WHO' normative functions in the field of …...by USP 20-22 April 2015, Rockville, USA 6th INTERNATIONAL MEETING OF WORLD PHARMACOPOEIAS – co-hosted by SFDA/ChPC, Su Zhou, China

1 Dr S. Kopp, TSN/WHO

WHO' normative functions in the field of pharmaceuticals

What can WHO offer ?

Dr Sabine Kopp

Group Lead, Medicines Quality Assurance

Technologies Standards and Norms

Regulation of Medicines and Other Health Technologies

Essential Medicines and Health Products

World Health Organization


World Health Assembly – Constitution, basic legal texts and Resolutions


WHO Expert Committees rules and procedures WHO Basic Documents

Constitution of WHO Expert Committees:

chapter V, article 18; chapter VIII, articles 38-40 For normative function - pharmaceuticals:

Chapter 2, article 2 (u): " to develop, establish and promote international standards with respect to food, biological, pharmaceutical and similar products;"

Regulations for Expert Advisory Panels and Committees, including, Annex – Rules of Procedure for Expert Committees


WHO Governing bodies – DG Report on WHO Expert Committee on Specifications for Pharmaceutical Preparations meetings


What is a WHO Expert Committee?

Official Advisory Body to Director-General of WHO

Established by World Health Assembly or Executive Board

Governed through rules and procedures

Participation in Expert Committee (EC) meetings:

Members ("Experts") selected from WHO Expert Advisory Panels

Technical advisers

Observers: - international organizations, - NGOs, - professional associations…


Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP)

Covers today WHO’s guidance for medicines quality assurance:

Development

Production

Quality Control

Quality related regulatory guidelines

Inspection

Distribution and supply

lifecycle of medicines

from development to delivery to the patient


ECSPP adopts WHO GXPs, guidance texts and guidelines in medicines quality assurance

Total - without Ph.Int. - of :

More than 75 CURRENT official WHO

guidance texts and guidelines for

medicines quality assurance, including

8 (6 updates, 2 new published in 2014)

9 (6 updates, 3 new published in 2015)


http://www.who.int/medicines/areas/quality_safety/quality_assurance/en/




5th Edition of Ph.Int. in press! http://apps.who.int/phint/en/

Monographs

on pharmaceutical substances

on specific dosage forms

general on dosage forms

texts on methods of analysis

monographs on radiopharmaceuticals

and physical standards

International Chemical Reference Substances (ICRS)


WHO Partners in the Expert Committee on Specifications for Pharmaceutical Preparations

National and regional authorities

International organizations (UNAIDS, UNFPA, UNICEF,

World Bank, WIPO, WTO, WCO, etc)

International professional and other associations,

NGOs (including consumer associations, MSF,

industry: IFPMA-IGPA- WSMI, FIP, WMA, etc)

Members of the WHO Expert Advisory Panel on the

International Pharmacopoeia and Pharmaceutical

Preparations


How to become a "WHO Expert"?

Official nomination process

Upon proposal to WHO in consultation with:

Member State/national government (citizenship)+

WHO Regional Office (in accordance with

Member State) +

WHO Headquarters

First period of 4 years

Possibility to renew


WHO Partners in the Expert Committee on Specifications for Pharmaceutical Preparations

Specialists from all quality assurance related areas,

including regulatory, university, industry

WHO Collaborating Centres (official nomination

process) – usually national quality control labs

Pharmacopoeia Commissions and Secretariats,

national institutions and institutes ..

Regional and interregional groups (ICH, ASEAN, etc)


Outcome of the WHO Expert Committee?

Report of the WHO Expert Committee:

- Summarizes discussion

- Gives recommendations to WHO + Member States

- Includes newly adopted guidelines;

- Is presented to WHO Governing Bodies for final comments, endorsement and implementation by Member States

constitutes WHO technical guidance


When does the ECSPP start development of a guideline/guidance/GXP?

Based on recommendations by :

World Health Assembly resolutions (e.g. WHA 20.34, GMP - Good manufacturing practices)

Executive Board resolutions (e.g. EB37.R9 delegating certain functions of INN Programme to DG based on advice from Experts)

International Conference of Drug Regulatory Authorities (e.g. 10th +11th ICDRA – FDC guidelines + Certification Scheme for pharmaceutical starting materials moving into international commerce)

Other WHO programmes and clusters (e.g. necessity for quality control specifications for specific medicines of major public health interest)

Expert Committee (e.g. revision of general methods included in The International Pharmacopoeia)


How does the WHO Expert Committee consultation process work?

Step 1. Preliminary consultation and drafting

Step 2. Draft guidelines

Step 3. Circulation for comments

Step 4. Revision process

.......... (back to step 2 and 3 as often as needed)


Additional steps for developments of specifications

To cover "practical" steps, such as:

Provision of samples

Laboratory studies and scientific research for suitability of

test specifications

For details full process adopted by the ECSPP

http://www.who.int/medicines/publications/pharmacopoeia/An

nex1-TRS992.pdf?ua=1


How does the WHO Expert Committee consultation process work? (2)

WHO Expert Committee (EC) meeting if guideline adopted, published in EC report as Annex

If specification adopted, published in The International

Pharmacopoeia

-> if not back to steps 2-4 (as on previous slide)

DG report to WHO Governing bodies

Recommendation to Member States for

implementation




49th WHO Expert Committee on Specifications for Pharmaceutical Preparations (13-17 October 2014)

Adopted:

Annex 1. Procedure of the development of monographs

for inclusion in The International Pharmacopoeia

(revision);

Annex 2. Updating mechanism for the section on

radiopharmaceuticals in The International

Pharmacopoeia (revision);

Annex 3. Supplementary guidelines on good

manufacturing practices: validation; Appendix 7: non-

sterile process validation (revision);



Adopted:

Annex 4. General guidance for inspectors on “hold-

time” studies (new);

Annex 6. Recommendations for quality requirements

when plant-derived artemisinin is used as a starting

material in the production of antimalarial active

pharmaceutical ingredients (revision);

Annex 7. Guidelines on registration requirements to

establish interchangeability (revision);



Adopted:

Annex 8. Guidance on the selection of comparator

pharmaceutical products for equivalence assessment

of interchangeable multisource (generic) products

(revision);

Annex 9: Good review practices guidelines for

regulatory authorities (new).



Adopted:

16 technical supplements to the WHO model guidance

for the storage and transport of time- and temperature-

sensitive pharmaceutical products were adopted

for publication in a format which is appropriate for

the large volume of this guidance (Annex 5).



Adopted for inclusion in The International

Pharmacopoeia:

For maternal, newborn, child and adolescent health

medicines:

Dexamethasone sodium phosphate (revision)

Dexamethasone phosphate injection

For antiviral medicines, including antiretrovirals:

Atazanavir sulfate

Atazanavir capsules



For anti-tuberculosis medicines:

Kanamycin for injection (revision)

For medicines to treat tropical diseases:

Albendazole chewable tablets (revision)

Levamisole hydrochloride (revision)

Pyrantel embonate (revision)

Pyrantel chewable tablets (revision)

Pyrantel tablets (revision)



For other anti-infective medicines:

Fluconazole capsules

Fluconazole injection

For medicines for anaesthesia, pain and palliative care:

Dextromethorphan hydrobromide

General monographs for dosage forms:

Rectal preparations (revision of the general monograph

on suppositories)



Analytical methods:

Disintegration test for suppositories and rectal

capsules (revision of the chapter titled Disintegration

test for suppositories)

Disintegration test for tablets and capsules (revision)

Following the implementation of the revised general

monograph on parenteral preparations the Committee

adopted the proposed endotoxin limits for 11 parenteral

dosage form monographs lacking such specification,

together with related updates to relevant monographs.



The Committee also adopted

12 newly characterized International Chemical

References Substances (ICRS)

workplan for new monographs to be included in The

International Pharmacopoeia


WHO Governing bodies, EB May 2015



Topics of 50th WHO Expert Committee on Specifications for Pharmaceutical Preparations (12-16 October 2015)

Good pharmacopoeial practices (GPhP) - subject to

concurrence by the world pharmacopoeias on the final

edited text

FIP-WHO technical guidelines: points to consider in the

provision by health-care professionals of children-

specific preparations that are not available as

authorized products

Guidance on GMP: inspection report + Model certificate

Good Trade and Distribution Practices



WHO Certification scheme on the quality of

pharmaceutical products moving in international

commerce – (Q & A)

Guidelines on the conduct of surveys of the quality of

medicines

Guidance for organizations performing in vivo

bioequivalence studies

WHO general guidance on variations to multisource

pharmaceutical products

Guidance on good data and record management practices



Collaborative procedure between the World Health

Organization (WHO) prequalification team medicines

and national medicines regulatory authorities in the

assessment and accelerated national registration of

WHO-prequalified pharmaceutical products and

vaccines

Good Manufacturing Practices (GMP) for biological

products, adopted by the Expert Committee on

Biological Standardization held concurrently


Specifications for inclusion in the PhInt

For maternal, newborn, child and adolescent health medicines:

Estradiol cypionate

Levonorgestrel (revision)

Magnesium sulfate (confirmed)

Magnesium sulfate injection (confirmed)

Misoprostol

Misoprostol dispersion

Misoprostol tablets

Norethisterone (revision)

Norethisterone tablets



Artemether injection (revision)

For anti-tuberculosis medicines:

Cycloserine (revision)

Cycloserine capsules (revision)

For medicines for chronic diseases and for mental health:

Carbamazepine

Carbamazepine tablets

Carbamazepine chewable tablets

Carbamazepine oral suspension



For other anti-infective medicines:

Clindamycin hydrochloride

Clindamycin hydrochloride capsules

Flucytosine

Flucytosine infusion

For other medicines:

Dextromethorphan hydrobromide

Dextromethorphan oral solution



-> For the Supplementary section

Levomethorphan limit tests for dextromethorphan-containing

finished products

Chapter on reference substances and reference spectra

-> Workplan for new monographs to be included in PhInt

International Chemical Reference Substances (ICRS)

The Committee endorsed release of 9 ICRS newly

characterized by the custodian centre, the European

Directorate for the Quality of Medicines and HealthCare

(EDQM) and released by the ICRS Board


Efforts towards pharmacopoeial convergence facilitated by WHO

DRAFT Good Pharmacopoeial Practices (GPhP) and beyond

5th INTERNATIONAL MEETING OF WORLD PHARMACOPOEIAS co-hosted

by USP 20-22 April 2015, Rockville, USA

6th INTERNATIONAL MEETING OF WORLD PHARMACOPOEIAS – co-

hosted by SFDA/ChPC, Su Zhou, China – 21-23 September 2015

Next meeting: 7th International Meeting of World Pharmacopoeias – co-

hosted by MHLW/PMDA/JP, Japan - 13-15 September 2016


Capacity building of national quality control laboratories facilitated by WHO

External quality assurance assessment

scheme for pharmaceutical QC labs (EQAAS)

Phase 6 in 2015 with two tests in one mailing

User-fee based at preferential fees far below cost for

participants from lower- and middle-income countries


Examples of recent "success stories"

MODEL QUALITY ASSURANCE SYSTEM FOR

PROCUREMENT AGENCIES (MQAS) recommended by ECSPP

– and adopted as Interagency guideline + implemented by:

UNICEF

UNDP

UNFPA

World Bank

WHO

Plus others such as MSF


Importance of international convergence

WHO guidelines and good practices translated into

Chinese, French, Russian, Spanish and

requested in other languages

Requests for permission to translate WHO

quality assurance working documents into

other languages, e.g. Chinese


谢谢 شكرا

Thank You! Merci beaucoup!

Спасибо

¡muchas gracias!