Transcript The WHO Prequalification of Medicines Programme Dossier Assessment Update Rutendo Kuwana Technical Officer Prequalification of Medicines Program WHO.

The WHO Prequalification of Medicines
Programme
Dossier Assessment Update
Rutendo Kuwana
Technical Officer
Prequalification of Medicines Program
WHO
5 Key Assessment Stages
EOI Publication
Application Received
Screening
Assessment
Prequalification
Variation
Requalification
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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
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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
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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
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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
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Product dossiers accepted for assessment:
2005 – 2011 (as at 1st November 2011)
2005
HIV
67
TB
17
Malaria
3
Repr Health
Influenza
Diarrhoea
NTD
Total Accptd 87
Total Submitted
2006
2007
2008
2009
2010
2011
42
9
5
56
25
17
7
10
59
90
42
12
9
4
1
68
92
24
11
3
7
7
1
53
83
21*
16
6
7
0
1
35
51
26(19)
17 (11)
8 (5)
3 (0)
0 (0)
2 (1)
1(1)
37
57
* Includes 2 products (Water for Injection) not included in any of the EoIs
(…) dossiers accepted for assessment
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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.
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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
st
Total WHO PQd as at 1 November 2011 - 263
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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
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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
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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
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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 BCSbased 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
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PQ Dossier Variation Guidance
Three 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
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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)
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Status of RQ Applications – Oct 2011
PQd by
Due for
2005
RQ*
Appln Rcd Withdrawn at
RQ Stage
Deadline
extended
Pending
104
47
29
6
3
9
TB
8
5
3
1
1
0
Malaria
3
2
1
1
0
0
115
54
33
8
4
9
HIV
Total
* Adjusted to exclude cancellations/withdrawals before due date for
RQ
25 products approved in 2006 (15 innovators) – 10 generics are due
for requalification
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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
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