WHO Prequalification of Diagnostics WHO/UNICEF Technical Briefing Seminar

WHO Prequalification of Diagnostics

WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies 29 Oct – 2 November, Geneva

Anita SandsDiagnostics & Laboratory Technology Team

Department of Essential Medicines & Health Products

2 | Technical Briefing Seminar on Essential Medicines Policies, Geneva l 29 Oct – 2 Nov 2012

Regulation of diagnostics (IVDs)

Regulation specifically for diagnostics is often poorly understood and/or poorly enforced

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

Procurement policies drive supply of quality assured products

– often acting as de facto regulatory control


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.


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


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


Prequalification of Diagnostics

Application by Manufacturer

Meets Requirements

DossierAssessment

Manufacturing Site Inspection

Laboratory Evaluation

Product Prequalified

Post Market Surveillance


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


Prioritization 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




Meets Requirements

DossierAssessment






Dossier: requirements Dossier must demonstrate that the

IVD conforms to the Essential Principles of Safety and Performance of Medical Devices (GHTF/SG1/N41R9:2005)Key ComponentsProduct description

Design and manufacturing information

Product performance specifications & associated validation and verification studies

Labelling

Commercial history

Regulatory history

Quality management system


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 characteristicsClinical (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

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:039:0034:0049:EN:PDF






Meets Requirements

DossierAssessment






Inspection: requirements The manufacturer must demonstrate

that the IVD is produced under a functional quality management system e.g. conforms to ISO 13485:2003Key ComponentsQuality management system including documentation requirements Management responsibilityincluding customer focus, quality policyResource managementincluding human resources, work environmentProduct realizationincluding production and service provision, control of monitoring and measuring devices Measurement, analysis and improvementincluding control of nonconforming product, improvement


Inspection: requirementsDossier submission data – to confirm is true

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




Meets Requirements

DossierAssessment






Laboratory evaluation: protocol

Panel name No. of specimens WHO HIV specimen reference panel

460 HIV positive 658 HIV negative

Lot-to-lot variation panel 16 member 2-fold dilution series of 10 specimens (n=160)

HIV seroconversion panels 8 panels (n=52)

HIV mixed titre panel 1 panel (n=25)

WHO reference preparation 2 panels (n=7)

If Ag/Ab assay

HIV p24 antigen panel 1 panel (n=25)

HIV culture supernatant 6 member 2-fold dilution series of 10 subtypes

Specimens are characterised by

– 3rd generation EIA (Ab) – 4th generation EIA (Ab/Ag)– HIV-1 24 antigen EIA (Ag) – HIV-1/2 line immunoassay

(Ab only)


Laboratory 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

Parameter (HIV) RDTs EIAsSensitivity ≥99% 100%

Specificity ≥98% ≥98%

Inter-reader variability

≥5% N/A

Invalid rate ≥5% ≥5%




Meets Requirements

DossierAssessment






Prequalification: 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




Meets Requirements

DossierAssessment






Post-market surveillance

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


PQDx 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


Products eligible for procurement

http://www.who.int/diagnostics_laboratory/procurement/purchase/en/index.html


Contact us

Contact us by email

[email protected]

WHO Prequalification of Diagnostics programme

website

http://www.who.int/diagnostics_laboratory/evaluations/en/

Documents

WHO Prequalification of Diagnostics WHO/UNICEF Technical Briefing Seminar