WHO Prequalification of Diagnostics WHO Technical Briefing Seminar on Essential Medicines and Health...
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Transcript of WHO Prequalification of Diagnostics WHO Technical Briefing Seminar on Essential Medicines and Health...
WHO Prequalification of Diagnostics
WHO Technical Briefing Seminar on Essential Medicines and Health Products
WHO HQ, Geneva, 28 October - 1 November 2013
Mercedes Pérez GonzálezDepartment of Essential Medicines & Health Products
2 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Regulation of diagnostics (IVDs)Regulation of diagnostics (IVDs)
Regulation specifically for diagnostics is often poorly understood and/or poorly enforced
Production of many diagnostic products has been moved to countries with less strict regulatory framework.
Different categories of IVDs regulated differently– HIV IVDs, particularly for blood screening, attract greatest
stringency– Degree of stringency is usually risk-based– Risk perception is different in different settings
Different regulatory versions of the same product
3 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Who sets international standards?Who sets international standards?
Organization
International Organization for Standardization (ISO)
Certification of ISO compliance is made by an independent agency.
Global Harmonization Task Force (GHTF) Comprised on national regulators & industry.Issues guidance on specific topics related to medical devices including IVDs.
International Medical Device Regulators Forum (IMDRF) - replaced GHTF
Comprised on national regulators.Maintains GHTF guidance documents.
Clinical and Laboratory Standards Institute (CLSI)
Issues guidance documents specific for testing processes.
4 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Role of WHO Role of WHO
To provide normative guidance to Member States on when and how to use IVDs to guide clinical decision-making
– WHO ART guidelines
To provide recommendations on quality and performance of IVDs through the WHO Prequalification of Diagnostics programme according to international standards
To increase in-country capacity to effectively regulate & to monitor quality of diagnostics in their market
5 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
To promote and facilitate access to safe & appropriate diagnostic technologies of good quality in an equitable manner
– Through adoption of GHTF guidance and ISO requirements
Customers– WHO Member States – UN agencies – Funding and procurement agencies
Aim of WHO Prequalification of Diagnostics Aim of WHO Prequalification of Diagnostics
6 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Prequalification of Diagnostics Prequalification of Diagnostics
Application by Manufacturer
Meets Requirements
DossierAssessment
Manufacturing Site Inspection
Laboratory Evaluation
Product Prequalified
Post Market Surveillance
7 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Application: requirements Application: requirements
Manufacturer may submit application at any time to [email protected]
– Must use the Prequalification of Diagnostics application form
– Instructions for the completion of the application form contains information to help fill the form
8 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Prioritization of PQDx applicationsPrioritization of PQDx applications
Comment Current prioritization criterion
Ensure continuity of supply and quality of products procured
Already listed on WHO/UN procurement scheme and procured by UN organizations in significant levels
Focus on priority disease areas – highest historical procurement
Assist diagnosis of infection with HIV-1/HIV-2, or malaria
Bringing testing closer to the community Rapid test format
Ensure known supply chain; no duplication of effort, best possible prices
Original product manufacturers
Focus on unmet market / procurement needs Few other prequalified products exist in the product category such as CD4, VL
9 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Prequalification of Diagnostics Prequalification of Diagnostics
Application by Manufacturer
Meets Requirements
DossierAssessment
Manufacturing Site Inspection
Laboratory Evaluation
Product Prequalified
Post Market Surveillance
10 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Dossier: requirements Dossier: requirements Based on best international practice (ISO,
EN, GHTF, CLSI); follow the content of the GHTF STED
Looks into critical aspects for WHO Member States often not dealt with/dealt with from a local prospective by SRAs (stability, IFU, RA, etc.).
Dossier must demonstrate that the IVD conforms to the Essential Principles of Safety and Performance of Medical Devices (GHTF/SG1/N41R9:2005)
11 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Dossier: requirements Dossier: requirements
Key Components
Product description
Design and manufacturing information
Product performance specifications & associated validation and verification studies
Labelling
Commercial history
Regulatory history
Quality management system
12 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Dossier: submission Dossier: submission
Clinical evidence to validate performance claims– One clinical evaluation* performed by Manufacturer– One clinical evaluation* performed independently
• Must clearly relate to the product undergoing prequalification (same name, same product code, same regulatory version)
*The EC Common Technical Specifications (CTS) for IVDs 2009 are a useful guide
http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:039:0034:0049:EN:PDF
Performance characteristics
Clinical (diagnostic sensitivity) including seroconversion sensitivity
Clinical (diagnostic) specificity
Positive and negative predictive values (high/low prevalence)
Different clinical stages
Geographical distribution (consider intended use setting)
Genotypic differences
13 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Prequalification of Diagnostics Prequalification of Diagnostics
Application by Manufacturer
Meets Requirements
DossierAssessment
Manufacturing Site Inspection
Laboratory Evaluation
Product Prequalified
Post Market Surveillance
14 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Inspection: requirementsInspection: requirements
The manufacturer must demonstrate that the IVD is produced under a functional quality management system e.g. conforms to ISO 13485:2003
Key Components
Quality management system including documentation requirements
Management responsibilityincluding customer focus, quality policy
Resource managementincluding human resources, work environment
Product realizationincluding production and service provision, control of monitoring and measuring devices
Measurement, analysis and improvementincluding control of nonconforming product, improvement
15 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Inspection: requirementsInspection: requirements
Dossier submission data – to confirm is true
Production
QC and lot release– QC panels should be challenging enough to detect failure or drift– Independence and adequately staffed QA/QC department– Deviation reporting procedures observed
WHO related/end user issues - IFU- stability (transport, in-use, expiry dates)- training- complaints reporting mechanisms
16 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Prequalification of Diagnostics Prequalification of Diagnostics
Application by Manufacturer
Meets Requirements
DossierAssessment
Manufacturing Site Inspection
Laboratory Evaluation
Product Prequalified
Post Market Surveillance
17 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Evaluations performedEvaluations performed
WHO evaluation protocols followed, based on existing international standards and best practice and adapted to assay type
Performance and operational characteristics
WHO Collaborating Centres performs evaluation under supervision of WHO
WHO Composite Reports of all products produced
– Report 17 to be released
18 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Laboratory evaluation: outcomeLaboratory evaluation: outcome
If RDT, results are read by 3 independent readers
Two production lots are submitted to assess lot-to-lot variation
Results of the WHO laboratory evaluation must meet the acceptance criteria
EIA (Laboratory) RDT (Point of Care or Laboratory)
HIV serology
Sensitivity: 100% Specificity: ≥ 98%
Sensitivity ≥ 99% Specificity ≥ 98%Inter-reader variability ≤5%Invalid rate ≤5%
HCV serology
Sensitivity: 100% Specificity: ≥ 98%
Sensitivity ≥ 98% Specificity ≥ 97%Inter-reader variability ≤5%Invalid rate ≤5%
HBsAg serology
Sensitivity: 100% Specificity: ≥ 98%
Sensitivity 100% Specificity ≥ 98%Inter-reader variability ≤5%Invalid rate ≤5%
19 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Prequalification of Diagnostics Prequalification of Diagnostics
Application by Manufacturer
Meets Requirements
DossierAssessment
Manufacturing Site Inspection
Laboratory Evaluation
Product Prequalified
Post Market Surveillance
20 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Prequalification: decisionPrequalification: decision
Final prequalification outcome depends on: – Results of dossier assessment and acceptance of action plan – Results of inspection and acceptance of action plan
• no critical nonconformities outstanding– 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
21 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
PQDx fast track procedure PQDx fast track procedure
The process relies on provision of relevant “evidence” of certification issued by a stringent regulatory authority (SRA) or their authorised representative(s)
Submitted evidence will be considered for its suitability in satisfying WHO requirements.
This applies to– the dossier assessment (product design and development), – and/or inspections of the site of manufacture and the quality
system – And/or the laboratory evaluation
22 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
PQDx assessment status for all productsPQDx assessment status for all products
WHO website updates the status of each product undergoing PQDx assessment monthly
http://www.who.int/diagnostics_laboratory/pq_status/en/index.html
23 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Products eligible for procurementProducts eligible for procurement
http://www.who.int/diagnostics_laboratory/procurement/purchase/en/index.html
24 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Prequalification of Diagnostics Prequalification of Diagnostics
Application by Manufacturer
Meets Requirements
DossierAssessment
Manufacturing Site Inspection
Laboratory Evaluation
Product Prequalified
Post Market Surveillance
25 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Post-market surveillancePost-market surveillance
Should be the onus of the manufacturer, but poorly executed
WHO PQDx complaint form for end users to report issues– http://
www.who.int/diagnostics_laboratory/procurement/complaints/en/index.html
– GHTF/SG2-N54R8:2006• Medical Devices Post Market Surveillance: Global Guidance for Adverse
Event Reporting for Medical Devices– GHTF/SG2-N57R8:2006
• Medical Devices Post Market Surveillance: Content of Field Safety Notices
Pilot project on PMS– Regulatory capacity building– Capacity building at the NRL level
26 | WHO Technical Briefing Seminar on Essential Medicines and Health Products , Geneva l 31 October 2013
Contact us Contact us
Contact us by email
WHO Prequalification of Diagnostics programme
website
http://www.who.int/diagnostics_laboratory/evaluations/en/