update on who prequalification of ivds · update on who prequalification of ivds geneva, 11 march...

WHO PREQUALIFICATION PROGRAMME

Update on WHO Prequalification of IVDs

Geneva, 11 March 2016

Mercedes Perez Gonzalez

Anita Sands

Prequalification Team - Diagnostics

World Health Organization


Outline

• Progress and Pipeline

• Ongoing concerns

• Addressing the challenges

• Update on post-qualification activities


WHO Prequalified IVDs

> Broadcast email sent when each product is prequalified

> List of prequalified products and each of their PQ Public Reports is available at

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

Products prequalified in 2015 Total products prequalified to date

17, including 8 malaria RDTs 55 IVDs


What’s new? (1)

> PQ scope expanded to include

• HPV assays

• HIV assays intended for self-testing

• G6PD assays (for administration of primaquine and tafenoquine for

radical cure of P. vivax)

> Alternative mechanism for WHO PQ performance evaluation

• Shift performance evaluations to current pre-assessment phase

• Expanding network of evaluating sites

• Establish requirements and assess laboratories

• Provide opportunity to manufacturers to mandate evaluations to

WHO assessed laboratories


What’s new? (2)

> Updated guidance on how to report changes • Currently available for public comment

> Development of the Emergency Use Assessment and Listing as an emergency quality assurance mechanism for the listing of products outside of PQ scope in the context of a PHEIC

• Ebola (6 products listed)

• Zika


HIV RDTs in the Pipeline

Product name Product code(s) Manufacturer name Dossier review

On-site inspection

Laboratory evaluation

Aware™ HIV-1/2 OMT REF-98164, REF-98166 and

REF-98169

Calypte Biomedical

Corporation u u u

First Response® HIV 1-2-0 Card test I05FRC30, I05FRC60,

I05FRC05, I05FRC01

Premier Medical

Corporation Ltd F u u

BioTracer™ HIV 1/2 Rapid Card 11112 Bio Focus Co., Ltd. F R u

Genie™ Fast HIV 1/2 72330, 72327 Bio-Rad R u u

OraQuick HIV 1/2 Rapid Antibody Test 5x4-0010, 5x4-0012 OraSure Technologies,

Inc. u u u

u

DPP® HIV 1/2 Assay 65-9500-1 Chembio Diagnostic

Systems, Inc. u u u

u

RightSign HIV 1.2.O rapid test

cassette (Whole blood/Serum/Plasma) IHIV-C42W

Hangzhou Biotest

Biotech Co,Ltd abbreviated

assessment F u

Alere HIV Combo 7D2842, 7D2843 and

7D2343SET Alere Medical Co. Ltd. F u u

MP Diagnostics MULTISURE HIV

Rapid Test 43031-020

MP Biomedicals Asia

Pacific Pte. Ltd. abbreviated

assessment R

Diagnostic Kit for HIV(1+2) Antibody

(Colloidal Gold) V2

KH-R-02, R-401-50-C-2, and

A-GOLD-01

Shanghai Kehua

Bioengineering Co.,

Ltd. 1 S 1


HIV EIAs and Supplemental Assays

HIV EIAs

HIV Supplemental


On-site inspection


Enzygnost HIV Integral 4 OPKR035, OPKR055, OPKR055Q, OUVP175

Siemens Healthcare Diagnostics Products GmbH

abbreviated assessment u u


On-site inspection


MP Diagnostics HIV Blot 2.2 11030-018 and 11030-036 MP Biomedicals Asia Pacific Pte. Ltd. u R

abbreviated assessment

Geenius HIV 1/2 Confirmatory Assay with Geenius HIV1/2 Confirmatory Controls

72460 and 72329 Bio-Rad u u u


HIV Virological Technologies

Product name Product code(s) Manufacturer

name Dossier review

On-site inspection


Xpert HIV-1 Quant with GeneXpert Instrument Systems (GeneXpert Dx)

GeneXpert Dx Model GX-I Product Codes/catalogue numbers: GXI-1-L and GXI-1-D. GeneXpert Dx Model GX-II Product Codes/catalogue numbers: GXII-1-L, GXII-1-D, GXII-2-L, and GXII-2-D.Etc.

Cepheid abbreviated

assessment u 1

Alere q HIV-1/2 Detect 270110050, 270110010, 270300001 Alere Technologies GmbH u 1 1

Aptima HIV-1 Quant Dx Assay PRD- 03000, PRD-03002, PRD-03001, 303014, PRD-03003, 303095

Hologic, Inc. abbreviated

assessment u 1

Generic HIV Charge Virale TR001-250IC and TR001-440IC Biocentric abbreviated

assessment 1 S

SAMBA HIV-1 Semi-Q Test 4100-12, I19-0004, I19-0005, S01-001, S01-0002 Diagnostics for the Real World Ltd R

Xpert® HIV-1 Qual Assay Xpert® with GeneXpert Dx, GeneXpert Infinity-48s, and GeneXpert Infinity-80

GXXVI-4-L, GXXVI-4-D, GXXVI-8-L, GXXVI-8-D, GXXVI-12-L, GXXVI-12-D, GXXVI-16-L, GXXVI-16-D GeneXpert Infinity-48s: INFINITY48-16, INFINITY48-16-EUROPE, INFINITY48-24, INFINITY48-24-EUROPE, INFINITY48-32, INFINITY48-32-EUROPE, INFINITY48-40, INFINITY48-40-EUROPE, INFINITY48-48, INFINITY48-48-EUROPE etc.

Cepheid abbreviated

assessment u 1


HCV Assays


name Dossier review

On-site inspection


Enzygnost Anti-HCV 4.0 OPFM035 and OPFM055

Siemens Healthcare Diagnostics Products GmbH

abbreviated assessment u

Multisure HCV Antibody Assay 43130-020 MP Biomedicals Asia Pacific Pte. Ltd.

abbreviated assessment u 1

INNOTEST HCV Ab IV 80068, 80330 Fujirebio Europe NV abbreviated assessment u

abbreviated

assessment

Murex HCV Ag/Ab Combination (4J24) 4J24-01 and 4J24-02 DiaSorin South Africa (Pty) Ltd

abbreviated assessment u

HCV Antibody ELISA Kit PT-HCV-96 Pishtaz Teb Zaman Diagnostics R S

Monolisa HCV Ag-Ab ULTRA V2 72561, 72562 Bio-Rad abbreviated assessment u

MONOLISA Anti-HCV PLUS Version 3 72340, 72341 Bio-Rad abbreviated assessment u

HCVSCAN 3-303-20, 3-003-100 EY Laboratories Ltd F 1

SD BIOLINE HCV 02FK10 Standard Diagnostics, Inc. F u 1

RightSign HCV rapid test cassette (Serum/Plasma)

IHCV-C31W Hangzhou Biotest Biotech Co,Ltd

abbreviated assessment F 1

Oraquick HCV RDT 1001-0274, 1001-0270 Orasure Technologies abbreviated assessment u 1

Xpert® HCV Viral Load with GeneXpert Dx, GeneXpert Infinity-48s, and GeneXpert Infinity-80

Product Codes/catalog numbers: GXHCV-VL-CE-10. GeneXpert Dx: GXI-1-L, GXI-1-D, GXII-1-L, GXII-1-D, GXII-2-L, GXII-2-D, GXIV-1-L, , GXIV-1-D, , GXIV-2-L, , GXIV-2-D, , GXIV-3-L, etc.

Cepheid abbreviated assessment u


HBV and HPV Assays

HBV Assays

HPV Assays


On-site inspection


DS-EIA-HBsAg-0,01 B-1252, B-1254, B-1255, B-1256, B-231

RPC "Diagnostic Systems" u u u

Bioelisa HBsAg 3.0 3000-1158 and 300-1159 Biokit S.A. u u 1

Enzygnost HBsAg 6.0 OPIH035 and OPIH055 Siemens Healthcare Diagnostics Products GmbH

abbreviated assessment u u

SD BIOLINE HBsAg 01FK10W Standard Diagnostics 1 u 1

RightSign HBsAg rapid test cassette (Serum/Plasma)

IHBSG-C31-W Hangzhou Biotest Biotech Co,Ltd

abbreviated assessment F 1


name Dossier review

On-site inspection


careHPV Test 614015 QIAGEN GmBH 1 R


Ongoing concerns

> Quality of product dossier submissions

• The quality of the data submitted in the product dossiers remains

incomplete or low quality.

• Mainly an issue for HIV and malaria RDTs, and hepatitis submissions.

• However, quality has improved in subsequent submissions from the

same manufacturer.

> Quality management systems

• Site inspections continue to identify major and critical non-conformities

> Access to appropriate specimens for certain laboratory

evaluations (oral fluid, EID, certain levels of VL)


Addressing the Challenges

> PQ Technical Guidance Series • TGS 1 Standards applicable to the WHO Prequalification of in vitro diagnostics, final version published.

• TGS 2 Establishing stability of an in vitro diagnostic for WHO Prequalification, draft for public review.

• In development:

o Guidance on Performance Studies that will encompass both Analytical Studies and Clinical Studies.

o Guidance document on Instructions for Use.

> Sample product dossiers for WHO PQ • CD4 IVD for POC, final version published

• HIV RDT for HIV self-testing, draft for public review

• HIV POC EID and VL in development

> Alternative performance evaluation mechanism (in development) and strategic partnerships


Update on post-qualification activities


Updated guidance on how to report changes

> New classification of changes:

Changes are defined either as reportable or non-reportable

All substantial changes and certain administrative changes

associated with a prequalified IVD are considered as reportable

changes

These must be reported via submission of the WHO document

PQDx_119 “Change Report Form for a WHO Prequalified In

Vitro Diagnostic”

The document is currently out for public comment.


WHO post-market surveillance of IVDs

Reactive PMS

Evaluation of EQA/QC data

Pre-distribution

Possible issuance of Field Safety Notice

Post-distribution Complaint

Possible Field Safety Corrective Action

Lot verification testing

Proactive PMS

Any class of IVD


Proactive PMS for IVDS: lot testing

> Lot verification by suitably qualified laboratory using SOPs

so that each lot testing event is consistent

> Through physical inspection of packaging, labelling, IFU

− Looking for breaches of packaging that might affect stability

> Testing of samples from each lot of the same IVD

− Against a well-characterized panel of specimens

− Same panel for both pre-distribution and post-distribution lot testing

> Lot acceptance criteria (pass/fail) for inspection and testing


Proactive PMS for IVDs: evaluation of EQA/QC data

> Review data from EQA

schemes (proficiency

testing) and end-user QC

− Greatest value when there

are many users are of the

same assay

> Useful to report differences

in performance such as this

example of a shift (lot to lot)


Reactive post-market surveillance of IVDs

> Reporting of administrative

and technical complaints by

end-users/procurers/

implementers

− As soon as you become

aware

> Ensures that any necessary

investigation is conducted

Reactive PMS

Possible issuance of Field Safety Notice

Complaint

Possible Field Safety Corrective Action


Reactive PMS: Field Safety Corrective Action

> A FSCA is triggered when there is an unacceptable

increase in risk associated with use of the IVD

> the manufacturer should reduce a risk of death or serious

deterioration in the state of health associated with the use of an

IVD

> FSCAs may include:

− return of IVD to supplier (recall), IVD modification (including IFU), IVD

exchange (swap-out), IVD destruction, retrofit by purchased of IVD

according to manufacturer modification\design control (usually related

to instruments)


Reactive PMS: Field Safety Notice

> If a FSCA is undertaken

− E.g. change to reading time to improve specificity, shortening of expiry date for a particular lot, etc.

> End-users will be informed using a Field Safety Notice sent by the manufacturer, via their in-country distributor

> End-users should follow instructions of FSN and contact WHO when in doubt


WHO normative guidance on PMS

> Roles/responsibilities of stakeholders

> Forms

− IVD complaint form

− Manufacturer complaint investigation report

− Field Safety Corrective Action report

− Lot testing data collection & report

> Notices

− Field Safety Notice


Complaints submitted to WHO

> In total, 38 complaint notifications to WHO

− False negative x9

− False positive x5 (+1 combined with FN)

− Invalid rate x8

− Defective product x5

− Mislabelling x3

− Safety x2

− Miscellaneous x2

> Mostly complaints resolved through agreed FSCA

(modification of IFU, return of devices, revised design, etc.)


Where to find information

> Contact us by email

− [email protected]

> Sign up for our mailing list

− By emailing [email protected]

> Check our website

− Post-market surveillance

− http://www.who.int/diagnostics_labora

tory/postmarket/en/

> Complaints and product alerts

− http://www.who.int/diagnostics_labora

tory/procurement/complaints/en/

update on who prequalification of ivds · update on who prequalification of ivds geneva, 11 march...

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