WHO-FIND Malaria RDT Evaluation Programme: an international collaboration for

quality control of malaria RDTs

Jane Cunningham, WHO/GMP

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Background • 1st WHO meeting on role of mRDTs

in 1999

• Survey in 2005 found dramatic increased number of commercially available RDTs (200+ products; 60+ manufacturers)

• Product selection hampered by reports of variable performance in field trials, lack of reference standards and general weak or unregulated environments.

• Field trials are expensive, not possible across many products, specific in time and population

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International collaboration (2003-2008)

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WHO-FIND strategy for QA of RDT-based diagnosis

Supply chain management Transport and storage End users Appropriate training and instructions

Management of positive and negative results

Monitoring of commodity supply and disease rates

Stage 1: Product testing Evaluate product performance

Stage 2: Lot testing Confirm product quality on arrival in country before dissemination to the field

Stage 3: QC at point of use (positive control wells)

Ensure that RDTs have maintained accuracy through transport and storage

–Before purchase

–Before distribution

–Before use

Manufacture ISO 13485 === WHO PQ

Availability of common reference standards

Current Product Testing Comparative evaluation of commercially-available antigen-detecting malaria

rapid diagnostic tests – RDTs.

Evidence of quality manufacturing

RDTs to specimen bank with temperature monitor

Review of results by technical group Results released to manufacturers

Performance versus panel

Stability Ease-of-Use assessment

Longer-term stability test by manufacturer

Final publication

Open call EOI

5 years

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• For the detection of Plasmodium falciparum (Pf) in all transmission settings the panel detection score (PDS) against Pf samples should be at least 75% at low parasite densities (200 parasites/μL).

• For the detection of Plasmodium vivax (Pv) in all transmission settings the panel detection score (PDS) against Pv samples should be at least 75% at low parasite densities (200 parasites/μL).

• The false positive rate should be less than 10%. • The invalid rate should be less than 5%.

PT results form basis for WHO Procurement criteria & lab evaluation component of WHO PQ Dx Programme

WHO Tender issued 2013: 53 products eligible (25 Pf, 26 combo, 1 pan; 1 Pv only)

Further considerations: ● Stability ● Ease of use and training requirements ● Price ● Lot testing

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Lot Testing – volume of RDT lots tested

59 139

243 236

365

567 521

0

200

400

600

800

1000

1200

2007 2008 2009 2010* 2011* 2012 Jan-Jun2013

Recomm

endation of the G

lobal Fund

Prod

uct

test

ing

roun

d 1

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Limitations of current system

• Need to reduce costs ++ to ensure sustainability and reasonable manufacturer fees

• Need to standardize panels across time and space and provide results on a continual (not interval) basis

• Need to make panels available to manufacturers (same as are

used for product testing and lot-testing) • Need to provide countries with standard, reliable, acceptable

materials for lot-testing (there will be increased requirement for in-country testing of RDTs in the future)

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Current and future Reference materials for RDT QC

Aim: -To partially replace parasite samples by recombinant antigens to evaluate the performance and stability of RDTs at different levels. -To standardize common reference materials at all QC levels from manufacturers to users of RDTs.

Sample type Details Product Testing

Lot Testing

ManufacPanels

Cultured P. falciparum 20 isolates 200 parasites/ul

X X X

Wild-type P. falciparum 200 p/ul and 2000 p/ul Africa, Asia, South America

X X

Wild-type P. vivax 200 p/ul and 2000 p/ul Asia and South America

X X

Negative samples ANA, rheumatoid factor, etc. Clean negative Other tropical diseases

X

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Process

Overall Structure of Evaluation Process

Manufacture site quality ISO13485 or WHO/PQ +/-

other

Full PT

~ Periodic / random blinded

panels

PANELS AVAILABLE FOR

MANUFACTURERS

Standardized in-house QC

Lot-testing

POC (field) testing

Inadequate performance

Oversight process (WHO?)

Screen

Manufacturers access same panels as are used for product testing, lot-testing, field QC

1 2

3 4

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Acknowledgements • FIND • TDR • US CDC • Hospital for Tropical Disease, UK • Queensland Institute of Medical Research, Australia • Army Malaria Institute, Australia • Research Institute Tropical Medicine, The Philippines • Institute Pasteur Cambodia • Collection sites: CIDEIM (Colombia), DMR (Myanmar), KEMRI

(Kenya), EHNRI (Ethiopia), IHRDC (Tanzania), IMT (Peru), IPB (Central Africa Republic), IPM (Madagascar), UCAD (Senegal), UL (Nigeria)