Active Pharmaceutical Ingredient Prequalification

Transcription

1 Active Pharmaceutical Ingredient Prequalification Dr Antony Fake WHO Prequalification of Medicines Programme S.3.2 Impurities, Malaysia, 29 September 2011

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3 Abbreviations PQP Prequalification of Medicines Programme API Active Pharmaceutical Ingredient Drug substance. FPP Finished Pharmaceutical Product APIMF A Drug Master File API-PQ Active Pharmaceutical Ingredient Prequalification CPQ document Confirmation of API Prequalification document 3 API and DMFs - IGDRP October 2013

4 Prequalification Programme In order to have good quality medicines you must have: Good quality Active Pharmaceutical Ingredients. 4

5 Prequalification of Medicines Programme The API Prequalification Procedure is one of three activities undertaken by the Prequalification of Medicines Programme. These are: Prequalification of Medicines (2001). Prequalification of Quality Control Laboratories (2004). Prequalification of Active Pharmaceutical Ingredients (2011). 5

6 Prequalification of Medicines Programme Prequalification of Medicines Programme (PQP) is run by the World Health Organization and is based in Geneva. PQP has an interest in: HIV/AIDS, Tuberculosis, anti-malarial, Reproductive Health, Neglected tropical diseases, and Zinc medicines. 6

7 Prequalification of Medicines website 7

8 Prequalification of Medicines Programme PQP originated from recognition by international medicine procurers that medicines procured should be of good quality. The therapeutic areas of interest to procurers were largely not addressed by Stringent Regulatory Authorities (SRAs). An independent quality assurance body was required to assess many medicines of interest to procurers. WHO was asked to host this programme. To-date PQP has prequalified nearly 400 medicines. 8

9 API Prequalification 9

10 What is API Prequalification? It is a scheme for manufacturers of APIs that are used in medicinal products for HIV, TB, Reproductive Health, Neglected tropical diseases and Malaria. 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 It is part of the Prequalification of Medicines Programme, WHO based in Geneva. 10

11 Why is Prequalification of APIs needed? 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: There is often a relative scarcity of API. There are significant geographical distances between API and FPP manufacturers, i.e. between China and India. The quality of the API manufacturer may not be clear. This creates basic problems for FPP manufacturers to find and establish contact with potential API manufacturers. 11

12 Why is Prequalification of APIs needed? API Prequalification is intended to facilitate the identification of API sources by drug product manufacturers and support the availability of quality medicines. API Prequalification is intended to act as a resource for national regulatory authorities who do not have the means to undertake API assessment themselves. m 12

13 Benefits to API manufacturers 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. API s can be prequalified independent of an FPP application. Recognition by national regulatory authorities. 13

14 Benefits 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. Reduced API assessment requirements (PQP) Reduced post-prequalification variation (changes) requirements. Recognition by national regulatory authorities 14

15 Application Invitation Application Assessment (GMP) Assessment (Quality) Decision Publishing 15

16 5th 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 5 th EOI has been announced. It essentially covers those APIs listed in the associated FPP EOIs for HIV, anti-tb, Malaria, reproductive health neglected tropical diseases. 16

17 5th Invitation for EOI APIs FOR MEDICINAL PRODUCTS FOR HIV AND RELATED DISEASES Abacavir Atazanavir Darunavir Didanosine Efavirenz Emtricitabine Etravirine Lamivudine Lopinavir Nelfinavir Nevirapine Raltegravir Ritonavir Stavudine Tenofovir Zidovudine APIs FOR ANTIMALARIAL MEDICINAL PRODUCTS Amodiaquine Artemether Artesunate Dihydroartemisinin Lumefantrine Mefloquine Piperaquine Pyrimethamine Pyronaridine Sulfadoxine APIs FOR ANTI-TUBERCULOSIS MEDICINAL PRODUCTS Amikacin Capreomycin Cycloserine Ethambutol Ethionamide Isoniazid Kanamycin Levofloxacin Moxifloxacin Ofloxacin Para-Aminosalicylic Acid (PAS) Para-Aminosalicylate sodium (PAS Sodium) Prothionamide Pyrazinamide Rifampicin Streptomycin Terizidone APIs FOR NEGLECTED TROPICAL DISEASE MEDICINAL PRODUCTS Albendazole Diethylcarbamazine citrate Mebendazole Praziquantel APIs FOR REPRODUCTIVE HEALTH PRODUCTS Desogestrel Estradiol cypionate Estradiol valerate Ethinylestradiol Etonogestrel Levonorgestrel Medroxyprogesterone acetate Mifepristone Misoprostol Norethisterone enanthate Norgestrel Oxytocin API FOR PRODUCTS USED IN THE TREATMENT OF DIARRHOEA Zinc sulfate 17

18 Application Invitation Application Assessment (GMP) Assessment (Quality) Decision Publishing 18

19 Application An application for API Prequalification is made by the API manufacturer, or agent. An applicant does not need to be supplying API to a WHO Prequalified FPP to seek API prequalification. Fees were introduced in September

20 Fees No Fee for first time applicants No Fee for first application of a specific API $3000 for second application of a specific API $5000 for third application of a specific API $8000 for further applications The fee covers both assessment and inspection activities See for information on numbers of applications received. 20

21 Application An application should consist of: 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). 21

22 Assessment Quality (APIMF) Invitation Application Assessment (GMP) Assessment (Quality) Decision Publishing 22

23 Assessment Quality (APIMF) PQP does not align itself with any particular pharmacopoeia or regulator guidance. PQP recognises the major pharmacopoeias (Ph.Int., EP, USP, JP) and international guidance, ICH, FDA, EMA, EDQM etc. 23

24 APIMF - 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. Guideline_Quality.pdf 24

25 Assessment GMP There are two ways to demonstrate GMP compliance at the API manufacturing facility. 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. 25

26 Assessment GMP Assessment of GMP compliance at the site of API manufacture takes into account: 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. The WHO will perform an inspection if, after assessment and requests for information, GMP compliance can not be established. 26

27 Assessment GMP Each inspection will consist of a PQP lead inspector and a PQP co-inspector. In addition, an inspector from the responsible national agency is always invited as an observer An inspector from a developing/recipient country may also be invited. 27

28 Publishing Invitation Application Assessment (GMP) Assessment (Quality) Decision Publishing 28

29 Publishing List of PQ APIs Website (Public) + WHOPIRs Website (Public) Confirmation Document - CPQ (Private) 29

30 Publishing The date of prequalification is the date when the API is published on the WHO List of Prequalified Active Pharmaceutical ingredients. 30

31 WHO List of Prequalified APIs Publically available 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 31

32 WHOPIR WHO does not issue GMP Certificates. The outcome of successful inspections are published on the PQP website. Unsuccessful inspections are not published. 32

33 Confirmation of API PQ document (CPQ) Provided to the API manufacturer for distribution at their discretion 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. Intended for: UN agencies, National medicine authorities, FPP manufacturers 33

34 Summary: API Prequalification API Prequalification is a standalone procedure for API manufacturers only. API prequalification includes a quality and GMP assessment. Prequalified APIs are publicly listed as APIs of verified quality and GMP. Efforts are being to increase the recognition of PQ APIs by NMRA to further increase the value of participation. 34

35 Further information The PQ website is a good source of information, please read. Or me at: Fakea@who.int Thank you 35