WHO Prequalification of Diagnostics

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 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


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 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)


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


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

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




Meets Requirements

DossierAssessment






Evaluations 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


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

EIA (Laboratory) RDT (Point of Care or Laboratory)

HIV serologySensitivity: 100% Specificity: ≥ 98%

Sensitivity ≥ 99% Specificity ≥ 98%Inter-reader variability ≤5%Invalid rate ≤5%

HCV serologySensitivity: 100% Specificity: ≥ 98%

Sensitivity ≥ 98% Specificity ≥ 97%Inter-reader variability ≤5%Invalid rate ≤5%

HBsAg serologySensitivity: 100% Specificity: ≥ 98%

Sensitivity 100% Specificity ≥ 98%Inter-reader variability ≤5%Invalid rate ≤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


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


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




Meets Requirements

DossierAssessment






Post-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

http://www.who.int/diagnostics_laboratory/procurement/complaints/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