1. WHO GMP Certification Scheme
M. Mitra
Former Dy. Drugs Controller (I),
CDSCO, HQ, New Delhi

2. To assess compliance of GMP
WHO GMP CERTIFICATION
Originally promugulated in 1969 and revised in Main objectives were :
Guidelines be developed for official inspections of dug manufacturing facilities
To assess compliance of GMP
This would facilitate implementation of the scheme
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3. WHO GMP CERTIFICATION
With 191 countries members in the scheme a solution was found for international commerce between these countries. The scheme offered a solution for those countries which did not have a developed regulatory agency yet wanted to import drugs.
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5. WHO GMP CERTIFICATION
Basic principles of WHO Good Manufacturing Practice is similar to any established GMP requirement. Allied documents like Schedule M, CFRs, ASEAN GMP, etc are all similar in nature. Anyone following any established GMP procedure will automatically understand the principles in the other GMP requirements.
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6. WHO GMP CERTIFICATION
WHO GMP requirements have been developed taking into account the principles in various GMP texts and also considering the requirements of developing countries. These requirements are not for domestic use but for international trade.
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7. WHO GMP CERTIFICATION
There are around 1000 (?) WHO GMP certified manufacturing establishments in the country, with West Zone leading followed by the South, North and the East Zones.
New Applications are coming in everyday due to increase in exports of drugs, India being a major exporter of Drugs & Pharmaceuticals Globally.
Other purchasers like the State governments, ESI etc. have also started (erroneously) asking for the certificates as preconditions.
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8. WHO GMP ensures the following: Avoidance of Cross- Contamination
WHO GMP CERTIFICATION
WHO GMP ensures the following:
Avoidance of Cross- Contamination
Prevention of Mix-ups
Provide Traceability
Accountability of actions
Responsibility
Product Performance Guarantee
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9. Documents and Literature
WHO GMP CERTIFICATION
Understanding WHO GMP
Documents and Literature
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10. A series of reports known as the WHO Technical Report Series (TRS) are available.
WHO GMP CERTIFICATION
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11. WHO GMP CERTIFICATION
Other documents A WHO Guide to Good Manufacturing Practice (GMP) Requirements (WHO/VSQ/97.02) (for validation)
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13. WHO GMP CERTIFICATION
Various other documents are available with WHO which is freely available for users. WHO website is the best source for getting information. Similarly documents of other established Regulatory agencies can expand knowledge and understanding
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14. What are the Certificates?
WHO GMP CERTIFICATION
Issue of Certificates
What are the Certificates?
Three types of Certificates are recommended by the WHO.
These are:
Product Certificate (COPP) (TRS 823, 863)
Statement of Licensing Status (TRS 823, 863)
Batch Certificate (TRS 823, 863)
There is another Certificate – Site Certificate. Described later
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15. WHO GMP CERTIFICATION
The member state shall attest the following conditions of a manufacturer if required to attest a product for the certification:
A specific product is authorized to be placed in the market of the exporting country, if not why not
The manufacturing plant is subject to regular inspections for WHO GMP compliance
All product information, including labeling is currently authorized in the certifying country.
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16. WHO GMP CERTIFICATION
Conditions to be satisfied before opting for the scheme by any member country
Effective national licensing system for products, manufacturers and distributor
Effective control of quality of products, including independent laboratory
A technically competent, experienced, resourceful National Pharmaceutical inspectorate, as part of NDRA having legal powers for investigations
Administrative capacity to issue Certificates and quickly notify WHO and other member countries
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17. Understanding the Technical Report Series
WHO GMP CERTIFICATION
Understanding the Technical Report Series
TRS 823 – Salient features
PART I Quality Management in the Drug Industry – Philosophy & Essential Elements
Quality Assurance
Good Manufacturing Practice
Quality Control
Sanitation & Hygiene
Validation
Complaints
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18. Contract Production & Analysis Self-inspection and quality audits
WHO GMP CERTIFICATION
PART I contd.
Product recalls
Contract Production & Analysis
Self-inspection and quality audits
Personnel (including key personnel)
Equipment
Premises
Material
Documentation
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19. PART II : Good Practices – Production & Quality Control
WHO GMP CERTIFICATION
PART II : Good Practices – Production & Quality Control
Good Practices in Production
Includes General requirements, prevention of cross contamination and bacterial contamination, processing operations, packaging operations
Good Practices in Quality Control
Control of starting material and intermediate, bulk, and finished products, test requirements, production record review, stability studies
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20. A Model Certificate Format is also presented
WHO GMP CERTIFICATION
PART III: Supporting and Supplementary Guidelines
Sterile pharmaceutical Products
General requirements (air classifications), manufacture of sterile preps, personnel, premises, equipment, sanitation, processing, sterilization, filtration, finishing, quality control,
Good Manufacturing Practice for Active Pharmaceutical Ingredients
Explanation, general considerations, personnel, premises, equipment, sanitation, documentation, retention of records and ref samples, production,
Form and content of inspector’s report
Validation of analytical procedures
A Model Certificate Format is also presented
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21. TRS 863 – Salient features Useful guidelines:
WHO GMP CERTIFICATION
TRS 863 – Salient features
Useful guidelines:
Guidelines for Stability Testing
Guidelines for Validation
Import Procedure for Drugs
Guidelines for implementation of the Scheme (including model certificate)
Guidelines on import procedures for pharmaceutical products
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22. WHO GMP CERTIFICATION
TRS 885 – Salient features
GMP – Authorised Persons - Role, Functions & Training
Role and position of authorized person, implementation of the quality system, education and training., routine duties of an authorized person,
GMP – Supplementary Guidelines for the Manufacture of Pharmaceutical Excepient
General considerations, self inspection and quality audits, use of equipment, cleaning programme, starting material, rejected and recovered materials, returned excepients, storage practices, specifications, BPRs, change control and process validation, prevention of cross contamination, blending, microbial contamination, water systems, packaging, quality control etc.
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23. Good Practices for National Control Laboratories
WHO GMP CERTIFICATION
TRS 902 – Salient features
Good Practices for National Control Laboratories
Basic elements of GMP (definition)
GMP for Sterile Products – revision
Inspections
National GMP Inspectorate
Guidelines on Packaging of Pharmaceutical Products
Storage areas
Labels
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24. GMP for radio pharmaceuticals GMP for Pharmaceutical Products HACCP
WHO GMP CERTIFICATION
TRS 908 – Salient features
GMP for radio pharmaceuticals
GMP for Pharmaceutical Products
Main principles
HACCP
Guidance on GMP: Inspection report
Guide to good storage practices for pharmaceuticals
Model Certificate of a Pharmaceutical Product
Site Certificate – does not replace the Product certificate
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25. Active Pharmaceutical Ingredients API Herbal
WHO GMP CERTIFICATION
TRS 917 – Salient features
Active Pharmaceutical Ingredients API
Herbal
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26. TRS 929 – Salient features Concept of sampling of starting materials
Heating ventilation and air conditioning
Validation
Water for pharmaceutical use
..\GMP matters\WHO_TRS_929.pdf
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27. TRS 937 – Salient features One of the most important TRS
Supplementary guidelines on GMP for HVAC
(Supplementary guidelines on GMP for Herbals)
Supplementary guidelines on GMP : Validation
HVAC Water Systems
Cleaning
Analytical Method
Computerized Systems
Qualification of systems and equipment
Non-sterile process validation
Good Distribution Practices for pharmaceutical products
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28. How to Certify a Product
WHO GMP CERTIFICATION
How to Certify a Product
Certification of products are done after thorough examination of the product and the facilities where these are manufactured
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29. The facilities are Inspected NRA Inspectors with good knowledge of GMP
WHO GMP CERTIFICATION
How to Certify a Product
The facilities are Inspected NRA Inspectors with good knowledge of GMP
The inspection may take two or more days
Certificates are issued by the Issuing Authority on the recommendation of the joint report
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30. Requirements Procedures Main Requirements Product Procedures
WHO GMP CERTIFICATION
Requirements
Procedures Main Requirements
Product
Procedures
Facilities
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31. The basic requirements of the product are: Product design
WHO GMP CERTIFICATION
Requirements
Product
The basic requirements of the product are:
Product design
Stability Studies
Process validation
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32. Requirements Procedures
WHO GMP CERTIFICATION
Requirements
Procedures
All actions taken in the facility which leads to the production of the final product as per specification.
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33. Requirements Facilities
WHO GMP CERTIFICATION
Requirements
Facilities
This encompasses the building, machinery, services and utilities, manpower etc. These are guided towards making a properly designed product.
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37. 2. Sanitation and hygiene 3. Validation 4. Complaints and recalls
WHO GMP CERTIFICATION
Inspection Points
1. Quality Management
2. Sanitation and hygiene
3. Validation
4. Complaints and recalls
5. Contract production and analysis
6. Self Inspection
7. Personnel
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38. 13. Active pharmaceutical ingredients
WHO GMP CERTIFICATION
Discussions:
8. Premises
9. Equipment
10. Materials
11. Documentation
12. Sterile production
13. Active pharmaceutical ingredients
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39. WHO GMP CERTIFICATION
GMP consists of various activities which an be grouped together as follows:
Training - induction, ongoing, refresher etc.alonwith such documents like SOP, training calendar, assessment etc.
Cleaning sanitation and hygiene - may also include workers entry procedure, cleaning of the premises etc
Validation and calibration - qualification of machinery, equipment etc.
Storage - apart from normal ware-housing facilities, this should also address quarantine, procedure Etc.
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40. Self inspections and audits
WHO GMP CERTIFICATION
movement of manpower, material - uni-flow movement, movements control etc.
Quality assurance –
Quality control
Documentation - must include MFR, BPR, SOP Documents control & distribution, cleaning, training, and document regulating and recording other activities
Change control –
Self inspections and audits
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41. Lack of knowledge on the part of applicants Lethargic mindset
WHO GMP CERTIFICATION
Usual Problems faced by Regulatory Agencies:
Fund problems
Lack of knowledge on the part of applicants
Lethargic mindset
Back to original condition after Certification
Usual Problems faced by applicants:
Sometimes lack of Knowledge on the part of auditors
Teacher as well as Examiner status
Lack of time for thorough auditing
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42. subscription1.jsp?sesslan=1 http://www.who.int/medicines/organization/
WHO GMP CERTIFICATION
Useful Web Sites:
subscription1.jsp?sesslan=1
qsm/activities/qualityassurance/gmp/gmpcover.html
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43. WHO GMP CERTIFICATION
M. Mitra Former Dy. Drugs Controller (India), CDSCO (M)
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44. Thank you
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