QUALITY CONTROL AND QUALITY

ASSURANCE
QUALITY;
Quality means the totality of features and characteristics of a product or service that bear on its
ability to satisfy given needs
Quality refers to the sum of the attributes or properties that describe a product. These are
generally expressed in terms of specific product characteristics such as length, width, color and
specific gravity.
Quality is a blend of:
– Fitness of purpose, adequacy of functioning and reliability, for the price paid
– Design and manufacturing characteristics tailored to meet customer’s
requirements during service
– Availability when required

Responsibilities of the Pharmaceutical Quality Unit

1. To establish the quality system

 Establish the quality management system to describe how the firm complies
CGMPs and operates to maintain a state of control
 Keep current with good industry practices, and applicable to the mission of your
operation.
2. To audit compliance to the quality system
 Audit for compliance to policies and procedures: on paper vs. practice
 Report on the performance of the quality system, including trends, that help
decision making for targeted actions
3. To establish procedures and specifications
 Ensure that procedures and specifications are appropriate and followed

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  Ensure that the procedures and specifications of firms under contract are also appropriate
and followed, i.e., maintain control and take responsibility for third-party services
providers (contract manufacturers, contract laboratories, etc.)
4. To establish manufacturing controls

 Ensure that appropriate manufacturing in-process controls are implemented

 Ensure in-process controls are performed during manufacturing operations and results are
satisfactory
5. To perform laboratory tests or examinations

 Perform laboratory testing of components, containers, in-process materials, packaging

materials and drug product using validated methods against scientifically-derived, fit-for-
purpose specifications
 Approve or reject drug products manufactured, processed, packed, or held under contract
by another company, i.e., final product release is not delegated to a contractor
 Perform retests or reexamine approved components, drug product containers and closures
after long storage or exposure to adverse conditions
6. To review and approve or reject all things CGMP

 Review and approve/reject any document that gives work instructions and set
requirements such as procedures, protocols, test methods, and specifications—including
changes to these documents
 Review and approve/reject reprocessing and rework procedures
 Review and approve/reject production batch records and make the final decision to
release a product lot into commerce.

7. To ensure investigation of nonconformance

 Ensure investigation is conducted and root cause is eliminated for production and control
record errors, discrepancies, and failure to meet specification, including quality attributes
 Review complaints to determine if it relates to a failure to meet specification, if so
investigate and report to FDA if it is serious and unexpected

8. To keep management informed

 Report on product, process and system risks—and keep management informed

 Report on outcome of regulatory inspections and ensure responses are complete and
managed to verifiable closure—and keep management informed

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9. To describe responsibilities in writing

 Have a complete and compliant procedure that describes responsibilities

 Follow the procedure

10. To remain independent

 Ensure there is no conflict of interest between regulatory responsibilities and actual daily
activities
 Be independent reviewer and approver with respect to manufacturing and process/
product development units

QUALITY CONTROL
DEFINITION:
“Quality control (QC) is a procedure or set of procedures intended to ensure that a manufactured
product or performed service adheres to a defined set of quality criteria or meets the
requirements of the client or customer”
OR
“A system of maintaining standards in manufactured products by testing a sample of the output
against the specification”
EXPALANATION:
 Control: An evaluation to indicate needed corrective responses; the act of guiding a
process in which variability is attributable to a constant system of chance causes.
 Quality Control: The observation techniques and activities used to fulfill requirements
for quality.
 Quality control, or QC for short, is a process by which entities review the quality of all
factors involved in production
 ISO 9000 defines quality control as "A part of quality management focused on fulfilling
quality requirements".
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  Quality control (QC) is a procedure or set of procedures intended to ensure that a
manufactured product or performed service adheres to a defined set of quality criteria or
meets the requirements of the client or customer.
 Quality Control refers to the checks carried out on a product by workers, during stages of
its manufacture. These checks may include, simply ensuring that components are
positioned correctly, or that they are the correct type and size.
 A final quality check should include, testing the product to ensure it is to the correct
standard, before it is distributed to the retailer / customer. A combination of visual checks
and automated checks (by sensors and computers) are usually carried out.

QUALITY CONTROL PROCEDURE IN PHARMACEUTICAL INDUSTRY

The word ”Quality“ refers to the characteristics of a product from both qualitative and
quantitative point of view. It refers to the quality of process as well as the product itself. The
word “Control“ implies a procedure by which decisions may be made regarding whether
production is proceeding according to the plan and meeting the standards established previously.
The quality of a pharmaceutical product is standard, which is designed after a long research and
development. Here quality does not concern with active substance but the quality depends upon
many other factors such as excipients and product development procedures.
The pharmaceutical industry is responsible to design, test and produce dosage form, which
provides quality, purity, stability, safety, uniformity of contents and physiological availability to
the consumer.

THE AUTHORITY OF PROCESS CONTROL

The maintenance of quality of a drug depends upon each and every person and setup in industry.
To provide Quality Assurance; Quality Function and Quality Control must be maintained.

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Quality Assurance:
Quality Assurance means that it can be said with confidence that Quality Function is being
performed adequately the Quality Assurance group of company provides a strict supervision in
all parts of each step. Its function is to inspect various phases of production so that the final
product should be of highest quality. The monitoring of records, procedures, systems, facilities,
labeling personnel and performing tests is the responsibility of Quality Assurance Group. The
Quality Assurance may be the part of Quality Control Department or it may work independently
under its own manager.
QUALITY VARIATION:

When the quality of any drug is given by industry, then it is responsible for any variation from
the standard. Quality Variation may occur due to any mistake during the whole process i.e. from
the reception of raw material up to the final product in the packaged form.
The risk of error increases as the material increases and the method become very complicated.
The general sources causing product Quality Variation during manufacturing are as follows:

SOURCES OF VARIATIONS:
1. MATERIALS:
a. Variations among suppliers of same substances.
b. Variations among batches from same suppliers.
c. Variations within a batch.
2. MACHINES
a. Variation of equipment of same process.
b. Difference in adjustments of equipment.
c. Aging of machines and improper care.
3. METHODS
a. Wrong procedure.
b. Inadequate procedure.
c. Negligence in procedure by chance.
4. MEN
a. Improper working conditions.
b. Inadequate training and understanding.
c. Lack of interest and emotional upheavals.
d. Dishonesty fatigue and carelessness.
QUALITY VARIATION CONTROL:
The mistakes can be controlled, minimized or eliminated by material control; packaging control
and GMP variations can be controlled when Quality Control, Quality Function, and Quality
Assurance work side by side.

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MATERIAL CONTROL
 control procedure:
Controlling each and every step of process can control variations.
Control can be divided into:
• Manufacturing practice control.
• Packaging control.
• Distribution control.
 MATERIAL CONTROL: It starts just after the reception of materials. Most of the
materials that are active substances, excipients, packaging and printed materials are
received by the industry from suppliers. Thus there should be adequate established
system for the receipt, testing and storage of all these supplies. There should be a
complete record of all the procedures and tests. In the material following things are
included:
• Drug substances.
• Excipients.
• Packaging and printed materials.
 After the reception of material, it is kept in a definite area. Thus before laboratory testing,
proper containers, labels, lot number, expiry dates etc. all are checked.
 The material is stored in a proper way either they are arranged alphabetically or they are
differentiated depending upon physical nature.
 Then samples are taken for laboratory testing and a label (Sampled) is fixed on material.
In case of active constituents, percentage purity, adulteration, expiry date, lot number,
exact packing etc is checked.
 In case of printing and packaging material especially the color of label, weight of label
and cartons and gram mage etc. is checked.
 If the material is up to the mark, then a label (Passed) is pasted on it and it is placed at its
proper place.

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  On the other hand, if it is substandard, then it is kept in “Rejected Area” and sent back to
the supplier.
MANUFACTURING PRACTICES CONTROL:
 Successful GMP is difficult to attain but to some extent, it can be modified and
controlled. Specific procedures can be applied to attain the best quality.
 In case of manufacturing, following controls are important:
 Personnel.
 Equipment and building.
 Control of record.
 Production procedure control.
(A). PERSONNEL:
 Usually properly educated and well-trained persons should be in the industry.
 There should be proper selection and training in all departments i.e. production,
packaging, labeling, etc.
 There should be general lectures for less educated persons who work in the labeling or
packaging section in an understandable language.
 They should be made aware of the fact that what is the importance of life saving.
 They should be warned about all the dangers of their mistakes and errors.
 There should be properly educated supervisors working above the workers.
 The supervisors should always be there so that in case of any trouble or question, they
must be available.
 All the workers should be properly checked and all the processes at different steps should
also be monitored by highly educated and experience persons who may not only be well
qualified but experienced as well.
(B). EQUIPMENT AND BUILDING:
 The equipments and building used in storage, processing, checking and packaging should
be of a suitable design, size, construction and location.
 In case of equipments, these should be constructed in a proper size and proper way. The
size should be such that complete batch can be processed all at once.
 The surfaces of equipments should be non-reactive, non-absorptive and non-additive.
 The equipment should be constructed and fitted in such a way that it is easy to replace,
easy to wash easy to operate and easy to empty.
 In case of building, there should not be any contamination i.e. the tablet and liquid
section should be separated completely and even there should be complete separation in
tablet machines. It means that machines should have separate cabinet.
(C) CONTROL OF RECORD:
 The records such as master formula record and batch production record must be
maintained.

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1. MASTER FORMULA RECORD:
a. The master formula record must be prepared for each product.
b. It must be signed by a competent and responsible person.
c. The language must be so that it may not be miss-interpreted.
d. It should be checked by another competent person and must be countersigned.
e. The master formula varies from production to production and from batch to batch.
f. Master formula record include the following information:
i. Name of the product, dosage form and strength.
ii. Complete list of ingredients including excipients.
iii. Quality by weight or volume of each and every ingredient.
iv. Standards or specifications of each ingredient.
v. Any calculated excess of an ingredient.
vi. Theoretical yield and termination of process.
vii. Manufacturing and control instructions, specifications and precautions.
viii. Complete description of closures, containers, labeling, packaging and other
finishing materials
2. BATCH PRODUCTION RECORD:
a. Batch production record must be prepared, maintained and controlled for each batch of
a product.
b. It must be retained for about 5-years after product distribution.
c. Batch production record should have following information in addition to master
formula record.
i. Batch number.
ii. Code number.
iii. Manufacturing date.
iv. Expiry date.
(D). PRODUCTION PROCEDURE CONTROL:
 The processes of manufacturing are operated according to the established rules from the
reception of material up to delivery of final product.

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  A complete list of ingredients along with their quantities is delivered to the Production
Department. It is called Master Formula of that batch. It contains all the information of
that batch i.e. procedures and equipments to be used and precautions to be taken, etc.
 This master formula is taken into the store and all the materials for the batch are weighed
and delivered to Production Department. All ingredients are rechecked and tested in
laboratory.
 In the production procedure control, some tests are done during the process, which is
called “In Process Quality Control (IPQC)”
 The IPQC is under Quality Control Department.
 Both Quality Control and Production Departments are responsible for the production
procedure control. IPQC tests for different dosage forms are as under:
1. IPQC TESTS FOR TABLETS:
a) Drug contents determination.
b) Moisture contents of granules.
c) Assay of active ingredients.
d) Weight variation of uncoated tablets.
e) Hardness test.
f) Disintegration test.
2. IPQC TESTS FOR SYRUPS AND SUSPENSIONS:
a) Drug contents determination.
b) Assay of active ingredients.
c) pH.
d) Weight per ml.
e) particle size
3. IPQC TESTS FOR SEMI-SOLIDS:
a) Drug contents determination.
b) Assay of active ingredients.
c) Uniformity and homogeneity test.
d) Viscosity and specific gravity test.
e) Filling test.
f) Leakage test.
4. IPQC TESTS FOR INJECTABLES:
a) Drug contents determination.
b) Assay of active ingredients.
c) pH.
d) Pyrogen test.
e) Stability test.
f) Leakage test.
g) Checkup of particulate matters.

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PACKAGING CONTROL:
 The packaging control is usually completed before manufacturing of product.
 When the product come in packaging section, it should be packed in recommended
containers and there should not be any mistake in case of labeling and writing of batch
number, etc.
 The packaging material is used according to the nature and distribution of product.
DISTRIBUTION CONTROL
 The responsibilities of Quality Control Department are not finished even after the
distribution of finished dosage form in the market.
 The samples of each batch are kept in record and these samples are selected during
packaging and are in the same packs as they are marketed.
 These are kept for years in order to examine or test the material for any purpose or
necessary demand.
QUALITY CONTROL AND ITS ORGANIZATION
 It is a combination of all the characteristics of a product that determine the degree of
acceptability of the product.
 The PMA (Pharmaceutical Manufacturing Association) says that the quality of a product
is its degree of possession of those characteristics designed and manufactured with and
which contribute to the performance of extended functions when the product is used as
directed.
 The central idea of Quality Control is that quality must be built into the product during
research and development and production.
 Central control as it applies to pharmaceutical industry is the organized effort within an
entire establishment to design product and assure the specified quality in each unit of
product distributed.
 It the responsibility of pharmaceutical company to design tests and procedures to produce
dosage form that contains exact quantity and quality of drugs, which is acceptable,
reproducible, convenient and elegant.
PRODUCTION CHARACTERISTICS:
The most important pharmaceutical characteristics are:
– Identity.
– Purity.
– Potency.
– Uniformity.
– Stability.
– Safety and efficacy.
– Physiological availability.
– Therapeutic activity.

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ORGANIZATION OF QUALITY CONTROL:
The individual responsible for the quality of drug product in a pharmaceutical company is
generally the director of Quality Control. He should report to the president or vice-president and
should be on the same organizational level as that of Production Manager. Only the highest level
of management should review his decisions about quality.
ORGANIZATIONAL CHART OF QUALITY CONTROL:

DEPARTMENTS OF FUNCTIONAL QUALITY CONTROL

There are five departments of functional Quality Control chart. These are discussed one by one.
– Specification & Analytical Department
– Biological Testing Laboratory
– Central Release Office
– Inspection & Checking
– Chemical Testing Laboratory
1. SPECIFICATION AND ANALYTICAL DEPARTMENT:
 Quality of the finished product depends upon quality of the raw material used in the
manufacturing operation.
 This department is responsible to analyze raw material and the product according to the
specifications.
 Following are the specifications, which must be considered to maintain quality of the
product.
Solubility. Identification.
Particle size. Surface tension.

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 Loss on drying. Residue on ignition.
Crystal shape. Viscosity,etc.
 These are the specifications originated by the efforts of Quality Control research during
product development.
 All specifications include those requirements, which are applicable to federal and state
Government’s official compendia.
 The major cost of Quality Control lies in the testing of product throughout manufacturing
operations.
2. CHEMICAL TESTING LABORATORY:
 Every lot of every shipment of raw material and every lot of finished product, which can
be controlled by physical and chemical tests, is tested in the ”Chemical Testing Lab”.
 This requires a well-equipped chemical lab properly staffed for better performance of
great number of chemical analysis.
 It should be located in an accessible area and protected from noise and vibrations
common in manufacturing operations.
3. BIOLOGICAL TESTING LABORATORY:
 A number of finished products require biological assay. Biological tests are not confined
to a group of products recognized as biologicals in drug industry; since a number of
pharmaceutical products such as parenterals require sterility and pyrogen testing before
release to market.
 Biological lab should have essential animals.
 The staff in the biological testing lab should be well trained.
4. CENTRAL RELEASE OFFICE:
 The record resulting from the exercise of Quality Control functions throughout all the
steps of manufacturing and packaging operations are voluminous. Quality Control
organization is responsible to check these records.
 The record provides complete history of each lot of each product manufactured and
therefore makes it possible to construct the relevant features of any package distribution
into the market.
 The assay and access of central release office to records together with its liaison
(communication and co-operation.)with all manufacturing and packaging operations
makes it possible for the group to investigate customers’ complaints about product
quality.
5. INSPECTION AND CHECKING:
 The responsibility for inspection and sampling of every shipment of raw material
received and every lot of finished goods turned over for distribution falls within the
province of Quality Control Inspectors.

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  The selection of samples of raw material and finished goods is an important aspect of
Quality Control function.
SPECIFICATIONS FOR PACKAGING MATERIALS:
BOTTLE:
o Capacity.
o Material (Glass, Plastic, Aluminum).
o Weight of bottle.
o Thread of bottle.
o Cap material (Rubber, Plastic coated).
o Thickness.
COTTON:
o Type.
o Moisture contents.
1. SILICA BAG:
o Weight.
o Capacity.
CARTON:
o Dimensions (Notches, Locking system).
o Quality of Board (Grammage).
o Printings.
o Color (lovibond, Tinctometer is used; the local industries have an album of colors).
LABEL:
o Dimensions.
o Printing.
o Weight.
o Striations (Lines on Paper).

QUALITY ASSURANCE
DEFINITION:
“The maintenance of a desired level of quality in a service or product, especially by means of
attention to every stage of the process of delivery or production.”
OR
“A program for the systematic monitoring and evaluation of the various aspects of a project,
service, or facility to ensure that standards of quality are being met.”

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EXPLANATION
 Assurance: The act of giving confidence, the state of being certain or the act of making
certain.
 Quality Assurance: The planned and systematic activities implemented in a quality
system so that quality requirements for a product or service will be fulfilled.
 Quality assurance (QA) is a way of preventing mistakes or defects in manufactured
products and avoiding problems when delivering solutions or services to customers
 ISO 9000 defines as "part of quality management focused on providing confidence that
quality requirements will be fulfilled".
 Principle. “Quality assurance” is a wide-ranging concept covering all matters that
individually or collectively influence the quality of a product.
 It is the totality of the arrangements made with the object of ensuring that
pharmaceutical products are of the quality required for their intended use.
 Quality assurance therefore incorporates GMP and other factors, including those outside
the scope of this guide such as product design and development.
 Quality control is an important stage in any business. A manufacturer needs to regularly
check his products before shipping to clients to make sure there are no defects.
 A service industry often asks clients for evaluations after the completion of a job to make
sure its employees are making good on the company’s performance promises.
 In some of these cases, negative results can have only minor consequences, like a quick
adjustment in the manufacturing process or further training for an employee. But there
are some industries where quality control is extremely crucial and where the
consequences for quality negligence can be very serious, and even harmful.
 These are the healthcare industries, and specifically, the pharmaceutical industry.
 Quality assurance is a wide ranging concept covering all matters that individually or
collectively influence the quality of a product.
 It is the totality of the arrangements made with the object of ensuring that pharmaceutical
products are of the quality required for their intended use.
 QA is the heart and soul of quality control QA = QC + GMP /Other Quality Systems
Quality
 In Pharma industry quality assurance is a broad concept covering all matters that
collectively or individually influence the quality of drug or product. Quality assurance in
pharmaceutical can be divided into four major areas:
1. Quality control
2. Production
3. Distribution and
4. Inspections.

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QUALITY ASSURANCE PROCEDURES IN PHAMACEUTICAL INDUSTRY
Quality Assurance is a dynamic process It is a journey towards the destination
According to QA, products are designed and developed in a way that takes account of the
requirements of GMP and other associated codes such as those of good laboratory practice
(GLP) and good clinical practice (GCP).
The five process involve in quality assurance are:
 Technology transfer
 Validation
 Documentation
 Assuring quality of products
 Quality improvement plans

TECHNOLOGY TRANSFER
 Receipt of product design documents from research centre
 Receipt of the trial and error data and its final evaluation
 Distribution of documents received from research centre
 Checking and approval of documents generated based on research centre documents i.e. batch
manufacturing record
 Scale-up and validation of product

VALIDATION

 Preparation of Validation Master plans for facility/equipments/process Utility, Cleaning and all the sections
of the validation
 Approval of protocol for validation of facility/ equipment/product/ process/Utility
 Team member for execution of validation of facility/equipment / product/ process
 Final approval of the facility/ equipment/product/ process/Utility validation Quality

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DOCUMENTATION

– Main objective To establish, monitor and record “Quality” for all aspects of Good Manufacturing Practices
(GMP) and other Quality System pertaining
– Type of documents
 Standard operating procedures
 Protocols of tests,
 Results
 Reports Quality

Laboratory records:

– Description and identification of sample received

– Description of method of testing
– Record of all data secured in the course of the test
– Record of test results and how they compare with standards of identity, strength and quality
– Record of all deviations and modification of test
– Record of standardization of reference standards
– Record of calibration of equipments

Documentation control

– Controlled distribution and archiving of documents

– Control of changes made by proper change control procedure
– Approval of all documents

ASSURING QUALITY OF PRODUCTS

– CGMP training
– SOP compliance
– Audit of facility for compliance
– Line clearance
– In-process counter checks
– Critical sampling
– Record verification
– Release of batch for marketing
– Investigation of market complaints

QUALITY IMPROVEMENT PLAN

– Feedback received from the compliance team

– Customer complaint history
– Proposals for corrective and preventive actions
– Annual Products review
– Trend analysis of various quality parameters for products, environment and water
– Review of the Deviations, Change Controls, Out Of Specifications and Failures.

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Flow chart of RM/PM inspection:

Flow chart of finished product inspection:

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QUALITY ASSURANCE AND STANDARDS
Standards are the key to effective quality management. They may be international, national,
organizational or project standards.
 Product standards
 Process standards
 In process Standards
 Raw material and Packaging Material Standards
 Testing Standards
 Equipment and Instrument Standards
 Working and Reference Standards
IMPORTANCE OF STANDARDS
– Encapsulation of best practice- avoids repetition of past mistakes.
– They are a framework for quality assurance processes - they involve checking
compliance to standards.
– They provide continuity - new staff can understand the organization by understanding the
standards that are used.

DIFFERNCE B/W QUALITY ASSURANCE AND QUALITY CONTROL

QUALITY CONTROL QUALITY ASSURANCE

QC is a set of activities for
DEFINITION ensuring quality in products.
The activities focus on
identifying defects in the actual
products produced.
QC aims to identify (and
FOCUS ON correct) defects in the finished
product. Quality control,
therefore, is a reactive process
The goal of QC is to identify
GOAL defects after a product is
developed and before it's
released
QA is a set of activities for
ensuring quality in the processes
by which products are developed
QA aims to prevent defects with a
focus on the process used to make
the product. It is a proactive
quality process
The goal of QA is to improve
development and test processes so
that defects do not arise when the
product is being developed

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 Finding & eliminating sources
HOW of quality problems through
tools & equipment so that
customer's requirements are
continually met.
The activities or techniques used
WHAT to achieve and maintain the
product quality, process and
service
Quality control is usually the
RESPONSIBILITES responsibility of a specific team
that tests the product for defects
Validation/Software Testing is
EXAMPLE an example of QC
When statistical tools &
STATISTICAL techniques are applied to
TECHNIQUE finished products (process
outputs), they are called as
Statistical Quality Control
(SQC) & comes under QC.
AS A TOOL QC is a corrective tool
Establish a good quality
management system and the
assessment of its adequacy.
Periodic conformance audits of the
operations of the system.
Prevention of quality problems
through planned and systematic
activities including documentation
Everyone on the team involved in
developing the product is
responsible for quality assurance.
Verification is an example of QA
Statistical Tools & Techniques can
be applied in both QA & QC.
When they are applied to
processes (process inputs &
operational parameters), they are
called Statistical Process Control
(SPC); & it becomes the part of
QA.
QA is a managerial tool
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