FDA] A barrier or system that is equiped with Grade
B (ISO 5) or even higher cleanness air handling units and can isolate completely the internal
environment from external environment (e.g clean room and operators). [Chinese GMP
Guidelines, Annex1]
K
Kit
Any preparation to be reconstituted or combined with radionuclides in the final
radiopharmaceutical, usually prior to its administration. [Directive 2001/83/EC]
Knowledge Management
A systematic approach to acquire, analyse, store and disseminate information related to products,
manufacturing processes and components. [EU GMP Guide, Annex 15, ICH Q10]
L
Labelling
Information on the immediate or outer packaging. [Directive 2001/83/EC]
The action involving the selection of the correct label, with the required information, followed by
line clearance and application of the label. [Guide to Good Storage Practices for
Process of identifying a pharmaceutical product including the following information, as

appropriate: name of the product, active ingredient(s), type and amount, batch number, expiry
date, special storage conditions or handling precautions, directions for use, warnings and
precautions, names and addresses of the manufacturer and/or the supplier. [Good Distribution
Laboratory Information Management System (LIMS)

LIMS, like MES, belong to the plant management levels. They are used to record and document
quality-related values e.g. for inspection of incoming goods or so-called In-Process Controls
(IPC) for the process running time.
Laminar Flow
(see also Unidirectional Airflow (UDAF))
An airflow moving in a single direction and in parallel layers at constant velocity from the
beginning to the end of a straight line vector. [Guidance for Industry: Sterile Drug Products
The method that the air flows unidirectional with the stable symmetrical way and enough rate. It
can continuously remove the particles at the critical operation area. [Chinese GMP Guidelines,
Annex1]
Large-Volume Parental
Sterile solutions intended for parenteral application with a volume of 100 ml or more in one
container of the finished dosage form. [Main Principles for Pharmaceutical Products, WHO]
Leukapheresis
Separation of leukocytes by removing whole blood from the donor, separating the leukocytes,
and returning the formed elements and plasma back to the donor. [Canadian GMP Guidelines,
Annex 14]
Leuko Reduced Component

Component units that have been treated by centrifugation, filtration or other methods to reduce
the amount of leukocytes per unit to a level below a standard acceptable value. [Canadian GMP
Lifecycle
All phases in the life of a product from the initial development through marketing until the
product’s discontinuation. [EU GMP Guide, Annex 15, ICH Q8]
Lifecycle Concept
An approach to computer system development that begins with (PMA CSVC) identification of
the user’s requirements, continues through design, integration, qualification, user validation,
control and maintenance, and ends only when commercial use of the system is discontinued.
[PIC/S PI 011-3]
Ligand
An agent with a strong affinity to a metal ion. [ICH Q3A]
Limit of Detection (LOD)

The lowest amount of analyte in a sample which can be detected but not quantitated as an exact
value. The Limit of Detection is mostly a parameter of limit tests. [PIC/S PI 006-3]
Limit of Quantification (LOQ)

The lowest amount of analyte in a sample which can be quantitatively determined with defined
precision and accuracy under the stated experimental conditions. [PIC/S PI 006-3]
Limit of Quantitation (LOQ)

The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a
sample which can be quantitatively determined with suitable precision and accuracy. The
quantitation limit is a parameter of quantitative assays for low levels of compounds in sample
matrices, and is used particularly for the determination of impurities and/or degradation products.
[ICH Q2]
Liquefiable Gas
Those which, at the normal filling temperature and pressure, remain as a liquid in the cylinder.
[EU GMP Guide, Glossary]
Liquefied Gas
A gas which, when packaged for transport, is partially liquid (or solid) at a temperature above –
50 °C. [EU GMP Guide, Annex 6]
Long Term
Testing Stability studies under the recommended storage condition for the re-test period or shelf
life proposed (or approved) for labeling. [ICH Q1A]
Look-back
Documented procedure to trace biological medicinal substances or products which may be
adversely affected by the use or incorporation of animal or human materials when either such
materials fail release tests due to the presence of contaminating agent(s) or when conditions of
concern become apparent in the source animal or human. [EU GMP Guide, Annex 2]
The process of identifying current or previous donations from a donor subsequently confirmed
positive for a transfusion-transmitted agent in order to identify and notify consignees and
recipients of suspect blood components from that donor, and retrieve available components. A
lookback may be initiated through a traceback investigation or by a report of seroconversion or
infection in a donor. [Canadian GMP Guidelines, Annex 14]
Loop Testing
Checking the installed combination of elements characterising each type of input/output loop.
[PIC/S PI 011-3]
Lot see Batch

Lot Number see Batch Number
Lowest-Observed Effect Level (LOEL)

The lowest dose of substance in a study or group of studies that produces biologically significant
increases in frequency or severity of any effects in the exposed humans or animals. [ICH Q3C]
M
Management with Executive Responsibility
Those senior employees of a manufacturer who have the authority to establish or make changes
to the manufacturer‘s quality policy and quality system. [21 CFR Part 820, FDA]
Manifold
Equipment or apparatus designed to enable one or more gas containers to be filled
simultaneously from the same source. [EU GMP Guide, Glossary]
Equipment or apparatus designed to enable one or more gas containers to be emptied and filled at
a time. [EU GMP Guide, Annex 6]
A unit for connecting a cylindrical pipe fitting, having a number of lateral outlets, for connecting
one pipe with several others used in the Radiosynthesizer Unit. [Canadian GMP Guidelines
2009, Annex 5]
Manufacture / Production
All operations of purchase of materials and products, Production, Quality Control, release,
storage, distribution of medicinal products and the related controls. [EU GMP Guide, Glossary]
All operations of receipt of materials, production, packaging, repackaging, labelling, relabelling,

quality control, release, storage, and distribution of APIs and related controls. [EU GMP Guide,
Part II, ICH Q7]
Production, quality control and release and delivery of radiopharmaceuticals from the active
substance and starting materials. [EU GMP Guide, Annex 3]
All operations of purchase of materials and products, production, quality control, release, storage
and distribution of finished products, and the related controls. [Guide to Good Storage Practices
for Pharmaceutical Products, WHO]
All operations of purchase of materials and products, production, packaging, labelling, quality
control, release, storage and distribution of pharmaceutical products, and the related controls.
[Guide to Good Distribution Practices for Pharmaceuticals, WHO]
Part of preparation. It involves all processes and operations in the preparation of a medicinal
product, from receipt of materials, through processing and packaging, to its completion as a
finished product. [PIC/S PE 010-4]
All operations involved in the preparation of a phase 1 investigational drug from receipt of
materials through distribution including processing, storage, packaging, labeling, laboratory
testing, and QC. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
(fabrication) All operations including purchase of materials and products, production, quality
control, release, storage, distribution and related controls. [Canadian GMP Guidelines 2009,
Annex 5]
Manufacturer
Holder of a Manufacturing Authorization as described in Article 40 of Directive 2001/83/EC.
[EU GMP Guide, Glossary]
Any person who designs, manufactures, fabricates, assembles, or processes a finished [medical]
device. Manufacturer includes but is not limited to those who perform the functions of contract
sterilization, installation, relabeling, remanufacturing, repacking, or specification development,
and initial distributors of foreign entities performing these functions. [21 CFR Part 820, FDA]
A person who takes responsibility for and is involved in any aspect of the manufacture of a phase
1 investigational drug. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Manufacturer/Importer of Investigational Medicinal Product Any person engaged in activities for

which the authorization referred to in Article 13(1) of Directive 2001/20/EC is required. [EU
GMP Guide, Annex 13]
In connection with investigational medicinal products, any holder of the authorization to

manufacture/import. [Canadian GMP Guidelines 2009, Annex 13]
Manufacturing Batch Record

Records demonstrating that the batch of a drug was fabricated in accordance with the approved
master production documents. [Canadian GMP Guidelines 2009]
Manufacturing Material
Any material or substance used in or used to facilitate the manufacturing process, a concomitant
constituent, or a byproduct constituent produced during the manufacturing process, which is
present in or on the finished [medical] device as a residue or impurity not by design or intent of
the manufacturer. [21 CFR Part 820, FDA]
Manufacturing Scale Production

Manufacture at the scale typically encountered in a facility intended for product production for
marketing. [ICH Q5C]
Marker
Chemically defined constituents of a herbal material utilized for control purposes. They may or
may not contribute to the clinical efficacy. When they contribute to the clinical efficacy,
however, evidence that they are solely responsible for the clinical efficacy may or may not be
available. Markers are generally employed when constituents of known therapeutic activity are
not known or are not clearly identified, and may be used to identify the herbal material or
preparation or calculate their quantity in the finished product. [Specific Pharmaceutical Products,
WHO]
Marketing Authorization (product licence, registration certificate)

A legal document issued by the competent drug regulatory authority that establishes the detailed
composition and formulation of the product and the pharmacopoeial or other recognized
specifications of its ingredients and of the final product itself, and includes details of packaging,
labelling and shelf-life. [Main Principles for Pharmaceutical Products, WHO]
A legal document issued by the competent medicines regulatory authority for the purpose of
marketing or free distribution of a product after evaluation for safety, efficacy and quality. It
must set out, inter alia, the name of the product, the pharmaceutical dosage form, the quantitative
formula (including excipients) per unit dose (using INNs or national generic names where they
exist), the shelf-life and storage conditions, and packaging characteristics. It species the
information on which authorization is based (e.g. “The product(s) must conform to all the details
provided in your application and as modified in subsequent correspondence”). It also contains
the product information approved for health professionals and the public, the sales category, the
name and address of the holder of the authorization, and the period of validity of the
authorization. Once a product has been given marketing authorization, it is included on a list of
authorized products – the register – and is often said to be “registered” or to “have registration”.
Market authorization may occasionally also be referred to as a “licence” or “product licence”.
[Good Distribution Practices for Pharmaceutical Products, WHO]
A legal document issued by Health Canada, authorizing the sale of a drug or a device based on
the health and safety requirements of the Food and Drug Act and its associated Regulations. The
marketing authorization may be in the form of a Notice of Compliance (NOC), Drug
Identification Number (DIN), a device licence for classes II, III and IV medical devices, or a
natural product number (NPN) or homeopathic DIN (DIN-HM). [Canadian GMP Guidelines
2009]
Mass Balance
The process of adding together the assay value and levels of degradation products to see how
closely these add up to 100% of the initial value, with due consideration of the margin of
analytical error. [ICH Q1A, Canadian CMP-Guidelines 2009]
Master Cell Bank (MCB)

An aliquot of a single pool of cells which generally has been prepared from the selected cell
clone under defined conditions, dispensed into multiple containers and stored under defined
conditions. The MCB is used to derive all working cell banks. The testing performed on a new
MCB (from a previous initial cell clone, MCB or WCB) should be the same as for the MCB,
unless justified. [ICH Q5A, Q5B, Q5D]
Master Formula
A document or set of documents specifying the starting materials with their quantities and the
packaging materials, together with a description of the procedures and precautions required to
produce a specified quantity of a finished product as well as the processing instructions,
including the in-process controls. [Main Principles for Pharmaceutical Products, WHO]
A document or set of documents specifying the raw materials with their quantities and the
packaging materials, together with a detailed description of the procedures and precautions
required to produce a specified quantity of a finished product as well as the processing
instructions, including the in-process controls. [Canadian GMP Guidelines, Annex 3, Annex 5]
Master Production Document (MPD)

Documents that includes specifications for raw material, for packaging material and for
packaged dosage form, master formula (including composition and instructions as described in
the definition above), sampling procedures, and critical processing related SOPs, whether or not
these SOPs are specifically referenced in the master formula. [Canadian GMP Guidelines 2009]
Master Record
A document or set of documents that serve as a basis for the batch documentation (blank batch
record). [Main Principles for Pharmaceutical Products, WHO]
Material
A general term used to denote raw materials (starting materials, reagents, solvents), process aids,
intermediates, APIs and packaging and labelling materials. [EU GMP Guide, Part II, ICH Q7,
Guide to Good Storage Practices for Pharmaceuticals, WHO]
Matrixing
The design of a stability schedule such that a selected subset of the total number of possible
samples for all factor combinations is tested at a specified time point. At a subsequent time point,
another subset of samples for all factor combinations is tested. The design assumes that the
stability of each subset of samples tested represents the stability of all samples at a given time
point. The differences in the samples for the same drug product should be identified as, for
example, covering different batches, different strengths, different sizes of the same container
closure system, and, possibly in some cases, different container closure systems. [ICH Q1A]
The concept of matrixing may also apply in other areas such as validation. [Canadian GMP
Guidelines 2009]
Maximum Theoretical Residual Impurity

Gaseous impurity from a possible backflow that remains after the cylinder pre-treatment process
before filling. The calculation of the maximum theoretical residual impurity is only relevant for
compressed gases and assumes that the gases behave as perfect gases. [EU GMP Guide, Annex
6]
Mean Kinetic Temperature

A single derived temperature that, if maintained over a defined period of time, affords the same
thermal challenge to a drug substance or drug product as would be experienced over a range of
both higher and lower temperatures for an equivalent defined period. The mean kinetic
temperature is higher than the arithmetic mean temperature and takes into account the Arrhenius
equation. When establishing the mean kinetic temperature for a defined period, the formula of J.
D. Haynes (J. Pharm. Sci., 60:927–929, 1971) can be used. [ICH Q1A]
Media Fill
Method of evaluating an aseptic process using a microbial growth medium. (Media fills are
understood to be synonymous to simulated product fills, broth trials, broth fills etc.). [PIC/S PI
007-6]
Medical Gas
Any gas or mixture of gases manufactured, sold or represented for use as a drug. [Canadian GMP
Guidelines 2009]
Medical Officer
A person registered and licensed under the laws of a province to practice the profession of
medicine. [Canadian GMP Guidelines, Annex 14]
Medicated Premix see Drug Premix
Medicinal Gas
Any gas or mixture of gases classified as a medicinal product (as defined in Directives
2001/83/EC and 2001/82/EC). [EU GMP Guide, Annex 6]
Medicinal Plant
Plant the whole or part of which is used for medicinal purpose. [EU GMP Guide, Glossary]
Medicinal plants are plants (wild or cultivated) used for medicinal purposes. [Specific
Medicinal Product
Any substance or combination of substances presented for treating or preventing disease in
human beings or animals. Any substance or combination of substances which may be
administered to human beings or animals with a view to making a medical diagnosis or to
restoring, correcting or modifying physiological functions in human beings or in animals is
likewise considered a medicinal product. [EU GMP Guide, Glossary, Directive 2001/83/EC]
Metazoan
Organism of multicellular animal nature. [ICH Q5D]
Method Validation
Method validation is conducted where non-compendial analytical methods are included in the
application to confirm that the applicants’ proposed analytical methods are suitable for
regulatory purposes. A side-by-side comparison with a compendial method, if available, should
be included. Method verification is conducted where the methods are compendial, to confirm
whether the product as compounded can be analyzed satisfactorily by the official method.
[Inspection, WHO]
Minimum Exposure Time

The shortest period for which a treatment step will be maintained. [ICH Q5A]
Minimum Pressure Retention Valve

A cylinder valve, which maintains a positive pressure above atmospheric pressure in a gas
cylinder after use, in order to prevent internal contamination of the cylinder. [EU GMP Guide,
Annex 6]
Mobile Cyrogenic Vessel

Mobile thermally insulated container designed to maintain the contents in a liquid state. In the
Annex, this term does not include the tankers. [EU GMP Guide, Annex 6]
Modified Release
Dosage forms whose drug-release characteristics of time course and/or location are chosen to
accomplish therapeutic or convenience objectives not offered by conventional dosage forms such
as a solution or an immediate release dosage form. Modified release solid oral dosage forms
include both delayed and extended release drug products. [ICH Q6A]
Modifying Factor
A factor determined by professional judgment of a toxicologist and applied to bioassay data to
relate that data safely to humans. [ICH Q3C]
Monitor
A person appointed by, and responsible to, the sponsor for monitoring and reporting the progress
of the trial and for the verification of data. [Specific Pharmaceutical Products, WHO] The act of
conducting a planned sequence of observations or measurements of control parameters to assess
whether a CCP is under control. [Hazard and Risk Analysis in Pharmaceutical Products, WHO]
Monosepsis (axenic)
A single organism in culture which is not contaminated with any other organism. [EU GMP
Guide, Annex 2]
Mother Liquor
The residual liquid which remains after the crystallization or isolation processes. A mother liquor
may contain unreacted materials, intermediates, levels of the API and/or impurities. It may be
used for further processing. [EU GMP Guide, Part II, ICH Q7, Chinese GMP Guidelines, Annex
2]
MRA Country
A country that is a participant to a mutual recognition agreement with Canada. [Canadian GMP
Guidelines 2009]
Multi-Centre Clinical Trial

A clinical trial conducted according to a single protocol but at more than one site, and therefore
by more than one investigator, in which the trial sites may be located in a single Member State,
in a number of Member States and/or in Member States and third countries. [Directive
2001/20/EC]
Multi-suite Complex
Facility where each suite is dedicated to the fabrication of a biological drug. Suites are located
within the same building and are independent from one another. [Canadian GMP Guidelines,
Annex 2]
Multi-use Area
Area where more than one biological drug substance or drug product is manufactured.
Manufacturing is either concurrent or on a campaign basis. [Canadian GMP Guidelines, Annex
2]
Multiple-Dose-Container
Container that permits withdrawal of successive portions of the contents without changing the
strength, quality or purity of the remaining portion for articles intended for parenteral use only.
Multiproduct
More than one approved product, licensed product, IND drug, or separate process. [Guidance for
Multiproduct Facility
A facility that manufactures, either concurrently or in campaign mode, a range of different
biological medicinal substances and products and within which equipment train(s) may or may
not be dedicated to specific substances or products. [EU GMP Guide, Annex 2]
Mutual Recognition Agreement (MRA)

The “appropriate arrangement” between the Community and an exporting third country
mentioned in Article 51(2) of Directive 2001/83/EC and Article 55(2) of Directive 2001/82/EC.
[EU GMP Guide, Annex 16] (accord de reconnaissance mutuelle (ARM)) An international
agreement that provides for the mutual recognition of compliance certification for Good
Manufacturing Practices for drugs. [Canadian GMP Guidelines 2009]
N
Negative Control
Refers to the sterility test controls that may be used to identify a "false positive" test result.
Growth in the media sterility test, or environmental monitoring, or negative product controls may
contribute to the verification of a ""false positive"" test finding and an invalid test result. [PIC/S
PI 012-3]
Negative Product Control

Product or simulated product of known or undoubted sterility that is tested during the same test
session as the product test samples. Negative product controls should be exposed to a terminal
sterilization process, such as exposure to steam sterilization, gamma-irradiation etc, and be
packaged in a similar manner to the test sample in terms of manipulations required of the test
operator. [PIC/S PI 012-3]
Network
(a) An interconnected, or interrelated group of nodes.
(b) An interconnected communications facility. A local Are Network (LAN) is a high bandwidth
(allowing a high data transfer rate) computer network operating over a small area such as an
office or group of offices. [PIC/S PI 011-3]
Neurotoxicity
The ability of a substance to cause adverse effects on the nervous system. [ICH Q3C]
New Drug Product

A pharmaceutical product type, for example, tablet, capsule, solution, cream, etc., which has not
previously been registered in a region or Member State, and which contains a drug ingredient
generally, but not necessarily, in association with excipients. [ICH Q6A]
New Drug Substance

The designated therapeutic moiety that has not been previously registered in a region or member
state (also referred to as a new molecular entity or new chemical entity). It can be a complex,
simple ester, or salt of a previously approved drug substance. [ICH Q3A, Q3B, Q6A]
New Molecular Entity

An active pharmaceutical substance not previously contained in any drug product registered with
the national or regional authority concerned. A new salt, ester, or non-covalent-bond derivative
of an approved drug substance is considered a new molecular entity for the purpose of stability
testing under this guidance. [ICH Q1A]
No-Carrier-Added
Indicates the status of a radionuclide sample where no stable atom of the same element has been
added purposely. [Canadian GMP Guidelines, Annex 3, Annex 5]
No-impact System
This is a system that will not have any impact, either directly or indirectly, on product quality.
These systems are designed and commissioned according to GEP only. [Main Principles for
No-Observed-Effect Level
The highest dose of substance at which there are no biologically significant increases in
frequency or severity of any effects in the exposed humans or animals. [ICH Q3C]
Non-conformity
The nonfulfillment of a specified requirement. [21 CFR 820, FDA] A deficiency in a
characteristic, product specification, process parameter, record, or procedure that renders the
quality of a product unacceptable, indeterminate, or not according to specified requirements.
Non-critical Parameter / Non-critical Component

A processing parameter or component within a system where the operation, contact, data control,
alarm or failure will have an indirect impact or no impact on the quality of the product. [Main
Non-endogenous Virus
Viruses from external sources present in the Master Cell Bank. [ICH Q5A]
Non-interventional Trial
A study where the medicinal product(s) is (are) prescribed in the usual manner in accordance
with the terms of the marketing authorization. The assignment of the patient to a particular
therapeutic strategy is not decided in advance by a trial protocol but falls within current practice
and the prescription of the medicine is clearly separated from the decision to include the patient
in the study. No additional diagnostic or monitoring procedures shall be applied to the patients
and epidemiological methods shall be used for the analysis of collected data. [Directive
2001/20/EC]
Non-return Valve
Valve, which permits flow in one direction only. [EU GMP Guide, Annex 6]
Non-specific Model Virus

A virus used for characterization of viral clearance of the process when the purpose is to
characterize the capacity of the manufacturing process to remove and/or inactivate viruses in
general, i.e., to characterize the robustness of the purification process. [ICH Q5A]
Nonfiber Releasing Filter

Any filter, which after appropriate pretreatment such as washing or flushing, will not release
fibers into the component or drug product that is being filtered. [21 CFR Part 210, FDA]
Normal Operating Range

The range that the manufacturer selects as the acceptable values for a parameter during normal
operations. This range must be within the operating range. [Main Principles for Pharmaceutical
Products, WHO]
O
On-line
Measurement where the sample is diverted from the manufacturing process and not returned to
the process stream. [Guideline on Process Validation for Finished Products, EMA]
Ongoing / Continued Process Verification

Documented evidence that the process remains in a state of control during commercial
manufacture. [Guideline on Process Validation for Finished Products, EMA]
Open Isolator System

Are designed to allow for the continuous or semi-continuous ingress and/or egress of materials
during operations through one or more openings. Openings are engineered (e.g., using
continuous overpressure) to exclude the entry of external contamination into the isolator.
[Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing cGMP, FDA]
Open System
An environment in which system access is not controlled by persons who are responsible for the
content of electronic records that are on the system. [21 CFR Part 11, FDA]
A blood collection and/or processing system which has been breached but where every effort is
made to prevent external contamination by using sterilized materials and aseptic handling
techniques in a clean environment. [Canadian GMP Guidelines, Annex 14]
Operating Environment
Those conditions and activities interfacing directly or indirectly with the system of concern,
control of which can affect the system’s validated state. [PIC/S PI 011-3]
Operating Limit
The minimum and/or maximum values that will ensure that product and safety requirements are
met. [Main Principles for Pharmaceutical Products, WHO]
Operating Range
The range of validated critical parameters within which acceptable products can be
manufactured. [Main Principles for Pharmaceutical Products, WHO]
Operating System
A set of software programs provided with a computer that function as the interface between the
hardware and the applications program. [PIC/S PI 011-3]
Operational Condition (see also In Operation)

This condition relates to carrying out room classification tests with the normal production
process with equipment in operation, and the normal staff present in the room. [Main Principles
for Pharmaceutical Products, WHO]
Operational Qualification (OQ)

The documented verification that the facilities, systems and equipment, as installed or modified,
perform as intended throughout the anticipated operating ranges. [EU GMP Guide, Annex 15]
The documented verification that the system or sub-system performs as intended throughout all
anticipated operating ranges. [PIC/S PI 006-3]
The documented action of demonstrating that process equipment and ancillary systems work
correctly and operate consistently in accordance with established specifications. [Canadian GMP
Guidelines 2009]
Operator
Any individual participating in the aseptic processing operation, including line set-up, filler,
maintenance, or other personnel associated with aseptic line activities. [Guidance for Industry:
Instruction to process, package and/or ship a certain number of units of investigational medicinal
product(s). [EU GMP Guide, Annex 13, Canadian GMP Guidelines 2009, Annex 13, Specific
Out of Specification (OOS)

Includes all suspect results that fall outside the specifications or acceptance criteria established in
new drug applications, official compendia, or by the manufacturer.
Outsourced Activity
Activities conducted by a contract acceptor under a written agreement with a contract giver.
[ICH Q10]
Over-the-Counter Drug
These are drugs that can be sold from licensed dealers without professional supervision and
without prescriptions. These drugs are suitable for selfmedication for minor diseases and
symptoms. [Inspection, WHO]
Overkill Sterilization Process

A process that is sufficient to provide at least a 12 log reduction of microorganisms having a
minimum D value of 1 minute. [Guidance for Industry: Sterile Drug Products Produced by
Aseptic Processing – cGMP, FDA]
P
Packaging
All operations, including filling and labelling, which a bulk product has to undergo in order to
become a finished product.
Note: Sterile filling would not normally be regarded as part of packaging, the bulk product being
the filled, but not finally packaged, primary containers.
[EU GMP Guide, Glossary; Main Principles for Pharmaceutical Products, WHO; PIC/S PE 010-
4]
Packaging Batch Record

Records demonstrating that the batch of a drug was packaged in accordance with the approved
master production documents. [Canadian GMP Guidelines 2009]
Packaging Material
Any material employed in the packaging of a medicinal product, excluding any outer packaging
used for transportation or shipment. Packaging materials are referred to as primary or secondary
according to whether or not they are intended to be in direct contact with the product. [EU GMP
Guide, Glossary; PIC/S PE 010-4]
Any material intended to protect an intermediate or API during storage and transport.
[EU GMP Guide, Part II; ICH Q7]
Any material, including printed material, employed in the packaging of a pharmaceutical

product, but excluding any outer packaging used for transportation or shipment. Packaging
materials are referred to as primary or secondary according to whether or not they are intended to
be in direct contact with the product. [Guide to Good Storage Practices for Pharmaceuticals,
WHO; Main Principles for Pharmaceutical Products, WHO]
Labels, printed packaging materials and those components in direct contact with the dosage
form. (refer to C.02.002) [Canadian GMP Guidelines 2009]
Parallel Market
see Unauthorized Market
Parametric Release
A system of release that gives the assurance that the product is of the intended quality based on
information collected during the manufacturing process and on the compliance with specific
GMP requirements related to Parametric Release. [EU GMP Guide, Annex 17]
Parametric release is one type of RTR testing. Parametric release is based on process data (e.g.,
temperature, pressure, time for terminal sterilization, physiochemical indicator) rather than the
testing of material and/or sample for specific attribute. [ICH Q8, Q&A]
A validated system of release that gives the assurance that the product is of the intended quality
based on information collected during the manufacturing process and on the compliance with
specific GMP requirements related to Parametric Release. [Canada GMP Guidelines 2009,
Annex 5]
Parental Cell
Cell to be manipulated to give rise to a cell substrate or an intermediate cell line. For microbial
expression systems, it is typical to also describe the parental cells as the host cell. For
hybridomas, it is typical to also describe the parental cells as the cells to be fused. [ICH Q5D]
Parental Use
Administration of a drug by means of hypodermic syringe, needle or other instrument through or
into the skin or mucous membrane. [Canadian GMP Guidelines 2009]
Pedigree
A complete record that traces the ownership of and transactions relating to a pharmaceutical
product as it is distributed through the supply chain. [Good Distribution Practices for
Percentage of Theoretical Yield

The ratio of the Actual yield (at any appropriate phase of manufacture, processing, or packing of
a particular drug product) to the theoretical yield (at the same phase), stated as a percentage. [21
CFR Part 210, FDA]
Performance Indicator
Measurable values used to quantify quality objectives to reflect the performance of an
organization, process or system, also known as “performance metrics” in some regions. [ICH
Q10]
Performance Qualification (PQ)

The documented verification that the facilities, systems and equipment, as connected together,
can perform effectively and reproducibly, based on the approved process method and product
specification. [EU GMP Guide, Annex 15]
Permitted Daily Exposure (PDE)

The maximum acceptable intake per day of residual solvent in pharmaceutical products. [ICH
Q3C]
Pharmaceutical
All products related to pharmacy, including starting materials (active pharmaceutical ingredients
and excipients), finished dosage forms, and biological and other specific products. [Hazard and
Risk Analysis, WHO]
Pharmaceutical Excipient
Substances, other than the active ingredient, which have been appropriately evaluated for safety
and are included in a drug delivery system to:
 aid in the processing of the drug delivery system during its manufacture,
 protect, support or enhance stability, bioavailability, or patient acceptability,
 assist in product identification, or
 fenhance any other attribute of the overall safety and effectiveness of the drug during
storage or use. [Starting Materials, WHO]
Pharmaceutical Isolator
A containment device which utilises barrier technology to provide an enclosed, controlled
workspace. [PIC/S PE 010-4]
An arrangement of physical barriers that are integrated to the extent that the isolator can be
sealed in order to carry out a routine leak test based on pressure to meet specified limits.
Internally it provides a workspace, which is separated from the surrounding environment.
Manipulations can be carried out within the space from the outside without compromising its
integrity. [PIC/S PI 014-3]
Pharmaceutical Product
Any material or product intended for human or veterinary use presented in its finished dosage
form or as a starting material for use in such a dosage form, that is subject to control by
pharmaceutical legislation in the exporting state and/or the importing state. [Main Principles for
Any medicine intended for human use or veterinary product administered to food-producing
animals, presented in its finished dosage form or as a starting material for use in such a dosage
form, that is subject to control by pharmaceutical legislation in both the exporting state and the
importing state. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Any product intended for human use, or veterinary product intended for administration to food-
producing animals, presented in its finished dosage form, which is subject to control by
pharmaceutical legislation in either the exporting or the importing state and includes products for
which a prescription is required, products which may be sold to patients without a prescription,
biologicals and vaccines. It does not, however, include medical devices. [Good Distribution
Any substance or combination of substances which has a therapeutic, prophylactic or diagnostic

purpose, or is intended to modify physiological functions, and is presented in a dosage form
suitable for administration to humans. [Specific Pharmaceutical Products, WHO]
Pharmaceutical Quality System (PQS)

Management system to direct and control a pharmaceutical company with regard to quality. [ICH
Q10]
Pharmacist
A holder of a degree or diploma in pharmacy from a recognized higher institution of learning and
is registered or licensed to practice pharmacy. [Inspection, WHO]
Pharmacopoeial Discussion Group (PDG)

The three-party Pharmacopoeial Discussion Group consisting of representatives from the
European Directorate for the Quality of Medicines (EDQM) in the Council of Europe, the
Ministry of Health, Labour and Welfare (MHLW) of Japan, and the United States
Pharmacopoeial Convention, Inc (USP). [ICH Q4B]
Pharmacopoeial Text
The pharmacopoeial monographs, general test chapters, and analytical methods emanating from
the three regional pharmacopoeias. [ICH Q4B]
Pharmacovigilance System
A system used by the marketing authorization holder and by Member States to fulfil the tasks
and responsibilities listed in Title IX and designed to monitor the safety of authorized medicinal
products and detect any change to their risk-benefit balance. [Directive 2001/83/EC]
Pharmacovigilance System Master File

A detailed description of the pharmacovigilance system used by the marketing authorization
holder with respect to one or more authorized medicinal products. [Directive 2001/83/EC]
Phase 1 Investigational Drug

A new drug or biological drug that is used in phase 1 of a clinical investigation. The term also
includes a biological product that is used in vitro for diagnostic purposes. [Guidance for
Pilot Plant Scale

The production of the drug substance or drug product by a procedure fully representative of and
simulating that to be applied at manufacturing scale. The methods of cell expansion, harvest, and
product purification should be identical except for the scale of production. [ICH Q5C]
Pilot Scale Batch

A batch of a drug substance or drug product manufactured by a procedure fully representative of
and simulating that to be applied to a full production scale batch. For solid oral dosage forms, a
pilot scale is generally, at a minimum, one-tenth that of a full production scale or 100,000 tablets
or capsules, whichever is the larger. [ICH Q1A]
Piping & Instrument Diagrams (P&IDs)

Engineering schematic drawings that provide details of the interrelationship of equipment,
services, material flows, plant controls and alarms. The P&ID also provide the reference for each
tag or label used for identification. [PIC/S PI 006-3]
Plant Functional Specification

Specifications that document functions, standards and permitted tolerances of systems (plant) or
system components (equipment) and which define the operating capabilities of the equipment.
[PIC/S PI 006-3]
Plasma
The fluid portion of whole blood collected, stabilized against clotting and separated from the red
blood cells. [Canadian GMP Guidelines, Annex 14]
Plasmapheresis
Separation of plasma from whole blood and the continuous or intermittent return of red blood
cells and formed elements to the donor. Plasma collected by plasmapheresis may be used either
as source plasma for further manufacturing or fresh frozen plasma for transfusion. [Canadian
Plateletpheresis
Separation of platelets from whole blood and the continuous or intermittent return of red blood
cells, with or without platelet-reduced plasma, to the donor. If plasma is collected as a final
product during plateletpheresis, the regulations for plasmapheresis apply. [Canadian GMP
Platform Manufacturing
The approach of developing a production strategy for a new drug starting from manufacturing
processes similar to those used by the same applicant to manufacture other drugs of the same
type (e.g., as in the production of monoclonal antibodies using predefined host cell, cell culture,
and purification processes, for which there already exists considerable experience). [ICH Q11]
Polymorphic Form
Different crystalline forms of the same drug substance. These can include solvation or hydration
products (also known as pseudo-polymorphs) and amorphous forms. [ICH Q3A]
Polymorphism
The occurrence of different crystalline forms of the same drug substance. This may include
solvation or hydration products (also known as pseudopolymorphs) and amorphous forms. [ICH
Q6A]
Positive Control
Refers to the sterility test controls that may be used to define a "false negative" test result. An
absence of growth of test challenge micro-organisms in the growth promotion, validation or
"stasis" tests would result in a "false negative" test finding and an invalid test result. [PIC/S PI
012-3]
Positron Emitting Radiopharmaceutical (PER)

Drugs labelled with positron emitting radionuclides or containing positron emitting radionuclides
that exhibit spontaneous transformation of unstable nuclei through positron decay. [Canadian
Post Donation Information (PDI)

Information related to a donor or a donation made available to the collection facility following a
donation. The information can be provided by the donor or other source. It may adversely affect
the safety and/or quality of the donated blood/component. PDI does not include errors, accidents
or anomalies that occur during screening or later during collection, processing or testing but are
discovered at some point after the donation is made. [Canadian GMP Guidelines, Annex 14]
Potency
The measure of the biological activity using a suitably quantitative biological assay (also called
potency assay or bioassay), based on the attribute of the product which is linked to the relevant
biological properties. [ICH Q6B]
The activity or amount of active moiety, or any form thereof, indicated by label claim to be
present. [Canadian GMP Guidelines 2009]
Potential Impurity
An impurity that theoretically can arise during manufacture or storage. It may or may not
actually appear in the new drug substance. [ICH Q3A]
Pre-Approval Batch
Pilot or laboratory-scale batches, upon which the application is based, e.g. batches used for
pivotal clinical trials and/or those used for bioavailability, bioequivalence and stability studies,
and scale-up batches. [Inspection, WHO]
Pre-Determined Acceptance Criteria

The criteria assigned, before undertaking testing, to allow evaluation of test results to
demonstrate compliance with a test phase of delivery requirement. [PIC/S PI 006-3]
Precision
The precision of an analytical procedure expresses the closeness of agreement (degree of scatter)
between a series of measurements obtained from multiple sampling of the same homogeneous
sample under the prescribed conditions. Precision may be considered at three levels:
repeatability, intermediate precision and reproducibility.
Precision should be investigated using homogeneous, authentic samples. However, if it is not

possible to obtain a homogeneous sample it may be investigated using artificially prepared
samples or a sample solution. The precision of an analytical procedure is usually expressed as the
variance, standard deviation or coefficient of variation of a series of measurements. [ICH Q2]
Precursor
A chemical substance or molecule which exists as an ingredient, reactant, or intermediate that is
used for the chemical or radiochemical synthesis of a particular desired end product. [Canadian
GMP Guidelines 2009, Annex 5]
Preparation
Handling and radiolabelling of kits with radionuclide eluted from generators or radioactive
precursors within a hospital. Kits, generators and precursors should have a marketing
authorization or a national licence. [EU GMP Guide, Annex 3]
All operations of purchase of materials and products, production, quality control, release,
storage, delivery of medicinal products and the related controls. Note: The simple provisioning
of medicinal products according to authorized instructions and without necessitating
pharmaceutical technical knowledge, where medicinal products are made ready for immediate
application (e.g. dissolution of a powder for immediate application according to the instructions
in the package leaflet of an authorized product), is normally not normally considered as
preparation. [PIC/S PE 010-4]
Prequalification
The activities undertaken in defining a product or service need, seeking expressions of interest
from enterprises to supply the product or service, and examining the product or service offered
against the specification, and the facility where the product or service is prepared against
common standards of good manufacturing practice (GMP). The examination of the product or
service and of the facility where it is manufactured is performed by trained and qualified
inspectors against common standards. Once the product is approved, and the facility is approved
for the delivery of the specified product or service, other procurement agencies are informed of
the approval. Prequalification is required for all pharmaceutical products regardless of their
composition and place of manufacture or registration, but the amount and type of information
requested from the supplier for use in the assessment by the procurement agency may differ.
[Sampling Operations, WHO]
Pressure Cascade
A process whereby air flows from one area, which is maintained at a higher pressure, to another
area at a lower pressure. [Main Principles for Pharmaceutical Products, WHO]
Preventive Action
Action to eliminate the cause of a potential non-conformity or other undesirable potential
situation. Note: Preventive action is taken to prevent occurrence whereas corrective action is
taken to prevent recurrence. [ISO 9000:2005, ICH Q10]
Action taken to eliminate the cause of a potential discrepancy or other undesirable situation to
prevent such an occurrence. [Guidance for Industry: Quality Systems Approach to
Pharmaceutical cGMP Regulations, FDA]
Primary Batch
A batch of a drug substance or drug product used in a formal stability study, from which stability
data are submitted in a registration application for the purpose of establishing a re-test period or
shelf life, respectively. A primary batch of a drug substance should be at least a pilot scale batch.
For a drug product, two of the three batches should be at least pilot scale batch, and the third
batch can be smaller if it is representative with regard to the critical manufacturing steps.
However, a primary batch may be a production batch. [ICH Q1A]
Primary Containment
A containment system that prevents the escape of a biological agent into the immediate working
environment. This includes the use of closed containers or biological safety workstations
together with safe working procedures. See also containment. [EU GMP Guide, Glossary]
Principal Investigator
The responsible leader of the team if a trial is conducted by a team of individual investigators at
a trial site Investigator. [EU GMP Guide, Annex 13]
Procedural Control
Manufacturing methodologies executed in such a manner as to prevent or minimize
contamination. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Procedure
Description of the operations to be carried out, the precautions to be taken and measures to be
applied directly or indirectly related to the manufacture of a medicinal product. [EU GMP Guide,
Glossary, ICH Q7]
Process Aid
Materials, excluding solvents, used as an aid in the manufacture of an intermediate or API that
do not themselves participate in a chemical or biological reaction (e.g. filter aid, activated
carbon, etc). [EU GMP Guide, Part II, ICH Q7]
This refers to the materials (e.g. filter aid, activated carbon, etc, excluding solvents), used as an
aid in the production of an intermediate or API that do not participate in a chemical or biological
reaction itself. [Chinese GMP Guidelines, Annex 2]
Process Analytical Technologies (PAT)

System for designing, analyzing, and controlling manufacturing through timely measurements
(i.e., during processing) of critical quality and performance attributes of raw and in-process
materials and processes, with the goal of ensuring final product quality. [ICHQ8, PAT – A
Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance,
FDA]
Process Capability Index

A process capability index CpK represents the true measure of process capability
CpK = (X – LSL)/3s
or = (USL – X)/3s
where
LSL = Lower specification limit
USL= Upper specification limit
X = Mean
s = Standard deviation
[PIC/S PI 006-3]
Process Capability Study

A process capability study is a statistical method that compares process information (e.g. X and
s) to the upper and lower specification limits. [PIC/S PI 006-3]
Process Characterization of Viral Clearance

Viral clearance studies in which non-specific “model” viruses are used to assess the robustness
of the manufacturing process to remove and/or inactivate viruses. [ICH Q5A]
Process Design
Defining the commercial manufacturing process based on knowledge gained through
development and scale-up activities. [Guidance for Industry: Process Validation: General
Principles and Practices, FDA]
Process Evaluation Studies of Viral Clearance

Viral clearance studies in which “relevant” and/or specific “model” viruses are used to determine
the ability of the manufacturing process to remove and/or inactivate these viruses. [ICH Q5A]
Process Performance Qualification (PPQ)

Establishing confidence that the process is effective and reproducible. [Guideline on General
Principles of Process Validation, FDA]
Process Qualification
Confirming that the manufacturing process as designed is capable of reproducible commercial
manufacturing. [Guidance for Industry: Process Validation: General Principles and Practices,
FDA]
Process Robustness
Ability of a process to tolerate variability of materials and changes of the process and equipment
without negative impact on quality. [ICH Q8, TRS 981 Annex 2, WHO]
Process Validation
The documented evidence that the process, operated within established parameters, can perform
effectively and reproducibly to produce a medicinal product meeting its predetermined
specifications and quality attributes. [EU GMP Guide, Annex 15]
Documented evidence which provides a high degree of assurance that a specific process will
consistently result in a product that meets its predetermined specifications and quality
characteristics. [Main Principles for Pharmaceutical Products, WHO]
Documented verification that the integrated system functions as intended, in its normal operating
environment. (The term Performance Qualification may be used also). Note: Processes may be
proven also by documented verification through appropriate testing that the finished product
produced by a specified process meets all release requirements. This may be called Product
Qualification. [PIC/S PI 006-3]
Establishing by objective evidence that a process consistently produces a result or product

meeting its predetermined specifications. [21 CFR Part 820, FDA]
The collection and evaluation of data, from the process design stage through commercial
production, which establishes scientific evidence that a process is capable of consistently
delivering quality products. [Guidance for Industry: Process Validation: General Principles and
Practices, FDA]
Establishing documented evidence with a high degree of assurance, that a specific process will
consistently produce a product meeting its predetermined specifications and quality
characteristics. Process validation may take the form of Prospective, Concurrent or Retrospective
Validation and Process Qualification or Re-validation. [Canadian GMP Guidelines 2009]
Process-related Impurity
Impurities that are derived from the manufacturing process. They may be derived from cell
substrates (e.g., host cell proteins, host cell DNA), cell culture (e.g., inducers, antibiotics, or
media components), or downstream processing (e.g., processing reagents or column leachables).
[ICH Q6B]
Processing
That part of the preparation of a medicinal product involving the dosage form. [PIC/S PE 010-4]
Any fabricating step performed between the collection of blood and the issuing of a component.
Procuring
Obtaining, acquiring, purchasing or buying medicinal products from manufacturers, importers or
other wholesale distributors. [EU GDP Guidelines]
Product
Components, manufacturing materials, in- process devices, finished devices, and returned
devices. [21 CFR Part 820, FDA]
Product Lifecycle
All phases in the life of the product from the initial development through marketing until the
product's discontinuation. [ICH Q9]
Product Performance Qualification

Establishing confidence through appropriate testing that the finished product produced by a
specified process meets all release requirements for functionality and safety. [Guideline on
General Principles of Process Validation, FDA]
Product Quality Review (PQR)

Regular periodic or rolling quality reviews of all licensed medicinal products, including export
only products, should be conducted with the objective of verifying the consistency of the existing
process, the appropriateness of current specifications for both starting materials and finished
product to highlight any trends and to identify product and process improvements. Such reviews
should normally be conducted and documented annually, taking into account previous reviews.
[EU GMP Guide, Part I]
Regular quality reviews of APIs should be conducted with the objective of verifying the
consistency of the process. Such reviews should normally be conducted and documented
annually. [EU GMP Guide, Part II]
Product Realisation
Achievement of a product with the quality attributes appropriate to meet the needs of patients,
health care professionals, and regulatory authorities (including compliance with marketing
authorization) and internal customers requirements. [ICH Q10]
Product Recall
A process for withdrawing or removing a pharmaceutical product from the pharmaceutical
distribution chain because of defects in the product, complaints of serious adverse reactions to
the product and/or concerns that the product is or may be counterfeit. The recall might be
initiated by the manufacturer, importer, wholesaler, distributor or a responsible agency. [Good
Distribution Practices for Pharmaceutical Products, WHO, Inspection, WHO]
Product Specification File (PSF)
A reference file containing, or referring to files containing, all the information necessary to draft
the detailed written instructions on processing, packaging, quality control testing, batch release
and shipping of an investigational medicinal product. [EU GMP Guide, Annex 13, Canadian
Product-related Impurity
Molecular variants of the desired product (e.g., precursors, certain degradation products arising
during manufacture and/or storage) which do not have properties comparable to those of the
desired product with respect to activity, efficacy, and safety. [ICH Q6B]
Product-related Substance
Molecular variants of the desired product formed during manufacture and/or storage which are
active and have no deleterious effect on the safety and efficacy of the drug product. These
variants possess properties comparable to the desired product and are not considered
impurities. [ICH Q6B]
Product-specific Cleaning
Cleaning procedure performed to ensure removal of product residuals from non-dedicated
product-contact equipment/ containers which includes appropriate assays to validate the
effectiveness of the cleaning. [Canadian GMP Guidelines, Annex 2]
Product/ Service
The intended results of activities or processes, products/services can be tangible or intangible.
[Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Production
see Manufacture
Production Batch
A batch of a drug substance or drug product manufactured at production scale by using
production equipment in a production facility as specified in the application. [ICH Q1A]
Production Cell
Cell substrate used to manufacture product. [ICH Q5A]
Cell substrate used to fabricate the product. [Canadian GMP Guidelines 2009, Annex 2]
Production Supervisor
The person responsible for supervision should be in the department where the production takes
place. He/she should be aware of what is going on and able to ensure that the process is carried
out in the prescribed manner. [PIC/S PE 010-4]
Prohibited Drug
These are drugs with toxicity or side-effects that outweigh their therapeutic usefulness, so that
public health and welfare are protected by prohibiting their production, manufacture, export,
import, trade, distribution, supply, possession or use, except in amounts required for medical and
scientific research. Prohibited drugs are normally determined by the national or supranational
registration/ licensing authority. [Inspection, WHO]
Prospective Validation
Validation carried out before routine production of products intended for sale. [EU GMP Guide,
Annex 15]
Validation carried out during the development stage on the basis of a risk analysis of the
production process, which is broken down into individual steps, these are then evaluated on the
basis of past experience to determine whether they may lead to critical situations. [Main
Establishing documented evidence that a process, procedure, system, equipment or mechanism

used in manufacture does what it purports to do based on a pre-planned validation protocol.
[PIC/S PI 006-3]
Protocol
A document that describes the objective(s), design, methodology, statistical considerations and
organization of a trial. The term protocol refers to the protocol, successive versions of the
protocol and protocol amendments. [Directive 2001/20/EC]
A document which gives the background, rationale and objectives of the trial and describes its
design, methodology and organization, including statistical considerations, and the conditions
under which it is to be performed and managed. It should be dated and signed by the
investigator/institution involved and the sponsor, and can, in addition, function as a contract.
[Good Manufacturing Practices: Specific Pharmaceutical Products, WHO]
Proven Acceptable Range (PAR)

A characterized range of a process parameter for which operation within this range, while
keeping other parameters constant, will result in producing a material meeting relevant quality
criteria. [ICH Q8]
Public Key Infrastructure, PKI

Public Key Infrastructure (PKI) provides a framework for secure communication, using a
combination of public-key cryptography and Digital Certificates. PKIs can exist within many
different domains but essentially there are two types: public PKI and private PKI. [PIC/S PI 011-
3]
Public Key Infrastructure, private

is deployed by a corporation for the benefit of its business and any related parties (e.g.
customers, suppliers). [PIC/S PI 011-3]
Public Key Infrastructure, public

(using ‘Trusted Third Parties’) are deployed on open systems, such as the Internet and facilitate
security between previously unrelated parties. [PIC/S PI 011-3]
Public Service Obligation
The obligation placed on wholesalers to guarantee permanently an adequate range of medicinal
products to meet the requirements of a specific geographical area and to deliver the supplies
requested within a very short time over the whole of the area in question. [Directive 2001/83/EC]
Pure Culture
(culture pure) A culture broth/ medium containing a single type of microorganism. [Canadian
Purge
To remove the residual gas from a container/system by first pressurizing and then venting the gas
used for purging to 1.013 bar. [EU GMP Guide, Annex 6]
Purified Water
Demineralised water, deionised water. [Pharmacopoea Europaea]
Purity
The extent to which a raw material or a drug in dosage form is free from undesirable or
adulterating chemical, biological, or physical entities as defined by specifications. [Canadian
Purity Test
To ensure that all the analytical procedures performed allow an accurate statement of the content
of impurities of an analyte, i.e. related substances test, heavy metals, residual solvents content,
etc. [ICH Q2]
Pyrogen
A substance that induces a febrile reaction in a patient. [Guidance for Industry: Sterile Drug
Q
Q4B Outcome
Produced by the Q4B evaluation process, information concerning how the evaluated
pharmacopoeial text can be used. The Q4B Outcome is included as part of the topic-specific
Q4B annex developed as a result of each favourable evaluation. [ICH Q4B]
QC Laboratory Inspection
On-Site assessment of the adherence to Good Quality Control Laboratory Practice is normally
part of a GMP Inspection. Contract QC Laboratories authorized according to Article 13.1 of
Directive 2001/20/EC are also subject to these inspections. Laboratory inspection for compliance
with GLP Principles is performed in accordance with guidelines given in the annexes to
Directive 90/18/EEC and is not part of this document. Inspections performed in laboratories
analyzing samples taken from trial subjects are likewise not included.
[Compilation of Community Procedures on Inspections and Exchange of Information, EMA]
Qualification(see also Validation)

Action of proving that any equipment works correctly and actually leads to the expected results.
The word validation is sometimes widened to incorporate the concept of qualification. [EU GMP
Guide, Glossary, EU GDP Guidelines, Main Principles for Pharmaceutical Products, WHO]
The process of acquiring and evaluating data that establishes the biological safety of an
individual degradation product or a given degradation profile at the level(s) specified. [ICH
Q3A, Q3B]
Action of proving and documenting that equipment or ancillary systems are properly installed,
work correctly, and actually lead to the expected results. Qualification is part of validation, but
the individual qualification steps alone do not constitute process validation. [ICH Q7]
The risk based systematic and documented evidence that facilities, rooms or equipment work
correctly, are suitable for the intended purpose and actually give the expected results. [PIC/S PE
010-4]
Identification of equipment attributes related to the performance of a particular function or

functions and allocation of certain limits or restrictions to those attributes. [PIC/S PI 006-3]
Qualification Batch
Those batches produced by the RU to demonstrate its ability to reproduce the product. [TRS 961
Annex 7, WHO]
Qualification Threshold
A limit above (>) which a degradation product should be qualified. [ICH Q3A, Q3B]
Qualified Person (QP)

The person defined in Article 48 of Directive 2001/83/EC and Article 52 of Directive
2001/82/EC. [EU GMP Guide, Annex 16]
Quality
The suitability of either a drug substance or drug product for its intended use. This term includes
such attributes as the identity, strength, and purity. [ICH Q6A, Q8]
The degree to which a set of inherent properties of a product, system or process fulfills
requirements (see ICH Q6A definition specifically for “quality” of drug substance and drug
(medicinal) products.). [ICH Q9]
A measure of a product’s or service’s ability to satisfy the customer’s stated or implied needs.
The totality of features and characteristics that bear on the ability of a [medical] device to satisfy
fitness-for-use, including safety and performance. [21 CFR Part 820, FDA]
Quality Assurance (QA)

The sum total of the organized arrangements made with the object of ensuring that all APIs are
of the quality required for their intended use and that quality systems are maintained. [EU GMP
Guide, Part II, ICH Q7]
A wide-ranging concept covering all matters that individually or collectively inuence the quality
of a product. It is the totality of the arrangements made with the object of ensuring that
pharmaceutical products are of the quality required for their intended use. [Good Distribution
Practices for Pharmaceutical Products, WHO, Inspection, WHO]
Proactive and retrospective activities that provide confidence that requirements are fulfilled.
The actions, planned and performed, to provide confidence that all systems and elements that
influence the quality of the product are working as expected individually and collectively.
[Canadian GMP Guidelines Annex 14]
Quality Assurance Program

Comprehensive system of an establishment for manufacturing safe, effective, and quality
products according to regulatory requirements. This program includes preventing, detecting, and
correcting deficiencies that may compromise product quality. [Canadian GMP Guidelines,
Annex 14]
Quality Assurance Unit see Quality Control Unit
Quality Attribute
A molecular or product characteristic that is selected for its ability to help indicate the quality of
the product. Collectively, the quality attributes define identity, purity, potency and stability of the
product, and safety with respect to adventitious agents. Specifications measure a selected subset
of the quality attributes. [ICH Q5E]
Quality Audit
An examination and assessment of all or part of a quality system with the specific purpose of
improving it. A quality audit is usually conducted by outside or independent specialists or a team
designated by the management for this purpose. Such audits may also be extended to suppliers
and contractors. [Inspection, WHO]
A systematic, independent examination of a manufacturer‘s quality system that is performed at

defined intervals and at sufficient frequency to determine whether both quality system activities
and the results of such activities comply with quality system procedures, that these procedures
are implemented effectively, and that these procedures are suitable to achieve quality system
objectives. [21 CFR Part 820, FDA]
Quality by Design (QbD)

A systematic approach that begins with predefined objectives and emphasises product and
process understanding and process control, based on sound science and quality risk management.
[EU GMP Guide, Annex 15, ICH Q8]
Quality Control (QC)

Quality Control is that part of Good Manufacturing Practice which is concerned with sampling,
specifications and testing, and with the organization, documentation and release procedures
which ensure that the necessary and relevant tests are actually carried out and that materials are
not released for use, nor products released for sale or supply, until their quality has been judged
to be satisfactory. [EU GMP Guide, Part I]
Checking or testing that specifications are met. [EU GMP Guide, Part II, ICH Q7]
Covers all measures taken, including the setting of specifications, sampling, testing and
analytical clearance, to ensure that starting materials, intermediates, packaging materials and
finished pharmaceutical products conform with established specifications for identity, strength,
purity and other characteristics. [TRS 961 Annex 7, WHO]
The steps taken during the generation of a product or service to ensure that it meets requirements
and that the product or service is reproducible. [Guidance for Industry: Quality Systems
Approach to Pharmaceutical cGMP Regulations, FDA]
A component of a QA program that includes the activities and controls used to determine the
accuracy and reliability of the establishment’s personnel, equipment, reagents, and operations in
the fabricating of blood components including testing and product release. [Canadian GMP
Guidelines Annex 14]
Quality Control Unit

Any person or organizational element designated by the firm to be responsible for the duties
relating to quality control. [21 CFR Part 210, FDA]
An organizational element with authority and responsibility as defined by 21 CFR Part 211.22.
[Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
One or more individuals designated by, and reporting directly to, management with defined
authority and responsibility to assure that all quality assurance policies are carried out in the
organization. [Canadian GMP Guidelines, Annex 14]
Quality Management (QM)

Accountability for the successful implementation of the quality system. [Guidance for Industry:
Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Quality Manual
Document specifying the quality management system of an organization. [ISO 9000:2005, ICH
Q10]
Quality Objective
A means to translate the quality policy and strategies into measurable activities. [ICH Q10]
Specific measurable activities or processes to meet the intentions and directions as defined in the
quality policy. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP
Regulations, FDA]
Quality Plan
The documented result of quality planning that is disseminated to all relevant levels of the
organization. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP
Regulations, FDA]
Quality Planning
Part of quality management focused on setting quality objectives and specifying necessary
operational processes and related resources to fulfil the quality objectives. [ISO 9000:2005, ICH
Q10]
A management activity that sets quality objectives and defines the operational and/or quality
system processes and the resources needed to fulfill the objectives. [Guidance for Industry:
Quality Policy (QP)

Overall intentions and direction of an organization related to quality as formally expressed by
senior management. [ISO 9000:2005, ICH Q10]
The overall intentions and direction of an organization with respect to quality, as established by
management with executive responsibility. [21 CFR Part 820, FDA]
A statement of intentions and direction issued by the highest level of the organization related to
satisfying customer needs. It is similar to a strategic direction that communicates quality
expectations that the organization is striving to achieve. [Guidance for Industry: Quality Systems
Quality Risk Management (QRM)

A systematic process for the assessment, control, communication and review of risks to the
quality of the drug (medicinal) product across the product lifecycle. [EU GDP Guidelines, ICH
Q9, TRS 961 Annex 7, WHO]
A systematic process for the assessment, control, communication and review of risks to the
quality of the medicinal product. It can be applied both proactively and retrospectively. [ICH Q9,
Q10, Canadian GMP Guidelines 2009]
Quality System (QS)

The sum of all aspects of a system that implements quality policy and ensures that quality
objectives are met. [EU GDP Guidelines, ICH Q9]
An appropriate infrastructure, encompassing the organizational structure, procedures, processes

and resources, and systematic actions necessary to ensure adequate confidence that a product (or
services) will satisfy given requirements for quality. [Good Distribution Practices for
The organizational structure, responsibilities, procedures, processes, and resources for
implementing quality management. [21 CFR Part 820, FDA]
Formalized business practices that define management responsibilities for organizational

structure, processes, procedures, and resources needed to fulfill product/service requirements,
customer satisfaction, and continual improvement. [Guidance for Industry: Quality Systems
Quality Target Product Profile (QTPP)

A prospective summary of the quality characteristics of a drug product that ideally will be
achieved to ensure the desired quality, taking into account safety and efficacy of the drug
product. [ICH Q8]
Quality Unit
An organizational unit independent of production which fulfills both Quality Assurance and
Quality Control responsibilities. This can be in the form of separate QA and QC units or a single
individual or group, depending upon the size and structure of the organization. [EU GMP Guide,
Part II, ICH Q7]
A group organized within an organization to promote quality in general practice. [Guidance for
Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Quantitation Limit
The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a
sample which can be quantitatively determined with suitable precision and accuracy. The
quantitation limit is a parameter of quantitative assays for low levels of compounds in sample
matrices, and is used particularly for the determination of impurities and/or degradation products.
[ICH Q2]
Quarantine
The status of starting or packaging materials, intermediate, bulk or finished products isolated
physically or by other effective means whilst awaiting a decision on their release or refusal. [EU
GMP Guide, Glossary, Main Principles for Pharmaceutical Products, WHO, PIC/S PE 010-4]
The status of materials isolated physically or by other effective means pending a decision on
their subsequent approval or rejection. [ICH Q7]
Effective restriction of the availability of material or product for use (physically or by system),
until released by the quality control department. [Canadian GMP Guidelines 2009]
R
Racemate
A composite (solid, liquid, gaseous, or in solution) of equimolar quantities of two enantiomeric
species. It is devoid of optical activity. [ICH Q6A]
Radio Synthesizer Unit (RSU)

A closed-system device for the synthesis of radioactive drug substances used in the
manufacturing of PERs. The system may be controlled by graphical computer software
programs. [Canadian GMP Guidelines, Annex 5]
Radioactive Concentration
Amount of radioactivity per unit volume such as mCi/ml or MBq/ml. [Canadian GMP
Guidelines, Annex 3, Annex 5]
Radioactivity
Spontaneous decay of unstable nuclei and is quantified as the number of disintegrations per unit
of time as given in Becquerel (Bq) or Curie (Ci) units. [Canadian GMP Guidelines, Annex 3,
Annex 5]
Radionuclide
A nuclide with an unstable or excited nucleus (imbalance of protons and neutrons) which will
undergo spontaneous transformation with emissions of subatomic particles and/or photons of
energy. [Canadian GMP Guidelines, Annex 3]
Radionuclide Generator
Any system incorporating a fixed parent radionuclide from which is produced a daughter
radionuclide which is to be obtained by elution or by any other method used in a
radiopharmaceutical. [Directive 2001/83/EC]
Radionuclide Precursor
Any other radionuclide produced for the radio-labelling of another substance prior to
administration. [Directive 2001/83/EC]
Radiopharmaceutical
Any medicinal product which, when ready for use, contains one or more radionuclides
(radioactive isotopes) included for a medicinal purpose. [EU GMP Guide, Glossary, Directive
2001/83/EC]
Random Sample
Sample in which the different fractions of the material have an equal probability of being
represented. [Sampling Operations, WHO]
Randomization
The process of assigning trial subjects to treatment or control groups using an element of chance
to determine the assignments in order to reduce bias. [EU GMP Guide, Annex13, Canadian GMP
Randomization Code
A listing in which the treatment assigned to each subject from the randomization process is
identified. [EU GMP Guide, Annex 13, Canadian GMP Guidelines 2009, Annex 13]
Range
The range of an analytical procedure is the interval between the upper and lower concentration
(amounts) of analyte in the sample (including these concentrations) for which it has been
demonstrated that the analytical procedure has a suitable level of precision, accuracy and
linearity. [ICH Q2]
Rapidly Dissolving Product

An immediate release solid oral drug product is considered rapidly dissolving when not less than
80% of the label amount of the drug substance dissolves within 15 minutes in each of the
following media: (1) pH 1.2, (2) pH 4.0, and (3) pH 6.8. [ICH Q6A]
Raw Data
Any work-sheets, records, memoranda, notes, or exact copies thereof, that are the result of
original observations and activities and which are necessary for the reconstruction and evaluation
of a work project, process or study report, etc. Raw data may be hard/paper copy or electronic
but must be known and defined in system procedures. [PIC/S PI 011-3]
Raw Material
A general term used to denote starting materials, reagents, and solvents intended for use in the
production of intermediates or APIs. [EU GMP Guide, Part II, ICH Q7]
Any substance, other than in-process drug or packaging material, intended to be used in the
manufacture of drugs, including those that appear in the master formula but that do not appear in
the drug such as solvents and processing aids. [Canadian GMP Guidelines 2009]
Reagent
A substance other than a starting material, intermediate, or solvent that is used in the
manufacture of a new drug substance. [ICH Q6A, Q3A]
Real-Time Release Testing (RTRT)

The ability to evaluate and ensure the quality of in-process and/or final product based on process
data, which typically include a valid combination of measured material attributes and process
controls. [ICH Q8]
Receiving Unit (RU)The involved disciplines at an organization where a designated product,
process or method is expected to be transferred. [TRS 961 Annex 7, WHO]
Reconciliation
A comparison, making due allowance for normal variation, between the amount of product or
materials theoretically and actually produced or used. [EU GMP Guide, Glossary]
A comparison between the theoretical quantity and the actual quantity. [Main Principles for
A comparison, making due allowance for normal variation, between the amount of product or
materials theoretically produced or used and the amount actually produced or used. [Canadian
Recovered Plasma
The liquid portion of a single donation of whole blood separated from cellular components and
intended for further manufacture. [Canadian GMP Guidelines, Annex 14]
Recovery
The introduction of all or part of previous batches (or of redistilled solvents and similar products)
of the required quality into another batch at a defined stage of manufacture. It includes the
removal of impurities from waste to obtain a pure substance or the recovery of used materials for
a separate use. [EU GMP Guide, Glossary, Main Principles for Pharmaceutical Products, WHO,
Canadian GMP Guidelines 2009]
Reference Sample (see also Retention Sample)

Sample of a batch of starting material, packaging material or finished product which is stored for
the purpose of being analyzed should the need arise during the shelf life of the batch concerned.
Where stability permits, reference samples from critical intermediate stages (e.g. those requiring
analytical testing and release) or intermediates, that are transported outside of the manufacturer’s
control, should be kept. [EU GMP Guide, Annex 19]
Reference Standard, Primary

A substance that has been shown by an extensive set of analytical tests to be authentic material
that should be of high purity. This standard can be: (1) obtained from an officially recognised
source, or (2) prepared by independent synthesis, or (3) obtained from existing production
material of high purity, or (4) prepared by further purification of existing production material.
[EU GMP Guide, Part II, ICH Q7]
Reference Standard, Secondary

A substance of established quality and purity, as shown by comparison to a primary reference
standard, used as a reference standard for routine laboratory analysis. [EU GMP Guide, Part II,
ICH Q7]
Regulated User
The regulated Good Practice entity, that is responsible for the operation of a computerised
system and the applications, files and data held thereon. [PIC/S PI 011-3]
Regulatory Authority
A government agency or other entity in an MRA country that has a legal right to control the use
or sale of drugs within that country and that may take enforcement action to ensure that drugs
marketed within its jurisdiction comply with legal requirements. [Canadian GMP Guidelines
2009]
Relative Humidity
The ratio of the actual water vapour pressure of the air to the saturated water vapour pressure of
the air at the same temperature expressed as a percentage. More simply put, it is the ratio of the
mass of moisture in the air, relative to the mass at 100% moisture saturation, at a given
temperature. [Main Principles for Pharmaceutical Products, WHO]
Releasing Officer
The person who releases the prepared medicinal products. This person may be the Responsible
Person. [PIC/S PE 010-4]
Relevant Genotypic and Phenotypic Marker

Those markers permitting the identification of the strain of the cell line which should include the
expression of the recombinant protein or presence of the expression construct. [ICH Q5B]
Relevant Virus
Virus used in process evaluation studies which is either the identified virus, or of the same
species as the virus that is known, or likely to contaminate the cell substrate or any other reagents
or materials used in the production process. [ICH Q5A]
Remanufacturer
Any person who processes, conditions, renovates, repackages, restores, or does any other act to a
finished [medical] device that significantly changes the finished device‘s performance or safety
specifications, or intended use. [21 CFR Part 820, FDA]
Repeatability
Repeatability expresses the precision under the same operating conditions over a short interval of
time. Repeatability is also termed intra-assay precision. [ICH Q2]
Reporting Threshold
A limit above (>) which an impurity should be reported. Reporting threshold is the same as
reporting level in Q2B. [ICH Q3A]
A limit above (>) which a degradation product should be reported. [ICH Q3B]
Representative Sample
Sample obtained according to a sampling procedure designed to ensure that the different parts of
a batch or the different properties of a non-uniform material are proportionately represented.
A sample that consists of a number of units that are drawn based on rational criteria such as
random sampling and intended to assure that the sample accurately portrays the material being
sampled. [21 CFR Part 210, FDA]
Reprocessing
The reworking of all or part of a batch of product of an unacceptable quality from a defined stage
of production so that its quality may be rendered acceptable by one or more additional
operations. [EU GMP Guide, Glossary]
Introducing an intermediate or API, including one that does not conform to standards or
specifications, back into the process and repeating a crystallization step or other appropriate
chemical or physical manipulation steps (e.g., distillation, filtration, chromatography, milling)
that are part of the established manufacturing process. Continuation of a process step after an in-
process control test has shown that the step is incomplete is considered to be part of the normal
process, and not reprocessing. [EU GMP Guide, Part II, ICH Q7]
Subjecting all or part of a batch or lot of an in-process drug, bulk process intermediate (final
biological bulk intermediate) or bulk product of a single batch/ lot to a previous step in the
validated manufacturing process due to failure to meet predetermined specifications.
Reprocessing procedures are foreseen as occasionally necessary for biological drugs and, in such
cases, are validated and pre-approved as part of the marketing authorization. [Main Principles for
Pharmaceutical Products, WHO, Canadian GMP Guidelines 2009]
Reproducibility
Reproducibility expresses the precision between laboratories (collaborative studies, usually
applied to standardization of methodology). [ICH Q2]
Requirement
The explicit or implicit needs or expectations of the patients or their surrogates (e.g., health care
professionals, regulators and legislators). In this document, “requirements” refers not only to
statutory, legislative, or regulatory requirements, but also to such needs and expectations. [ICH
Q9]
Responsible Person
The person who is ultimately responsible for all aspects of the preparation of medicinal products
including the release of these items. This person must have sufficient scientific and technical
education and experience to perform this duty. [PICS/S PE 010-4]
Retention Sample (see also Reference Sample)

A sample of a fully packaged unit from a batch of finished product. It is stored for identification
purposes. For example, presentation, packaging, labelling, patient information leaflet, batch
number, expiry date should the need arise during the shelf life of the batch concerned. There may
be exceptional circumstances where this requirement can be met without retention of duplicate
samples e.g. where small amounts of a batch are packaged for different markets or in the
production of very expensive medicinal products. For finished products, in many instances the
reference and retention samples will be presented identically, i.e. as fully packaged units. In such
circumstances, reference and retention samples may be regarded as interchangeable [EU GMP
Guide, Annex 19]
Sample collected as part of the original sampling process and reserved for future testing. The size
of a retention sample should be sufficient to allow for at least two confirmatory analyses. In
some cases statutory regulations may require one or more retention samples, each of which
should be separately identified, packaged and sealed. [Sampling Operations, WHO]
Retest Date
The date after which samples of the drug substance should be examined to ensure that the
material is still in compliance with the specification and thus suitable for use in the manufacture
of a given drug product. [ICH Q1A]
The date when a material should be re-examined to ensure that it is still suitable for use. [ICH
Q7]
The date when a material should be re-examined to ensure that it is still suitable for use. [EU
GMP Guide, Part II, Guide to Good Storage Practices for Pharmaceuticals, WHO, Canada GMP
Guidelines 2009]
Retest Period
The period of time during which the drug substance is expected to remain within its specification
and, therefore, can be used in the manufacture of a given drug product, provided that the drug
substance has been stored under the defined conditions. After this period, a batch of drug
substance destined for use in the manufacture of a drug product should be re-tested for
compliance with the specification and then used immediately. A batch of drug substance can be
re-tested multiple times and a different portion of the batch used after each re-test, as long as it
continues to comply with the specification. For most biotechnological/biological substances
known to be labile, it is more appropriate to establish a shelf life than a re-test period. The same
may be true for certain antibiotics. [ICH Q1A]
The period of time during which a drug substance can be considered to remain within the
specifications and therefore acceptable for use in the fabrication of a given drug product,
provided that it has been stored under defined conditions, after this period, the batch is re-tested
for compliance with specifications and then used immediately. [Canadian GMP Guidelines 2009]
Retrospective Validation
Validation of a process for a product which has been marketed based upon accumulated
manufacturing, testing and control batch data. [EU GMP Guide, Annex 15, PIC/S PI 006-3]
Involves the evaluation of past experience of production on the condition that composition,
procedures, and equipment remain unchanged. [Main Principles for Pharmaceutical Products,
WHO]
Return
Sending back to the manufacturer or distributor of a medicinal product which may or may not
present a quality defect. [EU GMP Guide, Glossary]
Revalidation
A repeat of the process validation to provide an assurance that changes in the process/equipment
introduced in accordance with change control procedures do not adversely affect process
characteristics and product quality. [EU GMP Guide, Annex15, PIC/S PI 006-3]
Repeated validation of an approved process (or a part thereof) to ensure continued compliance
with established requirements. [Main Principles for Pharmaceutical Products, WHO]
Repetition of the validation process or a specific portion of it. [PIC/S PI 011-3]
Reversible Toxicity
The occurrence of harmful effects that are caused by a substance and which disappear after
exposure to the substance ends. [ICH Q3C]
Rework
Action taken on a nonconforming product so that it will fulfill the specified DMR requirements
before it is released for distribution. [21 CFR Part 820, FDA]
Reworking
Subjecting an intermediate or API that does not conform to standards or specifications to one or
more processing steps that are different from the established manufacturing process to obtain
acceptable quality intermediate or API (e.g., recrystallizing with a different solvent). [EU GMP
Subjecting an in-process drug, a bulk process intermediate (final biological bulk intermediate), or
final product of a single batch/lot to an alternate manufacturing process due to a failure to meet
predetermined specifications. Reworking is an unexpected occurrence and is not pre-approved as
part of the marketing authorization. [Canadian GMP Guidelines 2009]
Risk
The combination of the probability of occurrence of harm and the severity of that harm. [ICH
Q9, ISO/IEC Guide 51, Guidance for Industry: Quality Systems Approach to Pharmaceutical
Risk Acceptance
The decision to accept risk (ISO Guide 73). [ICH Q9]
Risk Analysis
Method to assess and characterize the critical parameters in the functionality of an equipment or
process. [EU GMP Guide, Annex 15] The estimation of the risk associated with the identified
hazards. [ICH Q9]
Risk Assessment
The systematic process of organizing information to support a risk decision to be made within a
risk management process. It consists of the identification of hazards and the analysis and
evaluation of risks associated with exposure to those hazards [ICH Q9, Guidance for Industry:
Risk Communication
The sharing of information about risk and risk management between the decision maker and
other stakeholders. [ICH Q9]
Risk Control
Actions implementing risk management decisions (ISO Guide 73). [ICH Q9]
Risk Evaluation
The comparison of the estimated risk to given risk criteria using a quantitative or qualitative
scale to determine the significance of the risk. [ICH Q9]
Risk Identification
The systematic use of information to identify potential sources of harm (hazards) referring to the
risk question or problem description. [ICH Q9]
Risk Management
The systematic application of quality management policies, procedures, and practices to the tasks
of assessing, controlling, communicating, and reviewing risk. [ICH Q9, Guidance for Industry:
Risk Management Plan

A detailed description of the risk management system. [Directive 2001/83/EC]
Risk Management System

A set of pharmacovigilance activities and interventions designed to identify, characterize,
prevent or minimise risks relating to a medicinal product, including the assessment of the
effectiveness of those activities and interventions. [Directive 2001/83/EC]
Risk Priority Number (RPN)

A numeric assessment of risk assigned to a process, or steps in a process, as part of failure mode
effects analysis (FMEA). Each failure mode gets a numeric score that quantifies likelihood of
occurrence, likelihood of detection and severity of impact. The product of these three scores is
the RPN for that failure mode. RPN = severity rating × occurrence rating × detection rating.
[TRS 981 Annex 2, WHO]
Risk Reduction
Actions taken to lessen the probability of occurrence of harm and the severity of that harm. [ICH
Q9]
Risk Review
Review or monitoring of output/results of the risk management process considering (if
appropriate) new knowledge and experience about the risk. [ICH Q9]
Risk-benefit Balance
An evaluation of the positive therapeutic effects of the medicinal product in relation to the risks
as defined in point 28, first indent. [Directive 2001/83/EC]
Robustness
The robustness of an analytical procedure is a measure of its capacity to remain unaffected by
small, but deliberate variations in method parameters and provides an indication of its reliability
during normal usage. [ICH Q2]
S
Safety Study
Any study relating to an authorized medicinal product conducted with the aim of identifying,
characterising or quantifying a safety hazard, confirming the safety profile of the medicinal
product, or of measuring the effectiveness of risk management measures. [Directive 2001/83/EC]
Sample
A portion of a material collected according to a defined sampling procedure. The size of any
sample should be sufficient to allow all anticipated test procedures to be carried out, including all
repetitions and retention samples. If the quantity of material available is not sufficient for the
intended analyses and for the retention samples, the inspector should record that the sampled
material is the available sample (see Sampling record) and the evaluation of the results should
take account of the limitations that arise from the insufficient sample size. [Sampling Operations,
WHO]
Sampler
Person responsible for performing the sampling operations. [Sampling Operations, WHO]
Sampling
Operations designed to obtain a representative portion of a pharmaceutical product, based on an
appropriate statistical procedure, for a defined purpose, e.g. acceptance of consignments or batch
release. [Good Distribution Practices for Pharmaceutical Products, WHO]
Sampling Frequency
Established period for collecting samples. [PIC/S PI 007-6]
Sampling Method
That part of the sampling procedure dealing with the method prescribed for withdrawing
samples. [Sampling Operations, WHO]
Sampling Plan
Description of the location, number of units and/or quantity of material that should be collected,
and associated acceptance criteria. [Sampling Operations, WHO]
Sampling Procedure
The complete sampling operations to be performed on a defined material for a specific purpose.
A detailed written description of the sampling procedure is provided in the sampling protocol.
Sampling Record
Written record of the sampling operations carried out on a particular material for a defined
purpose. The sampling record should contain the batch number, date and place of sampling,
reference to the sampling protocol used, a description of the containers and of the materials
sampled, notes on possible abnormalities, together with any other relevant observations, and the
name and signature of the inspector. [Sampling Operations, WHO]
Sampling Unit
Discrete part of a consignment such as an individual package, drum or container. [Sampling
Operations, WHO]
Scaffold
A support, delivery vehicle or matrix that may provided structure for or facilitate the migration,
binding or transport of cells and/or bioactive molecules. [EU GMP Guide, Annex 2]
Scale Up
Increase in the production scale, for example, from pilot plant to production plant. [Canadian
Steps in the fermentation process whereby the production cell line/seed line is expanded until it
reaches a sufficient concentration for seeding the seed and/or production bioreactors. [Canadian
Seed Lot
Seed lot system: A seed lot system is a system according to which successive batches of a
product are derived from the same master seed lot at a given passage level. For routine
production, a working seed lot is prepared from the master seed lot. The final product is derived
from the working seed lot and has not undergone more passages from the master seed lot than
the vaccine shown in clinical studies to be satisfactory with respect to safety and efficacy. The
origin and the passage history of the master seed lot and the working seed lot are recorded.
Master seed lot: A culture of a micro-organism distributed from a single bulk into containers in a
single operation in such a manner as to ensure uniformity, to prevent contamination and to
ensure stability. A master seed lot in liquid form is usually stored at or below –70 °C. A freeze-
dried master seed lot is stored at a temperature known to ensure stability. Working seed lot: A
culture of a micro-organism derived from the master seed lot and intended for use in production.
Working seed lots are distributed into containers and stored as described above for master seed
lots. [EU GMP Guide, Glossary]
Collection of appropriate containers, whose contents are of uniform composition, stored under
defined conditions. In contrast to cell bank, seed lot may describe collections of plasmids,
viruses etc. For master and working seed lots, refer to definitions provided for MCB and WCB.
[Canadian GMP Guidelines 2009, Annex 2]
Selected Sample
Sample obtained according to a sampling procedure designed to select a fraction of the material
that is likely to have special properties. A selected sample that is likely to contain deteriorated,
contaminated, adulterated or otherwise unacceptable material is known as an extreme sample.
Self Audit
An assessment, undertaken under the responsibility of the same organization in order to monitor
the validity of the quality assurance system and the compliance with this guide. It can be
conducted by designated competent person(s) from the organization or assisted by external
experts. [PIC/S PE 010-4]
Self-contained Area
Premises which provide complete and total separation of all aspects of an operation, including
personnel and equipment movement, with well established procedures, controls and monitoring.
This includes physical barriers as well as separate air-handling systems, but does not necessarily
imply two distinct and separate buildings. [Main Principles for Pharmaceutical Products, WHO]
Self-contained Facility
Means a premise that provides complete and total separation of all aspects of the operation,
including personnel and equipment movement, with well established procedures, controls and
monitoring. This includes physical barriers and separate utilities such as air handling systems. A
self-contained facility does not necessarily imply a distinct and separate building. [Canadian
Semipermeable Container
Containers that allow the passage of solvent, usually water, while preventing solute loss. The
mechanism for solvent transport occurs by absorption into one container surface, diffusion
through the bulk of the container material, and desorption from the other surface. Transport is
driven by a partial-pressure gradient. Examples of semi-permeable containers include plastic
bags and semi-rigid, low-density polyethylene (LDPE) pouches for large volume parenterals
(LVPs), and LDPE ampoules, bottles, and vials. [ICH Q1A]
Sending Unit (SU)The involved disciplines at an organization from where a designated product,
process or method is expected to be transferred. [TRS 961 Annex 7, WHO]
Senior Management
Top management officials in a firm who have the authority and responsibility to mobilize
resources. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP
Regulations, FDA]
Person(s) who direct and control a company or site at the highest levels with the authority and
responsibility to mobilise resources within the company or site. [ICH Q10]
Sensitivity
Capacity of the test procedure to record small variations in concentration of a component, with a
defined degree of precision. [PIC/S PI 006-3]
Serious Adverse Event (SAE) (see also Adverse Event)

Any untoward medical occurrence or effect that at any dose results in death, is life-threatening,
requires hospitalisation or prolongation of existing hospitalisation, results in persistent or
significant disability or incapacity, or in a congenital anomaly or birth defect. [Directive
2001/20/EC]
Serious Adverse Reaction (SAR)(see also Adverse Reaction)

An adverse reaction which results in death, is life-threatening, requires inpatient hospitalisation
or prolongation of existing hospitalisation, results in persistent or significant disability or
incapacity, or is a congenital anomaly/birth defect. [Directive 2001/83/EC]
Serum
The liquid portion of clotted blood. [Canadian GMP Guidelines, Annex 14]
Service Level Agreement (SLA)

A service level agreement or contract is a negotiated agreement between the customer and
service provider that defines the common understanding about materials or service quality
specifications, responsibilities, guarantees and communication mechanisms. It can either be
legally binding, or an information agreement. The SLA may also specify the target and minimum
level performance, operation or other service attributes. [TRS 961 Annex 9, WHO]
Severity
A measure of the possible consequences of a hazard. [ICH Q9]
Shelf Life Specification

The combination of physical, chemical, biological, and microbiological tests and acceptance
criteria that determine the suitability of a drug substance throughout its re-test period, or that a
drug product should meet throughout its shelf life. [ICH Q1A]
Shelf-Life(see also Expiry Date) he time period during which a drug product is expected to
remain within the approved shelf life specification, provided that it is stored under the conditions
defined on the container label. [ICH Q1A]
The period of time during which a pharmaceutical product, if stored correctly, is expected to
comply with the specification as determined by stability studies on a number of batches of the
product. The shelf-life is used to establish the expiry date of each batch. [Good Distribution
The time interval during which a drug product is expected to remain within the approved
specification provided that it is stored under the conditions defined on the label and in the
proposed containers and closure. [Canadian GMP Guidelines 2009]
Shift
Scheduled periods of work or production, usually less than 12 hours in length, staffed by
alternating groups of workers. [PIC/S PI 007-6]
Shipping
The operation of packaging for shipment and sending of ordered medicinal products for clinical
trials. [EU GMP Guide, Annex 13, Canadian GMP Guidelines, Annex 13]
Shipping (or dispatch) is the assembly, packing for shipment, and sending of ordered medicinal
products for clinical trials. [Specific Pharmaceutical Products, WHO]
Signed / Signature
The record of the individual who performed a particular action or review. This record can be
initials, full handwritten signature, personal seal, or authenticated and secure electronic
signature. [EU GMP Guide, Part II, ICH Q7]
Simulated Product
A material that closely approximates the physical and, where practical, the chemical
characteristics (e.g. viscosity, particle size, pH etc.) of the product under validation. In many
cases, these characteristics may be satisfied by a placebo product batch. [EU GMP Guide, Annex
15, PIC/S PI 006-3]
Site Acceptance Test (SAT)

Final acceptance of an equipment or system by the customer, performed at the site where the
equipment/system will be operated.
Solvent
An inorganic or organic liquid used as a vehicle for the preparation of solutions or suspensions in
the manufacture of an intermediate or API. [EU GMP Guide, Part II, ICH Q7]
An inorganic or an organic liquid used as a vehicle for the preparation of solutions or

suspensions in the synthesis of a new drug substance or the manufacture of a new drug product.
[ICH Q3A, Q6A]
Somatic Cell
Cells, other than reproductive (germ line) cells, which make up the body of a human or animal.
These cells may be autologous (from the patient), allogeneic (from another human being) or
xenogeneic (from animals) somatic living cells, that have been manipulated or altered ex vivo, to
be administered in humans to obtain a therapeutic, diagnostic or preventive effects. [EU GMP
Guide, Annex 2]
Source Code
An original computer program expressed in human-readable form (programming language),
which must be translated into machine-readable form before it can be executed by the computer.
[PIC/S PI 011-3]
Source Plasma
Plasma collected by plasmapheresis and used for further manufacture. [Canadian GMP
Specific Activity
Amount of radioactivity per unit mass or per mole such as mCi/mg, MBq/mg or mCi/mole,
MBq/mole. [Canadian GMP Guidelines, Annex 3, Annex 5]
Specific Model Virus

Virus which is closely related to the known or suspected virus (same genus or family), having
similar physical and chemical properties to those of the observed or suspected virus. [ICH Q5A]
Specific Test
A test which is considered to be applicable to particular new drug substances or particular new
drug products depending on their specific properties and/or intended use. [ICH Q6A]
Specification
A list of tests, references to analytical procedures, and appropriate acceptance criteria that are
numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to
which a material should conform to be considered acceptable for its intended use. "Conformance
to specification" means that the material, when tested according to the listed analytical
procedures, will meet the listed acceptance criteria. [EU GMP Guide, Part II, ICH Q7, ICH Q6A,
Q6B, Guidance for Industry cGMP for Phase 1 Investigational Drugs, FDA]
A list of detailed requirements with which the products or materials used or obtained during
manufacture have to conform. They serve as a basis for quality evaluation. [Main Principles for
Any requirement with which a product, process, service, or other activity must conform. [21
CFR Part 820, FDA]
Means a detailed description of a drug, the raw material used in a drug, or the packaging material
for a drug and includes:
 a statement of all properties and qualities of the drug, raw material or packaging material
that are relevant to the manufacture, packaging, and use of the drug, including the
identity, potency, and purity of the drug, raw material, or packaging material,
 a detailed description of the methods used for testing and examining the drug, raw
material, or packaging material, and
a statement of tolerances for the properties and qualities of the drug, raw material, or packaging
material. [Canadian GMP Guidelines 2009]
Specification (Release)
criteria that determine the suitability of a drug product at the time of its release. [ICH Q1A]
Specification (Shelf Life)

criteria that determine the suitability of a drug substance throughout its re-test period, or that a
drug product should meet throughout its shelf life. [ICH Q1A]
Specificity
The ability to assess unequivocally the analyte in the presence of components which may be
expected to be present. Typically these might include impurities, degradants, matrix, etc. Lack of
specificity of an individual analytical procedure may be compensated by other supporting
analytical procedure(s). [ICH Q2]
Specified Degradation Product

A degradation product that is individually listed and limited with a specific acceptance criterion
in the new drug product specification. A specified degradation product can be either identified or
unidentified. [ICH Q3B]
Specified Impurity
An impurity that is individually listed and limited with a specific acceptance criterion in the new
drug substance specification. A specified impurity can be either identified or unidentified. [ICH
Q3A]
An identified or unidentified impurity that is selected for inclusion in the new drug substance or
new drug product specification and is individually listed and limited in order to assure the quality
of the new drug substance or new drug product. [ICH Q6A]
Spiking
The addition of a known amount of a compound to a standard, sample or placebo, typically for
the purpose of confirming the performance of an analytical procedure. [TRS 961 Annex 7,
WHO]
Sponsor
An individual, company, institution or organization which takes responsibility for the initiation,
management and/or financing of a clinical trial. [EU GMP Guide, Annex 13]
A person who takes responsibility for and initiates a clinical investigation. [Guidance for
An individual, company, institution or organization which takes responsibility for the initiation,
management and/or financing of a clinical trial. When an investigator independently initiates and
takes full responsibility for a trial, the investigator then also assumes the role of the sponsor.
[Specific Pharmaceutical Products, WHO]
An individual, corporate body, institution or organization that conducts a clinical trial. [Canadian
Sporicidal Process
A gaseous, vapour or liquid treatment applied to surfaces, using an agent that is recognised as
capable of killing bacterial and fungal spores. The process is normally validated using biological
indicators containing bacterial spores. The number of spore log reductions is not specified in this
definition, but a target of six log reductions is often applied. The process is applied to internal
surfaces of the isolator and external surfaces of materials inside the isolator, when conventional
sterilization methods are not required. The application of a sporicidal process to isolators is not
considered to be a sterilization process in the same way as, for example, a sealed container
subjected to a validated dry heat, moist heat or irradiation process. [PIC/S PI 014-3]
Stakeholder
Any individual, group or organization that can affect, be affected by, or perceive itself to be
affected by a risk. Decision makers might also be stakeholders. For the purposes of this
guideline, the primary stakeholders are the patient, healthcare professional, regulatory authority,
and industry. [ICH Q9]
An individual or organization having an ownership or interest in the delivery, results, and metrics
of the quality system framework or business process improvements. [Guidance for Industry:
Quality Systems Approach for Pharmaceutical cGMP Regulations, FDA]
Standalone System
A self-contained computer system, which provides data processing, monitoring or control
functions but which is not embedded within automated equipment. This is contrasted with an
embedded system, the sole purpose of which is to control a particular piece of automated
equipment. [PIC/S PI 011-3]
Standard Operating Procedure (SOP)

An authorized, written procedure giving instructions for performing operations not necessarily
specific to a given product or material, but of a more general nature (e.g. equipment operation,
maintenance and cleaning, validation, cleaning of premises and environmental control, sampling
and inspection). Certain SOPs may be used to supplement product-specific master and batch
production documentation. [WHO: TRS 961 Annex 7, Inspection, Main Principles for
Pharmaceutical Products, Good Distribution Practices for Pharmaceutical Products]
A written procedure giving instructions for performing operations not necessarily specific to a
given product or material but of a more general nature (e.g., equipment operation, maintenance
and cleaning, validation, cleaning of premises and environmental control, sampling and
inspection). Certain SOPs may be used to supplement product-specific master and batch
production documents. [Canadian GMP Guidelines 2009]
Starting Material
Any substance used in the production of a medicinal product, but excluding packaging materials.
A material used in the synthesis of a new drug substance that is incorporated as an element into
the structure of an intermediate and/or of the new drug substance. Starting materials are normally
commercially available and of defined chemical and physical properties and structure. [ICH
Q3A]
Any substance of a defined quality used in the production of a pharmaceutical product, but
excluding packaging materials. [Main Principles for Pharmaceutical Products, WHO]
Any substance entering a production facility for use in the production of a drug product.
All biological and chemical materials used in the manufacture of biological products, excluding
excipient. [Chinese GMP Guidelines, Annex 3]
Stasis Test
Also referred to as an inhibition test, which is performed to ensure that there are no inhibitory
substances remaining in the product and that the media is still capable of supporting the growth
of micro-organisms at the end of the sterility test incubation period. This test is not mandatory
but it may be useful to confirm the inactivation of antimicrobial substances in products where a
marginal test methodology is employed routinely, after an initial successful test validation.
[PIC/S PI 012-3]
State of Control
A condition in which the set of controls consistently provides assurance of continued process
performance and product quality. [EU GMP Guide, Annex 15, ICH Q10]
Sterile
Free of any viable organisms. (In practice, no such absolute statement regarding the absence of
microorganisms can be proven, see sterilization.). [PIC/S PI 007-6]
Free from viable microorganisms. [Canadian GMP Guidelines 2009]
Sterile Product
For purposes of this guidance, sterile product refers to one or more of the elements exposed to
aseptic conditions and ultimately making up the sterile finished drug product. These elements
include the containers, closures, and components of the finished drug product. [Guidance for
Sterility
Sterility is the absence of living organisms. The conditions of the sterility test are given in the
European Pharmacopoeia. [EU GMP Guide, Glossary]
Sterility Assurance Level (SAL)

Probability that a batch of product is sterile. (SAL is expressed as 10 -n). [PIC/S PI 007-6]
Sterility Assurance System

The sum total of the arrangements made to assure the sterility of products. For terminally
sterilized products these typically include the following stages:
(a) Product design
(b) Knowledge of and, if possible, control of the microbiological condition of starting materials
and process aids ( e.g. gases and lubricants).
(c) Control of the contamination of the process of manufacture to avoid the ingress of
microorganisms and their multiplication in the product. This is usually accomplished by cleaning
and sanitization of product contact surfaces, prevention of aerial contamination by handling in
clean rooms, use of process control time limits and, if applicable, filtration stages.
(d) Prevention of mix up between sterile and non sterile product streams.
(e) Maintenance of product integrity.
(f) The sterilization process.
(g) The totality of the Quality System that contains the Sterility Assurance System e.g. change
control, training, written procedures, release checks, planned preventative maintenance, failure
mode analysis, prevention of human error, validation calibration, etc. [EU GMP Guide,
Annex17]
Sterility Test
Test performed to determine if viable microorganisms are present. [PIC/S PI 007-6]
Sterilization
Validated process used to render a product free of viable organisms. Note: In
a sterilization process, the nature of microbiological death of reduction is described by an
exponential function. Therefore, the number of microorganisms which survive
a sterilization process can be expressed in terms of probability. While the probability may be
reduced to a very low number, it can never be reduced to zero. [PIC/S PI 007-6]
Sterilizing Filter
A filter used to render a material sterile. Sterilizing filters have a rated pore size of 0.2 µm or
less. [Canadian GMP Guidelines 2009]
Sterilizing Grade Filter

A filter that, when appropriately validated, will remove all microorganisms from a fluid stream,
producing a sterile effluent. [Guidance for Industry: Sterile Drug Products Produced by Aseptic
Stock Preparation
A product, which is prepared for stock and is available for dispensing. [PIC/S PE 010-4]
Storage
The storing of pharmaceutical products and materials up to their point of use. [Guide to Good
Storage Practices for Pharmaceuticals, WHO]
Storage Condition Tolerance

The acceptable variations in temperature and relative humidity of storage facilities for formal
stability studies. The equipment should be capable of controlling the storage condition within the
ranges defined in this guideline. The actual temperature and humidity (when controlled) should
be monitored during stability storage. Short term spikes due to opening of doors of the storage
facility are accepted as unavoidable. The effect of excursions due to equipment failure should be
addressed, and reported if judged to affect stability results. Excursions that exceed the defined
tolerances for more than 24 hours should be described in the study report and their effect
assessed. [ICH Q1A]
Strength
The concentration of the drug substance (for example, weight/ weight, weight/volume, or unit
dose/volume basis), and/or
 The potency, that is, the therapeutic activity of the drug product as indicated by
appropriate laboratory tests or by adequately developed and controlled clinical data
(expressed, for example, in terms of units by reference to a standard). [21 CFR Part 210,
FDA]
Stress Testing (drug product)

Studies undertaken to assess the effect of severe conditions on the drug product. Such studies
include photostability testing (see ICH Q1B) and specific testing on certain products, (e.g.,
metered dose inhalers, creams, emulsions, refrigerated aqueous liquid products). [ICH Q1A]
Stress Testing (drug substance)

Studies undertaken to elucidate the intrinsic stability of the drug substance. Such testing is part of
the development strategy and is normally carried out under more severe conditions than those
used for accelerated testing. [ICH Q1A]
Strongly Suspected Human Carcinogen

A substance for which there is no epidemiological evidence of carcinogenesis but there are
positive genotoxicity data and clear evidence of carcinogenesis in rodents. [ICH Q3C]
Structural Integrity (software)

Software attributes reflecting the degree to which source code satisfies specified software
requirements and conforms to contemporary software development practices and standards.
[PIC/S PI 011-3]
Structural Testing
Examining the internal structure of the source code. Includes low-level and high-level code
review, path analysis, auditing of programming procedures and standards actually used,
inspection for extraneous “dead code”, boundary analysis and other techniques. Requires specific
computer science and programming expertise. [PIC/S PI 011-3]
Structural Verification
An activity intended to produce documented assurance that software has appropriate structural
integrity. [PIC/S PI 011-3]
Subculture
Splitting of a cell population by a defined procedure to reduce the cell concentration or density
and make possible cell expansion. [Canadian GMP Guidelines, Annex 2]
Suite
Functional manufacturing area consisting of one or more rooms with shared air handling and
personnel access and which is segregated from the rest of the facility. It contains a separate air
supply and exhaust, separate personnel access/egress and separate process equipment. It does not
necessarily include a separate supply of water, compressed air/gas or steam, provided that
suitable engineering controls are in place to prevent product contamination of these systems. A
suite is referred to as a facility within a facility. [Canadian GMP Guidelines, Annex 2]
Supplier
A person providing pharmaceutical products and materials on request. Suppliers may be agents,
brokers, distributors, manufacturers or traders. Where possible, suppliers should be authorized by
a competent authority. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Supplying
All activities of providing, selling, donating medicinal products to wholesalers, pharmacists, or
persons authorized or entitled to supply medicinal products to the public. [EU GDP Guidelines]
Supporting Data
Data, other than those from formal stability studies, that support the analytical procedures, the
proposed re-test period or shelf life, and the label storage statements. Such data include
 stability data on early synthetic route batches of drug substance, small scale batches of
materials, investigational formulations not proposed for marketing, related formulations,
and product presented in containers and closures other than those proposed for marketing,
 information regarding test results on containers, and
 other scientific rationales.
[ICH Q1A]
System
A group of equipment with a common purpose. [EU GMP Guide, Annex 15]
A regulated pattern of interacting activities and techniques which are united to form an organised
whole. [EU GMP Guide, Glossary, Canadian GMP Guidelines 2009]
System Acceptance Test Specification

The system acceptance test specification is a description of those tests to be carried out to permit
acceptance of the system by the user. Typically it should address the following:
 System functionality
 System performance
 Critical parameters
 Operating procedures
The tests should ensure that the product operates as indicated in the functional specification and
meets the user requirements as defined in the URS. The tests typically include limit, alarms and
boundary testing. The System Acceptance Test Specification is a contractual document and, as
such, should be approved by both the supplier/ developer/ integrator and the end user. An
example procedure for producing a System Acceptance Test Specification is given in a GAMP
Guide Appendix. [PIC/S PI 011-3]
System Software
Software designed to facilitate the operation and maintenance of a computer system and its
associated programs, such as operating systems, assemblers, utilities, network software and
executive programs. System software is generally independent of the specific application. [PIC/S
PI 011-3]
System Specification
Describe how the system will meet the functional requirements. [PIC/S PI 011-3]
T
Tank
Static thermally insulated container designed for the storage of liquefied or cryogenic gas. They
are also called “Fixed cryogenic vessels”. [EU GMP Guide, Annex 6]
Tanker
In the context of the Annex, thermally insulated container fixed on a vehicle for the transport of
liquefied or cryogenic gas. [EU GMP Guide, Annex 6]
Target Material
A chemical substance which is bombarded with nuclear particles to produce a desired
radionuclide. [Canadian GMP Guidelines, Annex 5]
Technology Transfer Report

A documented summary of a specific technology transfer project listing procedures, acceptance
criteria, results achieved and conclusions. Any deviation should be discussed and justified. [TRS
961 Annex 7, WHO]
Temperature-controlled
Includes any environment in which the temperature is actively or passively controlled at a level
different from that of the surrounding environment within precise predefined limits. [TRS 961
Annex 9, WHO]
Temperature-modified
Includes any environment in which the temperature is predictably maintained at a level different
from that of the surrounding environment, but is not actively or passively controlled within
precise predefined limits. [TRS 961 Annex 9, WHO]
Teratogenicity
The occurrence of structural malformations in a developing fetus when a substance is
administered during pregnancy. [ICH Q3C]
Terminal Sterilization
The application of a lethal agent to sealed, finished drug products for the purpose of achieving a
predetermined sterility assurance level (SAL) of usually less than 10-6 (i.e., a probability of a
nonsterile unit of greater than one in a million). [Guidance for Industry: Sterile Drug Products
Sterilizing a drug in its final closed container. [Canadian GMP Guidelines 2009]
Therapeutic Activity
Therapeutic activity refers to the successful prevention, diagnosis and treatment of physical and
mental illnesses, improvement of symptoms of illnesses, as well as beneficial alteration or
regulation of the physical and mental status of the body and development of a sense of general
well-being. [Specific Pharmaceutical Products, WHO]
Time- and Temperature-sensitive Pharmaceutical Product (TTSPP)

Any pharmaceutical good or product which, when not stored or transported within predefined
environmental conditions and/or within predefined time limits, is degraded to the extent that it no
longer performs as originally intended. [TRS 961 Annex 9, WHO]
Tissue Engineered Product (TEP)

A product that
 Contains or consists of engineered cells or tissues, and
 Is presented a having properties for, or is used in or administered to human beings with a
view to regenerating, repairing or replacing a human tissue
A tissue engineered product may contain cells or tissues of human or animal origin, or both. The
cells or tissues may be viable or non-viable. It may also contain additional substances, such as
cellular products, bio-molecules, bio-materials, chemical substances, scaffolds or matrices.
Products containing or consisting exclusively of non-viable human or animal cells and / or
tissues, which do not contain any viable cells or tissues and which do not act principally by
pharmacological, immunological or metabolic action, shall be excluded from this definition.
[Regulation (EC) No 1394/2007]
Total Containment Glove Box

An aseptic suite of totally enclosed environment at negative pressure, whose primary purpose is
to maintain a sterile environment with the additional purpose of radioactivity workspace
localization. [Canadian GMP Guidelines, Annex 3]
Total Organic Carbon (TOC)

A nonspecific analytical procedure that involves oxidizing the residue to carbon dioxide, and
then measuring the generated carbon dioxide.
Total Radioactivity
Amount of radioactivity present in the total volume of a reconstituted preparation or total volume
of an eluate or solution used for reconstitution/labelling purposes, expressed as mCi/total volume
(ml) or MBq/total volume (ml). [Canadian GMP Guidelines, Annex 3]
Traceback
The process of investigating a report of a suspected transfusion-associated infection in order to
identify a potential implicated donor. The purpose of the investigation is to determine whether
any donor who contributed to the transfusion is infected with, or positive for, serologic markers
of the same infectious agent, and to retrieve available blood components from that donor, and to
notify consignees and recipients of components collected from the same donor. [Canadian GMP
Traditional Approach
A product development approach where set points and operating ranges for process parameters
are defined to ensure reproducibility. [EU GMP Guide, Annex 15, Guideline on Process
Validation for Finished Products, EMA]
Transfer Device
A fixed or removable device, which allows material to be transferred into and out of a container
or a pharmaceutical isolator, without exposing it to the external environment. [PIC/S PE 010-4]
Transgenic
An organism that contains a foreign gene in its normal genetic component for the expression of
biological pharmaceutical materials. [EU GMP Guide, Annex 2]
Transit
The period during which pharmaceutical products are in the process of being carried, conveyed,
or transported across, over or through a passage or route to reach the destination. [Good
Distribution Practices for Pharmaceutical Products, WHO]
Transport
Moving medicinal products between two locations without storing them for unjustified periods
of time. [EU GDP Guidelines]
Trend
A statistical term referring to the direction or rate of change of a variable(s). [ICH Q9]
TTSPP
see Time- and Temperature- sensitive Pharmaceutical Product
Turbulent Flow
Turbulent flow, or non-unidirectional airflow, is air distribution that is introduced into the
controlled space and then mixes with room air by means of induction. [Main Principles for
U
ULPA Filter
Ultra-low penetration air filter with minimum 0.3 µm particle retaining efficiency of 99.999
percent. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP,
FDA]
Unauthorized Market / Parallel Market

The unauthorized market consists of wholesale establishments and retail outlets distributing or
selling drugs without authorization from a competent authority. [Inspection, WHO]
Unblinding
The disclosure of the identity of a blinded product. [Directive 2003/94/EC]
Unexpected Adverse Reaction

An adverse reaction, the nature, severity or outcome of which is not consistent with the summary
of product characteristics. [Directive 2001/83/EC]
Unidentified Degradation Product

A degradation product for which a structural characterization has not been achieved and that is
defined solely by qualitative analytical properties (e.g., chromatographic retention time). [ICH
Q3B]
Unidentified Impurity
An impurity for which a structural characterization has not been achieved and that is defined
solely by qualitative analytical properties (e.g., chromatographic retention time). [ICH Q3A, see
also: ICH Q6A]
Unidirectional Airflow
An airflow moving in a single direction, in a robust and uniform manner, and at sufficient speed
to reproducibly sweep particles away from the critical processing or testing area. [Guidance for
Unidirectional airflow is a rectified airflow over the entire cross-sectional area of a clean zone
with a steady velocity and approximately parallel streamlines (see also turbulent flow). (Modern
standards no longer refer to laminar flow, but have adopted the term unidirectional airflow.)
[Main Principles for Pharmaceutical Products, WHO]
Uniformity
A starting material may be considered uniform when samples drawn from different layers do not
show significant differences in the quality control tests which would result in non-conformity
with specifications. The following materials may be considered uniform unless there are signs to
the contrary: organic and inorganic chemicals, purified natural products, various processed
natural products such as fatty oils and essential oils, and plant extracts. The assumption of
uniformity is strengthened by homogeneity, i.e. when the consignment is derived from a single
batch. [Sampling Operations, WHO]
Unique Device Identifier (UDI)

An identifier that adequately identifies a device through its distribution and use by meeting the
requirements of §830.20 of 21 CFR Part 820 Quality System Regulation. A unique device
identifier is composed of:
 A device identifier – a mandatory, fixed portion of a UDI that identifies the specific
version or model of a device and the labeler of that device, and
 A production identifier – a conditional, variable portion of a UDI that identifies one or
more of the following when included on the label of the device:
 The lot or batch within a device was manufactured,
 The serial number of a specific device,
 The expiration date of a specific device,
 The date a specific device was manufactured.
 For an HCT/P regulated as a device, the distinct identification code required by
§1271.290(c) of this chapter. [21 CFR Part 820, FDA]
Universal Product Code (UPC)
The product identifier used to identify an item sold at retail in the United States. [21 CFR Part
820, FDA]
Universal Test
A test which is considered to be potentially applicable to all new drug substances, or all new
drug products, e.g., appearance, identification, assay, and impurity tests. [ICH Q6A]
Unplanned (Emergency) Change

An unanticipated necessary change to a validated system requiring rapid implementation, also
known as a “hot-fix“. [PIC/S PI 011-3]
Unprocessed Bulk
One or multiple pooled harvests of cells and culture media. When cells are not readily accessible,
the unprocessed bulk would constitute fluid harvested from the fermenter. [ICH Q5A]
Unspecified Degradation Product
A degradation product that is limited by a general acceptance criterion, but not individually listed
with its own specific acceptance criterion, in the new drug product specification. [ICH Q3B]
Unspecified Impurity
An impurity that is limited by a general acceptance criterion, but not individually listed with its
own specific acceptance criterion, in the new drug substance specification. [ICH Q3A]
User (see also Regulated User)

The company or group responsible for the operation of a system. The GxP customer, or user
organization, contracting a supplier to provide a product. In the context of this document it is,
therefore, not intended to apply only to individuals who use the system, and is synonymous with
Customer. [PIC/S PI 011-3]
Utility Software
Computer programs or routines designed to perform some general support function required by
other application software, by the operating system, or by system users. [PIC/S PI 011-3]
V
Validation (see also Qualification, see also Verification)
A documented program that provides a high degree of assurance that a specific process, method,
or system will consistently produce a result meeting pre-determined acceptance criteria. [EU
GMP Guide, Part II, ICH Q7]
Action of proving, in accordance with the principles of Good Manufacturing Practice, that any
procedure, process, equipment, material, activity or system actually leads to the expected results.
[EU GMP Guide, Glossary, Main Principles for Pharmaceutical Products, WHO]
The risk based, systematic, GMP compliant and documented evidence that a defined process
actually leads reproducibly to the required results. [PIC/S PE 010-4]
Action of proving and documenting that any process, procedure or method actually and
consistently leads to the expected results. [TRS 961 Annex 7, WHO]
Establishing documented evidence that provides a high degree of assurance that a specific
process will consistently produce a product meeting its predetermined specifications and quality
attributes. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing, FDA]
Confirmation, through the provision of objective evidence, that the requirements for a specific
intended use or application have been fulfilled. (Reference: The ASQ Auditing Handbook, 3rd
edition, ASQ Quality Audit Division, J.P. Russell, Editor) [Guidance for Industry: Quality
Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Confirmation by examination and provision of objective evidence that the particular

requirements for a specific intended use can be consistently fulfilled. [21 CFR Part 820, FDA]
The documented act of demonstrating that any procedure, process, and activity will consistently
lead to the expected results. Includes the qualification of systems and equipment. [Canadian
To verify and document that the buildings and facilities of the manufacturing site, procedures,
processes and other procedures of the manufacturing control and quality control provide the
anticipated results. [Japan MHLW Ministerial Ordinance No. 179, 2004]
Validation Master Plan (VMP)

The VMP is a high-level document that establishes an umbrella validation plan for the entire
project and summarizes the manufacturer’s overall philosophy and approach, to be used for
establishing performance adequacy. It provides information on the manufacturer’s validation
work programme and defines details of and timescales for the validation work to be performed,
including a statement of the responsibilities of those implementing the plan. [TRS 961 Annex 7,
WHO, Main Principles for Pharmaceutical Products, WHO]
A document providing information on the company’s validation work programme. It should

define details of and timescales for the validation work to be performed. Responsibilities relating
to the plan should be stated. [PIC/S PI 006-3]
Validation Protocol / Validation Plan (VP)

A written plan stating how validation will be conducted and defining acceptance criteria. For
example, the protocol for a manufacturing process identifies processing equipment, critical
process parameters/operating ranges, product characteristics, sampling, test data to be collected,
number of validation runs, and acceptable test results. [EU GMP Guide, Part II, ICH Q7]
A document describing the activities to be performed in a validation, including the acceptance

criteria for the approval of a manufacturing process – or a part thereof – for routine use. [Main
A written plan stating how validation will be conducted, including test parameters, product
characteristics, production equipment, and decision points on what constitutes acceptable test
results. [PIC/S PI 006-3]
Validation Report (VR)

A document in which the records, results and evaluation of a completed validation programme
are assembled and summarized. It may also contain proposals for the improvement of processes
and/or equipment. [Main Principles for Pharmaceutical Products, WHO]
Document reporting the validation activities, the validation data and the conclusions drawn.
[PIC/S PI 006-3]
Valve
Device for opening and closing containers. [EU GMP Guide, Annex 6]
Vector
An agent of transmission, which transmits genetic information from one cell or organism to
another, e.g. plasmids, liposomes, viruses. [EU GMP Guide, Annex 2]
Vegetable Drug
see Crude Plant
Vendor
Person who is the fabricator of the item (raw material, packaging material, medicinal ingredients,
reagents). [Canadian GMP Guidelines 2009]
Vent
To remove the residual gas from a container/system down to 1,013 bar, by opening the
container/system to atmosphere. [EU GMP Guide, Annex 6]
Vent Filter
Non-shedding porous material capable of removing viable and non-viable particles from gases
passing in and out of a closed vessel. [PIC/S PI 007-6]
Verification (see also Validation)

The application of methods, procedures, tests and other evaluations, in addition to monitoring, to
determine compliance with the GMP principles/ quality risk management activities. [Main
Principles for Pharmaceutical Products, WHO, TRS 981 Annex 2, WHO]
Confirmation by examination and provision of objective evidence that specified requirements

have been fulfilled. [21 CFR Part 820, FDA, Guidance for Industry: Quality Systems Approach
to Pharmaceutical cGMP Regulations, FDA]
Veterinary Drugs
Drugs that are administered to food-producing and companion animals. [Canadian GMP
Guidelines 2009]
Viral Clearance
Elimination of target virus by removal of viral particles or inactivation of viral infectivity. [ICH
Q5A]
Viral Vector
A vector derived from a virus and modified by means of molecular biology techniques in a way
as to retain some, but not all, the parental virus genes, if the genes responsible for virus
replication capacity are deleted, the vector is made replication-incompetent. [EU GMP Guide,
Annex 2]
Virus
Intracellularly replicating infectious agents that are potentially pathogenic, possessing only a
single type of nucleic acid (either RNA or DNA), are unable to grow and undergo binary fission,
and multiply in the form of their genetic material. [ICH Q5A]
Virus Removal
Physical separation of virus particles from the intended product. [ICH Q5A]
Virus-like Particle
Structures visible by electron microscopy which morphologically appear to be related to known
viruses. [ICH Q5A]
W
Water for Injection (WFI)
Aqua ad iniectabilia, ultra pure water, distilled water. [Pharmacopoea Europaea]
Wholesale
To sell drugs, other than at retail sale, where the seller's name does not appear on the label of the
drugs. [Canadian GMP Guidelines 2009]
Wholesale Distribution of a Medicinal Product

All activities consisting of procuring, holding, supplying or exporting medicinal products, apart
from supplying medicinal products to the public. Such activities are carried out with
manufacturers or their depositories, importers, other wholesale distributors or with pharmacists
and persons authorized or entitled to supply medicinal products to the public in the Member
State concerned. [Directive 2001/83/EC]
Working Cell Bank (WCB)

A culture of cells derived from the master cell bank and intended for use in the preparation of
production cell cultures. The working cell bank is usually stored at -70°C or lower. [EU GMP
Guide, Glossary]
A homogeneous pool of micro-organisms or cells, that are distributed uniformly into a number of
containers derived from a MCB that are stored in such a way to ensure stability and for use in
production. Working virus seed (WVS) – as above but in relation to viruses, working transgenic
bank – as above but for transgenic plants or animals. Zoonosis: Animal diseases that can be
transmitted to humans. [EU GMP Guide, Annex 2]
The WCB is prepared from aliquots of a homogeneous suspension of cells obtained from
culturing the MCB under defined culture conditions. [ICH Q5A, Q5B, Q5D]
Cell bank prepared from aliquots of a homogenous suspension of cells obtained from culturing
the fully characterized MB under defined culture conditions. [Canadian GMP Guidelines 2009,
Annex 2]
Working Session
A defined period where available evidence indicates that the appropriate working conditions are
maintained. [PIC/S PE 010-4]
A set of conditions encompassing upper and lower processing limits and circumstances,
including those within standard operating procedures, that pose the greatest chance of process or
product failure (when compared to ideal conditions). Such conditions do not necessarily induce
product or process failure. [Guidance for Industry Sterile Drug Products Produced by Aseptic
Worst Case
A condition or set of conditions encompassing upper and lower processing limits and
circumstances, within standard operating procedures, which pose the greatest chance of product
or process failure when compared to ideal conditions. Such conditions do not necessarily induce
product or process failure. [EU GMP Guide, Annex 15, Main Principles for Pharmaceutical
Products, WHO, PIC/S PI 006-3]
A set of conditions encompassing upper and lower processing limits and circumstances,
including those within standard operating procedures, that pose the greatest chance of process or
product failure (when compared to ideal conditions). Such conditions do not necessarily induce
product or process failure. [Guidance for Industry Sterile Drug Products Produced by Aseptic
Y
Yield, Actual
The quantity that is actually produced at any appropriate phase of manufacture, processing, or
packaging of a particular drug product. [21 CFR Part 210, FDA]
Yield, Expected
The quantity of material or the percentage of theoretical yield anticipated at any appropriate
phase of production based on previous laboratory, pilot scale, or manufacturing data. [EU GMP
Yield, Theoretical
The quantity that would be produced at any appropriate phase of production, based upon the
quantity of material to be used, in the absence of any loss or error in actual production. [EU
GMP Guide, Part II, ICH Q7]
The quantity that would be produced at any appropriate phase of manufacture, processing, or
packing of a particular drug product, based upon the quantity of components to be used, in the
absence of any loss or error in actual production. [21 CFR Part 210, FDA]
Z
Zoonosis
Animal diseases that can be transmitted to humans. [EU GMP Guide, Annex 2]

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A

Abuse of Medicinal Products Lạm dụng thuốc

Accelerator Máy gia tốc

Acceptance Criteria Tiêu chí chấp nhận

Accuracy Sự chính xác

Action Level / Action Limit Giới hạn hành động

Any substance or mixture of substances intended to be used in the manufacture of a

Active Substance Hoạt chất dược dụng

Active Substance Gas Khí dược dụng

Advanced Electronic Signature Chữ ký điện tử/Chữ ký số

Adverse Event Yếu tố bất lợi

Adverse Reaction Phản ứng bất lợi

Air Lock Chốt gió

Air Separation Plant

Alert Level Mức độ cảnh báo

Alert Limit Giới hạn cảnh báo

(environmental monitoring) Established microbial or particulate levels giving early warning of

Analytical Procedure Quy trình phân tích

Annual Review Đánh giá hàng năm

Antibody, monoclonal (MAb)

API Starting Material Nguyên liệu đầu vào

Area Khu vực

Aseptic Area Khu vực vô trùng

Aseptic Filling Đóng vô trùng

Aseptic Manufacturing Area Khu vực sản xuất vô trùng

Aseptic Process Quy trình vô trùng

Aseptic Processing Facility Nhà xưởng sản xuất vô trùng

Aseptic Processing Room Phòng thao tác vô trùng

Aseptic Technique and Manipulation

A specific quantity of material produced in a process or series of processes so that it is expected

A defined quantity of pharmaceutical products processed in a single process or series of

Batch Number / Lot Number / Control Number Số lô - Số kiểm soát

Total number of viable microorganisms on or in a pharmaceutical product prior to sterilization.

Biological Activity Hoạt tính sinh học

Biological Agent Tác nhân sinh học

Biological Indicator (BI) Chỉ thị sinh học

Biometrics Sinh trắc học

Biosafety Level (BSL) Mức độ an toàn sinh học

Blinding Giả dược

Blood Component Thành phần máu

Blow / Fill / Seal Unit Máy thổi-đóng-hàn kín

Bracketing Lấy mẫu phân tầng

Brokering of Medicinal Products

Bug Lỗi phần mềm

Bulk Drug Thuốc bán thành phẩm

Bulk Product Bán thành phẩm

Campaigned Manufacture Sản xuất chiến dịch

Capability of a Process Hiệu năng quy trình

Carrier Chất mang

Certificate of Analysis (COA)

Certificate of Compliance (CoC)

Certificate of Pharmaceutical Product (CPP)

Certification of the Finished Product Batch

A formal system by which qualified representatives of appropriate disciplines review proposed

A written procedure that describes the action to be taken if a change is proposed

Chemical Development Studies

Chemical Transformation Step

Documented evidence to establish that cleaning procedures are removing residues to

Closed Isolator System

Colony Forming Units (CFU)