Changes to the WHO-FIND Malaria RDT Lot Testing Programme
For the last 9 years, FIND and WHO have coordinated an independent global quality assessment programme for malaria rapid diagnostic test (RDT) lots. The programme was funded initially by the Bill and Melinda Gates Foundation and the Global Fund to Fight AIDS, Tuberculosis and Malaria and, over the last 5 years, has been supported by UNITAID and USAID/JSI. The programme is designed to assess lot-to-lot variations in RDT performance in order to ensure that only malaria RDT lots that meet performance standards are used in endemic countries. Since 2011, lot testing has been mandatory for all Global Fund grant recipients and has been adopted by all other major RDT procurers.
From 2007 through 2016, the global lot testing programme tested more than 5000 RDT lots (representing over 900 million RDTs) destined for more than 70 endemic countries. The testing was conducted free of charge for health ministries, malaria control programmes, RDT procurers, implementing organizations and RDT manufacturers, using reference laboratories in Cambodia (Institut Pasteur [IPC]) and Philippines (Research Institute for Tropical Medicine [RITM]).
In an effort to promote sustainable quality assurance activities in countries and reduce the demand on centralized testing services, a new, partially decentralized lot testing model is planned for implementation in 2018. Although WHO is still in the process of securing funding for the new programme, information on the plans for the new lot testing scheme is provided below.
Vision for a future malaria RDT lot testing programme
Pilot decentralization with international reference centre support
The current model, funded exclusively by donors with FIND’s involvement, will end on 31 December 2017; therefore, this programme is now transitioning to a partially decentralized system that uses affordable and reproducible recombinant antigens to screen RDT lots instead of using clinical samples, which are expensive to collect, characterize and maintain. However, due to the differences between recombinant antigens and native proteins/clinical samples in terms of RDT reactivity, real/clinical or cultured parasites will always be used for confirmatory testing of suspected lot failures. Confirmatory testing against well-characterized specimens will be conducted at an international reference centre based at the The Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, United States of America.
The WHO Global Malaria Programme will be responsible for coordinating the decentralized scheme, which will be rolled out initially in a limited number of national reference laboratories in 10 countries in sub-Saharan Africa1 and four countries in Asia.2 Technicians at these laboratories have been trained to perform the new lot testing procedures. If funding is secured, these laboratories will only test those lots destined for deployment in their respective countries. In the case of suspected lot failures, CDC will support the laboratories by conducting confirmatory lot testing against archived and well-characterized cultures and/or wild-type samples.
How can lot testing be requested?
In 2018, all lot testing will need to be requested through a web-based database system https://extranet.who.int/malariardt. The system will then automatically direct the requester on where to ship the RDTs: either to the pilot lot testing laboratory or to the international reference laboratory. Requesters will first need to create an account. Once the request is logged, they will be able to track the progress of their lot testing request.
For all laboratories outside of this pilot network, all requests will be directed to the CDC, which will provide initial and, if required, confirmatory lot testing. In addition, any lots that are destined both for countries participating in the pilot lot testing and for other countries will be tested at the central lot testing laboratory.
Will lot testing laboratories charge a fee?
Widespread accessibility to lot testing services remains the goal. However, pilot laboratories are expected to mobilize resources in their country to support lot testing activities; this could involve charging a fee.
WHO is endeavouring to secure the resources required to support activities at CDC as well as central coordination and monitoring activities. At the moment, however, it is not clear whether fees may need to be introduced to cover all or part of the costs to support central level activities.
How does lot testing using recombinant panels differ from testing against clinical or cultured blood samples?
Recombinant antigens are not identical to native malaria proteins and therefore an RDT’s reactivity to a recombinant antigen will not necessarily be the same as its reactivity to a blood sample containing malaria parasites. For this reason, recombinant antigens are used to screen for changes in RDT reactivity, which could signal a decline in performance in the field. RDTs that fail to detect recombinant antigens will be sent for repeat testing at the international reference centre (CDC). If failure is confirmed, the RDTs will be subsequently tested against wild-type or cultured Plasmodium parasites to determine whether the reduced reactivity to the recombinant equates to reduced detection of clinical samples (with antigen concentrations comparable to 200p/µL).
Thus, recombinant panels will only be used to monitor changes in RDT reactivity, whereas wild-type samples will be used to guide the decision on lot failure during the confirmatory testing at the international reference centre.
Who will supply the recombinant antigen panels?
The recombinant panels that will be used at the international reference centre and in pilot laboratories will be purchased through FIND’s commercial partner. Panels for HRP2, pf-pLDH and pv-PDH are expected to be available by Q4 2017 (see http://www.microcoat.de/Products/recombinant-panels-for-malaria-diagnostic-tests/).
Will testing of RDT lots continue in the long term?
The new procedure for lot testing does not include “long-term testing”. Testing is currently being done 6 months prior the RDT’s expiry date. However, in the pilot countries, recombinant panels can be used to verify RDTs collected from the field whenever there is a complaint.
When will the new lot testing procedures apply?
The current lot testing services provided by IPC in Cambodia and RITM in Philippines will stop on 31 December 2017. If funding is secured by the pilot national laboratories and by WHO, the new programme will start on 15 December 2017. Therefore, final requests for lot testing at IPC and RITM will be accepted until 5 December in order to ensure there is enough time for shipping, testing and reporting.
Can additional countries participate in the new scheme and become pilot lot testing countries?
During the planned 18-month pilot phase, WHO will be unable to provide oversight and troubleshooting support to additional countries not included in the pilot lot testing programme. If the outcomes of the pilot phase are favourable, lot testing will be expanded to more national reference laboratories in the future.
Please do not hesitate to contact FIND or WHO should you require more information about this transition.
1 Ethiopia, Kenya, Madagascar, Malawi, Mozambique, Nigeria, Rwanda, Tanzania, Uganda and Zimbabwe
2 Cambodia, India, Myanmar and Philippines