This document discusses the history and development of harmonization, GMPs, and validation. It covers the early concepts and guidance from organizations in the 1980s such as the FDA, FIP, EOQC, APV, and PIC. It then discusses further regulatory guidance in the 1990s and the roles of organizations like PIC/S, WHO, ICH, IPEC, pharmacopeias, ISO, PDA, and ISPE in harmonizing standards. The document also briefly discusses medical device harmonization through organizations like the GHTF and concludes that exceptional progress has been made in harmonizing regulations globally to facilitate international supply of pharmaceuticals and medical devices.

1. Seminar on
HARMONIZATION,GMPs AND VALIDATION
Submitted to
SavitribaiPhule PuneUniversity
In Partial fulfilment of Requirements for the Award of Degree
of
MASTER OF PHARMACY
IN PHARMACEUTICAL
QUALITYASSURANCETECHNIQUES
Presented by-
Miss. Payal Ware
M. Pharmacy (PQAT) Semester -2
Roll No-15
Guide-
Dr. S.S Sonawane

2. PRESENTATION OUTLINE:
Introduction
Concept of validation in 1980s
Regulatory guidance from 1990s
Harmonization
Medical devices
Conclusion
References

3. INTRODUCTION:
Harmonization.
Development in other parts of world.
Consolidate global concepts of GMPs and validation.

4. CONCEPT OF VALIDATION IN 1980s:
1.U.S.FDA
2.FIP
3.EOQC
4.APV
5.PIC

5. U.S. FDA
Title 21 of the “Code of Federal Regulations”
No mention of Process validation
Only analytical method validation were discussed
Proposal withdrawal after 10years
Switch over non-sterile processes
First FIP and EOQC bodies to show interest in GMPs for non-sterile.
Process validation in 1987

6. FIP
(FEDERATION INTERNATIONAL PHARMACEUTIQUE)
Events
Conference in 1980
“Guidelines for Good
Validation Practice”
Validation
topics
Definition
Development phase
Production phase
Validation of existing
process
Revalidation
Responsibilities

7. Source
• EOQC(1980)
Events
• Symposium on
“Validation of
manufacturing
processes” in Geneva.
Validation topics
• Definitions
• Installations and
operational
qualifications
• Development and
manufacturing phase
• Change control
• Revalidation
Source
• APV(1981)
• International Association for
Pharmaceutical Technology
Events
• Symposium on
“Validation in practice”
Validation topics
• Sterile ,Semisolid and
solid dosage form
• Analytical method
• Stability evaluation
• Packaging validation
transfer
• Cost effectiveness

8. PIC
(Pharmaceutical Inspection convention)
Source
• PIC(Pharmaceutical
Inspection
Convention)(1989)
Events
• Guide to Good
Manufacturing
Practices of
Pharmaceutical
Products
Validation topics
• Validation of critical
processes
• Significant
amendments to
manufacturing
processes
• Sterilization processes
• Test method
stipulated

9. REGULATORY GUIDANCE FROM 1990s
ONWARDS:
U.S FDA
In 1990s validation topic was more focused because of FDA inspection.
All observation was written in form 483
“Warning letters” were stronger tool for them to enforce CGMP.
In 1997 101 warning letters were send out.
The role they played in CGMP was written down in CFR.
Areas they
defined
• Cleaning validation
• Computerized system validation
• Sterilization validation
• Support system validation
• Analytical method validation

10. Areas with serious deficiencies In number of letters
Process validation 35
Cleaning validation 15
Analytical method validation 9
Water system validation 6
Equipment operational
validation
5
Sterilization process validation 4
Reprocessing validation 3
Validation documentation 3
Computer system validation 2
Aseptic filling validation 2
Container system validation 2

11. PIC/S
(Pharmaceutical Inspection Convention scheme)
Founded in 1970 by European Free Trade Area(EFTA)
Initially 10 EFTA member countries.
According to EU law, the EU countries were not allowed to sign the agreement with other
countries outside.
Only EC was allowed.
The Committee is assisted in its task by 7 Sub-Committees (e.g. on the training of inspectors, on
GMDP harmonization, etc.), by an Executive Bureau
On 1 January 2004, PIC/S became independent and established its own Secretariat.

12. Members of PIC/S till 2017:

13. WHO
(The World Health Organization)
 WHO is intergovernmental organization
Established in 1948.
Consist total 194 member countries.
Introduction
General consideration
Quality management
Glossary
References
Guidelines are divided into 5 different parts:

14. Concerning with
the activities:
• Production and development
• Quality assurance
• Safety and efficacy
Covered
Guidelines:
• Quality of water for pharmaceutical use
• APIs
• Excipients
• Sterile drug product
• Biological drug product
• Investigational drug product
• Herbal drug product
• Radiopharmaceutical

15. GMP guidance in Comparison:
EU
GMP Guide
From 2001
US
CGMP
CFR 210.211
Japan
MHW Ordinance
ICH
API GMP
Q7A
WHO
GMP Pharm.
Production
PIC
Guide to GMP
AUS
From 2002
Canada
GMP Guidelines
2002

16. HARMONIZATION:
From wishful thinking to reality
ICH : The International Council for Harmonization
It’s a tripartite by: EU ,Japan and US
Established in 1990s
Aim was to improve the efficiency of drug development process and
registration of new drug products
And reduce Duplication
Published a guide on GMP for APIs

17. • EU
• European Federation of
Pharmaceutical Industries and
Associations(EFPIA)
• Ministry of Health, Labor and
Welfare(MHLW)
• Japan Pharmaceutical Manufacturers
Association(JPMA)
• FDA
• Pharmaceutical research and
Manufacturers of America(PhRMA)
Regulatory
Bodies:

18. Quality Guidelines Harmonized by ICH:

19. IPEC
(International Harmonization of Excipients
Standards )
Started as a informal discussion session in Orlando 1991
Evolved 100 member of companies , excipient manufactures & pharmaceutical users.
It is structured in 3 partner organization:
a. IPEC-Americas
b. IPEC-Europe
c. IPEC-Japan
Developed Audit guide

20. PHARMACOPEIAS
Pharmacopeial discussion group (PGD) was formed in 1989
Work was split between the three pharmacopeias:
a. USP
b. European pharmacopeia
c. Japanese pharmacopeia
Goal of this harmonization is to bring policies, monograph, standards , specification , analytical
methods and acceptance criteria

21. The international Organization For
Standardization
ISO is a multinational agency
Established in 1947
Purpose is to promote harmonization of processing, manufacturing & quality assurance among
industrial nations
ISO having two groups:
The ISO 9000 Series
-Developed in 1987
-popular with industrial operations
ISO 9001:2000
-Covers full range from design through development, manufacturing & production to supply
services

22. Three series documents are:
1.9000:2000 –fundamental & vocabulary
2.9001:2000- requirements
3.9004:2000-Guidelines for performance improvement.
 ISO 14644 ,was prepared by Technical Committee ISO/TC 209, Cleanrooms and associated
controlled environments.
ISO 14698, Cleanrooms and associated controlled environments - Bio contamination control:

23. PDA ( Parenteral Drug Association)
International association promoting Art& Science of pharmaceutical technology
High standard for products
Established third party inspection program
PDA has a GMP harmonization task force:
Assess to differences in GMP definition and implementation

24. ISPE
(International Society for Pharmaceutical
Engineering)
It is a worldwide nonprofit society of technical professionals.
It has developed guidance documents regarding planning,
construction,
qualifying and operating facilities.
Also established Baseline
 Guide that addresses the design, construction, commissioning, and qualification of facilities
designed for aseptic processing of formulated products.
The Guide is designed for use by industry for the design, construction of aseptic/sterile
manufacturing facilities.

25. MEDICAL DEVICES
National and Regional:
In 1993 Council of European Communities issued Medical Device Directive(MDD)
MDD was adopted to allow the health care industry to get benefits from European market
In 1998 all medical devices marketed in Europe must bear a CE mark.
That ensures the highest degree of safety and product quality of medical devices.
Other countries started with the regulations i.e. Canada and US

26. International:
In 1992 Global Harmonization Task force (GHTF) was formed.
Includes more then 30 nations
Recent efforts of organizations:
Opening its website
Form strong relationship with ISO/TC 210 committee
Harmonization documents:
SG1 Regulatory Requirements
SG2 Medical devices vigilance
SG3 Quality system Requirements
SG4 Auditing

27. CONCLUSION:
We have entered into the phase of global consolidation.
Exceptional jobs are been done in the area of harmonization
Harmonization helps pharmaceutical industries and medical devices industries in developing
new product under harmonized rules and supply them to the global market.

28. REFERENCES:
Nash A. Robert, Wachter H. Alfred, “Pharmaceutical Process Validation”, An
International Third Edition, Revised and Expanded, Published by Informa healthcare,
Edition Reprinted 2011 page no:823-853
SHAYNE COX GAD, “Pharmaceutical Manufacturing Handbook: Regulations and Quality”,
Published by John Wiley & Sons.Inc,2007, Page no:119-134.
 http://www.eoq.org/home.html
https://www.picscheme.org/en/legal-form
http://www.ipec.org/