Pharmaceutical

QA&QC

Elias S. (BA.Acc ,B.Pharm)

ch3: Concepts and Philosophy of
TQM,QC, GMP and ISO-9000
Pharmaceutical Quality Assurance

Outline

– Introduction and definitions

– Quality assurance of medicines

– Elements of quality assurance for pharmaceuticals

– QC & operational task of QC

– Quality assurance of drug procurement

1
 Rationale for this Module
 Quality medicines are safe, effective and efficient
tools for treatment of disease
 Poor quality (sub-standard) medicines may not
produce Desired effects, may cause harm
 Errors in production can lead to sub-standard medicines

 Quality Assurance principles can be used to:

– detect errors or problems in production

– ensure suppliers conform to standards and expectations

2
 Pharmaceutical Analysis
 To ensure the safety, efficacy, and quality of pharmaceutical products

– It is important to gain the information about the qualitative and

quantitative composition of substances

. i.e. to find out what a substance is composed of and exactly how much.

 Quantitative test

– measures the amount of a substance present

 Qualitative test

– determines whether the substance being tested for is present or

absent
 Pharmaceutical
analysis …
Focus point is:
. What to test? the drug product

. Why to test? ensures the safety, efficacy and quality of

pharmaceutical products

. How to test? compendial and non-compendial methods

presented in regulatory documents

. Analytical method used to achieve Qualitative

and quantitative analysis
 Determinants of Medicine Quality
.Identity: Active ingredient

.Purity: Not contaminated with potentially harmful

substances
. Potency: Usually 90– 110% of the labeled amount

. Uniformity: Consistency of color, shape, size

. Bioavailability: Interchangeable products?

. Stability: Ensuring medicine activity for stated period

 Total Qaulity management(TQM)

What is TQM?

TQM is the integration of all functions and processes within

an organization in order to achieve continuous
improvement of the quality of goods and
services(pharmaceutical products). The goal is customer
satisfaction.

Definition of Quality

• Definition of quality is dependent on the people defining it

• There is no single, universal definition of quality
03/06/2025
 Quality is…..
Invisible when GOOD
Impossible to ignore when
BAD
 What is Quality?
 Quality:
 Quality is the degree w/c a pharmaceutical product conforms the

standard
/specification

 Meeting requirements of specific customer needs

 Quality can be achieved by three managerial processes which

include:
– Quality planning (QP):
 The initial activity of the plan is to identify the customers
and their need
 Then develop product and process design to respond to
the need of the customers
 Quality …
– Quality control (QC):
. A regulatory process which measures the quality performance of the
products

. The activities of QC involve laboratory procedures

– Quality improvement (QI):

. Facilitates in improving deficiencies through the feedback from
customers or regulatory bodies

. The only way to achieve quality is to manufacture the product

correctly

. Quality cannot be achieved merely by checking, examination and

testing.

. “There should not be any compromise for quality”

 Terminology
. Quality Assurance (QA)
– It is the sum of all activities and responsibilities intended to
ensure the products meet all the applicable quality
specifications
in the final dosage form.

– “a planned system of activities designed to ensure effective

quality control.”

– Efficient QA program:

– To monitor and evaluate effectiveness of policies and

procedures of quality control
 Quality Relationship

Quality Management QA

GMP
Quality Assurance
QC/
GLP
GMP

Quality Control
Pharmaceutical manufacturing

Quality
product
 Quality Assurance
. QA:

– Covers all maters that individually or collectively influence

the quality of the product

– Is not the duty of one organization unit in the company alone

. The responsibility of all staff members who can influence

product quality

– Must be independent of financial pressure

– Must ensure the quality policies are followed

All Staff
 FACTORS IN DRUG QUALITY ASSURANCE
LEGISLATIVE IMPORT
FRAMEWORK & EXPORT
REGULATIONS CONTROL PACKAGING

HUMAN LABELLING &

RESOURCES- PRODUCT
PROFESSIONALS INFROMATION

DRUG
PRODUCT
RAW
QUALITY QC &
MATERIALS-
ANALYSIS
ACTIVE &
INACTIVE

TRANSPORT
MANUFACURING DISTRIBUTION
PROCESSES DISPENSING
STORAGE
& PROCEDURES & USE
 Components of Quality Assurance
. Internal Quality control: IQC
– Nature: Concurrent

– Performed by: lab staff

– Objective: Reliable results on a daily basis

. External quality assessment: EQA

– Nature: Retrospective to evaluate IQC

– Performed by: Independent agency

– Objective: Ensure inter-laboratory comparability

 Quality systems
Objectives

- To prevent risks

- To detect deviations

- To correct errors

- To improve efficiency

- To reduce costs
 Factors influencing quality
Pre analytical Analytical Post analytical

Right specimen Laboratory Recording

professionals

Right collection Reagents Interpretation

Right labeling Equipment Turnaround time

Right quantity Selection of test - SOP Report to right user

Right transport Records

Right storage Bio-Safety

The Quality Assurance
Cycle

Patient/Client Prep
Sample Collection
Personnel Competency
Reporting Test Evaluations
•Data and Lab
Management
•Safety
•Customer
Service Sample Receipt
and
Accessioning

Record Keeping

Quality Control Sample Transport

Testing
 Principal Activities of QA

1. QA ensures that products are formulated

and developed in accordance with QA principles
- Product quality begins with development process

- All of the development work should be

undertaken with a commitment to QA

- Enable easier adherence to QA principle in other area

of manufacturing
GxP Regulation Along the Drug
Life

NO GMP/GLP!!! GLP GCP GMP

GLP = study based GMP = process based

GCP = clinical based

 Principal Activities of QA …
2. QA identify all management responsibilities, with
written job description and organization diagram.

- Assist in ensuring that there are sufficient qualified

& experienced people available to carry out
their responsibilities.

3. QA provides SOPs for all manufacturing and testing

methods.

- State what should be done and how?

 Principal Activities of QA …

4. QA ensures that there are up-to-date written

procedures for supply and use of starting and packaging
material.

- Includes all the procedures relating to

purchasing, reception, sampling and testing materials.
 Principal Activities of QA …

5. QA ensures that there are up-to-date, written

procedures to control all starting materials,
intermediate and bulk products

– Proper management of all the handling &

storage of materials is essential
. Apply to all materials whether incoming,
intermediate or finished goods for sale.
 Principal Activities of QA …

6. QA system must also ensure that there are written, up-

to- date SOPs describing how the product is to be
processed and checked.

7. QA ensures that no product is released for

distribution before it has been checked by the authorized
person

- Product has been produced and controlled in

accordance with the established SOPs and
requirements of the marketing authorizations.
 Principal Activities of QA …

8. QA ensures that appropriate conditions are provided for all

storage & distributions

- During product development - Stability testing

indicates condition under which product must be stored

- Arrangement should be in place throughout the

storage and distribution chain to ensure that the product
will not be exposed to conditions that could adversely
affect it.
 Principal Activities of QA …

9. A QA system must ensure that there is a self inspection

process available and implemented, leading to program
of critical self evaluation and continuous improvements.

- There should be an internal audit function within department

(self-inspection)

- Is back up by quality audit, charged with looking at all

department & assessing the application of the quality system
within a company.
 Standard Operating Procedures (SOPs)
. SOP

– An authorized written procedure giving instructions

for
performing operations
. not necessarily specific to a given process, product or material

– describe in a detailed form the activities performed in

the laboratory

– Provide uniformity, consistency and reliability in each of the

activities performed in the laboratory

– Reduce systematic errors

– Provide training & guidance for new staff

 SOPs …
. SOPs should be
– written instructions that specify:

 how a test or procedure is to be performed

How a piece of equipment is operated, maintained and

calibrated.

– Written by the person performing the procedure or who knows

the procedure well.

– Supervisor reviewed for completeness and content.

– QA or QC staff approved
 SOP …
• QA is impossible without written guidelines of
SOP containing pre-analytic, analytic, and post
analytic instructions to perform a test.

• A particular SOP should have:

i. A title (concise & descriptive)

ii. Test name, test procedure, reagent used including the

limitation of the procedure and calculation
explanation
 SOP …
III. Principle of the test (type of rxn, sample or test
organism involved, reason for performing the test,
formula to determine the final result)

iv. Sample storage preservative condition

v. Report handling procedure ( reporting range, test &

critical value)

vi. Chemical handling technique

vii. Reference materials pertinent to specific procedure

 Consequences of QA breaches
• Poor Treatment Outcomes

• High Health Bills

• Treatment Failures & Deaths

• Loss of Confidence in the Health Services

• Enormous Economic Losses

• National Security Issue

. How to minimize the flow of poor-quality
medicines?

– Inspection

– Port-of-entry control

– Document verification
– Registration
 Good Manufacturing
Practice(orange guide)

Main concept
Concept of Good Manufacturing Practice
(GMP)
INTRODUCTION
What is good manufacturing practice
(GMP)?

Part of QA which ensures that

products are consistently produced &
controlled to the quality standards
appropriate to their use
GMP covers ALL
aspects of production; from the
starting materials, premises and
equipment to the training and personal
Good Manufacturing Practice (GMP) …
The regulation developed FDA for
pharmaceutical
industry
minimum requirements in the manufacturing processing
A basic principle of GMP is that quality cannot be
tested into a batch of product but must be built
into each batch of product during all stages
of the manufacturing process
It is designed to minimize the risks involved
in any pharmaceutical production that cannot be
eliminated through testing the final product
Quality should also be maintained during
production stage
GMP Implementation by Countries
Different country may use different GMP Guidelines:
WHO Guidelines
Country specific Guidelines (e.g. FDA)
How do GMPs of different countries compared?
At a high level, GMPs of various nations are very similar;
most require :

Equipment & facilities being properly designed,

maintained, & cleaned
SOPs be written & approved
An independent Quality unit (like QC and/or QA)
Well trained personnel & management
 What is c-GMP?
GMP is also sometimes referred to as "cGMP"

Usually see “ cGMP” where c = current, to emphasize

that the expectations are dynamic

C refers to current rules & regulations that serve

strictly follow the guidelines and manufacturing
procedures that are current & most up to date.
 What is c-GMP?
Manufacturers who agree to follow the cGMP
guidelines but still use 2 0 -2 5 year old machinery and
equipment to produce healthcare products

GMP forced many manufacturers to give up

on old practices and switch over to latest production
processes

Helped in avoiding contamination, errors and

mix ups while at the same time helping in production
of highest quality healthcare and pharmaceutical products
 Advantages of GMP
a. Prevent errors that cannot be eliminated through quality
control of finished products
unexpected contamination of products
incorrect labels on containers, which could mean that
patients receive the wrong medicine.
insufficient or too much active ingredient, resulting in
ineffective treatment or adverse effects.
b. Grantees credibility
A drug that contains little or none of the claimed
ingredient will not have the intended therapeutic effect
Poor Quality medicine leads to loss for:
Manufacturers, Healthy care
workers, Governments, end users
 Advantage of GMP …
c. Ensure all units of a medicine are of the same quality (with
in a specified parameters)

d. GMPhelps boost pharmaceutical export opportunities

Most countries will only accept import and sale of

medicines that have been manufactured to internationally
recognized GMP

Governments seeking to promote their countries export

of pharmaceuticals can do so by
omaking GMP mandatory for all pharmaceutical production, &
otraining their inspectorsin GMP requirements
 Basic Elements of GMP …
1.Personnel

2.Premises
3. Equipment

4.Documentation

5 . Production Control

6. Quality Control

7. Complaint and Product Recall

 Personnel
The establishment and maintenance of a satisfactory system of QA and the
correct manufacture of quality products relies upon people
Personnel requirements:
Adequate number of persons
With necessary qualifications
With practical experience

Individual responsibilities should be clearly understood by the

individuals
All personnel should be aware of GMP: Must receive training in
GMP: initial training, continuing training including hygiene standards

All responsible staff should have specific duties recorded in

individual written job descriptions
Prevent unauthorized access to Production areas, Storage areas, Quality
control
 Personnel …
Training, in accordance with a written, approved programme
Personnel in the production areas;
In the control laboratories; &
Those whose activities could affect the quality of the product

Training programmes should be available, approved by either the head

of Production or the head of Quality Control
Key Personnel
Key personnel (which normally should be full-time) positions
include:
Authorized person
Head of Production
Head of Quality Control
Heads of Production and Quality Control should be independent
of each other
 Personnel …
Key Personnel …

1. Should possess appropriate qualifications

Scientific education such as:

pharmaceutical sciences and technology

Chemistry

microbiology

chemical engineering
 Personnel …
Key Personnel …
2. Should posses appropriate experience
Practical experience
Manufacture and quality assurance

Preparatory period under professional guidance

sometimes needed
Education and experience should enable personnel
to take difficult decisions in an independent,
professional and scientific way
To resolve the problems encountered in manufacturing and
QC
 Personnel ...
Head of Production: Responsibilities

Approval and implementation of production

instructions, in-process QC and ensure strict
implementation
Ensures that production records are evaluated and
signed by designated person

Checks maintenance of production department,

premises and equipment
Ensures process validation and equipment calibration
Ensures initial and continuous training of
production personnel
 Personnel …
Head of Quality Control: Responsibilities
Approval or rejection of materials,e.g. packing materials,
intermediates, bulk and finished products, in accordance
with specifications
Ensures carrying out of necessary testing
Approval of quality control procedures,e.g. sampling and
testing; specifications
Checks maintenance of quality department, premises
and equipment
Ensures validation (including analytical
procedure validation)
Ensures initial and continuous training of QC personnel
 Personnel …
The Quality assurance head : Responsibilities

Ensuring Compliance with regulatory requirements and

international standards
Approval of the release of finished product for sale
Establishment and implementation of quality system
Review of all
QC testing results,
production documents,
results of in-process control, &
overall compliance to the specification for the finished
product prior to release
 Personnel …
Visitors or Untrained Personnel
Preferable not to enter production and control areas

If this is unavoidable, then they must be

given information in advance, particularly about
personal hygiene
protective clothing requirements
Must be accompanied and closely supervised at all
times
 Hygiene
A high level of hygiene should be practiced in
every aspect of the manufacture of pharmaceutical
products
The scope of sanitation covers
personnel
premises
equipment and apparatus
production materials and containers
products for cleaning and disinfection, and
anything that could become a source of
contamination to the product
 Personnel Hygiene
A high level of personal hygiene is required in production areas
should be instructed to wash their hands before entering
production areas
Eating, drinking, chewing or smoking, in the production
and storage areas should be prohibited
Direct contact should be avoided between
the operator's hands and the exposed product
with any part of the equipment that comes
into contact with the products
Every person entering the manufacturing
areas should wear protective garments
 Premises
Important aspects to be kept in mind to ensure the suitability
of the operations to be carried out in a given premises:
Location
Design
Construction
Maintenance
must be located, designed, constructed, adapted and
maintained to suit the operations to be carried out
should be situated in an environment which
presents minimal risk of causing contamination of products
 Premises …
Location
The land and buildings where the manufacturing
operations are located must contribute towards the
quality of the products

Premises must be located to

minimize risks of cross-contamination

permitting effective cleaning and maintenance
minimizing the build-up of dirt and dust
 Premises ...
The design should aim to:
Minimize risks of errors
Permit effective cleaning and maintenance
Avoid cross-contamination, build-up of dirt and
dust
Avoid any adverse effect on the quality of products

Prevent the entry of insects, birds and animals

into the building

Prevent the migration of extraneous material from

the outside into the building and from one area to
another
 Premises ...
Construction
Should be of Suitable materials
To ensure proper cleaning, no cracks, and the building
can withstand pressures, vibrations and other effects
Electrical supply is required
Suitable lighting (especially for visual on-line checks)
Temperature and relative humidity control
should be provided
materials and products have to be stored or
processed under controlled conditions.
Appropriate and effective ventilation
 Premises ...
Maintenance

Careful maintenance done

Repairs and maintenance should not present any hazard

to the quality of the products

Maintenance workshops should be separated from

production areas
 Premises …
Specific areas

Ancillary areas

Storage areas

Production areas
Quality control areas
 Ancillary Areas
Rest and refreshment rooms should be separated
from production & QC laboratory areas
Changing, washing and toilet areas should be
available and in appropriate numbers
Maintenance workshops separated from production

AIR
LOCK
FA C T O R Y CHANGE
ROOM TOILETS

CANTEEN
 Premises …
Storage areas
Storage areas of sufficient capacity

Separate and segregated areas for different

materials are recommended
starting materials
packaging materials
finished products
quarantined, released, rejected, returned and recalled
products and materials
Appropriate temperature and relative humidity
conditions within defined limits
 Premises ...
Production areas ...
Designed to Minimize risk of cross-contamination:
Separate facilities for other products such as some
antibiotics, hormones, cytotoxic substances
Non-pharmaceuticals normally not produced in the same facility,
e.g. pesticides, herbicides
Production areas should be effectively ventilated, with air
control facilities (including temperature and humidity)
Should have adequate and appropriate spaces for:
Personnel changing rooms, offices
Equipments
Documents and records
Sample storage
Testing areas
 Premises …
Quality Control areas
QC laboratories should be separated from production areas
Suitable design with sufficient space to avoid mix-ups and cross-
contamination
Suitable space for storage of samples, reference standards,
solvents, reagents and records
should be provided with effective ventilation and separate air
supply from production is recommended
Separate rooms for some instruments to protect them
from interference (e.g. electrical, vibration, moisture, etc.)
Balances and Dissolution apparatus (Vibration free)
IR and KF (Moisture sensitive)
 Equipment ...
Equipment used in the manufacture and testing of
pharmaceutical products must be
Located,
Designed,
Constructed, &
Maintained, to suit the operations to be carried out
The equipment should be located in areas of
production or testing to support
the operators in ensuring that the manufacturing process or
testing procedure is followed correctly
can prevent omission of steps in the process
avoid possible cross-contamination
 Equipment …
Design
can assist in easy cleaning and maintenance of equipment
Equipment design must aim:
to minimize cross-contamination, dust
to permit effective cleaning and maintenance
To avoid any adverse effect on the quality of
products
Cross- contamination
contamination in tablet compression and
packaging
machines is a common problem area
use of compressed air is common for moving dust and
 Equipment … … …
Construction material
should suit the operation
Should allow its use for the range of products
(production or testing)
Should not corrode or deteriorate
Should not influence the manufacturing or
testing procedure
Should not react with the product (very high
quality
stainless steel)
 Equipment …
Maintenance
Maintenance of equipment is important to ensure that the equipment will
operate or perform in accordance with its specifications
There must exist maintenance schedules for major pieces of equipment
Production equipment
should be designed so that it can be easily and thoroughly cleaned
Should not present any hazard to the products
Parts that come into contact with the product must be non-reactive
The equipment must be correctly labelled at all times (to show it is clean or
dirty, and ready for use)
Defective equipment
removed, or
clearly labelled (status label) (to prevent it from being used when it is
no longer capable of producing a good quality product)
 Equipment …
Quality Control Laboratory Equipments
The general principles of GMP are applicable to
production and QC equipments

Most requirements for Production Equipments are

applicable for laboratory equipment
maintenance, calibration, records, etc.

Defective equipment should be removed or labelled to

prevent analysts from using equipment for testing
IS0-9000
ISO 9000: A set of generic, internationally recognized
standards for quality management and quality
assurance
Applied to any organization, large or small, whatever
its product in any sector of activity
ISO is an auditable system – organization may be
certified to a market standard by outside agency
ISO 9000 predominant QMS today – adopted by 149
countries/economies
ISO 9001:2008 is the only standard in the series that
specifies the requirements of a QMS

03/06/2025
ISO 9001 FAMILY OF STANDARDS

ISO 9001:2008 QMS – Requirements

ISO 9000:2005 Fundamentals and vocabulary
ISO 19011:2011 Guidelines for auditing management systems
ISO 9004:2009 Managing for the sustained success of an
organization — A quality management approach

Only ISO 9001:2008 is auditable. The rest serve as references only.

03/06/2025
ISO-9000

 Quality Management:
Management activities and functions involved in
determination of quality policy and its implementation
through means such as quality planning, QA & QC
QMS :
A system comprised of quality planning, quality
improvement activities, the establishment of a set of quality
policies and objectives that will act as guidelines within an
organization, and QA and QC

03/06/2025
Quality Management Principles of ISO 9000
Customer focus
Leadership
Involvement of people
Process Approach – A set of interrelated activities which transforms
inputs into outputs
System approach to management – Manage set of interrelated
processes
Continual Improvement
Factual approach to decision making
Mutually beneficial supplier relationships

03/06/2025
The Process Approach
Every process require specific inputs, resources, activities,
outputs and customers
Need to perform:
Define and document the inputs
Define and document the kinds of resources that your processes use
Define and document the activities and their interactions
Define and document the responsibilities
Define and document the outputs

03/06/2025
 THE SYSTEM APPROACH
• Quality must be managed by a system to be effective
• A system is a set of interrelated or interacting
elements

03/06/2025
Cont…

 A well-designed and well-implemented QMS can and should

eliminate:
*Ineffectiveness *Inefficiencies
*Problems *Errors
*Inconsistencies *Malicious practice
*Uncertainties *Bad culture

03/06/2025
 Quality Control (QC)
. Each holder of a manufacturing authorization should
have
a quality control department
– QC department should be independent from other
departments.

. The QC department must have adequate resource.

– Adequate laboratory facilities or access to them.

e.g. government or contract laboratories

– Appropriately qualified, trained & experienced personnel

– Approved written procedures

The operational task of the quality control
department
• Sampling

• Inspecting

• Analytical testing

• Monitoring of all materials & environmental

conditions in the factory

• Releasing or rejecting material for production use &

finished products
 The targets of these activities are:
• Starting materials

• Packaging materials

• Intermediates

• Bulk products

• Finished products

• Environmental conditions
 Basic requirements for quality control

1. A sample should be undertaken by method and

personnel approved by the QC department.
- It must be carried out in such a way that it is
representative of the batch & in accordance with an
SOP

- QC personnel must have access to the production area

to undertake sampling when necessary.
 Basic requirements for quality control …
2. Validated test methods should be applied.

. The validation of test methods include verification of:

– Accuracy

– Precision

– Linearity

– Repeatability

– Robustness

– Specificity

. Test methods should be challenged to be able to demonstrate that

the
tests are able to give an accurate result on repeatable bases.
 Basic requirements for quality control …
- The method must be capable of being applied with precision

- The results obtained must be linear over a range of

acceptable response

- Finally the result must be repeatable over a number of

identical tests.

3. Records for sampling, inspecting, testing of materials,

intermediates and bulk and finished products need to
be kept
- This means that there will be traceability on what happened.
 Basic requirements for quality control …
4. The QC department should review and evaluate relevant production
documentation

- This review need to cover all quality aspects

- Ensures manufacturing documentations & the QA

documentation are in harmony.
5. The QC department should generate or review records for deviations & failure
investigations

- it is important that all deviation from the manufacturing

normal procedure are recorded or documented.

- Any impact on product quality must be assessed.

 Basic requirements for quality control …

6. QC ensures that ingredients used comply with the

qualitative and quantitative composition of the
finished product as approved in market authorization.

7. QCensures that proper containers are used

8. QCensures correct labeling of finished products

9.QC ensures batches are released by appropriate

authorization.
 Basic requirements for quality control …
10. Sample of starting materials & products are retained.

- Sufficient retention samples of the starting materials and the

finished products in its final pack should be kept for one year
past the expiry date.

- This is to allow for an evaluation of the product after it has

been

distributed should there be a need.

- It will also allow ongoing stability trial to be done

QC personnel must have access to production areas

. For example sampling & inspection

. This must be balanced because it may not be appropriate

– QC staff enter aseptic filling suites, or

– Areas where there is highly potent dangerous material

such as oncology/ cytotoxic materials.

 Head of QC responsibilities
. Approval or rejection of materials:
– Starting & packaging materials, intermediate, bulk and finished products

. Evaluation of batch records

. Carrying out necessary testing

. Approval of necessary QC procedures:

– Sampling instruction, Specifications, Test methods and other QC procedures.

. Maintenance of quality department, premises and equipment

. Validation (including analytical procedure and calibration

of Equipment’s)

. Initial and continuous training of QC personnel

Testing references: Pharmacopeial standards (USP, EP, BP,etc)
 Specification consists of test methods and their associated
acceptance criteria
 Criteria applicable to all drug products:
– Identity
– Strength
– Purity
– Testing methods
 Testing Method :

. Physicochemical analysis .
Microbiological analysis
 Additional specifications
– Tablet & capsules . Suspension and solutions
– pH of solution
– Disintegration
– Particle size of suspending drug
– Dissolution – Clarity of solution (turbidity)

– Stereo isomeric purity – Color of solution

– Viscosity
– Moisture (water)
– Volume of fill
– Residual solvents
– Preservative testing

– Microbial limits
 Quality Assurance for drug supply management
 Critical Elements in QA for Procurement

– Product selection
– Supplier qualification for medicine
selection
– Product certification
– Contract specification – Inspection of
shipment
– appropriate
– laboratory testing
storage, transport,
Selection dispensing & use procedure
– Product monitoring system

Management Import
Use Procurement
system
Rational Local manufacturer
use
Distribution GMP

Storage condition,
expiry date
 GMP,inspection and licensing
Evaluation of product dossier

Product Selection

Use Procurement
Storage/handling
QA Product Specifications.
Prequalification
Tender contract
Monitoring of supplier
performance
Storage/distribution

Inspections/licensing
 Pharmaceutical QA
Pharmaceutical product QA

Pharmaceutical service QA
- Quality of raw materials, intermediate & finished products

- Maintaining quality products through the appropriate

storage, distribution, monitoring, & use by prescribers,
dispensers, & consumers
- Drug use review

- Clinical pharmacy services

- Other pharmacy services

• The following areas (GxP Quality Guidelines) are
monitored under Pharmaceutical QA
>GMP - Good Manufacturing Practice

>GLP - Good Laboratory Practice

>GDP - Good Distribution Practice includes all procurement &

transportation processes

>GSP - Good Storage Practice

>GPP - Good Prescribing Practice

>GDP - Good Dispensing Practice

>GRP - Good Review Practice, …

 Pharmaceutical Quality Assurance Framework
• Five critical elements to achieve the
expected treatment outcome:
1. Active pharmaceutical ingredients (API) has been
shown to be safe & effective for the treatment
2. Product is of suitable quality to provide an effective
outcome
3. Prescriber has accurately identified the need for the
treatment
4. Prescriber or dispenser has properly instructed the
patient on how to use the product
5. Patient compliance with the prescribed regimen
correctly
 Pharmaceutical Quality Assurance Framework …

• The first 2 items are product-specific issues, which are

the most easily addressed technically, whereas

• Items 3 & 4 are prescriber-specific & depends on the

prescribers‟ education, knowledge, & skills as well as
the rigorous enforcement of performance standards

• Item 5 is patient-specific issue that depends on the

patient‟s knowledge & commitment & the patient‟s
access to services
122
 How Is Quality Assessed?
. INSPECTION of products on arrival

. Visual inspection

. Product specification review (including expiration dates)

. LABORATORY TESTING for compliance with pharmacopoeial

standards
. International Pharmacopoeia

. European Pharmacopoeia
COA
. U.S. Pharmacopeia

. British Pharmacopoeia

. National Pharmacopoeia

. BIOAVAILABILITY DATA
 How Is Medicine Quality Assured? (1)
. Product selection
. Long shelf-life ; Acceptable stability

. Acceptable bioavailability

. Selection of appropriate suppliers

. Supplier pre-qualification; Request samples from new suppliers

. Request specific reports and data for certain medicines (e.g., bioavailability and
stability studies)

. Collect and maintain information on supplier performance

. Product certification
. GMP certificate of manufacturer
. Product/batch certification (COA)

. Random local testing

 How Is Medicine Quality Assured? (2)
. Contract and procurement specifications

. Pharmacopeia reference standard

. Local language for product label

. Standards for packaging to meet specific storage and

transport conditions
 How Is Medicine Quality Assured? (3)
. Appropriate storage, transport, dispensing, and
use procedures
.Pharmaceutical distribution & inventory control
procedures
.Provision for appropriate storage & transport including
adequate T 。 control, security, and cleanliness
.Explicit enforcement of cold chain procedures
.Appropriate dispensing: containers, labeling,
counseling
.Avoidance of repacking unless quality control in place
 How Is Medicine Quality Assured? (4)
. Product monitoring system

. Problem reporting: who, how, where, and to

whom; what additional measures; what follow-
up information

. Product recalls: hospital or country level

 Who Ensures Medicine
Quality?
. Drug
regulatory
authority

. Drug and . Physicians

Therapeutics and other
Committee
Medicine prescribers
Quality

. Hospital . Pharmacy
procurement (and dispensers)
office .Patients
Implications of Pharmaceutical QA for the DTC
. Providing technical advice on procurement of
pharmaceuticals

. Defining product specifications

. Generic medicines

. Bioavailability issues

. Stability issues

. Defining minimum laboratory testing

 Implications of Pharmaceutical QA for the
DTC …
. Providing technical advice to hospital departments

. Medicine transportation and storage

. Dispensing

. Analyzing product problem reports

. Quality complaints

. Medicine recall system

Quality assurance in drug supply management
. Targets:
– Product selection and specification

– Suppliers selection

– Product certification
– Contract specification

– Inspection of shipment

– Targeted laboratory testing

– Maintaining drug quality during storage, distribn & use

 Difference between QA & QC
SN QA QC
1 Helps us to build processes Helps us to implement the built
processes
2 Is duty of the complete team Is only the duty of the testing
team
3 Comes under the category of Comes under the category of
verification validation
4 Is considered process oriented Is considered product oriented
exercise exercise
5 Prevents the occurrence of Always detects, corrects &
issues, bugs, or defects in reports the bugs or defects in the
the application application
6 Doesn‟t involve executing Always involves executing
the program or code the program or code
 Difference between QA & QC ...
SN QA QC
7 Is done before quality control Is done only after QA activity is
completed

8 Can catch errors & mistakes Can catch errors QA cannot

QC cannot catch, that is why it catch, that is why it is
is considered low level activity considered high level activity

9 Is human-based checking of Is computer-based execution of

documents or files program or code

10 Planning done for doing a Means action has been taken on

process the process by executing it
 Difference between QA & QC ...
SN QA QC
11 Mainly focuses on Mainly focuses on identifying
preventing defects or bugs defects or bugs in the system
in the system
12 Is not considered a time Is always considered a time
consuming activity consuming activity
13 Makes sure that you are Makes sure that whatever we‟ve
doing the right things done is as per the requirement,
rightly, that is why it always means it is as per what we‟ve
comes under the category of expected, that is why it comes under
verification activity the category of validation activity
14 Is pro-active means it Is reactive means it identifies the
identifies weaknesses in the defects & also corrects the defects or
processes bugs
In-process Quality
Control (IPQC)
IN PROCESS QUALITY CONTROL (IPQC)

“TESTING”
 IPQC ...
• Definition: "It is a planned system in which samples are
taken and tested at various critical steps during the
manufacturing in accordance with the written
directions".
It monitors all the features of the product that may affect
its quality and prevent errors during processing
.
Manufacturing area
Packaging area
 PURPOSE
To control the procedure involved in manufacturing
To monitor all features which affect the quality
To detect significant human errors
To ensure quality of final product

To monitor and, if necessary, to adjust the process to

ensure that the product conforms to its specifications

It sometimes identifies a defective product batch

that can be corrected by rework
Various Instruments Used in IPQC Dep’t
Disintegration apparatus
Dissolution apparatus
Analytical balance
Friability testing apparatus
pH meter
Tablet hardness tester
Chromatographic methods
U.V Spectroscopy
Karl fisher Titrimeter
 Conditions for Designing of IPQC Test
Identify the types of formulation (tab, liquids, ointments)

Identify the critical steps involved in manufacturing of

the product

Identify the specification of parameters which conform

the parameters are within control
Define the frequency of checking for each parameter
 IPQC Tests for Various Dosage Forms
Tablets
a ) Content uniformity to assure uniformity in
potency for highly potent and low dose
drugs like digoxin.
b ) Dissolution test predicting bioavailability

c) Assay of active ingredients

d) Weight variation 20 tablets are taken and
weighed
No more than two tablets are out of the
percentage limit (90-110 %)
e) Hardness test the force required to break a
tablet in a diametric compression test
f) Disintegration test the time required for
the tablet to break

g) Friability Tablets that tend to powder, chip

or fragment during handling lack elegance
 IPQC Tests for Various Dosage Forms …
Syrups & Suspension
a ) Content uniformity
b) Assay of active ingredients
c) pH = affects the stability of the product
d) Appearance - color , odor, taste

Product is checked for uniform distribution of

color absence of air bubbles
e) Clarity test
 IPQC Tests for Various Dosage Forms …
INJECTABLES
a ) Content uniformity
b) Clarity test
c) pH
d) Pyrogen test
e) Stability test
f) Leakage test
g) Sterility test
 IPQC Tests for Various Dosage Forms …
Capsules
Wt variation
Assays
Content uniformity

Dissolution test
Disintegration time

Moisture content
 IPQC Tests for Various Dosage Forms …
PACKAGING
Line clearance must be given before starting
packaging operation
Print details on labels must be certified

Leakage testing bottles, ampoules, vials

must be performed

Objectives of Line clearance

To assure that no traces of previous product

To assure that correct materials brought for processing/

packing