WHO Prequalification of APIs - Shanghai 2014 1 |1 | 1 1 3.2.S.3.2 Impurities, Malaysia, 29 September...

WHO Prequalification of APIs - Shanghai 20141 |

11

3.2.S.3.2 Impurities,Malaysia, 29 September 2011

Active Pharmaceutical Ingredient (API)

Prequalification

Dr Antony Fake

WHO Prequalification Team - Medicines


API – Active Pharmaceutical Ingredient (drug substance)

FPP – Finished Pharmaceutical Product (drug product)

APIMF – Active Pharmaceutical Ingredient Master File (DMF)

API-PQ –Active Pharmaceutical Ingredient Prequalification

SRA – Stringent Regulatory Authority

GMP – Good Manufacturing Practice

PQP – Prequalification Team - Medicines

Abbreviations


Prequalification ProgrammePrequalification Programme

The Prequalification Team – Medicines (PQP) is responsible for ensuring that Medicines available to procurers (and national authorities) are of good quality.

In order to have good quality medicines you must have:

Good quality Active Pharmaceutical Ingredients.


The programme has two primary objectives:

To ensure there is available essential APIs and FPPs that are of good quality.

To support manufacturers of essential APIs and FPPs to meet international regulatory standards.

Prequalification ProgrammePrequalification Programme


API PrequalificationAPI Prequalification


What is API Prequalification?What is API Prequalification?

It is a scheme for manufacturers of APIs that are used in medicinal products for HIV, TB, Reproductive Health, Malaria, Neglected Tropical diseases and Zinc.

It seeks to verify and identify APIs that are of good quality and manufactured in compliance with GMP.

It commenced as a pilot project in October 2010.


Why is Prequalification of APIs needed?Why is Prequalification of APIs needed?

There is a relative scarcity of API.

There are significant geographical distances between API and FPP manufacturers, i.e. between China and India.

The quality and GMP status of the API manufacturer may not be clear.

Medicine manufacturers involved in the PQ programme (and in general) have difficulties in finding sources of quality APIs for Malaria, HIV, Reproductive Health and TB, because:

This creates basic problems for FPP manufacturers to find and establish contact with potential API manufacturers.


6th Invitation for EOI6th Invitation for EOI

Not all APIs are invited to apply for prequalification.

APIs are publicly invited through a published invitation for expression of interest (EOI).

A 6th invitation for Expressions of Interest (EOI) has now been announced.

It essentially covers those APIs listed in the associated FPP EOIs for HIV, anti-TB, Malaria, reproductive health neglected tropical diseases and Zinc.

See website for the invitation:

http://www.who.int/prequal/info_applicants/API_info_applicants.htm


6th Invitation for EOI6th Invitation for EOI

Invited Active Pharmaceutical Ingredient Therapeutic area

Abacavir, Atazanavir, Darunavir, Dolutegravir, Efavirenz, Emtricitabine, Etravirine, Lamivudine, Lopinavir, Nelfinavir, Nevirapine, Raltegravir, Ritonavir, Stavudine, Tenofovir, Zidovudine

HIV

Amodiaquine, Artemether, Artesunate, Dihydroartemisinin, Lumefantrine, Mefloquine, Piperaquine, Pyrimethamine, Pyronaridine, Sulfadoxine

Anti-malarial

Amikacin, Capreomycin, Clofazimine, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Kanamycin, Levofloxacin, Linezolid, Moxifloxacin, PAS, PAS Sodium, Prothionamide, Pyrazinamide, Rifampicin, Streptomycin, Terizidone

Anti-tuberculosis

Desogestrel, Estradiol cypionate, Estradiol valerate, Ethinylestradiol, Etonogestrel, Levonorgestrel, Medroxyprogesterone acetate, Mifepristone, Misoprostol, Norethisterone enanthate, Norgestrel, Oxytocin

Reproductive health

Albendazole, Diethylcarbamazine citrate, Mebendazole, Praziquante NTD

Zinc Sulphate Zinc

Oseltamivir, Zanamivir Influenza


Benefits to API manufacturersBenefits to API manufacturers

API’s can be prequalified independent of an FPP application.

Public recognition as a source of quality API, manufactured in compliance with GMP.

Serves as a point of difference between good quality and poor quality APIs.

Opportunities to verify compliance with GMP.

Opportunities to compile, revise and refine their regulatory documentation, leading to quicker acceptance by other national regulatory agencies.

API PQ is increasingly recognised by National authorities.


Benefits to FPP manufacturersBenefits to FPP manufacturers

Ease of identifying potential sources of quality API.

Identifying API manufacturers with robust quality systems in place.

Identifying API manufacturers that maintain good regulatory documentation, which may be used in regulatory submissions.


Prequalification of Medicines websitePrequalification of Medicines website

http://www.who.int/prequal


What is API Prequalification?What is API Prequalification?

API Manufacturer

API Prequalification

It is a scheme for API manufacturers only

There is no involvement by FPP manufacturers


ApplicationApplication

Invitation

Application

Assessment(GMP)

Assessment(Quality)

Decision

Publishing


ApplicationApplication

The PQ application form.

An APIMF (if not previously provided).

A Site Master File (if not previously provided).

Any further evidence of GMP at the facility (optional).

An application should consist of:


Assessment – Quality (APIMF)Assessment – Quality (APIMF)

Invitation

Application

Assessment(GMP)

Assessment(Quality)

Decision

Publishing


APIMF - Technical contentAPIMF - Technical content

Excellent technical guidance can be found in the module 3.2.S sections (pages 11 to 31) of the recently published guideline :

Guideline on submission of documentation for a multisource (generic) finished pharmaceutical product (FPP): quality part.

http://www.who.int/prequal/info_general/documents/generic_guide/Generic

Guideline_Quality.pdf


Assessment – GMPAssessment – GMP

By providing evidence of current compliance:– GMP certificates, inspection reports, CAPAs, the most

recently completed Product Quality Review (PQR) report.

or

By inspection by the WHO.

There are two ways to demonstrate GMP compliance at the API manufacturing facility.


Assessment – GMPAssessment – GMP

Inspections performed previously by WHO, a member of PIC/S, or an SRA.

Inspection must have occurred within 3 years of application.

Inspections must be API specific.

Assessment of GMP compliance at the site of API manufacture takes into account:

The WHO will perform an inspection if, after assessment and requests for information, GMP compliance can not be established.


PublishingPublishing

Invitation

Application

Assessment(GMP)

Assessment(Quality)

Decision

Publishing



List of PQ APIsWebsite (Public)

Confirmation Document (Private)

+ WHOPIRsWebsite (Public)



The date of prequalification is the date when the API is published on the WHO List of Prequalified Active Pharmaceutical ingredients.

http://www.who.int/prequal/info_applicants/API_PQ-List.htm


WHO List of Prequalified APIsWHO List of Prequalified APIs

WHO application number. INN name. Date of prequalification. Name of the applicant Sites of API manufacture. The APIMF version number. The API specification version

number.

• The primary and secondary packaging components.

• The assigned re-test period.

• The recommended storage conditions.

• Confirmation of API PQ document issue date

Intended for: UN agencies, National medicine authorities, FPP manufacturers, public

Publically available


Confirmation of API PQ documentConfirmation of API PQ document

The assigned WHO application number.

The INN name of the active pharmaceutical ingredient.

API manufacturer company name.

The API specification version number.

A copy of the API specifications.

The assigned re-test period.

The recommended storage conditions.

A copy of the assay and related substances test methods.

Provided to the API manufacturer for distribution at their discretion

Intended for: UN agencies, National medicine authorities, FPP manufacturers


Future of API PrequalificationFuture of API Prequalification

There is very positive feedback from FPP manufacturers whenever PQ of APIs is discussed.

Applications and the number of prequalified APIs continues to increase.

May 2014 Dec 2013 Dec 2012 Dec 2011

108 100 69 36 Total number of applications

61 51 28 8 Number of PQ APIs


New procedures and guidanceNew procedures and guidance

Elimination of paper based submission for APIs

Introduction of electronic document requirements

http://www.who.int/prequal/info_applicants/API_procedural_guidance.htm

Introduction of a new Amendment guidance

http://www.who.int/prequal/info_applicants/API_amendment_introduction.htm


Use among NMRAsUse among NMRAs

Efforts are being undertaken to increase the recognition of PQ APIs by NMRAs to further increase the value of participation and to reduce regulatory burden on NMRAs.

This includes the use of Prequalified APIs in non-PQP FPPs.

• CPQs are now recognised by regulators of the East African Community as a means of submitting API information.

• CPQs are actively considered by many Southern African Regulators as a means of verifying API information.

• South Africa is currently considering recognition of CPQs.


Further informationFurther information

The PQ website is a good source of information, please read.


AND, ALSO

Please email me (or visit) if you have any questions.

[email protected]

One email could save you a lot of time.


mailto:[email protected]


谢谢你

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