Assessment of Medicines Technical Briefing Seminar on Quality Assurance and Safety of Medicines Assessment of Medicines Dr M Stahl Head of Assessments Prequalification of Medicines Programme Quality Assurance and Safety: Medicines (QSM) Department of Essential Medicines and Pharmaceutical Policies (EMP) Health Systems and Services (HSS)

Invitation for Expression of Interest (EOI) Decided by WHO disease oriented programmes based on perceived need Requirements for inclusion; Included on the WHO Model List of Essential Medicines or An application for inclusion has been submitted to the EML EC and it can be shown to be likely to meet the criteria for inclusion (public health need, comparative effectiveness, safety and cost- effectiveness) or included in the current WHO treatment guideline

Acceptance for Assessment Main steps Application PQIF, BTIF, Dossier Screening Acceptance for Assessment Pre-Assessment Assessment Report Additional Data Prequalification LoP Requalification Pre-assessment: 1) Are there batch numbers for the various batches (bio, dissolution, stability-3, validation-3)? 2) Is the composition of these batches same as for unit batch? 3) Stability batches – at least 3, at least one production, the remaining at least pilot? 4) Comparison of BTIF and PQIF with respect to biobatch (number, composition, size).

Standards WHO standards as defined in WHO guidelines and International Pharmacopoeia If these do not exist, ICH guidelines are applied Same principles as for national regulatory approvals by stringent authorities Data on quality and efficacy/safety or interchangeability Compliance with GMP (finished product, APIs), GCP/GLP (bioequivalence studies) Some guidance documents are uniquely PQ (BCS based biowaiver etc). The fact that there is a WHO guidance does not necessarily mean PQ has to work according to it, in all its details.

Assessment sessions Assessment of the product dossier i.e. quality specifications (API and FPP), pharmaceutical development, stability, bioequivalence… Copenhagen assessment week - 20+ assessors - 5 days - once every two months - The assessment report is reviewed by a second assessor - both assessors sign the final report - Additional data requested if necessary; first by e-mail, then surface mail Handling of variations to prequalified product dossiers - Done in-house (Geneva) on a continuous basis If a biowaiver application, then a third Q assessor will sign off the Q report (as the assessors of dissolution data). Once the Q and BE reports are acceptable, i.e. the dossier is in principle ready for prequalification there will be a QA step…

Product dossiers accepted for assessment 2005 2006 2007 2008 2009 (30 Oct 2009) HIV 67 42 25 42 24 TB 17 9 17 12 10 Malaria 3 5 7 9 3 Repr Health - - 10 4 4 Influenza - - - 1 7 Diarrhoea - - - - 1 Total Dossiers Accepted 87 56 59 68 49 Total Dossiers Submitted 87 92 57

Currently under assessment As of 30 Oct 2009: 64 products for treatment of HIV/AIDS and related diseases 2 products for treatment of influenza (EOI 2008) 42 products for treatment of tuberculosis 17 products for treatment of malaria 13 reproductive health products (EOI 2006) 1 zinc product for treatment of diarrhoea (EOI 2008) Total 139

Dossier status on the web

Times Time (median) from receipt of a dossier to start of assessment: 47 days (2007) 33 days (2008) Time (mean) to prequalification: 26 months (2007) 23 months (2008; median 18.7 months, 19.1 months for generics only)

Characteristics of prequalified product

Products included in the WHO list of prequalified medicines (by therapeutic area)

Products included in the WHO list of prequalified medicines (cumulative numbers)

Products included in the WHO list of prequalified medicines by therapeutic area (cumulative numbers)

WHOPARs and WHOPIRs These are published in response to the WHA Resolution WHA57.14 of 22 May 2004, which requested WHO: "3. (4) to ensure that the prequalification review process and the results of inspection and assessment reports of the listed products, aside from proprietary and confidential information, are made publicly available;" A WHO Public Assessment Report (WHOPAR) is a summary of the quality and efficacy/safety assessments for a product at the time of prequalification and includes the Summary of Product Characteristics (SPC) and PIL

Variations 2008

Variations 2009 (as of 30 Oct)

Requalification of prequalified dossier (generics) Guidance adopted by EC in Oct 2009 Every 5 years (at least), earlier if omissions, fraud or batches not compliant with spec's Questions: Product acceptable according to current norms and standards? Quality of the FPP and its manufacturing processes consistent? Documents; Cover letter, summary of key product information (LoP – now, then), all variations, PQIF (according to current guidelines), prequalified and current API and FPP specifications and test methods, Product Quality Review.