This document discusses quality systems and audits in pharmaceutical manufacturing. It covers cGMP regulations which provide minimum standards for manufacturing drugs to ensure safety, identity, strength and quality. It describes quality assurance functions like assuring quality at every stage of manufacturing and coordinating with quality control. It also discusses the quality system approach of having management commitment to quality and establishing responsibilities. Key resources like human resources, infrastructure and work environment are also outlined.

1. ROLE OF QUALITY SYSTEMS AND AUDITS IN
PHARMACEUTICAL MANUFACTURING
ENVIRONMENT
A Presentation by: Mridul Bindra
Presented to: Dr. Kanchan Kohli
M. Pharma (Q.A.) {Jamia Hamdard}

2. CONTE NTS
cGMP
REGULATIONS1
QUALITY ASSURANCE
FUNCTIONS2
QUALITY SYSTEM
APPROACH3
MANAGEMENT
RESPONSIBILITIES4
RESOURCES5
REFERENCES
6

3. c G M P R E G U L AT I O N S
cGMP regulation is minimum current good
manufacturing practice for methods to be used in, and
the facilities or controls to be used for, the
manufacture, processing, packing, or holding of a drug
to assure that such drug meets the requirements of
the act as to safety, and has the identity and strength
and meets the quality and purity characteristics that it
purports or is represented to possess.
INTRODUCTION

4. c G M P R E G U L A T I O N
Batch: Specific quantity having uniform character and quality, within specified limits,
produced as single manufacturing order during same cycle of manufacture.
Component: Any ingredient intended for use in the manufacture of a drug product,
including those that may not appear in such drug product.
Lot number, control number, or batch number: Distinctive combination of letters,
numbers, or symbols, by which complete history can be determined.
Regulation: Rules made by a government or other authority in order to control the way
something is done or the way people behave.
Acceptance criteria: The product specifications and acceptance/rejection criteria, that
are necessary for making a decision.
DEFINITION

5. c G M P R E G U L A T I O N
→ Rodent treatments
→ Separate dispensing
areas for β lactum, sex
hormones, cytotoxic
substances etc.
→ Quarantine of drug
products before release
by the Q.C. unit.
→ Adequate fire
protection measures
→ Personnel shall be
suitably qualified and
experienced.
→ Practice good
sanitation and health
habits.
→ Number of personnel
employed be adequate
and direct proportion
to workload.
WAREHOUSING AREAPERSONNEL
→ Designed to allow the
production in uni-flow
with logical sequence
of operations.
→ Service lines be
designed, fixed and
constructed to avoid
accumulation of dust
PRODUCTION AREA
→ Rest and refreshment
rooms shall be
separate from other
areas
→ Facilities for changing,
storing clothes and
toilet purposes be
easily accessible and
adequate for number
of users
ANCILLARY AREAS
→ Quality control
laboratories shall be
independent of the
production areas
→ Take into account the
suitability of
construction materials
and ventilation
QUALITY CONTROL AREA

6. c G M P R E G U L A T I O N
→ Vessels and containers
be conspicuously
labelled
→ Products required to be
free from pathogens
→ Packaging lines be
independent and
segregated
→ Left-overs of packaging
operations are cleared
→ All personnel, shall
undergo medical
examination
→ A high level of personal
hygiene shall be
observed
→ Wear clean body
coverings
MANUFACTURING
OPERATIONS AND CONTROL
HEALTH, CLOTHING AND
SANITATION OF WORKERS
→ Free from waste, dust,
debris and similar
material
→ Well lit
→ No storage of materials
in manufacturing area
→ Cleaning procedure to
be followed
SANITATION IN
MANUFACTURING
→ Keep an inventory and
maintain records as per
schedule U.
→ Incoming material be
quarantined
→ Raw materials released
by Q.C. Department &
within shelf life be used
→ Place on the raised
platforms/racks
RAW MATERIALS
→ Located, designed,
constructed, adapted
and maintained to suit
the operations to be
carried out
→ Those in contact with
the product shall not
be reactive, additive or
adsorptive
EQUIPMENT

7. c G M P R E G U L A T I O N
→ Indicate concentration,
lot number, potency,
date on which
containers was opened
and storage conditions,
where appropriate.
→ Printing shall be done
in bright colours and in
a legible manner.
→ Documents designed,
prepared, reviewed
and controlled,
wherever applicable.
→ Data may be recorded
as electronic data.
→ Master Formulae and
detailed operating
procedures be
available in a hard copy
LABELS AND OTHER
PRINTED MATERIALS
DOCUMENTATION AND
RECORD
→ Totality of
arrangements made
with object to ensure
products are of quality
required for intended
use.
→ Products are not
released for sale or
supplied before
certified
QUALITY ASSURANCE
→ Assessment of all or
part of a system for
improving it.
→ To evaluate the
manufacturer‘s
compliance with gmp
→ To detect shortcomings
SELF INSPECTION AND
QUALITY AUDIT
→ Concerned with
sampling,
specifications, testing,
documentation,
release procedures to
ensure tests are
actually carried and
materials are not
released for use, sale
or supply until quality
judged to satisfactory.
→ Instruments be
calibrated and testing
procedures validated
before testing.
QUALITY CONTROL SYSTEM

8. c G M P R E G U L A T I O N
→ Records relating to all
manufacturing
procedures for each
product and batch size
to be manufactured
→ For each lot of every
active ingredient carry
out all the tests, except
sterility and pyrogens/
Bacterial Endotoxin
Test, & retain record for
3 months after the
date of expiry of the
last batch produced
from that API
MASTER FORMULA
RECORDS
REFERENCE SAMPLES
→ This includes
• Name of product
• Strength composition,
pack size, weight,
volume
• Special precaution
PACKING RECORDS
→ Based on the relevant
parts of the packaging
instructions.
BATCH PACKAGING
RECORDS
→ Based on the relevant
parts of the currently
approved master
formula.
→ This includes following
• Name of product
• Date and time of
intermediate stages
• Batch number
• Initials of operator
• Person carrying in and
out
• Product yield at each
stage
• Any problem be
recorded
BATCH PROCESSING
RECORDS

9. c G M P R E G U L A T I O N
→ Periodic audits of
warehousing practices
be followed at
distribution centers
→ Records for distribution
shall be maintained
→ If batch has to be
reprocessed, procedure
shall be authorized and
recorded
→ Recovery of the
product residue may be
carried out
DISTRIBUTION RECORDS
REPROCESSING AND
RECOVERIES
→ Validation be
conducted as per the
pre-defined protocols.
→ Validation of
processing, testing and
cleaning procedures.
VALIDATION AND PROCESS
VALIDATION
→ Product recall system
of defective products
be devised for timely
information of all
concerned stockists,
wholesalers, suppliers,
upto the retail level
within the shortest
period.
PRODUCT RECALL
→ Each complaint be
investigated/ evaluated
and records of
investigation and
remedial action taken
thereof shall be
maintained.
COMPLAINTS AND ADVERSE
REACTIONS

10. c G M P R E G U L A T I O N
Personnel
• Qualification, experience
and responsibilities of key
personnel
• Outline for arrangements
for training
• Record maintenance
Premises
• Description of
manufacturing areas
drawn to scale
• Brief description of
water system &
ventilation systems
Equipment
• Equipment used in
production and quality
control laboratories
• Qualification and
calibration for
computerized systems
validation.
Sanitation
• Written specifications
and procedures for
cleaning manufacturing
areas and equipment.
Documentation
• Necessary
documentation for the
manufacture
General Information
• Brief information of firm
• Manufacturing activities
permitted by licensing
authority
• Number of employees
• Any use of outside
technical assistance
• Description of QMS of firm
SITE
MASTER
FILE
→ Contain specific and factual
GMP about production and/or
control of manufacturing
preparations.
SITE MASTER FILE

11. c G M P R E G U L A T I O N
Quality Control
• Description of the
quality control system
and activities of quality
control department
Loan license
manufacture and
licensee
Distribution,
complaints and
product recall
• Arrangements for the
handling of complaints
and product recalls
Self inspection
• Short description of the
self-inspection system
Export of drugs
• Products exported to
different countries
• Complaints and product
recall, if any.
Production
• Description of
production operations
• Description of general
policy for process
validation
Site Master
File

12. Q UA L I T Y A S S U R A N C E F U N C T I O N S
INTRODUCTION
Quality assurance activities are processes and activities conducted to
assure that a product or service consistently satisfies its requirements
and is fit for its intended use.
In the pharmaceutical manufacturing environment, the activities
conducted to assure the product’s identity, strength, purity, potency,
and other quality attributes conform to approved specifications.

13. Q . A . F U N C T I O N S
F U N C T I O N S
Assure quality at every stage of
manufacturing
Plan and manage all activities of
quality assurance department
Coordinate with manufacturing
department
Coordinate with QC and R&D for
development of specifications and
analytical procedure
Review adequacy and relevance
of specifications and analytical
procedure with QC and R&D

14. Q . A . F U N C T I O N S
F U N C T I O N S
Coordinate technical audits of QC
labs to determine analytical quality
systems information
Ensure analytical instrumentation
is properly functioning, calibrated
and serviced
Maintenance of QC records
Routine GMP auditing
Records of release, quarantine and
rejection of components, finished
products, containers, closures and
labels

15. Q . A . F U N C T I O N S
F U N C T I O N S
Liaison with regulatory authorities
for new product manufacturing
licenses and renewal
Suggest and organise training
programmes to meet cGMP
regulations
Establish guidelines and
procedures on cGMP and GLP
Assist change control committee for
overall review of non- conformance,
failure investigations, etc
Follow reporting system to Quality
head on Daily/ Weekly/ Monthly
basis

16. Q . A . F U N C T I O N S
F U N C T I O N S
Warehousing of finished products
Warehousing of incoming
components, containers and
closures, labelling, etc.
Final release or rejection of every
batch for sale and distribution
Out of specification investigation and
control of non- conforming products
Handling of complaints and product
recalls

17. Q U A L I T Y S Y S T E M
A management commitment to
quality communicated throughout
organization
Identifying quality requirements
using risk management
Developing a quality policy, plan
and objectives
Providing the resources needed
to meet quality objectives
Establishing an organizational
structure with identified
responsibilities and authorities
Initiating corrective and
preventive actions as needed
Establishing methods for
evaluation of performance of
systems and processes
Q UA L I T Y S Y S T E M A P P R O A C H
W
H
Y

18. Q U A L I T Y S Y S T E M
Reduce recalls,
returned or
salvaged
products, and
defective
products entering
marketplace
Shorter and fewer
FDA inspections
by lowering the
risk of
Manufacturing
problems
Harmonize the
cGMP regulations
Provide the
necessary
framework for
implementing
quality by design
A F T E R I M P L E M E N TAT I O N

19. M A N A G E M E N T
M A N A G E M E N T R E S P E N S I B I L I T I E S
Provide leadership by
establishing a
commitment to
quality supported
by all levels of
management.
Building and
documenting a
quality system to
meet specified
quality and
regulatory
requirements.
Establish a quality
policy and objectives,
and quality plans
aligned
with the
organization’s
strategic plans.
Create an
organizational
structure with clearly
defined
responsibilities and
authorities to
perform quality
functions.
Assure appropriate
corrective and
preventive actions
are taken using
effective change
control procedures
And documented.
Review system by
establishing
appropriate
accountability system
in organization to
monitor & report
quality data & system
status.

20. M A N A G E M E N T
RESOURCE
INPUT
Results of
audits
Changes that
could affect
the quality
management
system
New or
revised
regulatory
requirements
as and when
issuedStatus of
preventive
and
corrective
actions
Process
performance
and product
conformity
Customer
feedback
RESOURCE
OUTPUT
Improvement
to maintain
effectiveness
of QMS and
its processes
Improvement
of product
related to
customer
requirement
Resource
needs
Follow-up
actions from
previous
management
reviews
Recommend
ations for
improvement

21. R E S O U R C E S
01
I
02
03
HUMAN RESOURCES
Personnel should periodically (at least once a year) undergo medical
examination and shall be free from communicable or contagious
diseases
Personnel shall be competent on the basis of appropriate
education, training, skills and experience.
Number of personnel employed shall be adequate and in direct
proportion to the workload.
R E S O U R C E S

22. R E S O U R C E S
01
II
02
03
INFRASTRUCTURE
Maintain and provide supporting services such as transport or
communication
Maintain buildings, workspace and associated utilities.
Provide and maintain process equipment (both hardware and
software)

23. R E S O U R C E S
01
III
04
02 05
03 06
WORK ENVIORNMENT
Documented health,
clothing & cleanliness of
personnel
Temporary workers are
trained and supervised by
trained personnel
Special arrangements
established and documented
for control of contaminated
product
Personnel shall bear clean
body covering appropriate
to their duties.
Smoking, eating, drinking,
chewing or keeping food and
drink not permitted in
production, laboratory and
storage areas.
Documented procedures or
work instructions to monitor
and control work environment
condition

24. R
E
S
O
U
R
C
E
S

25. R E F E R E N C E S
DRUG AND COSMETIC RULES
Pharmaceutical Manufacturing Handbook,
Regulations and Quality by Shayne Cox Gad.
Wiley-Interscience, A John Wiley and sons, Inc.,
Publications.
FDA, USA

26. THANKS