2. CONTENTS
HISTORY
INTRODUCTION
WHY GMP IS IMPORTANT
PRINCIPLES OF GMP
GMP GUIDELINES
COMPARISON BETWEEN DIFFERENT GMP
GUIDELINES
CONCLUSION
3. INITIATION OF GMP
Sulfathiazole tablets contaminated with
phenobarbital.
1941 – 300 people died/injured.
FDA to enforce and revise manufacturing and
quality control requirements.
1941 – GMP is born.
Thalidomide tragedy
Thousands of children born with birth defects due to
adverse drug reactions of morning sickness pill
taken by mothers.
4. WHAT IS GMP ?
GMP as per the WHO :
“ GMP is that part of quality assurance, which
ensures that products are consistently produced
and controlled to the quality standards appropriate
to their intended use and as required by the market
authorization.”
Above definition conclusion is that:
GMP is the part of the Quality assurance.
GMP’s main function is to be produced the quality
product consistently.
GMP must be meet the legal requirement of the
country.
5. WHAT IS CGMP ?
Usually see “cGMP” – where c = current, to
emphasize that the expectations are dynamic.
The “c” in cGMP stands for “current” requiring
companies to use technologies and systems that
are up to date in order to comply with the
regulations.
6. WHY GMP IS IMPORTANT
A poor quality medicine may contain toxic
substances that have been unintentionally added.
A medicine that contains little or none of the
claimed ingredient will not have the intended
therapeutic effect.
Unexpected contamination of products , causing
damage to health or even death.
Incorrect labels on containers, which could mean
that patients receive the wrong medicine.
7. PRINCIPLES OF GMP
Design and construct the facilities and equipments
properly
Follow written procedures and Instructions
Document work
Validate work
Monitor facilities and equipment
Write step by step operating procedures and work
on instructions
Protect against contamination
Control components and product related processes
Audits
8. GMP GUIDELINES
GMP as per Schedule “M”
GMP as per WHO
GMP as per MCA now known as MHRA
GMP as per TGA
GMP as per US FDA
GMP as per ICH guidelines
9. GMP IN INDIA
In India by the ministry of Health, multinational or
foreign enterprise
GMP was brought under legislation in June 1988.
Schedule M of drugs and Cosmetics Act of 1945.
Schedule M has 2 parts:
Part 1 which includes – GMPs
Part 2 which includes – plant requirement and
equipment
10. AREAS TO BE COVERED
General considerations
Personnel
Premises
Equipment
Sanitation
SOP’s
Raw Materials
Self Inspection and Audit
Master Formula Records
Batch Manufacturing Records
Validation and process validation
14. LOCATION
Geography, climate and economic factors.
Premises must be located to minimize risks of cross
– contamination, e.g. not located next to a factory
with high airborne levels of yeast.
Pollution control.
15. DESIGN
Minimize risks of errors
Effective cleaning
Effective maintenance
Maximum protection against entry of insects, birds
and animals
Separate facilities for other products such as some
antibiotics, hormones, cytotoxic substances
16. Specific areas
Production areas
Quality control areas
Weighing areas
Storage areas
Hygiene
Eating,Drinking,Smoking should not be allowed in
the Production area.
17. CONSTRUCTION
Measures should be taken to prevent cross-
contamination
Dust control measures (including extraction of dust
and air)
No areas for dust accumulation
Easily cleanable surfaces
Proper air supply
Use of HEPA filter’s
Finishing floors, walls and ceilings should be
smooth
18. EQUIPMENTS
Equipment shall be located, designed, constructed,
and maintained to suit the operation to be carried
out.
Should be made of non reactive material, such as
High grade of steel(316,302)
Equipment should be –
Calibrated
Checked
Labelled
Sterilized
19. SANITATION
Written procedures
Hygiene, health and clothing practices
Waste disposal
Implementation and training
Practices not permitted
Eating, smoking
Unhygienic practices
20. STANDARD OPERATING PROCEDURE
(SOP)
There shall be written Standard Operating
Procedure for each operation
It include-
For equipments
For sampling
For testing
For process
For packaging
21. RAW MATERIALS
An inventory should be maintained for raw
materials to be used at any stage of manufacture
Records should be maintain as per Schedule U
Should be purchased from approved sources
Must be checked by QC department on receipt
Should be labeled
22. SELF INSPECTION AND AUDIT
Regular independent inspection is necessary to
evaluate the manufacturer’s compliance with GMP
in all aspects of manufacturing
Procedure for self inspection shall be documented
indicating
evaluation
conclusion
recommendations for corrective action
23. MASTER FORMULA RECORDS
There shall be MFR relating to all manufacturing
procedures for each product and batch size to be
manufacture
IT SHOULD INCLUDE –
The name of the product
Quantity of all starting materials to be used
A statement of the expected final yield with acceptable
limits
Equipment to be used
Detailed stepwise processing instructions and the time
taken for each step
Any special precautions
Packing details
24. BATCH MANUFACTURING RECORDS
There shall be batch processing record for each
product.
During manufacturing or processing the following
information shall be recorded
It include –
The name of the product
The number of batch being manufactured
Dates and time of batch completion
Amount of product obtained
25. WAREHOUSING AREA
Warehousing area should be designed to ensure
good storage conditions.
Should be clean, dry and maintained with
acceptable temperature limits.
Should have appropriate house- keeping and
rodents, pests and vermin control.
Separate sampling area for active raw material and
excipients.
Every material stored should be labeled properly.
Fire prevention.
26. REFERENCE SAMPLES
Should be taken in sufficient quantity from each lot
of active ingredient to carry out all the tests
These samples should be retained for a period of 3
months after the date of expiry of the last batch
produced from that active ingredient
Samples of raw material should be stored in
suitable container (plastic or glass) as mentioned in
the SOP
Samples of finished formulations shall be stored in
the same containers in which the drug has been
actually marketed
27. VALIDATION AND PROCESS
VALIDATION
Essential part of GMP
Necessary to achieve the intended results
A written record is prepared summarizing recorded
result and conclusions shall be prepared,
documented and maintained
Should be necessary when –
Any new master formula or method of preparation
is adopted
For critical process
Any changes in the equipment or when using a new
equipment, it is first validated to demonstrate its
consistentency of required quality.
28. LABELS AND PRINTED MATERIALS
All containers and equipment should bear labels
Different colour coded labels should be used to
indicate the status of a product (for example under
test, approved, passed rejected)
The printing should be done in bright colours
The label should contain all the prescribed details
about the product.
29. QUALITY ASSURANCE
“Quality assurance is a wide ranging concept
covering all matters that individually and collectively
influence the quality of product.”
COMPONENT OF QUALITY ASSURANCE:
Quality management team
In process quality control team
Document development team
Process validation team
Drug regulatory affairs team
30. OBJECTIVE OF QA DEPARTMENT
Provide the high quality drug product to the patient.
Prevent and reduce the number of the recalls,
returned and defective product entering into the
market.
To help in getting quality by design
Increasing productivity
Improving risk management.
QUALITY ASSURANCE = QC + GMP
31. COMPARISON BETWEEN DIFFERENT
GMP GUIDELINES
At a high level, GMPs of various nations are very
similar, most require things like:
Equipment and facilities being properly designed,
maintained, and cleaned.
Standard operating procedures be written and
approved
Well trained personnel and management
An independent quality unit (like quality control and
quality assurance)
32. USFDA GUIDELINES
21 CFR Parts 210 and 211
(Drug industry)
21 CFR Part 820
(Medical device industry)
21 CFR Part 110
(Food industry)
21 CFR Part 606
(Blood industry)
33. EU GUIDELINES
Part I
Basic requirements for medicinal products
Part II
Basic requirements for active substances used as
starting materials
Part III
GMP related documents
34. Responsibilities of all personals should specified in
writing.
Defined area for packaging & labeling.
The signature of the person who perform each tests
with dates.
Manufacturers should have a system for evaluating
suppliers of critical materials.
A statement of test results & how they compare with
established acceptance criteria.
Product quality review.
35. A TIME LINE OF GMP
1938 – Federal food, Drug and Cosmetic act.
1941 – Initiation of GMP
1963 – Establishment of GMPs for drugs
1975 – cGMP for Blood and components Final rule
1978 – cGMP for Drugs and Medical Devices
1979 – GLPs final rule
36. LIST OF IMPORTANT DOCUMENTS IN
GMP
Policies
SOP
Master formula record
BMR
Validation protocols
Forms and formats
Records
37. ATTRIBUTES OF A GOOD DOCUMENT
Accurate
Clear
Consistent
Timely
Direct
Complete
Authorized
Simple
38. CONCLUSION
GMP results in product with in quality, i.e..
Maximum therapeutic effects and minimum toxic
effects.
GMP results minimum risk during production,
reduction in work load, wastage.
GMP covers each and every steps of production
from premises, raw materials, equipment, personal
training, personal hygienic of staff.
At a high level, GMPs of various nations are very
similar, most require things like equipment and
facilities being properly designed, maintained, and
cleaned, SOP etc
39. “QUALITY IS NOT TESTED IN
THE PRODUCT,
IT IS BUILT INTO THE
PRODUCT”.