Round 5 Malaria Policy Advisory Committee Meeting WHO HQ Geneva, 11 - PowerPoint PPT Presentation

WHO-FIND Malaria RDT Evaluation Programme: Product Testing Round 5 Malaria Policy Advisory Committee Meeting WHO HQ Geneva, 11 September 2014 Jane Cunningham Global Malaria Programme

Overview • Background • Overview of Product testing process • Round 5 results – what’s new ? • WHO procurement criteria • Market trends and impact on manufacturers • Future – Product testing and lot testing based on recombinant Ag panels – 2 – 2

Field trials are expensive, not possible across many products, specific in time and population 200+ malaria RDT in the market; 60+ manufacturers) – 3 – 3

International collaboration • Between 2002-2008, WHO, TDR, FIND, US CDC and other partners developed methods, characterized (microscopy, PCR, ELISA), diluted and stored wild type P. falciparum and P.vivax clinical samples from Africa, South America and South East Asia – 4 – 4

WHO-FIND strategy for QA of RDT-based diagnosis Supply chain management Transport and storage End users Manufacture Appropriate training and Product development instructions Availability of common Management of positive reference standards and negative results Stage 1: Product testing Monitoring of commodity supply and disease rates Evaluate product performance Stage 2: Lot testing Confirm product quality on arrival in country before distribution to the field Stage 3: QC at point of use (positive control wells) Ensure that RDTs have maintained accuracy through transport and storage Before Before Before purchase distribution use – 5 – 5

Current Product Testing Comparative evaluation of commercially-available antigen-detecting malaria rapid diagnostic tests – RDTs. $ R6 Evidence of quality Open call manufacturing EOI RDTs to specimen bank with temperature monitor Longer-term Performance Ease-of-Use Stability stability test by versus panel assessment manufacturer Review of results by technical group Results released to manufacturers Final publication 5 years

Product Testing (at US CDC) • Performance – panel detection score, false-positive and invalid rates – Phase 1 – 20 cultured P.falciparum samples; 2 lots; 1 RDT/lot @2000p/µl ; 2 RDT/lot @ 200p/µl + 20 clean negative samples in R6 – Phase 2 • P.falciparum (100), P.vivax (35), 2 lots; 1 RDT/lot @2000p/µl ; 2 RDT/lot @ 200p/µl • 1000 negative samples (mixed clean and other disease conditions) • Heat stability (4 ° C, 35 ° C, 45 ° C; 75% humidity x 60 days) • Ease of use assessment – blood safety, instructions quality, no. timed steps, RDT anomalies – 7 – 7

Malaria Antigen Targets for RDTs – 8 – 8

– 9 – 9

Antigen concentrations (HRP2,pLDH, aldolase) in panel samples Rounds 1-5 – 10 – 10

Performance measure: Panel detection score – 11 – 11

Rounds 1-5 • Published Rounds 1- 5 • 206 RDTs evaluated (147 unique products) • Round 5 : 42 RDTs (23 resubmissions (10 compulsory) 31 combo, 9 Pf, 2 pan (34 manufacturers) • Round 6 41 RDTs (30 combo, 11Pf (22 manufacturers)) – 12 – 12

Results: PDS @ 200 and 2000p/µL – 13 – 13

Combined Pf and Pv PDS – 14 – 14

PT results are the basis for WHO procurement criteria Eligible for tender: 58 RDTs (24 Pf, 31 combo, 2 pan; 1 Pv only) Further considerations: ● Stability ● Ease of use and training requirements ● Price ● Lot testing – 15 – 15

Compulsory resubmission – 10/22 • PDS Pf and PDS Pv were significantly lower in compulsory resubmissions as compared to voluntary resubmissions – 16 – 16

RDT anomalies – 17 – 17

WHO Prequalification of malaria RDTs WHO has started in 2007 the prequalification of malaria RDTs according to the following procedure: So far the following RDTs has been prequalified: • SD BIOLINE Malaria Ag P.f (05FK50/05FK53) • SD BIOLINE Malaria Ag P.f/Pan (05FK63 and 05FK60) WHO PQ Lab evaluation = WHO Malaria RDT Product Testing – 18 – 18

Panel Detection Score (PDS) of Malaria RDT submitted for lot-testing (for pre/post procurement) 100.00% 90.00% 80.00% 70.00% 60.00% 50.00% 40.00% 30.00% 20.00% 10.00% 0.00% 2007 2008 2009 Rd 1 2010 Rd 2 2011 Rd 3 2012 Rd 4 Jan-Jun Apr. May Dec Dec 2013 Not submitted to Product Testing 4.38% 0.35% 0.58% PDS* ≥ 75% 71.19% 88.49% 93.42% 95.76% 89.04% 94.18% 99.04% (high performance criteria) PDS* ≥ 50% 1.44% 0.00% 0.35% (WHO medium performance criteria) PDS* ˂ 50% including False Positive 28.81% 10.07% 6.58% 4.24% 6.58% 5.11% 0.38% (outside WHO criteria) – 19 – 19

RDT trends (2008-2013) Data provided by 29 manufacturers eligible for participation in the WHO RDT Product Testing Programme Source: WHO/GMP manufacturer survey 2014 Based on Global Fund and PMI data (compiled by CHAI and UNITAID) Three manufacturers won 90% of tenders in 2012 • • Four won 98% in 2013 90% of public sector supplies depends on 2 manufacturers • – 20 – 20

Impact on manufacturers • Following Round 5 – One prequalified product – Immunoquick Malaria falciparum (0502_K 25,50,100 Dipstick ) ( Biosynex) is delisted (PF PDS <75% and ++ red background – One market leader combination test , First Response pLDH- HRP2 Combo Test, I16FRC (Premier Medical Corporation) scored P.vivax PDS 74.3% (Pf PDS 85%). • Comparable to scores in Rounds 1 and 2 – PDS 75%. – 2014 NOT eligible for WHO tender or procurement – Procured by Ethiopia, Tanzania, DRC, Madagascar, Rwanda, India, Pakistan, Myanmar, Cambodia, Indonesia – 21 – 21

Limitations of current system • Need to reduce costs ++ to ensure sustainability and reasonable manufacturer payments • Need to standardize panels across time and space • 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) – 22 – 22

Recombinant antigen based system – 23 – 23 – 23

2013-2017 plan funded by UNITAID 2003 -2011 2011-2014 2015-2016 2017 Cost: $$$$ $$$$$ $$$ $ FUNDED

Thank you ! • FIND • 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) – 25 – 25