Prequalification of medicines

Transcription

1 Prequalification of medicines Wondiyfraw Worku WHO Prequalification Team 3.2.S.3.2 Impurities, Malaysia, 1 29 September 2011 CPHI Mumbai

2 Background In early 2000, there was an increasing demand for generics to reduce the cost of medicines for HIV-AIDS, thereby increasing access; There were multiple suppliers of generic products available. However, the quality of these products could not be assured. At the same time there was a lack of well-established drug regulatory systems within the affected countries. PQ Programme started in March 2001 as a pilot project to facilitate access to quality medicines used in the treatment of HIV/AIDS by providing advice on their acceptability. Later expanded to include medicines for Tuberculosis, Malaria, Reproductive Health, Influenza, Neglected Tropical Diseases, Zinc for diarrhoeal disease & most recently Hepatitis B & C CPHI Mumbai

3 WHO PQT Medicines Prequalification The WHO Prequalification Team Medicines (PQTm) undertakes two activities: Prequalification of Medicines (2001) Prequalification of Active Pharmaceutical Ingredients (2010) CPHI Mumbai

4 Structure of the Prequalification Team Prequalification Team Coordinator s office Vaccines Assessment Medicines Assessment Diagnostics Assessment Vector Control product assessment Inspections Administrative team CPHI Mumbai

5 Scope of Medicines Prequalification The scope of PQTm is specific to certain therapeutics areas. - HIV/AIDS; - Hepatitis B and C; - Malaria; - Tuberculosis; - Reproductive Health; - Influenza; - Zinc for diarrhoeal disease; - Neglected Tropical Diseases CPHI Mumbai

6 Invitations for expression of interest (EOIs) Lists of priority medicines (and APIs) invited for prequalification One EOI per therapeutic area Medicines eligible for prequalification are determined by WHO disease-oriented programmes (based on perceived medical need ) Usually based on inclusion in WHO treatment guidelines and/or WHO model list of essential medicines Mostly generics EOIs published on PQTm website and updated from time to time or based on a need CPHI Mumbai

7 Prequalification pathways Full assessment route Prequalification of SRA approved products Alternative listing - PEPFAR products - EU article 58 products - Health Canada access programme CPHI Mumbai

8 FPP prequalification process- full assessment route Application for FPP Pre-qualification Screening Accepted for assessment Quality API and FPP Efficacy and safety Biowaivers Bioequivalence studies Clinical trials GMP/GLP/GCP API manufacturing sites FPP manufacturing sites Clinical research sites. Assessment Assessment Accepted Accepted Accepted Final decision on prequalification Listing on WHO website CPHI Mumbai

9 Prequalification / listing Product is listed (prequalified) by WHO PQT once all requirements are met. A letter of prequalification is issued to the applicant. The published list of prequalified medicines (FPPs) is used by UN agencies, including UNAIDS, UNFPA and UNICEF, and other agencies/organizations involved in bulk purchasing of medicines such the Global Fund, Global Drug Facility, Medicines Sans Frontiers etc., to guide their procurement decisions Some WHO Member States also use the list for their national medicines procurement CPHI Mumbai

10 Dossier assessment Quality and Efficacy/Safety parts of dossier assessed in parallel Assessment process may involve several rounds of communication with applicants as long as the applicant continues to respond to questions Quality assurance step at the end of the assessment process Primarily WHO guidance documents and standards are applied Also ICH guidelines Recognized Pharmacopoeias: PhInt, USP, BP, EP, JP CPHI Mumbai

11 Dossier Format Multisource generic products - follows the modular format of the ICH Common technical document (CTD) M4 - Information should be summarized using templates QIS, QOS-PD, BTIF SRA -approved Multisource (Generic) or Innovator FPPs - WHO recognises scientific evaluation by the SRAs. - WHO may request additional data relating to use of the product in populations, settings or regions relevant to the prequalified product. - Additional information is included in WHOPARs if necessary after prequalification CPHI Mumbai

12 Guidance CPHI Mumbai

13 Some points to note Stability data on minimum of 2 pilot batches is required. In some cases, the second batch can be as few as 25,000 units. Required storage conditions are 40 o C/75%RH for accelerated study and 30 C / 75% RH for long term study ; 6 months accelerated and 6 months long-term stability data Bioequivalence comparator: PQTm lists on its website comparator products for the specific invited medicinal products: PQTm requires that the comparator medicine lots used in the Bioequivalence (BE) study are purchased from a stringent regulatory authority (SRA) market, if available. Please contact WHO PQ if you cannot find comparator product CPHI Mumbai

14 Prequalification fees PQ has been 100% donor funded activity. There is a need to recover some of the costs Impact of the new fee schedule is being monitored in consultation with manufacturers and other stake holders List of products that are deemed to have potentially low profit margins is published on PQTm website. Reduction of the annual fee, based on justification, can be requested. CPHI Mumbai

15 Time to prequalification of medicines (FPPs, median, full assessment) Median times (days) WHO time Company time Total time to PQ WHO times have been consistently below the target 270 days (median) since around 200 days since CPHI Mumbai

16 WHO and company time to prequalification of FPPs (days) 2,500 2,000 1,500 WHO time 1,000 Company time CPHI Mumbai

17 Support to applicants Detailed guidelines and model CTD dossier Additional product or therapeutic area specific guidance documents BE design advice for most of the invited medicines and review of study protocols Prompt response to questions or request for clarifications Face or face or virtual meetings when requested at any stage Pre-submission meetings - required by PQTm for all new applicants - to help the applicant resolve critical issues before submission Detailed dossier screening feedback Technical assistance - administered by a separate unit within WHO Market information on our website CPHI Mumbai

18 Value of Global Fund medicines procurement , by delivery Quality assurance category Total value (USD) Total value% Total volume (tablets, millions) Total volume % Antimalarial medicines A - WHO-prequalified 237,962,010 86% 4,089,970,185 89% A/B - WHO-prequalified and SRA-autho 9,840,917 4% 133,667,220 3% B - SRA-authorized 13,273,035 5% 240,650,177 5% ERP 10,761,427 4% 97,584,972 2% Not classified 3,817,218 1% 54,386,416 1% 275,654,607 11% 4,616,258,970 26% Antirerovirals A - WHO-prequalified 493,095,762 25% 3,298,802,196 31% A/B - WHO-PQ'd and SRA 756,824,309 39% 4,349,087,812 40% B - SRA-authorized 602,416,264 31% 2,742,338,756 25% Not classified 85,508,764 4% 370,619,566 3% 1,937,845,100 77% 10,760,848,330 60% 1st-line anti-tb medicines A - WHO-prequalified 74,959,045 58% 1,574,097,263 85% B - SRA-authorized 8,638,789 7% 69,618,146 4% ERP 31,101,399 24% 62,580,651 3% Not classified 14,577,526 11% 142,290,939 8% 129,276,760 5% 1,848,586,999 10% 2nd-line anti-tb medicines A - WHO-prequalified 76,652,069 41% 330,143,064 58% A/B - WHO-PQ'd and SRA 19,203,783 10% 55,811,548 10% B - SRA-authorized 83,845,953 45% 147,251,195 26% ERP 1,105,398 1% 810,180 0% Not classified 6,861,096 4% 39,724,078 7% 187,668,300 7% 573,740,065 3% Grand total 2,530,444, % 17,799,434,364 99% CPHI Mumbai

19 WHO Collaborative Registration Procedure WHO Prequalification is not a supra-national regulatory authority. WHO cannot by-pass National Medicines regulatory Authorities (NMRAs) WHO PQT does not therefore issue a marketing authorization Problem: Prequalified medicines not registered and available in the countries where they are needed. Solution: The collaborative registration process for accelerated registration of prequalified medicines in target countries NMRAs and manufacturers can take advantage of the WHO collaborative registration procedure to facilitate registration in the participating countries CPHI Mumbai

20 WHO PQ Collaborative Registration Procedure Submission WHO PQT NMRA Marketing authorisation CPHI Mumbai

21 Collaborative Registration Procedure KEY Principles Voluntary Applicable to products fully assessed by WHO PQT; Product and registration dossier in countries are "the same" as prequalified by WHO PQT. Shared confidential information to support NRA decision making in exchange for accelerated registration process NRA decision expected within 90 days; communicate within 30 days. CPHI Mumbai

22 Participating NMRAs Armenia Botswana Burkina Faso Burundi Cameroon *Caribbean Community (CARICOM) Cote d'ivoire Dem. Rep. Congo Eritrea Ethiopia Georgia Ghana Kenya Kyrgyzstan Lao PDR Madagascar Malawi Mali Mozambique Namibia Nigeria Philippines Senegal Sierra Leone South Africa Tanzania Uganda Ukraine Zambia Zanzibar Zimbabwe * CARICOM Member States: Antigua and Barbuda, Bahamas, Belize, Dominica, Grenada, Haiti, Jamaica, Montserrat, Saint Lucia, St. Kitts and Nevis, St Vincent and the Grenadines, Suriname and Trinidad and Tobago Associate Member States: Anguilla, Bermuda, British Virgin Islands, Cayman Islands and Turks and Caicos Islands As at 28 Nov 2017 CPHI Mumbai

23 Median time to registration *Including regulatory time and applicant time Days Days* As at 28 Nov 2017 CPHI Mumbai

24 Updates/developments We will now start to indicate a specific timeline for submission of responses for each deficiency letter that we send out The PQ list now indicates accepted API sites for each of the prequalified FPPs- additional information on API sources in addition to the prequalified APIs list. Possible expansion of PQ to cover additional medicines in the WHO Essential Medicines List is being discussed Pilot prequalification of biosimilar products to start soon CPHI Mumbai

25 Further information The PQ website is a good source of information. Contact persons: Medicines assessment: Dr. Matthias Stahl (stahlm@who.int) Technical assistance: Mr Rutendo Kuwana (kuwanar@who.int ) Collaborative registration procedure: Dr. Luther Gwaza (gwazal@who.int ) Thank you CPHI Mumbai