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1 Copenhagen, Denmark 24 – 27 September 2018
Update on Dossier Assessment and
Performance evaluation
Mark Lanigan
Mercedes Perez Gonzalez
Willy Urassa
Components of the prequalification (PQ) process
Copenhagen, Denmark 24 – 27 September 2018 2
Dossier review
Site inspection
Laboratory evaluation
Pre-submission form
Dossier review Site inspection
Laboratory evaluation
Dossier complete
Dossier screening
Eligible product
Yes
No
Dossier incomplete
Maintenance of PQ Status
Prequalification procedure
Prequalification decision
• PQ assessment based on existing evidence from prior
regulatory approval
• Comparison of requirements with existing mechanisms
• Benefit of existing evidence but independent decisions
• Avoids duplication of effort
• Reduces time taken to prequalify
Abridged assessment
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• Which products are considered?
◦ Product has been assessed by stringent regulatory
authority
◦ Product has rest-of-world (RoW) non-stringently
assessed version that is identical to the assessed
version
Abridged assessment
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Regulatory authority Risk classes undergoing
stringent assessment
European Union Annex II, List A
US Food and Drug Administration Class III
Health Canada Class IV
Therapeutic Goods Administration, Australia Class 4
Ministry of Health, Labour and Welfare, Japan Class III
Pre-submission form
Site inspection Laboratory evaluation
Eligible product
Yes
No
Maintenance of PQ Status
Abridged assessment
PREQUALIFICATION DECISION
Dossier Aspects
Demonstrate that the manufacturer has considered the
quality, safety and performance of its product in the
countries where WHO PQ IVDs are procured
Purpose of the dossier – unique PQ characteristics
• Programmatic suitability: specific emphasis on issues of
particular relevance to resource-limited settings, such as:
• Stability of products
• e.g. heat and humidity
• Suitable specimen type
• Labelling of products
• Ease of use
• training and material
• Performance evaluated in the global population
• Life cycle management of products
Purpose of the dossier – unique PQ characteristics
Number of new applications (Sept. 17 – Sept. 18)
34
Full assessment 27
Abridged assessment 7
Update on dossier assessment in 2017 – 2018*
Copenhagen, Denmark 24 – 27 September 2018
*September 2017 – September 2018
10
Update on dossier assessment in 2017 – 2018
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Assay type CD4 Cholera G6PD Hepatitis C HIV &
HIV/syphilis Malaria
Lateral flow rapid
diagnostic tests 2 1 2 2 15* 4
Enzyme
immunoassays 1* 1*
Nucleic acid test 1* 4*
Flow cytometer 1
* Including abridged assessments
Update on dossier assessment in 2017 – 2018
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Product No.
applications
received
No. of
applications
cancelled
No. of
applications in
dossier review
CD4 enumeration 3 2
Cholera 1
G6PD deficiency 2 1 1
Hepatitis C (RDT, EIA) 4 3
HIV (RDT, NAT, EIA) 18 6 6
HIV/Syphilis 2 1
Malaria 4 2
Total 34 9 11
Dossier review timelines 2017 - 2018
Number of dossier reviews completed:
(Sept. 17 – Sept. 18)
Prequalified
Rejected
11
4
1
Time taken to complete dossier review:
average [median] 198 [180] days
Update on dossier assessment – WHO perspective
• PQ working to increase transparency for manufacturers: through publication of WHO requirements, revision of WHO documents and alignment with other organizations, for example:
• Technical Specification Series
• Technical Guidance series
• Consultation with international experts on requirements for new eligible IVDs
• Participation and alignment with international harmonisation efforts and standardisation bodies
Dossier assessment: 2018 – 2019
• PQ continuing to review and improve processes based
on experience and feedback
• Continued publication of Technical Specifications
outlining the performance study criteria for eligible
IVDs
• Transition to TSS requirements as part of dossier
assessment and prequalification follow up
• Implementation of IMDRF “Table of Contents format:
• Dossiers
• Dossier reports
• Guidance documents
• Time extensions have flow-on impact:
• Scheduling availability of assessors
Performance evaluations
Independent verification of the performance of IVDs submitted for prequalification. Provide WHO an opportunity to verify performance aspects that are considered essential in resource-limited settings. The dataset obtained complements the verification and validation data submitted by the manufacturer in the product dossier and findings in the site inspection Conducted in WHO Prequalification Evaluating Laboratories using WHO protocols
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Performance evaluation of molecular technologies
• Assays are challenged with a focus on their use in resource-
limited settings and in the context of WHO guidelines
• Evaluation includes an analytical component and a clinical
component:
Analytical performance*: the ability of an IVD medical device to detect or
measure a particular analyte.
Clinical performance*: the ability of an IVD medical device to yield results
that are correlated with a particular clinical condition/physiological state
in accordance with target population and intended user.
Copenhagen, Denmark 24 – 27 September 2018
* IMDRF definition
17
Performance evaluation pathways
Option 1: Performance evaluation coordinated by WHO upon reception of a pre-
submission form:
• The performance evaluation is scheduled by WHO as soon as the product
is designated as meeting WHO prioritization criteria.
Option 2: Performance evaluation commissioned by the manufacturer and carried out at
a Prequalification Evaluating Laboratory listed by WHO
• The manufacturer selects a laboratory from the list of WHO
Prequalification Evaluating Laboratories
• The manufacturer will bear the cost of the evaluation and be responsible
for coordinating it directly with the laboratory
• The selected evaluating laboratory will inform PQ as soon as an evaluation
has been commissioned by a manufacturer
• A Pre-submission form is required prior to commencement of the
study
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• Malaria RDTs • Performance evaluation will from now on be coordinated by
WHO PQ
• No more round testing, evaluations performed on a rolling basis
• No more stability testing, dealt through dossier review
• Performance reports will be sent to individual manufacturers, results provided after each evaluation
• No more composite reports.
• Added analytes • Glucose 6 Phosphate Dehydrogenase
• Cholera RDTs
• Syphilis RDTs (Treponemal and non-treponemal)
• Expansion of scope to all HPV molecular technologies
Updates in 2018
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Prequalification: decision
20 Copenhagen, Denmark 18-21 September 2017
• Final prequalification outcome depends on: • Results of dossier assessment and acceptance of action plan
• Results of inspection(s) and acceptance of action plan
• No level 5 nonconformities outstanding for either dossier or for inspection
• Meeting the acceptance criteria for the laboratory evaluation
• WHO PQDx Public Report is posted on WHO website and product is added to the list of WHO prequalified products
• Product is then eligible for WHO and UN procurement
Post - Prequalification Activities
Maintenance of Prequalification Status
PQ Changes
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2015 2016 2017 2018
Number of reported
changes 13 33 39 26
Guidance on reporting changes to WHO
Guidance updated to
• Increase clarity for manufacturers on what is to be reported
• Provide descriptive generic examples of the changes to be reported
• Overview of how to determine the severity of a change and the WHO change assessment process
Thank you for your attention
Any questions?
Contact us by email: [email protected]
By emailing:
http://www.who.int/diagnostics_la
boratory/evaluations/en/
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25 Copenhagen, Denmark 24 – 27 September 2018
Thank you for your attention
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