the who prequalification of medicines programme dossier assessment update
DESCRIPTION
The WHO Prequalification of Medicines Programme Dossier Assessment Update. Rutendo Kuwana Technical Officer Prequalification of Medicines Program WHO. 5 Key Assessment Stages. Invitation for Expression of interest (EOI). A list of medicines invited for prequalification - PowerPoint PPT PresentationTRANSCRIPT
EMP TBS, 3 November 2011
The WHO Prequalification of Medicines Programme
Dossier Assessment Update
Rutendo Kuwana Technical Officer
Prequalification of Medicines ProgramWHO
EMP TBS, 3 November 2011
5 Key Assessment Stages
EOI Publication
Application Received
Screening
Assessment
Prequalification
Variation
Requalification
EMP TBS, 3 November 2011
Invitation for Expression of interest (EOI)
• A list of medicines invited for prequalification– Priority public health medicines – We can only accept product dossiers for medicines
included in this list
• List prepared by WHO clinical experts (HIV, TB, Malaria, RH, Influenza, Zinc, NTD) – Based on inclusion in treatment guidelines and/or WHO
model list of essential medicines
• Revised as needed to capture new developments
EMP TBS, 3 November 2011
Expressions of Interest
Currently 8 EoIs• Active Pharmaceutical Ingredients (API) – 2nd • HIV/AIDS – 10th • Influenza – 2nd
• Malaria – 9th • Neglected Tropical Diseases (NTD) – 1st • Reproductive Health – 5th
• Tuberculosis – 10th • Diarrhoea (Zinc) – 1st
EMP TBS, 3 November 2011
Paths for inclusion of a product in the list of prequalified products
• Prequalification of multisource generic products – Full review and inspection by PQP
• Prequalification of innovators– Approval based on marketing authorization issued by an NMRA
in ICH region and associated countries• Prequalification of generic products approved by SRA
– Approval based on SRA marketing authorization– For established generic products
• Recognition of temporary approvals / scientific opinions – USFDA PEPFAR approval/tentative approval– EMA article 58– Health Canada Access programme
EMP TBS, 3 November 2011
Screening
• Review data in the Application Form and Dossier
• Mainly qualitative review i.e. is the data there or not
• Some selected quantitative assessments done e.g. completeness of formulation tables, duration of studies
• Administrative and Technical Completeness
EMP TBS, 3 November 2011
2005 2006 2007 2008 2009 2010 2011
HIV 67 42 25 42 24 21* 26(19)TB 17 9 17 12 11 16 17
(11)Malaria 3 5 7 9 3 6 8 (5)Repr Health - - 10 4 7 7 3 (0)Influenza - - - 1 7 0 0 (0)Diarrhoea - - - - 1 1 2 (1)NTD - - - - - - 1(1)Total Accptd 87 56 59 68 53 35 37Total Submitted 90 92 83 51 57* Includes 2 products (Water for Injection) not included in any of the EoIs
(…) dossiers accepted for assessment
Product dossiers accepted for assessment: 2005 – 2011 (as at 1st November 2011)
EMP TBS, 3 November 2011
Administration of assessments
• Coordinator with a team of, – Quality assessors– BE assessors– Clinical assessors
• Six full time (in-house)• More than 50 temporary advisors (pool of external assessors)• Six sessions per annum (every other month) in CPH. Details of
meeting dates published on website• More than 30 assessors per session.
EMP TBS, 3 November 2011
2005 – 2011 Prequalification Stats
2005 2006 2007 2008 2009
2010 2011
HIV/AIDS 67 42 25 42 24 21 16
TB 17 9 17 12 11 16 2
Malaria 3 5 7 9 3 6 0
Influenza - - - 1 7 0 0
Diarrhoea - - - - 1 1 0
RH - - 10 4 7 7 2
NTD (DEC) - - - - - - 0
DEC: Diethylcarbamazine
Total WHO PQd as at 1st November 2011 - 263
EMP TBS, 3 November 2011
International standards for prequalification
• Primarily WHO guidance documents and standards – PQ main generic and variation guidelines– The WHO Bioequivalence and bio waiver guidelines– The WHO Stability guideline– International Pharmacopoeia– WHO GMP and GCP Guidelines
• ICH guidelines • Other guides issued by SRAs such as USFDA and EMA• Other recognized pharmacopoeias
– BP, EP, JP, USP
EMP TBS, 3 November 2011
New guidelines
• “Preparation” guideline: 10.375: Guideline on submission of documentation for a multisource (generic) finished pharmaceutical product (FPP): Preparation of product dossiers (PDs) in Common Technical Document (CTD) Format;
• “Quality” guideline: 10.373: Guideline on submission of documentation for a multisource (generic) finished pharmaceutical product (FPP): Quality part
EMP TBS, 3 November 2011
Key changes from the previous guideline
Reductions in requirements:- fewer batches required to establish the FPP shelf-life- process validation report for pilot batches no longer required (replaced by uniformity demonstration for the biolot)- reduced process validation/pharmaceutical development requirements for “established” generics
EMP TBS, 3 November 201113
Application of BCS in PQP
PQP has reviewed existing information on the bioavailability and dissolution data of the invited medicines
Identified some drug substances as eligible for a BCS-based biowaiver application - either monocomponent or fixed-dose combination (FDC) products
Monocomponent or FDC products containing other drug substances must be supported with in vivo BE data
EMP TBS, 3 November 201114
PQ Dossier Variation GuidanceThree main categories of variations, according to potential impact to quality of product and current
timelines we aim to achieve (achieved already)
• Notification - no or minimal impact: 30 days
• Minor change - potential minor impact: 60 days
• Major change - potential major impact: 60 days
EMP TBS, 3 November 201115
Requalification
Procedure for prequalification of pharmaceutical products requires holders of WHO-prequalified
products to submit a quality review after five years from the date of prequalification of the product, or when requested to do so by PQP (whichever date is
earlier)
EMP TBS, 3 November 2011
Status of RQ Applications – Oct 2011
PQd by 2005
Due for RQ*
Appln Rcd
Withdrawn at RQ Stage
Deadline extended
Pending
HIV 104 47 29 6 3 9
TB 8 5 3 1 1 0
Malaria
3 2 1 10 0
Total 115 54 33 8 4 9
* Adjusted to exclude cancellations/withdrawals before due date for RQ
25 products approved in 2006 (15 innovators) – 10 generics are due for requalification
EMP TBS, 3 November 201117
Current Affairs
• Revision of the Variation Guidelines• Published list of prequalified APIs and their specific attributes
(5)• Part 2(b) of WHOPAR including pictures of product• Part 8 of WHOPAR – variations now included• Publish prevailing timelines for key processes• New internal centralised and enhanced database• Information to applicants on how we prioritise assessments and
inspections• BCS biowaiver – to include Emtricitabine and Abacavir