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Definitions
Basic Concepts of Quality  Quality Assurance:
According to WHO, quality assurance is a wide-
Assurance and Quality ranging concept covering all matters that
individually or collectively influence the quality of
Control a product. With regard to pharmaceuticals,
Asst. Prof. Edison C. Santiago, RPh, RChT, MSc cand quality assurance can be divided into major
areas: development, quality control, production,
distribution, and inspections.
ISO 9000 defines as "part of quality
management focused on providing confidence
that quality requirements will be fulfilled"

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Definitions Difference between QA and QC

 Quality Control: Definition
ISO 9000 defines quality control as "A part of
 QA is a set of  QC is a set of
quality management focused on fulfilling
activities for ensuring activities for ensuring
quality requirements".
quality in the quality in products.
It is that part of GMP concerned with processes by which The activities focus
sampling, specification & testing, products are on identifying defects
documentation & release procedures which developed. in the actual products
ensure that the necessary & relevant tests  QA is a managerial produced.
are performed & the product is released for tool  QC is a corrective
use only after ascertaining it’s quality. tool

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Difference between QA and QC Difference between QA and QC

(Contd.) (Contd.)
What are its goals and What and how does it
on what does it focus? work?
 QA aims to prevent  QC aims to identify  Prevention of quality  The activities or
defects with a focus on (and correct) defects in problems through techniques used to
the process used to the finished product. planned and systematic achieve and maintain
make the product. It is Quality control, activities including the product quality,
a proactive quality therefore, is a reactive documentation. process and service.
process. process.  Establish a good quality  Finding & eliminating
 The goal of QA is to  The goal of QC is to management system sources of quality
improve development identify defects after a and the assessment of problems through tools
and test processes so product is developed its adequacy. Periodic & equipment so that
that defects do not and before it's conformance audits of customer's
arise when the product released. the operations of the requirements are
is being developed. system. continually met.

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Difference between QA and QC

(Contd.) Responsibilities of QA
Whose responsibility is it and
what is the example of it?  The QA department is responsible for
ensuring that the quality policies adopted by
 Everyone on the  Quality control is a company are followed.
team involved in usually the  It helps to identify and prepare the necessary
developing the responsibility of a SOPs relative to the control of quality.
product is responsible specific team that  It must determine that the product meets all
for quality assurance. tests the product for the applicable specifications and that it was
 Verification is an defects. manufactured according to the internal
example of QA.  Validation is an standards of GMP.
example of QC.  QA also holds responsible for quality
monitoring or audit function.

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Responsibilities of QA (Contd.) Responsibilities of QC

 QA functions to assess operations  QC is responsible for the day-to-day control
continually and to advise and guide them of quality within the company.
 This department is responsible for analytical
towards full compliance with all applicable
testing of incoming raw materials and
internal and external regulations. inspection of packaging components,
including labelling.
 They conduct in-process testing when
required, perform environmental monitoring,
and inspect operations for compliance.
 They also conduct the required tests on
finished dosage form.

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Responsibilities of QC (Contd.) Sources of Quality Variation

 QC plays a major role in the selection of Because of the increasing complexity of
qualified vendors from whom raw materials modern pharmaceutical manufacture arising
are purchased. Testing of representative
from a variety of unique drugs and dosage
samples is required, and in many cases, an
audit of vendor’s operations is necessary to forms, complex ethical, legal, and economic
determine their suitability and degree of responsibilities have been placed on those
compliance with GMPs prior to their being concerned with the manufacture of modern
approved. pharmaceuticals. An awareness of these
 The environmental areas for manufacturing factors is the responsibility of all those
of various dosage forms are tested and involved in the development, manufacture,
inspected by QC department. control, and marketing of quality products.

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Sources of Quality Variation

(Contd.) Control of Quality Variation
Following variables may affect ultimate 1. Raw material control
quality of product  Good raw material specifications must be written in
 Raw material precise terminology, must be complete, must
provide specific details of test methods, type of
 In process variations instruments, and manner of sampling must be
properly identified.
 Packaging material  Each raw material is sampled according to standard
sampling procedures and is sent to the quality
 Labeling control laboratory for testing according to written
procedures. If acceptable, it is moved to the release
 Finish product storage area, after being properly stickered to
indicate the item no., material name, lot no., release
 Manual Error date, reassay date and sign of QA inspector.

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1. Raw Material Control (Contd.)

 QA personnel should keep preservation samples

of active raw materials that consists of atleast
twice the necessary quantity to perform all tests
required, to determine whether the material
meets the established specifications. These
preservation samples should be retained for
atleast 7 years. Approved material should be
rotated so that the oldest stock is used first.
Raw materials may be classified into 2 groups:
 Active or therapeutic
 Inactive or inert

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2. In-process Items Control 2. In-Process Items Control (Contd.)

 Conformance to compendial standards as the sole There are some critical steps to be followed in this:
basis for judging the quality of a final dosage form  QA before start-up:
can be grossly misleading. As the final dosage - Environmental and microbiologic control and
forms are produced in millions of units, the no. Of sanitation
units assayed at the end is not likely to be - Manufacturing Working Formula Procedures
representative of more than a small fraction of the
- Raw Materials
actual production.
- Manufacturing Euipment
 The FDA-CGMP regulations emphasize
environmental factors to minimize cross-  QA at start-up:
contamination of products and errors, however, - Raw Material Processing
they do little to minimize within-batch and batch-to- - Compounding
batch variation. Therefore, it is important function - Packaging Materials Control
of the IPQA program to ensure that the final - Labels Control
produts have uniform purity and quality. - Finished Product Control

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3. Manufacturing Variation Control

 Monitoring environmental conditions under

which products are manufactured/stored

 Monitoring of air and water systems to prevent

contamination– Air Handling Units

 Monitoring of personnel

 Feedback and follow-up

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Quality Assurance Management 2. All Document-Classifications, Definitions and

Approval Matrix
Procedure
 In this SOP you will find all type of quality and
1. How to write Standard Operating Procedure? Technical/Master file documents to build up a
good quality management system for your
manufacturing sites, definition of documents,
 SOP describes standard SOP format that you can their classification, approval requirements and
use immediately for your quality procedure. retention requirements.

 SOP has instructions on how to write a formal  This procedure has schematic diagrams for your
understanding of how different types of
operating procedure for your systems which your documents are prepared and stored in a typical
people can follow everyday. documentation.

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3. Quality Documentation Management and

Change Control 4. Documentation Rule for GMP Documents

 This SOP describes how to generate new  This SOP describes the principles to be followed
quality documents or change control of existing in GMP documents, entry of data and
documents, review of quality documents,
satellite file management, role of document information, signature requirements and
author, approver, document control officer and correction technique of incorrectly entered data
satellite file administrator. or information.

 In this SOP you will also find numbering

systems of different quality documents like
audit files, SOP’s, forms, manuals, training
files, QA agreements, project files etc and their
effective archiving system.

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5. Quality Documentation- Tracking, Control and 6. Preparation, Maintenance and Change Control
Distribution of Master Documents
 In this SOP you will find mainly the role of  This SOP particularly focused on the
document control officer during the initiation, management of master file documents like
creation, circulation and approval of new quality specifications, control methods, raw materials,
related documents. finished goods and packaging specification and
test reports, formulation, stability files etc
 It also describes the procedure of modification required to generate during the product
and review of existing document using a registration in the market.
documentation database.
 This SOP gives instruction on their creation,
 Management of existing and superseded change control, numbering system, approval
documents is also a art of this procedure. requirements and maintenance in a simple
master file database.
 You will see all the forms referred during the
instruction are attached at the end of the  You will see all the forms referred during the
procedure. instruction are attached at the end of the
procedure.

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7. Deviation Report System 8. Example- Checklist for Batch Documentation

 It is a regulatory requirement to capture all sorts of  This SOP describes the identification of all
deviations evolves in your systems in order to documentation relevant to a production process
maintain the continuous improvement to your
processes and systems. in the form of “Batch Documentation Checklists”
and to ensure their collection by completion of
 This SOP describes how to categorize the deviations the checklists by Authorized Persons.
between production, audit, quality improvements,
technical deviations, customer complaints and
environmental, health and safety deviations.  This procedure is based on an example of tablet
packaging process described in the
 It describes the management responsibilities of ‘Manufacturing’ category.
initiating deviation, capture data, analysis,
investigation, determination of assignable causes,
generation of management report and initiatives to
be taken on corrective and preventative actions.

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9. Evaluation of Batch Documentation and 10. Raw Materials- Laboratory Testing and
Release of Sale Documentation

 This procedure describes the process of  This SOP describes the procedure for sampling,
collection, evaluation and record of batch location, pre-testing, testing and documentation
related document generated during the of all raw materials and components subject to
production of a batch before an authorized test, out of specification results, microbiological
person can release the batch for sale. tests and release procedure for passed raw
materials and components.
 This procedure is based on an example of tablet
packaging process described in the
‘Manufacturing’ category.

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11. Finished Goods- Laboratory Testing and Relationship Between QA, QC and
Documentation GMP
 This SOP describes the procedure for sampling,
location, pre-testing, testing and documentation Quality Assurance

of all finished products subject to test, reagents

and standards to be used for analysis,
management of out of specification results, Good Manufacturing
Practices

microbiological tests and release procedure for

passed finished goods.

Quality Control

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Total Quality Control Total Quality Control (Contd.)

 The concept of total quality control refers to the  In products and process designing, it considers
process of striving to produce a perfect product by a many parameters like:
series of measures requiring an organised effort at - Materials
every stage in production.
 Although the responsibility for assuring product - In-process and product control
quality belongs principally to QA personnel, it involves - Specification and tests for active ingredients,
many departments and disciplines within a company. excipients
To be effective, it must be supported by team effort. - Specific stability procedures of the product
 Quality must be built into a drug product during - Freedom from microbial contamination and
product and process, and it is influenced by the proper storage
physical plant design, space, ventilation, cleanliness - Containers, packaging and labelling
and sanitation during routine production.
- Product protection from moisture, light, volatility,
and drug/package interaction

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Total Quality Management

Total Quality Management (Contd.)
According to ISO, TQM is defined as:  The pharmaceutical industry is a vital segment of health
care system which is regulated heavily because; any
"A management approach of an mistake in product design or production can severe, even
fatal. The poor qualities of drug are not only a health
organisation centred on quality, based on hazard but also a waste of money for both government and
individual consumers. So, the maintenance of the quality
the participation of all its members and with continuous improvement is very important for
aiming at long term success through pharmaceutical industries. From this concept Total Quality
Management (TQM) was established. The aim of TQM is
customer satisfaction and benefits to all prevention of defects rather than detection of defects. So
TQM is very important for pharmaceutical industries to
members of the organisation and society." produce the better product and ensure the maximum
safety of healthcare system and also protect waste of
money for both government & individual consumers.

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Total Quality Management Total Quality Management

(Contd.) (Contd.)
 Total Quality Management consists of  Additionally, TQM will serve to improve
organization-wide efforts to install and make productivity and customer satisfaction.
permanent a climate in which an
organization continuously improves its ability  The concept of TQM requires the total
to deliver high-quality products and services commitment of senior level management and
to customers. While there is no widely supervision of all departments, operators,
agreed-upon approach, TQM efforts typically suppliers, and costumers.
draw heavily on the previously developed  It continually strives for process
tools and techniques of quality control. improvement that begins with product
 The production of quality pharmaceuticals
products requires embracing the principles of development and only concludes when
TQM. feedback and follow-up have been
completed.

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Activities in TQM Functions of TQM

TQM is the foundation for activities, which include:  Product quality criteria are established, and
 Commitment by senior management and all employees detailed specifications are written. Meticulous,
 Meeting customer requirements written procedures must be prepared for
 Reducing development cycle times
 Just in time/demand flow manufacturing
production and control. Raw material must be
 Improvement teams characterised and then purchased from
 Reducing product and service costs reputable, approved suppliers.
 Systems to facilitate improvement  Facilities must be designed, constructed, and
 Line management ownership controlled to provide the proper stable
 Employee involvement and empowerment
 Recognition and celebration
environment for protecting the integrity of
 Challenging quantified goals and benchmarking products. Equipments must be selected that is
 Focus on processes / improvement plans efficient and can be cleaned readily and
 Specific incorporation in strategic planning sanitised.

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Functions of TQM (Contd.) Functions of TQM (Contd.)

 Personnel must be trained properly. The  QA is ever present and gives approval
directions they use must be in writing, only after assessing and being assured
approved by responsible individuals. that the entire production process has
 Distribution departments are responsible been completed satisfactorily and that all
for controlling the shipping and handling the aspects of the GMPs have been
of products, using inventory-control
systems. satisfied.
 The marketing department must be
sensitive to the costumers’ needs and be
responsive to complaints.

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Advantages of TQM Disadvantages of TQM

 Improves reputation- faults and problems are  Initial introduction cost.

spotted and sorted quicker.  Benefits may not be seen for several
 Higher employee morale- workers motivated years.
by extra responsibility, team work and
 Workers may be resistant to change
involvement indecisions of TQM
 Lower cost- decrease waste as fewer
defective products and no need for separate.
 Quality control inspector

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Major Keywords of Quality

Assurance Calibration
 Calibration is defined as operation that,
under specified conditions, in a first step,
Calibration establishes a relation between the quantity
values with measurement uncertainties
provided by measurement standards and
Validation corresponding indications with associated
measurement uncertainties (of the calibrated
instrument or secondary standard) and, in a
Qualification second step, uses this information to
establish a relation for obtaining a
measurement result from an indication.

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Validation Validation (Contd.)

 Validation is a process of establishing Since a wide variety of procedures, processes, and
activities need to be validated, the field of validation
documentary evidence demonstrating that a is divided into a number of subsections including the
procedure, process, or activity carried out in following:
 Equipment validation
production or testing maintains the desired  Facilities validation
level of compliance at all stages. In Pharma  HVAC system validation
Industry it is very important apart from final  Cleaning validation
 Process Validation
testing and compliance of product with  Analytical method validation
standard that the process adapted to produce  Computer system validation
itself must assure that process will  Packaging validation
 Cold chain validation
consistently produce the expected results.

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1. Prospective Validation
Types of Validation
 Prospective validation is carried out during the development
stage by means of a risk analysis of the production process,
which is broken down into individual steps: these are then
Prospective Concurrent evaluated on the basis of past experience to determine
whether they might lead to critical situations.
Validation Validation  Where possible critical situations are identified, the risk is
evaluated, the potential causes are investigated and
assessed for probability and extent, the trial plans are drawn
up, and the priorities set. The trials are then performed and
Validation evaluated, and an overall assessment is made. If, at the end,
the results are acceptable, the process is satisfactory.
Unsatisfactory processes must be modified and improved
until a validation exercise proves them to be satisfactory.
This form of validation is essential in order to limit the risk of
Retrospective Repeated errors occurring on the production scale, e.g. in the
preparation of injectable products.
Validation Validation

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2. Concurrent Validation 3. Retrospective Validation

 Concurrent validation is carried out during  Retrospective validation involves the examination of
normal production. This method is effective only past experience of production on the assumption
that composition, procedures, and equipment
if the development stage has resulted in a remain unchanged; such experience and the results
proper understanding of the fundamentals of of in-process and final control tests are then
the process. evaluated. Recorded difficulties and failures in
 Concurrent validation together with a trend production are analysed to determine the limits of
process parameters. A trend analysis may be
analysis including stability should be carried out conducted to determine the extent to which the
to an appropriate extent throughout the life of process parameters are within the permissible
the product. range.
 Retrospective validation is obviously not a quality
assurance measure in itself, and should never be
applied to new processes or products.

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4. Revalidation or Repeated Validation

Qualification
 Revalidation is needed to ensure that changes
in the process and/or in the process  Qualification is defined as action of
environment, whether intentional or proving and documenting that equipment
unintentional, do not adversely affect process or ancillary systems are properly installed,
characteristics and product quality. work correctly, and actually lead to the
expected results. Qualification is part of
validation, but the individual qualification
steps alone do not constitute process
validation.

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Qualification (Contd.) Qualification (Contd.)

Qualification includes the following steps:  Operational qualification (OQ) –
 Design qualification (DQ)- Demonstrates that the
proposed design (or the existing design for an off- Demonstrates that all facets of the
the-shelf item) will satisfy all the requirements that process or equipment are operating
are defined and detailed in the User Requirements
Specification (URS). Satisfactory execution of the DQ correctly.
is a mandatory requirement before construction (or
procurement) of the new design can be authorised.  Performance qualification (PQ) –
 Installation qualification (IQ) – Demonstrates that the Demonstrates that the process or
process or equipment meets all specifications, is
installed correctly, and all required components and equipment performs as intended in a
documentation needed for continued operation are consistent manner over time.
installed and in place.

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2. To audit compliance to the Quality System

Role of QA in Pharma Industries
 Audit for compliance to policies and procedures:
1. To establish Quality Audit on paper vs. practice
 Report on the performance of the quality
 Establish the quality management system to system, including trends, that help
describe how the firm complies decision making for targeted actions
CGMPs and operates to maintain a state of
control

 Keep current with good industry practices, and

applicable to the mission of your operation.

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3. To establish procedures and specifications 4. To establish manufacturing controls

 Ensure that procedures and specifications are  Ensure that appropriate manufacturing in-
appropriate and followed. process controls are implemented.
 Ensure that the procedures and specifications of  Ensure in-process controls are performed during
firms under contract are also appropriate and manufacturing operations and results are
followed, i.e., maintain control and take satisfactory
responsibility for third-party services providers
(contract manufacturers, contract laboratories,
etc.)

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5. To perform laboratory tests 6. To review and approve or reject

 Perform laboratory testing of components,  Review and approve/reject any document that
containers, in-process materials, packaging materials gives work instructions and set requirements
and drug product using validated methods against such as procedures, protocols, test methods,
scientifically-derived, fit-for-purpose specifications and specifications—including changes to these
 Approve or reject drug products manufactured, documents
processed, packed, or held under contract by
 Review and approve/reject reprocessing and
another company, i.e., final product release is not
delegated to a contractor rework procedures
 Perform retests or reexamine approved components,  Review and approve/reject production batch
drug product containers and closures after long records and make the final decision to release a
storage or exposure to adverse conditions. product lot into commerce.

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7. To ensure investigation of nonconformance 8. To keep management informed

 Ensure investigation is conducted and root  Report on product, process and system risks
cause is eliminated for production and control  Report on outcome of regulatory inspections
record errors, discrepancies, and failure to meet and ensure responses are complete and
specification, including quality attributes managed to verifiable closure
 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

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9. To describe responsibilities in writing 10. To remain independent

 Have a complete and compliant procedure that  Ensure there is no conflict of interest between
describes responsibilities regulatory responsibilities and actual daily
 Follow the procedure activities
 Be independent reviewer and approver with
respect to manufacturing and process/ product
development units

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Control and Assurance of

2. Equipments and Buildings
Manufacturing Practices
 The building should provide adequate space for
1. Personnel the orderly placement of materials and
equipment to minimize any risks of mix-ups or
Important parts for a successful personnel are:
 Proper selection
cross-contamination between the drugs,
 Training excipients, packaging and labelling from the
 Motivation of Production time the materials are received to the time the
 Packaging products are released.
 Control
 The desired characteristics of equipments for
It is essential that the qualified personnel be employed to
supervise the formulation, Processing, Sampling, testing, producing quality products are numerous,
packaging and labelling of the drug product, and that however, the equipment should be of suitable
competent staff be placed in charge of the maintainance of size, accuracy and reproducibility.
machinery, equipment and sanitation.

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3. Control of records 4. Control of Production Procedures

 The records, such as Master Formula and Batch  To ensure that products have the intended
production records, should be prepared and characteristics of identity, strength, quality, and
maintained in accordance with established purity, production and the related in-process
procedures. quality control procedures should be rigidly
followed as required by the master formula
record or batch production record.

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5. Packaging Control 6. Validation

 A packaging record bearing an identification  Validation of a process is the demonstration

number is issued to the packaging section. This that controlling the critical steps of a process
record specifies the packaging materials to be results in products of repeatable attributes or
used, operations to be performed, and the causes a reproducible event.
quantity to be packaged.

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Control and Assurance of Finished

Summary
Products
 Unless the testing procedures by which the  The professional, social and legal responsibilities that
product quality is finally measured are rest with the pharmaceutical manufacturers for the
established on an equally sound basis,the entire assurance of product quality are tremendous. It is
system may be deficient. only through well-organized, adequated staffed, and
accurately performed process and dosage form
 Product failures causing rejections or recalls after control that adequate quality assurance can be
market introduction are serious and can be easily achieved.
detected and minimized by an effectively  The manufacturer is in a position to
administered quality testing program. ◦ Control the sources of product quality variation
 Therefore,the testing of the finished products for ◦ Ensure the correct and most appropriate manufacturing and
packaging practices
compliance with the established standards prior ◦ Assure that the testing results are in compliance with the
to release of the material for distribution is a standards or specifications
criticalfactor for quality control and assurance. ◦ Assure product stability

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Thank You!!!

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