(COURSE # PD-607)

Pharmaceutical Quality
Management-I)
Cr. Hr.03

1
 Chapter outline

INTRODUCTION:

• Understand the scope and objectives of Pharmaceutical quality management.

• Know different methods adopted in a pharmaceutical industry
regarding quality management.
• Components of quality management system.

STANDARDIZATION OF PHARMACEUTICALS:
a). An understanding of the testing quality control program and methods
adopted in a Pharmaceutical industry, dosage from control, process,
testing program and methods, physical, chemical and biological tests and
specifications, statistical quality control.
b). General understanding of total Quality assurance and measures to adopt
Quality Assurance in pharmaceutical industry. Good Manufacturing Practices
and Current Good Manufacturing Practices.

2
Lecture 1
 Learning Objectives of introduction of Pharmaceutical
Quality Management:
At the end of this lecture, students will be able to:

• Define the scope and objectives of Pharmaceutical quality

management.
• Explain the methods adopted in a pharmaceutical industry regarding
quality management.
• Describe the need for a systematic quality assurance process for
pharmaceutical products
• Enlist the key elements of the quality assurance process for
pharmaceuticals

4
 INTRODUCTION
⚫ Concept of quality according to U.S.F.D.A.
"Quality should be built into the product, and testing alone cannot be
relied onto ensure product quality".

⚫ building of quality into the product ??????

⚫ stage wise controls incorporates controls on all input resources.
 QMS

• Quality : degree of fines

• Management : coordinated activities
• System: set of interactions/integrated

elements Single system

To achieve Quality, mission, vision, goals, objectives

 QMS

• Structured collection of policies, procedures, processes.

 Objectives of Quality Management

• Provide high-quality drug product.

• Prevent or reduce the number of recalls
• Harmonise the cGMPs.
• To help in getting quality by design.
• To achieve success in business.

”
 Definition of Quality Management

• The W.H.O. guidelines of G.M.P. define quality management as

follows:
• Quality Management may be defined as:

“The aspects of management function that determines and

implements the “quality policy.”
 All members of the pharmaceutical industry are
encouraged to adopt
quality management system,
which include the following principles:
⚫ quality responsibility rests with top management.
⚫ Top management should identify and
communicate company quality objectives
⚫ Quality is affected at every stage of the industrial
cycle

⚫ Quality knows no functional boundaries,

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 Quality management system

Improvement of cGMP by modern QMS involves

• Quality
• Quality by design
• Risk management and risk assessment
• Corrective and preventive action(CAPA)
• The quality unit > Q.A and Q.C

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The basic concepts of Quality Assurance, Good Manufacturing
Practice and Quality Control are inter-related.

QUALITY RELATIONSHIP

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QUALITY ???

“The totality of features and characteristics of a product or

service that bear on its ability to satisfy stated or implied

needs”

ASSURANCE ???

“The act of giving confidence, the state of being certain or

the act of making certain”

 QUALITY ASSURANCE ???
□ According to WHO:
“QA is a wide ranging concept covering all matters that
individually or collectively influence the quality of a
product”

“Sum total of the organized arrangement made with object

of ensuring the medicinal products are of quality
required for their ultimate use".

□ According to ISO 9000:

“All those planned and systematic activities implemented
to provide adequate confidence that an entity will fulfill
requirements for quality”
 Aspects of Q.A

• Deals with all matters related to quality of the product

• Quality of medicine must meet the requirement of the intended
use OR (customer)
• Wide range concept covering many aspects that are outside
the scope of Q.C/ GMP.
• Sum total of the organized arrangements.
 Responsibilities of Q.A

• Review and approval of all the procedures related to

production, maintenance,
• Review of records and auditing and performed analysis.
• Quality assurance have some
key-words or key-phrases, which constitute the core of the
definition

These words or
phrases are as follows :

• (A) Quality of the product.

• (B) All matters / Wide ranging concept.
• (C) Ultimate user
• (D) Sum total of organized arrangement

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Lecture 2

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 Learning objectives

• At the end of this lecture, students will be able to

• Discuss quality parameters

• Explain total quality Assurance and measure to adopt
quality assurance.

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 CONCEPT OF QUALITY
Characteristics of pharmaceutical product to be as
quality product are:

□ Identity(name of
product/formulation/ name quantity of
API)
□ Strength
□ Safety
□ Purity
□ Efficacy
 All matters/wide ranging concept

• Pre production activities

• Production and Q.C activities
• Post production activities
 Ultimate user
• Effective medicine
• Reasonable price
• Easy availability
 Sum total of organized efforts

• Well organized working without wastage of time and money.

 cOMpONENTs OF Q.a. ACTIVITIES
Components of the Q. A. activities in any pharmaceutical organization.
The system of Q. A. should ensure that:
(i )Pharmaceutical products are designed and developed in a way that
takes account of the requirement of GMP. GLP. GVP. GCP etc.
(ii) Production and control operations are clearly specified in a written
form and GMP requirement are adopted.
(iii) Managerial responsibilities are clearly specified in job descriptions.

(iv) Arrangements are made for the manufacture, supply and use of the
correct starting and packaging materials.
(v) All necessary controls on starting materials, intermediate products,
and bulk products and other improves controls, calibrations and
validation are carried out.
(vi)The finished product is correctly processed and checked, according to
defined procedures.
(vii)Pharmaceutical products are not sold or supplied before the authorized
persons have certified.
(viii) Arrangements to ensure, the pharmaceutical products are stored by the
manufacturer, distributed and handled so that quality is maintained
throughout their shelf life.
(ix)Procedure of self-inspection and/or quality audit for the effectiveness of
the Q.A. system.
(x)Production environment and service to production operations are
monitored.
Deviation are adequately recorded, investigated and responded.
 RESPONSIBILITIES
• Attainment of quality objectives is the responsibility of Top/Senior
Management

In particular the top management is responsible for:

(I )Providing leadership.

(ii)Structure the organization.

(iii)Build quality system to meet the

requirement. (iv)Establish policies, objectives

and plans. (v)Review the system.

DOCUMENTS REQUIRED
(i) Company's Quality Policy.

(ii)Responsibilities of Q.A.

department. (iii)Job description of

Head of Q.A.
 sUMMary OF cOMpONENTs OF Q.a.
The system of Q.A. should ensure that-
1. Requirement of GMP,GLP etc.
2. Operations in a written form and GMP requirements are adopted.
3. Managerial responsibilities are clearly specified in job description.
4. Made arrangements.
5. All controls.
6. The finished product is correctly processed, and checked.
7. Certification.
8. Quality audit.
Lecture 3

33
 LEARNING OBJECTIVES:

At the end of this lecture, students will be able to:

• Define GMP
• Explain the components and activities of GMP
• Define Q.C

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Good manufacturing practice
 GOOD MANUFACTURING PRACTICE

Definition of Good Manufacturing Practice as per WHO

• Part of quality assurance.
Its is a system for ensuring that products are consistently produced
and controlled according to quality standards.
• It is designed to minimize the risks involved in any
pharmaceutical production that cannot be eliminated through
testing the final product.
 Contents

• GMP is part of Q.A

• Produce Quality product consistently
• Must follow the legal requirements of country
• Concerned with both production and quality control matters.
• Diminish the risk of mix-ups and contamination
 cGMP

• cGMP refers to the Current Good Manufacturing Practice

regulations enforced by the US Food and Drug Administration (FDA).
• CGMPs provide for systems that assure proper design, monitoring,
and control of manufacturing processes and facilities.
• GMP is sometimes referred to as cGMP, suggesting manufacturers
that they must employ technologies and systems that are up-to-date
(“current”) in order to comply with the regulation.

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 Components of GMP
(a) "All manufacturing processes should be clearly defined".(SOPs/
master production / control records/ doc review system)
(b) "Critical steps of manufacturing processes and any changes
made to the process validated".
(c) "All necessary facilities are provided ".
(d) "Instruction and procedures are written in clear and unambiguous
language”(SOPs)
(e)"Operators are trained to carry out procedures correctly".
(f)Records are made during manufacture to ensure
• all the steps required by the procedures and instructions have
been taken
• at the quantity and quality of the product are as expected,
• deviations are fully recorded and investigated.

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 (g) Records covering manufacture and distribution retained
appropriately .
(h) The proper storage and distribution of the product minimizes any
risk of their quality.
(i) A system is available to recall any batch of product from sale or
supply, as and when required.
(j) Complaints about marketed products are examined:
✔ the causes of quality defects investigated
✔ appropriate measures taken
✔ prevent recurrence.
• Documents Required
• Responsibilities of GMP department.
• Job description of Head of GMP.
Quality control
 QUALITY CONTROL ???

• Definition of Q.C. by WHO

• Sampling
• Specification
• Testing
• With the organization
• Documentation
• Release procedures

•
 • Definition of Q.C. by WHO ;
•
• "Q.C. is the part of GMP concerned with sampling, specifications,
testing, with the organization, documentation and release
procedures
• which ensure that the necessary and relevant test are actually
carried out and that materials are neither released for use, nor
products released for sale or supply, until their quality has been
satisfactory.
• Q.C. is not confined to Laboratory operations but must be involved
in all decisions concerning the quality of the product".
Lecture 4

47
 LEARNING OBJECTIVES:

At the end of this lecture, students will be able to:

• Explain the components of Q.C

• Define sampling in pharmaceutical plant.
• Explain the Guidelines for sampling.

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 COMPONENTS OF QUALITY CONTROL
Independence of Q.C. from production is fundamental.
Q.C head.
Major Components:
1. Adequate facilities, trained personnel and approved
procedures
must be available for

⚫ Starting material
⚫ Packaging
⚫ Intermediate bulk
⚫ Finished products
⚫ Environmental condition
⚫ The Q.C. labs should have minimum following faculties.

⚫ Chemical Testing Laboratory

⚫ Instrumental analysis lab
⚫ Microbiology and Toxicology lab
⚫ Provision for retained samples. (stability samples)
⚫ Documentation room
⚫ Various books
□ Trained personnel.
□ SOPs based Sampling, testing & analysis.(specifications, Q.C.
policy with procedures), SOPs recording system
2. Sampling of material.
3. Methods validation.
4. Records.(manually and instrument)
5. The finished product analysis.(qualitative and quantitative)
6. No batch released prior to certification.
7. Sufficient samples of starting materials and products must be retained to
permit further examination of the product if necessary;

Do as you have written, (SOP), and write what you have done. (Record)
 Documents required

• Responsibilities of Q.C department

• Job description of Q.C head
• Other activities
• Establish, validate, and implement all the q.c procedures, maintain
sufficient standards and reagents.
• Evaluate, maintain and store reference and working standards for
substances.
• Ensure the correct labeling of containers of materials and products.
• Ensure that the stability of API and product is monitored.
• Participate in the investigation of complaints related to quality of
the product.
• Participate in the environmental monitoring.
• Assess the finished product after evaluation, all relevant factors,
including the production conditions, I.P.Q.C. results, manufacturing
and packaging documentation, compliance with the specification
of the finished product and examination of the finished pack.
• The finished product must meet the legal requirements as per the
Law of land.
Sampling
 1. SAMPLING
⚫ In quality control activities "sampling" is one of the major activities.
includes;
⚫ Sampling area.
⚫ Sampling of sterile products.
⚫ Sampling procedure.
⚫ Reference samples.
⚫ Sampling of IPQC materials.
⚫ Sample of bulk finished and packed materials
 Sampling area

• Separate sampling area in ware house For

• API,
• Excipients,
• sterile materials.
• Separate area for sampling of liquids.
• Separate area for sampling of primary packaging materials.
• (secondary and tertiary may sampled on storage site )
• In process/bulk finished/packed materials sampled on
the location in the processing /packaging department.
Lecture 5

58
 Learning objectives

• At the end of this lecture students will be able to

• Discuss Major guidelines to be followed during sampling.

• Explain guideline for the retention samples
 Sampling of sterile products

• Under Aseptic conditions confirming to grade A, (not more than

100 particles of equal to 0.5 um or less)
• Aseptic sampling with sterile equipment.

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Sampling procedure(critical procedure)

1. The number of containers to be sampled, and the amount of

material to be taken from each container, shall be based upon

riter
ompone
confidence levels,
degree of precision
desired,
histor
is and
 2.
Sampling to avoid contamination or other adverse effects on
quality.
□ The containers that have been sampled should be marked and
resealed after sampling.
□ Care taken to avoid contamination or mix-ups of - or by
the material being sampled.
□ All sampling equipment that comes in contact with the
materials should be clean.
□ Some hazardous potent materials may require special
precautions.
□ Sampling equipment should be cleaned, sterilized before
& after each use & stored separately from the laboratory
equipment.
Sampling

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Procedures for sampling :

The containers of components selected shall be

• 1.Cleaned where necessary.

• 2.Opened, sampled and resealed in a manner designed.

• 3.Sterile equipment and aseptic sampling techniques when necessary.

• 4.If it is necessary to sample a component from the top, middle and bottom of its container, such
samples subdivisions shall not be composited for testing.

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• 5.Sample containers shall be identified to determine
following information.

• The name of the material sampled.

• The batch or/lot number.
• The number of the container from,
which sample has been taken.
• The signature of the person who has taken
the sample.
• The date of the sampling
• MARKED after sampling.
Reference samples/retained samples

A representative sample of a substance used in the

manufacturing of pharmaceutical product/ finished
pharmaceutical product.
Or
Retention samples.
Major guidelines

• Each lot of every active ingredient

(Quantity to carry out all the tests) ? 3 months after the
expiration of last batched produced.

• Samples of the finished formulation ? stored in same containers

as marketed
WHO guidelines

1. Retention samples of finished product ? 1year after Exp. date

Final packaging.
Under condition recommended.
If large (smaller packs can be used)

2. Samples of API ? 1 year beyond exp. date of finished product.

3. Other starting materials ? 2 years if stable
4. Size of Ret. sample of material /product? 2 full analysis
 U.S.F.D.A views

• Reserve sample ? Twice the quantity for all test.

• Retention time for all products(other than radio active ing. and
OTC product) ?1 year
• API in a radio active product ?
3 months after the expiration date of last batch (if Exp. date is 30
days or less )
6 months after the expiration date of last batch (if exp. date is
more 30 days )
• API in OTC drug product ? 3 years(after distribution of last lot)
• Finished product reserve sample ? 1year
 Things to consider

• Active R.M shall be retained for 1 year after the expiry of

finished product in which it is used.
• Finished product(other than radio active substance) shall be
retained for at least 1 year after expiry of finished product.
• Quantity: two full analysis.
• Finished product samples retained in their final packaging if large.
• Retained in the recommended conditions.
Lecture 6

73
 At the end of this lecture students will be able to

• Discuss the Sampling of IPQC/reference material.

• Describe total testing Activities in Q.C department
 Sampling of IPQC material

• Purpose
• Selection of parameters
• Specification

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 Sampling of IPQC materials

For Tab/Caps :
• Weight variation
• Disintegration time
• Dissolution time and rate
Liquid Preparation :
• Clarity
• pH
• Fill volumes
Semi solids :
• Viscosity
Packaging :
• Leak tests
• Overprinting details etc.
 Sampling of finished bulk and packed
finished product
• SOP for sampling.
• Tests at each stages of sampling.
 Documents required

• SOP/ R on sampling of

• R.M
• P.M
• IPQC material.
• Finished bulk product.
• Finished packed products.
Testing
 Testing

• Main activity of Q.C department.

Testing of materials involves testing of

• Active and inactive pharmaceutical ingredient.
• Primary, secondary and other packaging materials.
• In process materials.
• Finished bulk product.
• Finished packed products.

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81
 The regulatory guidance is available on following areas

1. Analytical Method Validation.

2. Laboratory reagents and media used in testing.
3. Calculation verification.
4. Use of laboratory animals.
5. Special testing requirements.
6. Test records.
7. Release of finished products for distribution.
8. Legal requirements.
 1) Analytical Method Validation

• Method Validation:
Process used confirm that analytical procedure used for
specific test is suitable for its intended use.
• Revalidation of analytical method becomes necessary if
??????
 (2) Laboratory reagents and media used in testing
• Prepared reagents must be properly labeled with details.
• Name and strength.
• Standardization factor.
• Shelf life, date of preparation.
• Storage conditions.
• Date of re-standardization (if applicable).
• Name, signature and date of person preparing and
standardizing it.
.
(3) Calculation verification
By Analyst

(4) Use of laboratory Animals

• Maintained and controlled acc.
to suitability for their intended
use.
• Adequate records should be maintained
• Appropriately quarantined
Lecture 7

86
 LEARNING OBJECTIVES

At the end of this lecture, students will be able to:

• Describe the special testing guidelines .

• Describe guidelines for animals used in testing.
• Explain guideline for IPQC, batch numbering and product review

87
 (5) Special testing requirements

• SOPs in writing for following specialized testing.

• Pyrogen testing.
• Sterility testing.
• Bacterial endotoxin test.
• Test for presence of foreign particles and harsh or abrasive
substance in ophthalmic preparations.
• Test for release of each active substance in controlled released
preparations.
 (6) Test Records
The analytical records includes

• Name of the material/product and where applicable dosage

form.
• Batch number and where appropriate, name of the
manufacturer and/or supplier.
• Reference to the relevant specifications and testing
procedures.
• Test results: observations, calculations.
• Dates of receipt, sampling and testing.
• Initials of the person who performed the testing.
• Initials of the person who verified the testing and the
calculations,
• A clear statement of release or rejection (or other status
decision) and the dated signature of the designated
responsible person.
• Quantity of product, code & Tests performed.
 (7) Release of Finished Product for
Distribution (Q.A authorized person)

SOP for the release procedure.

⚫ Every finished product must have a release specification and test method to
test these specification.
⚫ Every product must be tested according to the specifications by the approved
and validated test methods.
⚫ Complete batch documents must be reviewed by Q.A. along with the test
report of final finished product.
⚫ Only after full satisfaction of the reviewing authority(Q.A authorized person)
the product should be released specifying the exact quantity of product
released.
⚫ Products failing to meet the specification or any other relevant quality criteria
should be rejected.
❖ Reprocessing may be performed, if feasible, but the reprocessed product
should meet all specifications and other quality criteria prior to its acceptance
and release.
❖ Stability of such reprocessed products may be additionally monitored
throughout their shelf life.
 (8) Legal Requirements

• The finished product must comply with all legal requirements

as specified by the appropriate enforced laws in the country of
manufacture and sale or distribution.
• Documents Required

• SOP/R on calibration and validation of all analytical instruments.

• List of all major analytical instruments.
• Lists of chemicals / reagents / media used.
• Lists of Glassware’s.
• Lists of Books related to chemical and other analysis.
• Lists of Technical staff in Q. C. lab.
• Lists of Specification for RM/PM/Int./FG.
• SOP/R on releasing / rejecting of RM/PM/Int./F.G.
• SOP/R on reference / retained samples.
• SOP/R on assessment of finished product.
• Standard Test Procedures.
• Records of Analysis.
• SOP/R on reference and working standards.
• SOP/R on Handling of reagents/media etc.
• SOP/R on Management of Animal house.
• SOP/R on Sampling and Testing of IPQC materials.
• SOP/R on Testing and release of sterile products.
 I.P.Q.C.

□ Purpose is to assure batch uniformity and integrity of drug products.

□ Detailed written procedures for carrying out the IPQC activities within
the production area. Such as
□ In process controls and their limits.
□ Tests and examinations to be conducted.
□ Sampling procedure for IPQC materials of each batch.
□ In process specifications must meet specifications of the final finished product.
□ IPQC material tested for identity, strength, quality and purity as
appropriate and approved or rejected by Q.C unit, during production
process.
□ Rejected In process materials identified and controlled under
quarantine system designed to process their use in manufacturing or
processing operations for which they are unsuitable.
□ Performed mostly within the production area by production
personnel's, according to the methods approved by Q.C and results
recorded.
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 Documents required.
• SOP on IPQC
• Specification for IPQC material at predefined stages
in manufacturing.
• Test method for carrying out IPQC tests.
 Reference and working standards

• Reference standards are most pure substance of given molecule. It

is used for comparing the purity of a sample being analyzed.
• Secondary or working standard is comparable in quality with
original or reference standard.
 Documents required

• SOP/R on management of reference and working standard.

 Retained samples
• After the batch of finished pharmaceutical is packed certain
quantity of samples are kept aside for future. They are named as
1. Retained samples (WHO)
2. Reference samples (India and TGA)
3. Reserve samples (US FDA)
4. Controlled samples (Many pharma organization)
 Contd.

• Guidelines.
• Documents required SOP/R on retained samples
• Register for collection, storage, use and disposal of retained samples.
 Product review

• Before a manufactured/ packed finished product batch is released

or/ rejected all the documents related to that batch/ product should
be reviewed.
• All production quality control record should be reviewed and
any deviation should be thoroughly investigated.
• Record of investigation with follow-up action.
• Any discrepancies investigated and recorded.
 Production review

• Documents required
• SOP on production review
 Laboratory animals

• Animals used for quality control testing appropriately

quarantined before use.
• Animals maintained and controlled according to the suitability of
the intended use.
• Adequate records should be maintained for history of their use.
Documents required
• SOP on handling of laboratory animal.
• Register of the use of animals for testing purpose.
 Batch numbering

• Pharmaceutical manufacturing is a batch operation any

product history can be traced by the reference of a
batch number.
• SOP describing the details of the batch number is set up to
ensure the identification of each batch of intermediate,
bulk and finished product.
• Batch numbering SOP applied to processing stage and
to respective packaging stage shall be same (belongs to
homogenous mixture).
• Batch number allocation shall be recorded in the log book
or by electronic data processing system.
 Contd.

• Documents required
• SOP on batch no. system
• Record of batch no. allotted.
 CRITICAL POINTS
1. Critical procedures and
r ecords
□ Specificatio ns

□ Records

□ SOP’s

□ Site master file

□ Validation master plan

□ Self inspection

□ Assembling & operation of equipments

104
Q.C. OF RAW MATERIAL & FINISH PRODUCT
Outline of various QC test for different properties of product

105
 SOURCES OF VARIATION

PACK
A
PERSONNEL GING

LABELLIN
G

RAW DRUG
MATERIAL PRODUCT QC &
S QUALITY ANALY
SIS

MANUFACURI
NG TRANSPOR
PROCESSES T
& DISTRIBUT
STORAG
PROCEDURES ION
E
106
2) CRITICAL STAGES IN
FORMULATION

107
Q.C documentation

108
Q. C. Documentation:

Some important documents should be available in the Q.C. Department.

(i)Specification of R.M.. P.M.. Int., Finished products.
(ii) Sampling procedures of R.M., P.M., Int. and Finished products.
(iii) Testing procedures & records including analytical worksheets,
calculations and/or laboratory note books.
(iv) Analytical reports /or certificates.
(v) Data from environmental monitoring, where
required. (vi)Validation records of test methods, where
applicable.
(vii)Procedures for records of the calibration of instruments and
maintenance of
equipment.
(viii)All Q. C. documentation relating to a batch record.
(retained for one year after the expiry date of the
batch). (ix)Complete modification records shall be
maintained.
(x)Complete records of any testing and standardization of laboratory
reference standards, reagents and standard solutions.
(xi)Complete records of all stability testing performed.
Lecture 8

111
LEARNING OBJECTIVES

At the end of this lecture, students will be able

to: Describe types of stability studies
Define Self inspection and audits

112
STABILITY STUDIES
Stability studies

A pharmaceutical product may undergo change in appearance,

consistency, content uniformity, clarity (solution), moisture contents,
particle size and shape, pH, package integrity thereby affecting its stability
and the chemical reactions like hydrolysis, oxidation, reduction,
racemization etc. that occur in the pharmaceutical products,

lead to the formation of degradation product,

loss of potency of active pharmaceutical ingredient (API),
loss of excipient activity like antimicrobial preservative action and
antioxidants.

114
Stability of a pharmaceutical product

Stability :
The capability of a particular formulation in a specific container/
closure system to remain within its physical, chemical,
microbiological, toxicological, protective and informational
specifications.

Stability studies ensuring the maintenance of product quality, safety

and efficacy throughout the shelf life are considered as pre-
requisite for the acceptance and approval of any pharmaceutical
product.
Conducted in a planned way following the guidelines issued by ICH,
WHO and or other agencies.

115
• Quality
• Efficacy
• Safety

116
 Stability studies

• They allow evaluation of active pharmaceutical ingredient

(API) stability or drug product stability under the
influence of a variety of environmental factors such as
temperature, humidity and light.

• Data from these studies enable recommended

storage conditions, retest intervals and shelf lives
&labelling instructions to be established.
• A complex process because of involvement of a variety of
factors influencing the stability of a pharmaceutical
product.

• These factors include stability of the active ingredient(s);

interaction between active ingredients and excipients,
manufacturing process followed, type of dosage form,
container/closure system used for packaging and light,
heat and moisture conditions encountered during
shipment, storage and handling.
• Other are degradation reactions like oxidation, reduction,
hydrolysis or racemization,
Other benefits of stability studies at the
developmental stage or of the marketed products are

to provide a database that may be of value in selection of

adequate formulations, excipients and container closure
systems for development of a new product, to determine
shelf life and storage conditions for development of a new
product
• Stability Studies
Stability studies on finished products is an important activity under quality
system.
ICH guidelines give details about how to conduct these studies

(I )Tests should be performed that are indicative of stability.

(ii)Stability samples storage.
(iii) Results used to confirm or modify the prevailing shelf-life and
storage conditions.
(iv) The Q. C. department should establish expiry' date and shelf
life specification.
(v) Stability should be determined prior to marketing.
vi) Design and implementation of a written programme of on going,
follow- up stability on marketed products.

120
Programme
• A complete description of the drug in study.
• Testing parameter.
• Sufficient no. of batches.
• Testing schedules.
• Special storage condition.
• Adequate retention sample.
• Testing of drug require reconstitution.
• Accelerated stability studies and basic stability studies used
to support the tentative expiration dates.
Types

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• Real-Time stability testing
performed for longer duration of the test period in order to allow
significant product degradation under recommended storage conditions.

at the intermediate storage condition, a minimum of four test points,

including the initial and final time points, is recommended, for example, 0,
6, 9 and 12 months

• Accelerated stability testing

a product is stressed at several high (warmer than ambient) temperatures
and the amount of heat input required to cause product failure is
determined. This is done to subject the product to a condition that
accelerates degradation.
a minimum of three time points, including the initial and end points, for
example, 0, 3, and 6 months is recommended.
• Retained sample stability testing
This is a usual practice for every marketed product for which
stability data are required. In this study, stability samples,
for retained storage for at least one batch a year are
selected.
Eg. if a product has shelf life of 5 years, test samples at 3, 6, 9, 12, 18, 24, 36, 48, and
60 months
• Cyclic temperature stress testing
Not a routine testing method for marketed products.
cyclic temperature stress tests are designed on knowledge
of the product so as to mimic likely conditions in market
place storage. The period of cycle mostly considered is 24
hours which the marketed pharmaceuticals are most likely
to experience during storage.
126
• Penicillin contamination:
Procedures for detecting and measuring penicillin contamination in
drugs.

Penicillin manufacturing requires by the CGMP regulations to

establish a comprehensive control strategy designed to prevent
cross- contamination of other drugs with penicillin
Self inspection
 SELF INSPECTION
To evaluate manufacturer compliance with G.M.P in production and
quality control.
• For necessary corrective actions.
• Done routinely/special occasions.

The self-inspection SOP covers,

⚫ Items for self-inspection.
⚫ Self-inspection team.
⚫ Frequency of self-inspection.

A Quartely
Or Six months
⚫ Self-inspection report
observation
recommendation

⚫ Follow-up action.
• Following is a list of items for self inspection
• Personnel.
• Premises and personnel facilities.
• Maintenance of buildings and facilities.
• Maintenance of equipment’s.
• Storage of materials.
• Production and in-process control.
• Quality control.
• Documentation.
• Sanitation and hygiene.
• Validation and revalidation programmers.
• Calibration of instruments or measurement system.
• Recall procedures.
• Compliant management.
• Labels control.
Quality audits
Quality Audits

An examination and assessment of all parts of a quality system

with a specific purpose of improving it.
 Conducted by
• Outside or independent specialists.
• or a team designated by the management.
Audits may be extended to suppliers and contractors.

• The Q.C. department should have responsibility together with other

relevant departments for approving suppliers.
The supplier evaluation include
• a supplier history and
• nature of the materials to be supplied.
 Documents required

• SOP/R self inspection

• SOP/R on quality audit
• SOP/R on supplier audit

135
Terminologies
⚫ BATCH: quantity of starting, packaging, product processed in a single process.
⚫ BATCH No. : distinctive combination of no./ letters which identifies a batch on the label, batch
record, certificate of analysis.
⚫ CALIBRATION. set of operations, that establish, under specified conditions, the relationship b/w values
indicated by instrument or system for measuring , recording and controlling or the values represented by
a material measure, and the corresponding known values of reference standards.
⚫ CONTAMINATION: is the presence of an unwanted constituent, contaminant or impurity in a material.
⚫ CROSS CONTAMINATION: contamination of starting material, intermediate, or finished product with
another starting material or product.

⚫ IPQC: checks performed during production in order to monitor and adjust the process to ensure that
the product conforms to its specification.
⚫ INTERMEDIATE PRODUCT: Partially processed material that must undergo further manufacturing
steps before it becomes a bulk product.

⚫ FINISHED PRODUCT: product that has undergone all stages of production, including packaging and labelling.
⚫ VALIDATION; Action of proving, in accordance with principles of GMP, that any procedure,
process, equipment, material and activity or system actually lead to the expected result.
⚫ QUARENTINE: status of starting, or packaging materials, intermediate, or bulk or finished products
isolated physically , while a decision is awaited on their release, rejection, or reprocessing.

⚫ SOPs,: authorized written procedure giving instruction for performing operations

136
REFERENCES:
1. “Pharmaceutical Quality Assurance”, by M. A. Potdar, 2nd
edition, Nirali Publication chapter :05

2. “The Theory & Practice Of Industrial Pharmacy”, by Leon

lachman, H. A. Lieberman, J. L. Kanig, 3rd edition, Varghese
Publishing House, Hind Rajasthan Building Dadar, Bombay-400
014, p.g. 804-855

OTHER REFERENCES:
1. “Good manufacturing practices for pharmaceuticals” by Joseph
D. Nally