Update on WHO Prequalification of IVDs

Transcription

1 Update on WHO Prequalification of IVDs Geneva, 11 March 2016 Mercedes Perez Gonzalez Anita Sands Prequalification Team - Diagnostics World Health Organization

2 Outline Progress and Pipeline Ongoing concerns Addressing the challenges Update on post-qualification activities

3 WHO Prequalified IVDs Products prequalified in 2015 Total products prequalified to date 17, including 8 malaria RDTs 55 IVDs > Broadcast sent when each product is prequalified > List of prequalified products and each of their PQ Public Reports is available at y/evaluations/pq_list/en/

4 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- phase Expanding network of evaluating sites Establish requirements and assess laboratories Provide opportunity to manufacturers to mandate evaluations to WHO assessed laboratories

5 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

6 HIV RDTs in the Pipeline Product name Product code(s) Manufacturer name Dossier review On-site inspection Laboratory evaluation Aware HIV-1/2 OMT First Response HIV Card test REF-98164, REF and REF I05FRC30, I05FRC60, I05FRC05, I05FRC01 Calypte Biomedical Corporation u u u Premier Medical Corporation Ltd F u u BioTracer HIV 1/2 Rapid Card Bio Focus Co., Ltd. F R u Genie Fast HIV 1/ , Bio-Rad R u u OraQuick HIV 1/2 Rapid Antibody Test 5x4-0010, 5x OraSure Technologies, u Inc. u u u DPP HIV 1/2 Assay Chembio Diagnostic u Systems, Inc. u u u RightSign HIV 1.2.O rapid test cassette (Whole blood/serum/plasma) IHIV-C42W Alere HIV Combo MP Diagnostics MULTISURE HIV Rapid Test Diagnostic Kit for HIV(1+2) Antibody (Colloidal Gold) V2 7D2842, 7D2843 and 7D2343SET KH-R-02, R C-2, and A-GOLD-01 Hangzhou Biotest Biotech Co,Ltd F u Alere Medical Co. Ltd. F u u MP Biomedicals Asia Pacific Pte. Ltd. Shanghai Kehua Bioengineering Co., Ltd. R 1 S 1

7 HIV EIAs and Supplemental Assays HIV EIAs Product name Product code(s) Manufacturer name Enzygnost HIV Integral 4 OPKR035, OPKR055, OPKR055Q, OUVP175 Siemens Healthcare Diagnostics Products GmbH Dossier review On-site inspection Laboratory evaluation u u HIV Supplemental Product name Product code(s) Manufacturer name MP Diagnostics HIV Blot and Geenius HIV 1/2 Confirmatory Assay with Geenius HIV1/2 Confirmatory Controls Dossier review On-site inspection MP Biomedicals Asia Pacific Pte. Ltd. u R Laboratory evaluation and Bio-Rad u u u

8 HIV Virological Technologies Product name Product code(s) Manufacturer name Dossier review On-site inspection Laboratory evaluation 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 u 1 Alere q HIV-1/2 Detect , , Aptima HIV-1 Quant Dx Assay PRD , PRD-03002, PRD-03001, , PRD-03003, Alere Technologies GmbH u 1 1 Hologic, Inc. Generic HIV Charge Virale TR IC and TR IC Biocentric u 1 1 S SAMBA HIV-1 Semi-Q Test , I , I , S01-001, S 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, INFINITY EUROPE, INFINITY48-24, INFINITY48-24-EUROPE, INFINITY48-32, INFINITY48-32-EUROPE, INFINITY48- Cepheid 40, INFINITY48-40-EUROPE, INFINITY48-48, INFINITY48-48-EUROPE etc. Diagnostics for the Real World Ltd R u 1

9 Product name Enzygnost Anti-HCV 4.0 Multisure HCV Antibody Assay HCV Assays Product code(s) OPFM035 and OPFM055 Manufacturer name Siemens Healthcare Diagnostics Products GmbH MP Biomedicals Asia Pacific Pte. Ltd. INNOTEST HCV Ab IV 80068, Fujirebio Europe NV Murex HCV Ag/Ab Combination (4J24) 4J24-01 and 4J24-02 HCV Antibody ELISA Kit PT-HCV-96 Monolisa HCV Ag-Ab ULTRA V , Bio-Rad MONOLISA Anti-HCV PLUS Version , Bio-Rad DiaSorin South Africa (Pty) Ltd Pishtaz Teb Zaman Dossier review On-site inspection u Laboratory evaluation u 1 Diagnostics R S u u u u HCVSCAN , EY Laboratories Ltd F 1 SD BIOLINE HCV RightSign HCV rapid test cassette (Serum/Plasma) 02FK10 IHCV-C31W Standard Diagnostics, Inc. F u 1 Hangzhou Biotest Biotech Co,Ltd Oraquick HCV RDT , Orasure Technologies F 1 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- Cepheid L, GXII-2-D, GXIV-1-L,, GXIV-1-D,, GXIV-2-L,, GXIV-2-D,, GXIV-3-L, etc. u

10 HBV and HPV Assays HBV Assays Product name Product code(s) Manufacturer name DS-EIA-HBsAg-0,01 B-1252, B-1254, B-1255, B-1256, B- 231 Dossier review On-site inspection Laboratory evaluation RPC "Diagnostic Systems" u u u Bioelisa HBsAg and Biokit S.A. u u 1 Siemens Healthcare Diagnostics Enzygnost HBsAg 6.0 OPIH035 and OPIH055 Products GmbH 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 F 1 HPV Assays Manufacturer On-site Product name Product code(s) Dossier review name inspection carehpv Test QIAGEN GmBH 1 R Laboratory evaluation

11 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)

12 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

13 Update on post-qualification activities

14 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.

15 WHO post-market surveillance of IVDs Any class of IVD Proactive PMS Reactive PMS Lot verification testing Evaluation of EQA/QC data Pre-distribution Post-distribution Complaint Possible Field Safety Corrective Action Possible issuance of Field Safety Notice

16 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

17 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)

18 Reactive post-market surveillance of IVDs > Reporting of administrative and technical complaints by end-users/procurers/ implementers As soon as you become aware Reactive PMS Complaint > Ensures that any necessary investigation is conducted Possible Field Safety Corrective Action Possible issuance of Field Safety Notice

19 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)

20 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

21 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

22 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.)

23 Where to find information > Contact us by > Sign up for our mailing list By ing > Check our website Post-market surveillance tory/postmarket/en/ > Complaints and product alerts tory/procurement/complaints/en/