cGMP guidelines 21 CFR part 210 and 211

1. cGMP
Regulations
Presented By:
ASHUTOSH
AGARWAL
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2. TECH
SLIDLES
01
cGMP
guidelines
02
Explanation of
cGMP
Guidelines
03
Duties of Quality
Control Unit under
cGMP Regulations
04
References
05
INTRODUCTION
01
Table Of Contents
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3. INTRODUCTION
01
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4. ● The cGMP regulations for the manufacture of pharmaceutical products are
contained in Parts 210 and 211 of Title 21 of the Code of Federal
Regulations (CFR) [1].
INTRODUCTION
● Part 210 specifies the scope and applicability of the cGMP regulations and
defines terms used in the regulations.
● Part 210 also indicates that the regulations establish “minimum” cGMP
requirements and that products that are not manufactured under cGMP are
adulterated.
● Adulterated products and the persons responsible for the adulteration are
subject to regulatory action by the FDA.
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5. ● Part 211 contains specific good manufacturing practice requirements for
finished pharmaceuticals and is divided into Subparts A-K as follows:
cGMP Part 211
A. Scope
B. Organization and personnel
C. Buildings and Facilities
D. Equipment
E. Control and Component and Drug Product Containers
and Closure
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6. F. Production and Process Control
G. Packaging and Labelling Controls
H. Holding and Distribution
I. Laboratory controls
J. Records and Reports
K. Returned and Salvaged Drug Products
cGMP Part 211
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7. A. The regulations in this part contain the minimum current good
manufacturing practice for preparation of drug products for administration
to humans or animals.
B. The current good manufacturing practice regulations in this chapter as they
pertain to drug products; as they pertain to drugs that are also biological
products for human use; they are applicable to drugs that are also human
cells, tissues, and cellular and tissue-based products (HCT/Ps) and that are
drugs; supplement and do not supersede the regulations in this part unless
the regulations explicitly provide otherwise.
C. The requirements in this part shall not be enforced for OTC drug products
if the products and all their ingredients are ordinarily marketed and
consumed as human foods, and which products may also fall within the
legal definition of drugs by virtue of their intended use.
Scope
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8. Organization
and Personnel
Responsibi
lities of
quality
control
unit
Personnel
qualification
Personnel
responsib
ilities
Consultants
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9. Organization and Personnel Management
Responsibility
• Responsible for facility, quality system, organizational
structure, ensuring adequate resources
• Responsible for actions of those reporting to them
• Responsible for reviewing products annually, and
procedures routinely
• Responsible for providing adequate resources to
perform operations Facilities, personnel, training,
equipment, etc
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10. • Quality Unit Responsible for approval or rejection of
1. all components, raw materials, containers, closures,
subassemblies, packaging, labeled finished products, process
validation reports, procedures and product specifications
2. Investigative reports for non-conformances and out- of-
specifications (OOS’s)
• Quality Unit Responsible for reviewing production records and
ensuring that no errors have occurred (may include verification
activities)
• Responsible for releasing product for use Must be independent of
manufacturing
Organization and Personnel Management
Responsibility
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11. Building
and facilities
Design and
construction
features.
Lighting.
Ventilation, air
filtration, air
heating and
cooling.
Plumbing.
Sewage and
refuse.
Washing and
toilet facilities.
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12. Buildings and Facilities
• Buildings must be designed with adequate size and
space for operations (helps to eliminate mix-ups)
• Facilities must be validated
• There must be a good flow pattern for personnel,
materials, products and waste materials (flow from
clean to dirty)
• The facility must be easy to clean and sanitize
(surfaces, equipment, exposed cords, floors,
ceilings…)
• Environmental controls must be in place (clean rooms)
• Utilities must be validated (water systems, electrical,
etc)
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13. • Buildings and Facilities Must have engineering documents
describing the layout of the clean rooms – controlled documents
• Changes to the layout of the room after it has been validated must
go through change control procedures and may require
revalidation of the room
• Any changes that potentially impact the ventilation in the room
must be assessed for impact on the microbial levels in the room
• Microorganisms, particulates, and hazardous materials must be
controlled
Buildings and Facilities
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14. FOUR ILLUSTRATIONS IN ONE PLACE
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15. Equipment
Equipment
design, size,
and location.
Equipment
construction.
Equipment
cleaning and
maintenance.
Automatic,
mechanical,
and electronic
equipment.
Filters
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16. Equipment
• Equipment should be selected based on the
intended use and cleanability if it is to be in a
clean room
• Equipment must be placed in an appropriate
location (temperature, humidity, etc.)
• Equipment must be properly qualified
(Design, Installation, Operation, Performance)
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17. FOUR ILLUSTRATIONS IN ONE PLACE
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18. control of
components
General
requirements.
Receipt &
storage of
untested
components,
drug product
containers and
closures.
Testing and
approval or
rejection of
components,
drug product
containers and
closures.
Use of approved
components,
drug product
containers, and
closures.
Retesting of
approved
components,
drug product
containers, and
closures.
Rejected
components,
drug product
containers, and
closures.
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19. Component/Materials Control
• Suppliers must be evaluated and approved
and monitored for quality Incoming Materials
must be tested before they can be accepted for
use
• Materials must be placed in stores or issued
according to FIFO (stock rotation)
• Materials must be stored so that they are not
mixed up, damaged, or contaminated.
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20. Production
and process
control
Written
procedures;
deviations.
Charge-in of
components.
Calculation of
yield.
Equipment
identification.
Sampling and
testing of in-
process
materials and
drug products.
Time
limitations on
production.
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21. Production/Process Control
• Have & Follow Procedures: A good procedure is a written step-
by-step procedure that provides a roadmap for Controlled and
Consistent performance.
• Examples: – (Manufacturing) Work Instructions – Operating
Procedures – Testing Procedures – Quality Manual Deviations
must be recorded and justified
• Procedures should address… …verification of critical steps by a
second person …line clearance …monitoring of processes to
make sure they are in control …time limits and yield calculations
as appropriate checks for critical processes …gowning for
controlled environments (cleanrooms)
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22. Packaging
and
labeling
control
Materials
examination and
usage criteria.
Labeling
issuance.
Packaging and
labeling
operations.
Tamper-evident
packaging
requirements for
over-the-counter
human drug
products.
Drug product
inspection.
Expiration dating.
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23. Packaging and Labeling Control
• Label is a display of a written, printed or graphic matter upon the
immediate container of any article
• Labeling is the label and any other packaging material or
container that is printed (ex. IFU, advertising materials)
• Procedures must exist that document receiving, identity, storage,
handling, sampling, and testing of labels and ensure that integrity
is maintained throughout production and use of product
• Labeling must be separated physically in storage to avoid mix-ups
• Wording of labels cannot be changed unless the FDA is notified
• Labeling must be inspected prior to issuing to production
• All labels must be reconciled (accounted for) if not 100%
inspected.
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24. 24

25. Warehousing
procedures.
Distribution
procedures
Holding
and
distribution
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26. Holding and Distribution
• Warehousing procedures should address…
…Quarantine of drug products …storage of products
under appropriate conditions
• Distribution procedures should address… …FEFO
(First Expiring First Out) …traceability of product
lots/batches
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27. Records
and
reports
General
requirements.
Equipment
cleaning and use
log.
Component, drug
product
container,
closure, and
labeling records.
Master
production and
control records.
Batch production
and control
records.
Production record
review.
Laboratory
records.
Complaint files.
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28. Records and Reports
1. Quality Records are the proof that the procedures were followed
and they show traceability of product. Examples: – Lot History
Records – Laboratory Notebooks – Protocols – Reports –
Logbooks – Distribution Records – Complaint Files
2. Quality Records are legal documents and can be subpoenaed in a
court of law as evidence
3. Signatures on documentation have the same meaning as on any
kind of contract
4. Information must be recorded and signed for at the time of
performance on the original record
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29. Laboratory Controls
• Written procedures must be established & followed
• All actions must be documented at the time of
performance
• Calculations need to be recorded
• Second person must review records
• Data must be directly recorded into appropriate records
• Equipment, software, and methods must be validated
• An Out-of-Specification (OOS) result must be
investigated and a root cause identified
• Laboratory data is considered to be a quality record
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30. 30

31. Returned
drug
products.
Drug
product
salvaging.
Returned
savaged
drug
products
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32. Duties of Quality Control Unit under cGMP Regulations
The cGMP regulations assign specific duties to the
quality control unit.
The unit is required to 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.
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33. The responsibilities of the unit extend to approving or
rejecting drug products manufactured. processed, packed,
or held by contract manufacturers.
The organization must assure that the quality control unit
has adequate laboratory facilities for the testing and
approval (or rejection) of components, drug product
containers, closures, packaging materials, in-process
materials, and drug products.
Duties of Quality Control Unit under cGMP Regulations
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34. In addition to duties associated with the approval of
materials and finished products, the unit is also responsible
for approving or rejecting all procedures or specifications
impacting on the identity, strength, quality, and purity of the
drug product.
This includes review and approval of procedures for
production and process control, including any changes to
these procedures.
These procedures, and the responsibilities and procedures
applicable to the quality control unit within the
organization, must be written and followed.
Duties of Quality Control Unit under cGMP Regulations
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35. All specifications, standards, sampling plans, test
procedures, or other laboratory control mechanisms,
including any changes, must be in writing and reviewed
and approved by the quality control unit.
Written procedures describing the handling of all written
and oral complaints regarding a drug product are
required.
The quality control unit is responsible for reviewing any
complaint involving the possible failure of a drug product
to meet.
Duties of Quality Control Unit under cGMP Regulations
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36. References
1. cGMP guidelines; www.fda.gov
2. Shayne Cox Gad, Pharmaceutical Manufacturing
Handbook, Regulations and Quality,Wiley-
Interscience, A John Wiley and sons, Inc. Publications.
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37. THANK
YOU
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