11-03-2022

GLP
PHARMACEUTICAL QUALITY ASSURANCE
THIRD YEAR B. PHARM SEM VI

GLP:
• "Good Laboratory Practice (GLP) originated in the USA in the
1970s
• Replacing animals which had died during a study with new ones
(which had not been treated appropriately with the test
compound) without documenting
• Goals of GLP:
 GLP is a regulation covering the quality management of
non-clinical safety studies
 The aim of the regulation is to encourage scientists to
organize and perform their studies in a way which
promotes the quality and validity the test data.
 To point out the important difference between the
"science" of a study and the organization of a study.

1
 11-03-2022

• GLP does not tell scientists what tests to perform, or what the
scientific contents of a study plan (protocol) should be? There are
other guidelines for this aspect of studies (scientific guidelines).
• The important goals of GLP To help scientists obtain results that
are: Reliable, Repeatable, Auditable, Recognized by scientists
worldwide, GLP principles are a set of organizational
requirements, The purpose is not to assess the intrinsic scientific
value of a study.
• Benefits of GLP:
1. Promotes mutual recognition of study data across
international frontiers
2. Limiting waste of resources
3. Ensuring high quality results concerns the validity of test
data.
4. Ensuring comparability
5. Mutual recognition
6. GLP stipulates the conditions for the organization of
studies not the scientific content or value of studies.

• GLP does not tell scientists what tests to perform, or what the
scientific contents of a study plan (protocol) should be? There are
other guidelines for this aspect of studies (scientific guidelines).
• The important goals of GLP To help scientists obtain results that
are: Reliable, Repeatable, Auditable, Recognized by scientists
worldwide, GLP principles are a set of organizational
requirements, The purpose is not to assess the intrinsic scientific
value of a study.
• Benefits of GLP:
1. Promotes mutual recognition of study data across
international frontiers
2. Limiting waste of resources
3. Ensuring high quality results concerns the validity of test
data.
4. Ensuring comparability
5. Mutual recognition
6. GLP stipulates the conditions for the organization of
studies not the scientific content or value of studies.

2
 11-03-2022

Fundamentals of GLP:
• The GLP regulations set out the rules for good practice and help
researchers perform their work in compliance with their own pre-
established plans and standardized procedures.
• GLP defines the working environment under which studies are:
1. Planned: The study plan (protocol) is prepared at the beginning
of the study.
2. Performed: This refers to the standard operating procedures
(SOPs) which are a GLP requirement.
3. Recorded: The collection of raw data and the recording of
deviations, if any, during the study.
4. Reported: One of the problems identified before implementing
GLP was that study reports did not always reflect the study data
accurately.

5. Archieved: Since studies can be audited many years after their

completion, it is important that the study data, specimens,
samples and reports are properly archived.
6. Monitored: Monitoring by study staff, quality assurance
personnel and national inspectors helps to assure GLP
compliance.
All GLP texts, irrespective of their origin, stress the importance on
the following points five points:
✓ Resources: Organization, personnel, facilities and equipment
✓ Characterization: Test items and test systems
✓ Rules: Study plans (or protocols) and written procedures
✓ Results: Raw data, final report and archives
✓ Quality Assurance.

3
 11-03-2022

Definition and Principles of GLP

Good Laboratory Practice (GLP) is defined in the OECD Principles as “a quality
system concerned with organizational process and the conditions under which
non-clinical health and environmental safety studies are planned. performed,
monitored, recorded, archived and reported.”
• As per OECD guidelines, GLP principles include
1.Organization and Personnel
2. Quality assurance program
3. Facilities
4. Equipment, reagents and materials
5. Test systems o Physical/Chemical
6. Test and reference items
7. Standard operating procedures
8. Performance of study
9. Reporting of results
10. Archival

GENERAL PROVISIONS
Scope: These guidelines propose good laboratory practices for conducting nonclinical
laboratory studies that support or are intended to support applications for research or
marketing permits for products regulated by the Food and Drug Administration,
including food and color additives, animal food additives, human and animal drugs,
medical devices for human use, biological products, and electronic products.
Important Definitions:
• Act
• Test article
• Control article
• Nonclinical laboratory study
• Sponsor means
• Testing facility
• Test system
• Specimen
• Raw data
• Quality assurance unit
• Study director
• Study initiation date
• Study completion date

4
 11-03-2022

• Applicability to studies performed under grants and contracts: When a sponsor

conducting a nonclinical laboratory study intended to be submitted to or reviewed by
the Food and Drug Administration utilizes the services of a consulting laboratory,
contractor or grantee to perform a analysis or other service, it shall notify the
consulting laboratory, contractor or grantee that the service is part of a nonclinical
laboratory study that must be conducted in compliance with the provisions of these
guidelines.
• Inspection of a testing facility:
(a) A testing facility shall permit an authorized employee of the Food and Drug
Administration, at reasonable times and in a reasonable manner, to inspect the
facility and to inspect (and in the case of records also to copy) all records and
specimens required to be maintained regarding studies within the scope of this
part.
(b) he Food and Drug Administration will not consider a nonclinical laboratory
study in support of an application for a research or marketing permit if the
testing facility refuses to permit inspection.
ORGANIZATION AND PERSONNEL
1. Personnel
2. Testing facility management
3. Study director
4. Quality assurance unit

FACILITIES
General:
Each testing facility shall be of suitable size and construction to facilities the proper
conduct of nonclinical laboratory studies.
Animal care facilities:
(a) A testing facility shall have a sufficient number of animal rooms or area as needed
(b) A testing facility shall have a number of animal rooms or areas separate from those
described in paragraph
(c) Separate areas shall be provided, as appropriate, for the diagnosis treatment, and
control of laboratory animal diseases.
(d) When animals are housed, facilities shall exist for the collection and disposal of all
animal waste and refuse or for safe sanitary storage waste before removal from the
testing facility.
Animal supply facilities:
There shall be storage areas, as needed, for feed, bedding, supplies, and equipment.
Facilities for handling test and control articles:
As necessary to prevent contamination or mix-ups, there shall be separate areas for:
(1) Receipt and storage of the test and control articles.
(2) Mixing of the test and control articles with a carrier, e.g., feed.
(3) Storage of the test and control article mixtures.
Storage areas for the test and/or control article and test and control mixtures shall be
separate from areas housing the test systems.
Laboratory operation areas:
Specimen and data storage facilities:

5
 11-03-2022

EQUIPMENT
Equipment design:
Equipment used in the generation, measurement, or assessment of data and
equipment used for facility environmental control shall be of design and adequate
capacity to function according to the protocol and shall be suitably located for
operation, inspection, cleaning, and maintenance.
Maintenance and calibration of equipment
a) Adequately inspected, cleaned, and maintained. Equipment used for the
generation, measurement, or assessment of data shall be adequately tested,
calibrated and/or standardized.
b) The written standard operating procedures required under 58.81 (b)11 shall
set forth in sufficient detail the methods, materials, and schedules to be used in
the routine inspection, cleaning, maintenance, testing, calibration and/or
standardization of equipment. And shall specify, when appropriate, remedial
action to be taken in the event of failure or malfunction of equipment. The
written standard operating procedures shall designate the person responsible for
the performance of each operation.
c) Written records shall be maintained of all inspection, maintenance testing,
calibrating and/or standardizing operations.

TESTING FACILITIES OPERATION

A. Standard operating procedures
(a) A testing facility shall have standard operating procedures in writing setting forth
nonclinical laboratory study methods that management is satisfied are adequate to
ensure the quality and integrity of the data generated in the course of a study.
All deviations in a study from standard operating procedures shall be authorized by the
study director and shall be documented in the raw data. Significant changes in
established standard operating procedures shall be properly authorized in writing by
management.
(b) Standard operating procedures shall be established for, but not limited to, the following
(1) Animal room preparation.
(2) Animal care.
(3) Receipt, identification, storage, handling, mixing, and method of sampling of
the test and control articles.
(4) Test system observations.
(5) Laboratory tests,
(6) Handling of animals found moribund or dead during study.
(7) Necropsy of animals or postmortem examination of animals.
(8) Collection and identification of specimens.
(9) Histopathology
(10) Data handling, storage, and retrieval
(11) Maintenance and calibration of equipment.
(12) Transfer, proper placement, and identification of animals.

6
 11-03-2022

c) Each laboratory area shall have immediately available laboratory manuals and
standard operating procedures relative to the laboratory procedures being
performed. Published literature may be used as a supplement to standard
operating procedures.
d) A historical file of standard operating procedures, and all revisions thereof,
including the dates of such revisions, shall be maintained.

Reagents and solutions

All reagents and solutions in the laboratory areas shall be labeled to indicate
identity, titer or concentration, storage requirements, and expiration date.
Deteriorated or outdated reagents and solutions shall not be used.

Animal care
(a) There shall be standard operating procedures for the housing, feeding, handling,
and care of animals.
(b) All newly received animals from outside sources shall be isolated and their health
status shall be evaluated in accordance with acceptable veterinary medical practice.
(c) At the initiation of a nonclinical laboratory study, animals shall be free of any
disease or condition that might interfere with the purpose or conduct of the study.
(d) Warm-blooded animals, suckling rodents, used in laboratory procedures that
require manipulations and observations over an extended period of time or in
studies that require the animals to be removed from and returned to their home
cages for any reason (e.g., cnge cleaning, treatment.
(e) Animals of different species shall be housed in separate rooms when necessary.
(f) Animal cages, racks and accessory equipment shall be cleaned and sanitized
at appropriate intervals.
(g) Feed and water used for the animals shall be analyzed periodically to ensure that
contaminants known to be capable of interfering with the study and reasonably
expected to be present in such feed or water are n present at levels above those
specified in the protocol.
(h) Bedding used in animal cages or pens shall not interfere with the purpose or
conduct of the study and shall be changed as often a necessary to keep the
animals dry and clean.
(i) If any pest control materials are used, the use shall be documented Cleaning and
pest control materials that interfere with the study shall not be used.

7
 11-03-2022

TEST AND CONTROL ARTICLES

C. Mixtures of articles with carriers
(a) For each test or control article that is mixed with a carrier, tests
byappropriate analytical methods shall be conducted:
(1) To determine the uniformity of the mixture and to determine,
periodically,the concentration of the test or control article in the
mixture.
(2) To determine the stability of the test and control articles in the
mixture
b) Where any of the components of the test or control article carrier
mixture has an expiration date, that date shall be clearly shown on the
container. If more than one component has an expiration date, the
earliest date shall be shown.

PROTOCOL FOR CONDUCT OF A

NONCLINICAL LABORATORY STUDY
1. Protocol:
(a) Each study shall have an approved written protocol that
clearly indicates the objectives and all methods for the conduct
of the study The protocol shall contain, as applicable, the
following information:
1. A descriptive title and statement of the purpose of the
study.
2. Identification of the test and control articles by name,
chemical abstract number, or code number.
3. The name of the sponsor and the name and address of the
testing facility at which the study is being conducted.
4. The number, body weight range, sex, source of supply,
species, strain, substrain, and age of the test system
5. The procedure for identification of the test system.

8
 11-03-2022

PROTOCOL FOR CONDUCT OF A

NONCLINICAL LABORATORY STUDY
Protocol:
(a) Each study shall have an approved written protocol that
clearly indicates the objectives and all methods for the conduct
of the study The protocol shall contain, as applicable, the
following information:
6. A description of the experimental design, including the
methods for the control of bias
7. A description and/or identification of the diet used in the
study as well as solvents, emulsifiers, and/or other
materials used to solubilize or suspend the test or control
articles before mixing with the carrier.
8. Each dosage level, expressed in milligrams per kilogram of
body weight or other appropriate units, of the test or control
article to be administered and the method and frequency of
administration.

PROTOCOL FOR CONDUCT OF A

NONCLINICAL LABORATORY STUDY
Protocol:
(a) Each study shall have an approved written protocol that
clearly indicates the objectives and all methods for the conduct
of the study The protocol shall contain, as applicable, the
following information:
9. The type and frequency of tests, analyses, and
measurements be made.
10. The records to be maintained
11. The date of approval of the protocol by the sponsor and the
date signature of the study director
12. A statement of the proposed statistical methods to be used.

b) All changes in or revisions of an approved protocol and the

reasons therefor shall be documented, signed by the study
director, dated, and with the protocol.

9
 11-03-2022

PROTOCOL FOR CONDUCT OF A

NONCLINICAL LABORATORY STUDY
2. Conduct of a nonclinical laboratory study
(a) The nonclinical laboratory study shall be conducted in
accordance with the protocol.
(b) The test systems shall be monitored in conformity with the
protocol.
(c) Specimens shall be identified by test system, study, nature,
and date of collection.
(d) Records of gross findings for a specimen from postmortem
observations should be available to a pathologist when
examining that specimen histopathologically.
(e) All data generated during the conduct of a nonclinical
laboratory study, except those that are generated by
automated data collection systems, shall be recorded directly,
promptly, and legibly in ink.

REPORTS
1. Reporting of nonclinical laboratory study results
(a) A final report shall be prepared for each nonclinical
laboratory study and shall include, but not necessarily be
limited to, the following:
i. Name and address of the facility performing the study
and the dates on which the study was initiated and
completed.
ii. Objectives and procedures stated in the approved
protocol, including any changes in the original
protocol.
iii. Statistical methods employed for analyzing the data.
iv. The test and control articles identified by name,
chemical abstracts number or code number, strength,
purity, and composition or other appropriate
characteristics.

10
 11-03-2022

REPORTS
1. Reporting of nonclinical laboratory study results
(a) A final report shall be prepared for each nonclinical
laboratory study and shall include, but not necessarily be
limited to, the following:
v. Stability of the test and control articles under the
conditions of administration.
vi. A description of the methods used.
vii. A description of the test system used.
viii. A description of the dosage, dosage regimen, route of
administration, and duration.
ix. A description of all circumstances that may have
affected the quality or integrity of the data.
x. The name of the study director, the names of other
scientists or professionals, and the names of all
supervisory personnel, involved in the study.

REPORTS
1. Reporting of nonclinical laboratory study results
(a) A final report shall be prepared for each nonclinical
laboratory study and shall include, but not necessarily be
limited to, the following:
xi. A description of the transformations, calculations, or
operations performed on the data, a summary and
analysis of the data, and a statement of the conclusions
drawn from the analysis.
xii. The signed and dated reports of each of the individual
scientists or other professionals involved in the study.
xiii. The locations where all specimens, raw data, and the
final report are to be stored.
xiv. The statement prepared and signed by the quality
assurance unit.

11
 11-03-2022

REPORTS
1. Reporting of nonclinical laboratory study results
(b) The final report shall be signed and dated by the study
director.
c) Corrections or additions to a final report shall be in the form of
an amendment by the study director

12