good manufacturing practice for pharma people

1. Good Manufacturing Practices
The art of manufacturing
VIR VIKRAM
Associate Professor
Dept. of
Pharmacology
ISF COLLEGE OF PHARMACY
Mobile: +918146023334
Email: virvikram76@gmail.com

2. WHY DO WE NEED GMP?

3. What is GMP ?
GMP is that part of Quality assurance which ensures that the
products are consistently manufactured and controlled to
the Quality standards appropriate to their intended use
Good Manufacturing Practice is a set of regulations, codes
and guidelines for the manufacture of drug substances and
drug products, medical devices, in vivo and in vitro
diagnostic products and foods.

5. GMP REQUIRES AT EVERY STEPS

6. CGMP REGULATION
Report any injury or illness immediately to your supervisor.

7. What is cGMP ?
Usually see “cGMP” – where c = current, to emphasize that
the expectations are dynamic
All past GMPs are history….It is looking like in rear view
mirror and driving

8. GLP and GMP
• GMP:
– Protect the integrity and quality of manufactured product intended for human
use.
• GLP:
– Protect the integrity and quality of laboratory data used to support a product
application.

10. Some of the main risks are
1. Unexpected contamination of products, causing damage to health or even
death.
2. Incorrect labels on containers, which could mean that patients receive the
wrong medicine.
3. Insufficient or too much active ingredient, resulting in ineffective treatment or
adverse effects.

11. Good Manufacturing Practices
Worldwide Enforcement
1. Good Manufacturing Practices are enforced in the United States by the
FDA
2. In the United Kingdom by the Medicines and Healthcare Products
Regulatory Agency (MHRA)
3. GMPs are enforced in Australia by the Therapeutically Goods
Administration (TGA)
4. In India by the Ministry of Health (CDSCO)
5. Japan (PDMA), Gulf Countries (GCC), ICH guidelines
6. Many underdeveloped countries lack GMPs
7. The Myanmar Scientific and Technological Research Department (MSTRD)

12. Ten Principles of GMP
1. Design and construct the facilities and equipments properly
2. Follow written procedures and Instructions
3. Document work
4. Validate work
5. Monitor facilities and equipment
6. Write step by step operating procedures and work on instructions
7. Design ,develop and demonstrate job competence
8. Protect against contamination
9. Control components and product related processes
10. Conduct planned and periodic audits

13. Current Good Manufacturing Practices
• Title 21 CFR:
– Part 210: “ . . . In Manufacturing, Processing, Packing, or Holding of Drugs; General”
– Part 211: “ for Finished Pharmaceuticals”
– Part 600: Biologics
– Part 820: Medical Devices
Part 210: General Provisions 210.1 (a)
contain the minimum current good manufacturing practice for methods to be
used in, and the facilities or controls to be used for,
• 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.”

14. Part 210: General Provisions
210.1 (b)
“The failure to comply with any regulation set forth ... in the manufacture,
processing, packing, or holding of a drug shall render such drug to be adulterated
under section 501(a)(2)(B) of the act and such drug, as well as the person who is
responsible for the failure to comply, shall be subject to regulatory action.”
Part 211: Finished Pharmaceuticals
Subpart A: General Provisions
Subpart B: Organization and Personnel
Subpart C: Buildings and Facilities
Subpart D: Equipment
Subpart E: Control of Components and Drug Product
Containers and Closures
Subpart F: Production and Process Controls
Subpart G: Packaging and Labeling Control
Subpart H: Holding and Distribution
Subpart I: Laboratory Controls
Subpart J: Records and Reports
Subpart K: Returned and Salvaged Drug Products

15. Organization & Personnel
1. Responsibilities of quality control unit.
2. Personnel qualifications.
3. Personnel responsibilities.
4. Consultants.

16. PERSONNEL RESPONSIBILITIES
•Personnel shall wear clean clothing.
•Protective apparel such as head, face, hand and arm coverings
•Protect drug products from contaminations.
•Good sanitation and health habits.
•Only authorized personnel shall enter
•No persons with apparent illness or lesions are allowed to enter

18. HYGIENE AND SANITATION
PRACTICES
*Wash hands with
soap and water
– After using the toilet
– Before starting to work
– After blowing your nose
– After handling dirty things
– After touching body surface
– After eating

19. BUILDINGS AND FACILITIES
DESIGN AND CONSTRUCTION
FEATURES
Buildings should be of adequate
size, construction and location.
Adequate space for orderly
placement of equipment and
materials to prevent mix-ups.

20. BUILDING PREMISES
• GMP REQUIREMENTS:
1. Separate area for specific operation.
2. Easy to clean.
3. Easy to maintain.
4. Easy to operate.
5. Adequate space
6. Eliminate unnecessary traffic
Inadequate space and unnecessary traffic
cause mix-up and errors.

22. Operations should be performed in defined areas of adequate size
(1) Receipt, identification, storage, and withholding from use of
components, drug product containers, closures, and labeling, pending the
appropriate sampling, testing, or examination by the quality control unit
before release for manufacturing or packaging;
(2) Holding rejected components, drug product containers, closures, and
labeling before disposition;
(3) Storage of released components, drug product containers, closures, and
labeling;

23. (4) Storage of in-process materials;
(5) Manufacturing and processing operations;
(6) Packaging and labeling operations;
(7) Quarantine storage before release of drug products;
(8) Storage of drug products after release;
(9) Control and laboratory operations;
(10) Aseptic processing
For injectables should include--Floors, walls, ceilings of smooth, hard surfaces should be
• easily cleanable
• temperature and humidity controls
• filtered air supply, HEPA filters
• system for monitoring environmental conditions
• system for cleaning/disinfecting room/equipment
Types of Protection
•Level 1- General
•Level 2- Protected
•Level 3- Controlled

24. LIGHTING (Adequate lighting shall be provided)
VENTILATION, AIR FILTRATION, AIR HEATING AND COOLING
PLUMBING

26. EQUIPMENT
EQUIPMENT DESIGN,SIZE AND LOCATION
•Appropriate design
•Adequate size
•Suitably located
EQUIPMENT CONSTRUCTION
•Surfaces that contact components, in process materials, drug products shall not be
reactive, additive or absorptive
•Any substances e.g. lubricants, coolants shall not come into contact with components,
containers , closures, in process materials.
EQUIPMENT CLEANING AND MAINTENANCE
•Should be clean and sanitized at appropriate
intervals to prevent contaminations
•Written procedures shall be maintained and
must be followed.
•Records shall be kept of maintenance,
cleaning, sanitizing and inspection.

27. AUTOMATIC,MECHANICALAND
ELECTRONIC EQUIPMENT
•Include computers or related systems
•Should be calibrated
•Written records of calibration checks and
inspection shall be maintained
•Appropriate controls shall be exercised
•Back up file data shall be maintained
•Written records of the program shall be
maintained along with appropriate
validation data
•Hard copy or alternative systems e.g.
duplicates, tapes or microfilms shall be
maintained

28. Control of Components and Drug Product
Containers and Closures
211.80 - General requirements.
211.82 - Receipt and storage of untested components, drug product
containers, and closures.
211.84 - Testing and approval or rejection of components, drug product
containers, and closures.
211.86 - Use of approved components, drug product containers, and
closures.
211.87 - Retesting of approved components, drug product containers, and
closures.
211.89 - Rejected components, drug product containers, and closures.
211.94 - Drug product containers and closures.

29. General requirements
1. There shall be written procedures describing in sufficient detail the
receipt, identification, storage, handling, sampling, testing, and approval
or rejection of components and drug product containers and closures.
2. Components and drug product containers and closures shall at all times
be handled and stored in a manner to prevent contamination.
3. Bagged or boxed components of drug product containers, or closures
shall be stored off the floor and suitably spaced to permit cleaning and
inspection.
4. Each container or grouping of containers for components or drug
product containers, or closures shall be identified with a distinctive code
for each lot in each shipment received.

30. Testing and approval or rejection of components, drug product containers, and
closures
(a)Each lot of components, drug product containers, and closures shall be withheld
from use until the lot has been sampled, tested, or examined, as appropriate, and
released for use by the quality control unit.
(b) Representative samples of each shipment of each lot shall be collected for testing
or examination. The number of containers to be sampled, and the amount of material
to be taken from each container, shall be based upon appropriate criteria.

31. (c) For testing samples shall be collected in accordance with the following procedures:
(1) The containers of components selected shall be cleaned where necessary, by
appropriate means.
(2) The containers shall be opened, sampled, and resealed in a manner designed to
prevent contamination of their own/others.
(3) Sterile equipment and aseptic sampling techniques shall be used when necessary.
(4) Sample containers shall be identified so that the following information can be
determined: name of the material sampled, the lot number, the container from which
the sample was taken, the date on which the sample was taken, and the name of the
person who collected the sample.
(5) Containers from which samples have been taken shall be marked to show that
samples have been removed from them.

32. (d) Samples shall be examined and tested as follows:
(1) At least one test shall be conducted to verify the identity of each component of a
drug product. Specific identity tests, if they exist, shall be used.
(2) Each component shall be tested for conformity with all appropriate written
specifications for purity, strength, and quality.
(3) Containers and closures shall be tested for conformance with all appropriate
written procedures. In lieu of such testing by the manufacturer,
A certificate of testing may be accepted from the supplier
Visual identification is conducted on such containers/closures by the
manufacturer
Manufacturer establishes the reliability of the supplier's test results
through appropriate validation of the supplier's test results at appropriate
Intervals.

33. (4) When appropriate, components shall be microscopically examined.
(5) Each lot of a component, drug product container, or closure that is liable to
contamination with filth, insect infestation, or other extraneous adulterant,
microbiological contamination shall be examined against established specifications
for such contamination.

34. Packaging and labeling operations

35. Packaging and labeling operations

36. Packaging and labeling operations

37. Drug product inspection
a) Packaged and labeled products shall be examined during finishing
operations to provide assurance that containers and packages in the lot have
the correct label.
(b) A representative sample of units shall be collected at the completion of
finishing operations and shall be visually examined for correct labeling.
(c) Results of these examinations shall be recorded in the batch production or
control records.

38. Records and Reports

39. Confucius…
• I hear and I forget
I see and I remember
I do and I understand

40. Records and Reports
General requirements
(a) Any production, control, or distribution record that is required to be maintained for
a batch of a drug product shall be retained for at least 1 year after the expiration date of
the batch or, in the case of certain OTC drug products lacking expiration dating 3 years
after distribution of the batch.
(b) Records shall be maintained for all components, drug product containers, closures,
and labeling.
(c) All records or copies of such records, shall be readily available for authorized
inspection during the retention period.
d) Data can be used for evaluating, at least annually, the quality standards of each drug
product to determine the need for changes in drug product specifications or
manufacturing or control procedures.

41. Records and Reports
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.
Distribution records.
Complaint files.

44. Equipment cleaning and use log
A written record of major equipment cleaning, maintenance (except routine
maintenance such as lubrication and adjustments), and use shall be included in
individual equipment logs that show
date,
time,
product, and
lot number of each batch processed.
The persons performing and double-checking the cleaning and maintenance shall
date and sign or initial the log indicating that the work was performed.
Entries in the log shall be in chronological order.

45. Master production and control records
a) To assure uniformity from batch to batch
b) Prepared, dated, and signed by one person and independently checked, dated, and
signed by a second person.
c) Master production and control records shall include:
(1) The name and strength of the product and a description of the dosage form;
(2) The name and measure of each active ingredient per dosage unit or per unit of
weight or measure of the drug product, and a statement of the total weight or
measure of any dosage unit;

46. (3) A complete list of components designated by names or codes sufficiently specific
to indicate any special quality characteristic;
(4) An accurate statement of the weight or measure of each component
(5) A statement concerning any calculated excess of component;
(6) A statement of theoretical yield, including the maximum and minimum percentages
of theoretical yield
(7) A description of the drug product containers, closures, and packaging materials,
including a specimen or copy of each label and all other labeling signed and dated by
the person or persons responsible for approval of such labeling;
(9) Complete manufacturing and control instructions, sampling and testing procedures,
specifications, special notations, and precautions to be followed.

48. Component, drug product container, closure, and labeling records
Batch control & Performance recording
Production record review
Laboratory records

49. OVERALL VIEW OF GMP

52. THANK YOU ………