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
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Field trials are expensive, not possible across many products,
specific in time and population
200+ malaria RDT in the market; 60+ manufacturers)
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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
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WHO-FIND strategy for QA of RDT-based diagnosis
Supply chain management
Transport and storage
Manufacture
End users
Product development
Appropriate training and
instructions
Availability of common
reference standards
Management of positive
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
purchase
Before
distribution
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Before
use
Current Product Testing
Comparative evaluation of commercially-available antigen-detecting malaria
rapid diagnostic tests – RDTs.
$ R6
Evidence of quality
manufacturing
Open call
EOI
RDTs to specimen bank with
temperature monitor
Performance
versus panel
Stability
Ease-of-Use
assessment
Review of results by technical group
Results released to manufacturers
Final publication
5 years
Longer-term
stability test by
manufacturer
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
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Malaria Antigen Targets for RDTs
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Antigen concentrations (HRP2,pLDH, aldolase) in panel
samples Rounds 1-5
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Performance measure: Panel detection score
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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))
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Results: PDS @ 200 and 2000p/µL
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Combined Pf and Pv PDS
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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
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Compulsory resubmission – 10/22
• PDSPf and
PDSPv were
significantly
lower in
compulsory
resubmissions
as compared to
voluntary
resubmissions
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RDT anomalies
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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
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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
Apr.
2010 Rd 2
May
2011 Rd 3
Dec
4.38%
2012 Rd 4
Dec
0.35%
Jan-Jun
2013
0.58%
71.19%
88.49%
93.42%
95.76%
89.04%
94.18%
99.04%
1.44%
0.00%
10.07%
6.58%
Not submitted to Product Testing
PDS* ≥75%
(high performance criteria)
PDS* ≥50%
(WHO medium performance criteria)
PDS* ˂50% including False Positive
(outside WHO criteria)
28.81%
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0.35%
4.24%
6.58%
5.11%
0.38%
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
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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 pLDHHRP2 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
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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)
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Recombinant antigen based system
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2013-2017 plan funded by UNITAID
Cost:
2003 -2011
2011-2014
$$$$
$$$$$
2015-2016
$$$
FUNDED
2017
$
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)
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