The document outlines Good Manufacturing Practice (GMP) regulations to ensure the safety, quality, and efficacy of pharmaceutical products through established standards and methods. It emphasizes the importance of quality assurance and control systems, documentation, and deviation investigations, while defining roles and responsibilities within quality control units. Additionally, the need for regular audits, compliance with regulatory requirements, and a risk-based approach to manufacturing is discussed to prevent contamination and ensure product integrity.

2. Good Manufacturing Practice Regulations
Establishes minimum GMP for methods to be used, and the
facilities or controls to be used for, the manufacture, processing,
packing or holding of a drug to assure that the drug is
 Safe
 With appropriate identity and strength
 Meets quality and purity characteristics

3. cGMP: Current Trends
21st Century: Risk-Based Approach
 Risk-based assessment
 Up-to-date Science-based policies and standards
 Integrated Systems approach
Quality / Facilities and Equipment / Materials / Production /
Packaging and Labeling / Laboratory Control
 International cooperation
ICH: International Conference on Harmonization

4. cGMP: The Basics
 Quality Control
 Product meets specifications
 Quality Assurance
 Systems ensure control and consistency
 Validation, validation, validation
 Documentation
 If it is not documented, it did not happen

5. cGMP: Raw Materials
 Active ingredients
 Excipients
 Audit suppliers on regular basis
 Before entering into contract, review regulatory history
 Monitor regulatory compliance
 Test incoming raw material

6. cGMP: Buildings and Facilities
 Separate or defined areas as are necessary to
prevent contamination or mix-ups
 Air filtration systems (HVAC) in production areas
 Sanitation

7. cGMP: Production and Process Controls
Written production and process control procedures shall be
followed in manufacturing and shall be documented at the time
of performance.
Any deviation from these procedures shall be recorded and
explained or justified.
(“SOPs”)

8. cGMP: In Process Testing
 Must have written procedures and testing of product
while being manufactured to assure batch uniformity and
integrity
 Control procedures shall be established to monitor output
and to validate manufacturing processes that could cause
variability

9.  To assure that a drug
product meets applicable
standards of identity,
strength, quality and
purity at the time of use, it
shall bear an expiration
date determined by
appropriate stability
testing described in
Section 211.166.
 Expiration dates shall be
related to any storage
conditions stated on the
labeling, as determined by
stability studies described
in Section 211.166.
cGMP: Expiration Dating

10.  Company must have written procedures designed to assure
that correct labels, labeling and packaging materials are
used for drug products; such written procedures shall be
followed.
 Label mix ups have been a major reason for drug product
recalls.
cGMP: Packaging and Labeling Operations

11. Testing and release for distribution
 For each batch of drug product, there shall be laboratory
determination of satisfactory conformance to final
specifications for the drug product, including the identity and
strength of each active ingredient prior to release.
 There shall be appropriate laboratory testing, as necessary,
of each batch required to be free of objectionable
microorganisms.
cGMP: Laboratory Controls

12. A written testing program designed to assess stability
characteristics is required.
Stability testing results must be used in determining
storage conditions and expiration dates.
cGMP: Stability Testing

13. Production and control records shall be reviewed and approved
by the quality control unit to determine compliance with all
established, approved written procedures before a batch is
released or distributed.
 Product Impact Assessment
 Trend Analysis
 Distributed Product
cGMP: Production Record Review

14. Any unexplained discrepancy or the failure of a batch or
any of its components to meet any of its specifications must
be investigated whether or not the batch has already been
distributed.
 Investigate other batches of same drug product
 Investigate other drug products that may have been
associated with the specific failure or discrepancy
 Written record of investigation
cGMP: Deviation Investigations

15. Documenting the Investigation is Critical
 Hypotheses should be scientifically based
 Subject matter experts should be consulted throughout the
investigation, including the initial identification of hypotheses
 Once a hypothesis is identified, it must be investigated
 All hypotheses should be validated or invalidated
cGMP: Deviation Investigations (cont….)

16. Corrective and Preventative Action Program
 As part of deviation investigations...
 Root cause identification and definitive corrective actions
• Company Program / System should audit:
– Timeliness of corrective / preventative actions
– Effectiveness of actions
– Documentation
• Example:
– Environmental monitoring/Cleaning
cGMP: Deviation Investigations (cont….)

17. Corrective and Preventative Action Program (cont…)
 After an FDA inspection...
 Establish scientifically sound corrective and preventative actions
Realistic timeframes
 Ensure compliance with commitments to FDA
• Systems
• Specific Issues
E.g., Change Control / Training
cGMP: Deviation Investigations (cont….)

18. Quality control unit “shall have the responsibility and authority to
approve or reject all components, drug product containers,
closures, in-process materials, packaging material, labeling, and
drug products, and the authority to review production records to
assure that no errors have occurred or, if errors have occurred,
that they have been fully investigated.
The quality control unit shall be responsible for approving or
rejecting drug products manufactured, processed, packed, or held
under contract by another company.”
cGMP: Responsibility and Authority of
Quality Control

19.  Written procedures describing the handling of all
written and oral complaints
 Review by Quality Control unit
 Possible failure to meet any specification
 Determine need for deviation investigation
 Adverse Drug Experience report assessment
 Documentation of complaint and investigation or
reason for not investigating
cGMP: Complaints

20.  Contemporaneous documentation critical
 Laboratory and production records
 Trending analysis
 Data Integrity
 Internal review : OOS results, complaints, R&D
 External review: FDA inspections, business deals (due
diligence), and products liability cases
cGMP: Records and Reports

21.  Field Alert Reports
 Labeling
 Failure to meet specifications — STABILITY FAILURES
 Within 3 working days of receipt
 Warner Lambert criminal case
 Adverse Drug Experience Reports
 ASAP but no later than 15 calendar days of initial receipt
 Foreign and domestic
 Recall Procedures and Preparation
cGMP: Reports (cont….)

22.  Independent Audit Group
 Resources
 Authority
 Global Approach - Harmonization of Quality Standards
 Audit priority systems / specific issues
 Follow-up audits
cGMP: Auditing

24.  Get the facility design right from the start
 Validate processes
 Write good Procedures and follow
 Identify who does what
 Keep good records
 Train and develop staff
 Practice good hygiene
 Maintain facilities and equipment
 Design quality into the whole product life cycle
 Perform regular audits
Golden Rules of GMP

27.  QC: Quality control; separation of production and quality
control (test of a single item)
 QA: Quality assurance; introduction of a statistical approach
to quality control, a broader quality approach
 QM: Quality management; understanding quality as a general
approach, with involvement of (nearly) all parts of a company
 TQM: Total quality management; broadest quality approach,
integrates all parts of a company, including safety,
environmental protection …
Understanding ‘quality in the 20th century (2/2)

28. The manufacturer shall establish and implement an
effective pharmaceutical quality assurance system,
involving the active participation of the management
and personnel of the different services involved.

29.  You must have a system.
 The system must be GMP compliant (pharmaceuticals !).
 Use the tools and the methodology of ISO and TQM to add to
your GMP system in order to gain the utmost benefit !
 A well designed and maintained QA system will allow you
to relax … from time to time.
ISO or GMP ?

30.  ISO describes a system approach
 But fails to set standards (ISO lets the organisation set its own
levels)
 GMP has required national standards
 But lacks a system approach
 TQM is a management approach
 To long term success centered on “quality” through customer
satisfaction
 TQM is based on the participation of all members of an
organisation in continually improving processes, products and
services
ISO, GMP and TQM

32. Quality Control
Production
Quality Assurance
Quality
Operations
Production

33. Raw Material
Processing
Equipments
Manufacturing Plant
Operators
Environment
Manufacturing
In Process
Testing
Finish Product
Packaging
Storage
Dispatch
Customer
TOP Management
Statistical Analysis
Strict CAPA
Failure Analysis
APR
APQR
Deviation Management
Change Control
OOS Management
Customer Complaint
Validation

34.  Man
 Material
 Machinery
 Manuals/Methodology ( SOP)
 Motivation
The 5 M’s of Quality

35. Quality
Assurance
ProcedureUse
Storage/
Distribution
Selection
National Drug Policy
& Legal Framework
- Quality requirement
- Drug Registration

36. Business
• Establish if the company is
manufacturer or wholesaler;
• Assess the size of business in
terms of staff. Capital value,
Sales turnover. etc.
Manufacturing
• Ensure GMP compliance
• WHO Certification can be
used;
• Crosscheck with QA
system description
Quality
• Evaluate QA System:
• GMP requires companies to
have QC laboratories
Product
• Formulate decision from
regulatory status of a product
with well- established DRS;
• WHO Certification Scheme;
- Therapeutic equivalence

37. Pre analytical Analytical Post analytical
Right specimen
Laboratory
professionals
Recording
Right collection Reagents Interpretation
Right labeling Equipment Turnaround time
Right quantity Selection of test - SOP Report to right user
Right transport Records
Right storage Bio-Safety
Factors influencing Quality

38. There shall be a quality control unit that shall have the
responsibility and authority to approve or reject all components,
drug product containers, closures, in-process materials,
packaging material, labelling, and drug products, and the
authority to review production records to assure that no errors
have occurred or, if errors have occurred, that they have been
fully investigated.
The quality control unit shall be responsible for approving or
rejecting drug products manufactured, processed, packed, or
held under contract by another company.
FDA Requirements

39.  Unrealistic Commitments
 Process Execution
 Poorly Executed Unit Processes
 Inadequate Development Work
 Process Development
 Inadequate Batch Records
 Process Validation
 Data Integrity
 Supply Chain
 Facilities
 Quality System
Challanges

40. The paradigms are changing, the focus
is shifting and changes are inevitable

41. Quality Assurance Quality Control
Definition
QA is a set of activities for
ensuring quality in the
processes by which products are
developed.
QC is a set of activities for ensuring
quality in products. The activities
focus on identifying defects in the
actual products produced.
Focus on
QA aims to prevent defects with
a focus on the process used to
make the product. It is a
proactive quality process.
QC aims to identify (and correct)
defects in the finished product.
Quality control, therefore, is a
reactive process.
Goal
The goal of QA is to improve
development and test processes
so that defects do not arise when
the product is being developed.
The goal of QC is to identify defects
after a product is developed and
before it's released.
Statistical
Techniques
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.
When statistical tools & techniques
are applied to finished products
(process outputs), they are called as
Statistical Quality Control (SQC) &
comes under QC.

42. What
Prevention of quality problems
through planned and
systematic activities including
documentation.
The activities or techniques used to
achieve and maintain the product
quality, process and service.
How
Establish a good quality
management system and the
assessment of its adequacy &
conformance audit of the
operation system & the review
of the system itself.
Finding & eliminating sources of
quality problems through tools &
equipment so that customer's
requirements are continually met.
Example
Verification is an example of
QA
Validation/Software Testing is an
example of QC
Responsibility
Everyone on the team involved
in developing the product is
responsible for quality
assurance.
Quality control is usually the
responsibility of a specific team that
tests the product for defects.

43. “Quality is never an accident;
it is always the result of intelligent effort.”
- John Ruskin
Contact : hardik.mistry@hester.in