2. World Health Organization
28 March, 2017
The International Pharmacopoeia + International Chemical Reference Standards -
Dr Sabine Kopp – Caroline Mendy
Quality Assurance and Safety: Medicines
World Health Organization

3. The International Pharmacopoeia –Ph. Int.
Introduction
Ph. Int. - scope
WHO consultative procedure
What's new
Link with other programmes and organisations

4. International Pharmacopoeia Historical overview
World Health Organization
28 March, 2017
International Pharmacopoeia Historical overview
1874 Discussion on Unification of terminology and
composition of drugs
1902 First Conference organized by the
Government of Belgium
1906 Agreement on Unification of the Formulae of
Potent Drugs ratified by 19 states
1925 Brussels agreement (signed 1929)
League of Nations: “international pharmacopoeia”

5. International Pharmacopoeia Historical overview - 2 -
World Health Organization
28 March, 2017
International Pharmacopoeia Historical overview - 2 -
1937 First meeting (experts from B, CH, DK, F, NL,
UK, USA) - League of Nations
1947 Interim Commission of WHO takes up health
related work of League of Nations
1948 First World Health Assembly established
Expert Committee on Unification of
Pharmacopoeia

6. International Pharmacopoeia Historical overview - 3 -
World Health Organization
28 March, 2017
International Pharmacopoeia Historical overview - 3 -
WHA approved publication of Pharmacopoeia
Internationalis
WHO Expert Committee:
1951 named: Expert Committee on International
Pharmacopoeia
1959 named: Expert Committee on Specifications
for Pharmaceutical Preparations --> to date

7. International Pharmacopoeia
World Health Organization
28 March, 2017
International Pharmacopoeia
A collection of monographs and requirements for:
Drug substances
Excipients
Finished dosage forms
General methods and requirements:
dosage forms, e.g. tablets, liquid preparation for oral use
dissolution testing
Supplementary information, e.g. General Guidelines for Chemical Reference Substances
Infrared reference spectra

8. International Pharmacopoeia
World Health Organization
28 March, 2017
International Pharmacopoeia
Scope since 1975
Model List of Essential Medicines and
Medicines recommended and specifications needed by WHO Programmes, e.g. to treat Malaria, TB, HIV/AIDS and for children!
implementation: “ready for use” by Member States

9. World Health Organization
28 March, 2017
WHO Procedure for the preparation of drug Quality Control specifications (1) …..or why it takes so long….
Step 1: Identification of specific pharmaceutical products for which Quality Control (QC) specifications need to be developed, confirmation by all WHO parties concerned (Expert Committee, Specific disease programme, pre-qualification project team, etc.)
Step 2: Provision of contact details from manufacturers of the above products in collaboration with all parties concerned
Step 3: Contact manufacturers for provision of QC specifications and samples
Step 4: Identify and contact QC laboratories for collaboration in the project (2-3 laboratories depending on how many pharmaceutical products have been identified in step 1), Contract for laboratory work

10. World Health Organization
28 March, 2017
WHO Procedure for the preparation of drug Quality Control specifications (1) …..or why it takes so long….
Step 5: Prepare the contract for drafting the specifications and undertaking the necessary laboratory work
Step 6: Search for information on QC specifications available in the public domain
Step 7: Laboratory testing, development and validation of Quality Control Specifications
Step 8: Support WHO Collaborating Centre in the establishment of International Chemical Reference Substances
Step 9: Follow the consultative process, mailing of draft specifications to Expert Panel and specialists

11. World Health Organization
28 March, 2017
WHO Procedure for the preparation of drug Quality Control specifications (2) …..or why it takes so long….
Step 10: Discussion of comments with contract laboratories, WHO Collaborating Centres, additional laboratory testing to verify and/or validate specifications
Step 11: Consultation to discuss the comments and test results received as feed-back
Step 12: recirculation for comments
Step 13: as step 10
Step 14: Present the drafts to the WHO Expert Committee on Specifications for Pharmaceutical Preparations for possible formal adoption,
…if not adopted repetition of steps 11 to 13 as often as necessary

12. WHO does the work … with Partners
National and regional authorities
International organizations (UNAIDS, UNICEF, World Bank, etc.)
International professional and other associations, NGOs (including consumer associations, MSF, industry: IFPMA-IGPA-WSMI, FIP, WMA, etc.)
WHO Expert Panel on The International Pharmacopoeia and Pharmaceutical Preparations (official nomination process)
Specialists from all areas, regulatory, university, industry
WHO Collaborating Centres (official nomination process)
Pharmacopoeia Commissions and Secretariats, national institutions and institutes
Regional and interregional regulatory groups (ASEAN, ICH, etc)

14. International Pharmacopoeia
World Health Organization
28 March, 2017
International Pharmacopoeia
current: 4th Edition + 1st Supplement
Consolidated in :
2 Volumes - Vol. 1: pharmaceutical substances (A-O)
- Vol. 2: pharmaceutical substances (P-X) dosage forms + radiopharmaceuticals methods of analysis + reagents
1st Supplement - new requirements and revisions
Available in Publication, CD-ROM and Online

15. World Health Organization
28 March, 2017
4th Edition – new (1)
4th Edition
Monographs on antiretrovials (ARVs)
Revision of existing monographs
Improved presentation
Improved cross-referencing to general methods
Improved search functions for CD-ROM and online version
New notice on "manufacture"
New notice on impurities
New list of impurities shown to be controlled by tests

16. World Health Organization
28 March, 2017
4th Edition – new (2)
First Supplement
New monographs for ARVs, TB and Malaria medicines, medicines for children
Revisions, 125 IR reference spectra, supplementary info

17. New Ph. Int. monographs - adopted by 42nd WHO Expert Committee
Lumefantrine
Artemether and lumefantrine tablets
Rifampicin, isoniazid and ethambutol tablets
Rifampicin and isoniazid dispersible tablets
Rifampicin, isoniazid and pyrazinamide dispersible tablets
Zinc sulfate
Zinc sulfate tablets, paediatric
Zinc sulfate oral solution, paediatric
Magnesium sulfate injection

18. New Ph. Int. monographs - adopted by 43rd WHO Expert Committee
Efavirenz capsules
Efavirenz oral solution
Emtricitabine
Nevirapine
Nevirapine oral suspension
Nevirapine tablets
Zidovudine, Lamivudine and Nevirapine tablets

19. New Ph. Int. monographs - adopted by 43rd WHO Expert Committee
Artemether and Lumefantrine oral suspension
Chloroquine sulfate oral solution
Quinine sulfate tablets
Cycloserine
Cycloserine capsules
Ethambutol hydrochloride tablet
Mebendazole
Oseltamivir phosphate
Chewable Mebendazole tablets

20. New Ph. Int. monographs - adopted by 43rd WHO Expert Committee
The following monographs adopted subject to minor modifications:
Fludeoxyglucose (18F) injection
Gallium citrate (67Ga) injection
Technetium (99mTc) pentetate complex injection
Sodium pertechnetate (99mTc) injection (fission)
The following monographs adopted subject to minor modifications and final confirmation by IAEA:
Iobenguane (123I) injection
Sodium iodide (131I) injection
Sodium iodide (131I) solution
Sodium pertechnetate (99mTc) injection (non-fission)
Thallous chloride (201Tl) injection

21. New Ph. Int. Work Programme – adopted by WHO Expert Committee
Medicines for HIV/AIDS-related conditions
Antibacterials
Antifungal, antiprotozoal and antimycobacterial agents
Anti-epilectics
paediatric formulations (oral liquids and chewable tablets)
Anthelmintics
Palliative care
Reproductive health
Insulins
Large volume parenterals (eg glucose IV infusion)

22. International Chemical Reference Substances (ICRS)
World Health Organization
28 March, 2017
International Chemical Reference Substances (ICRS)
207 ICRS + 12 melting point reference substances
Established by WHO COLLABORATING CENTRE FOR CHEMICAL REFERENCE SUBSTANCES in Sweden
Primary reference standard
Linked to Ph.Int.
Price for ICRS US$ 70
Includes: - Directions for use
- Certificate of analysis
Monitoring and on-going stability testing
Can be used for tests and analysis not included in Ph.Int.

23. International Infrared Reference Spectra
World Health Organization
28 March, 2017
International Infrared Reference Spectra
Established by WHO COLLABORATING CENTRE FOR CHEMICAL REFERENCE SUBSTANCES in Sweden
155 International Infrared Reference Spectra
(125 published in
Ph.Int. 4th Ed. Suppl. 1)
IR-spectrum of lamivudine

24. Int. Ph. and links with other programmes and organizations
World Health Organization
28 March, 2017
Int. Ph. and links with other programmes and organizations
Collaboration with national and regional pharmacopoeias, incl. Brazilian Pharmacopoeia, Chinese Pharmacopoeia, JP, IP, Ph.Eur., USP, and PDG
Collaboration with national/regional regulatory authorities and quality control laboratories
Collaboration with international organizations (e.g. UNICEF, IAEA)
Links with Prequalification Programme - A United Nations Programme managed by WHO
Collaboration with manufacturers worldwide

25. Int. Ph. and links with other programmes and organizations
World Health Organization
28 March, 2017
Int. Ph. and links with other programmes and organizations
Monographs for antimalarials, anti-TB drugs, etc. (different clusters in WHO)
General requirements for products derived from plant materials (WHO Traditional Medicines Programme)
Monographs for radiopharmaceuticals (with International Atomic Energy Agency - IAEA)
Monographs for excipients (with Pharmacopoeial Discussion Group – PDG, IPEC)

26. UN Prequalification of Medicines Programme
International Pharmacopoeia (Ph.Int.) and its international chemical reference standards (ICRS) are essential tool for PQ activities
The Ph.Int. enjoys priority in the PQ Programme
BP, Ph.Eur. and USP methods should only be applied, where an Applicant has made specific commitments to do so in the dossier

27. UN Prequalification of Medicines Programme
The International Pharmacopoeia is the only reference source for many of the priority medicines dealing in the PQ programme, such as:
artemisinin-related Antimalarial products (e.g. artemether, artesunate, artenimol);
Antiretrovirals products (e.g. abacavir, efavirenz, nelfinavir mesilate, ritonavir);
Fixed-dose combinations (e.g. artemether/lumefantrine tablets, lamivudine/nevirapine/zidovudine tablets);
Paediatric formulations (e.g. artemether and lumefantrine oral suspension, paediatric didanosine liquid for oral use)

28. The International Pharmacopoeia's advantages (1)
1. Specifications validated internationally, through an independent scientific process
2. Input from WHO Collaborating Centres, national Drug Quality Control laboratories
3. Collaboration with manufacturers around the world, especially for new projects
4. Development considering the costs of analysis, i.e. using as few ICRS as possible

29. The International Pharmacopoeia's advantages (2)
5. Collaboration with standard-setting organizations and parties, including regional and national pharmacopoeias
6. Networking and close collaboration with WHO Member States, Drug Regulatory Authorities
7. Links with other WHO activities
8. FREE FOR USE by all Member States

30. Further questions ??????

31. Safe quality medicines