Lot Testing of malaria RDTs: achievements and lessons learned from a 7 year-long experience

Transcription

1 Lot Testing of malaria RDTs: achievements and lessons learned from a 7 year-long experience Incardona S., Luchavez J., Nhem S., Barnwell J., Champouillon N., Chiodini P., Luna C., Ménard D., Meth R., Rees-Channer R., Sornillo J., Bell D., Cunningham J., González IJ. ASTMH meeting October 28 th, 205 Implementation, testing, and development of malaria diagnostics

2 WHO-FIND malaria RDT evaluation programme Manufacture -Product development -Availability of common reference standards Supply chain management CDC (USA) Stage : Product testing Evaluate product performance Stage 2: Lot testing Confirm product quality on arrival in country before distribution in the field Transport and storage IPC (Cambodia) RITM (Philippines) Stage 3: QC at point of use (positive control wells) Ensure that RDTs have maintained accuracy through transport and storage End users -Appropriate training and instructions -Management of positive and negative results -Monitoring of commodity supply and disease rates PCWs evaluated in Uganda and Lao PDR Before purchase Before distribution Before use ASTMH meeting Philadelphia October 28th, 205 2

3 Specimen bank for product and lot testing and network of partner organizations Sample type Details Product testing Lot testing Manufacturers panel Culture P. falciparum Several strains at parasites/µl and 0 parasites/µl X X Patient derived P. falciparum p/µl and 0 p/µl from Africa, Asia, South America X X Patient derived P. vivax p/µl and 0 p/µl from Asia and South America X X Negative samples ANA; rheumatoid factor/ Clean negative / Other tropical diseases X X ASTMH meeting 3

4 Product testing results Rounds 2 to 5 - P. falciparum Evaluation of 70 unique products from 8 to 203 ASTMH meeting Philadelphia October 28th, 205 4

5 Evaluation of lots of malaria RDTs Objective: To control quality of RDT lots directly after purchase (pre-shipment) or before distribution in the field (post-shipment) Methods: Two laboratories (IPC in Cambodia and IRTM in Philippines) closely supervised, with annual EQA assessments, refreshing workshops, and 6- monthly proficiency testing Formal request to FIND from procurement agencies, RDT manufacturers, national programmes Shipment and testing of RDTs with turnover of 5 days between RDTs receipt and issue of report ASTMH meeting Philadelphia October 28th, 205 4

6 Volumes and quality of lots of RDTs tested since RDT lots submitted for routine Lot Testing, RDTs submitted for Lot Testing are increasingly of high quality; this reflects adherence of major RDT procurers to WHO recommendations for RDT procurement. 800 Number of RDT lots Year 204 testing volume was equivalent to 20 million RDTs (around 66% of RDT sales) ASTMH meeting Philadelphia October 28th, 205 6

7 Users of the RDT lot testing programme 7 to 204 Lot Testing is requested early in the procurement process by the RDT manufacturers (often on behalf of procurers) or by the procurers themselves (agencies, NGOs, IOs). Countries 4% Manufacturers* 40% NGOs/IO 34% Procurement agencies 22% Lot-tested RDTs were distributed in 48 countries, with 88% in sub-saharan Africa ASTMH meeting Philadelphia October 28th, 205 7

8 Other issues identified with the observation guide Issues of buffer evaporation in single use buffer vials were observed on 57 lots from 0 products of 3 manufacturers, up until end of > Notice of concern issued by WHO, procurement of single-use RDT kits on hold, and corrective actions underway with the manufacturers. ASTMH meeting Philadelphia October 28th, 205 8

9 Transition to a decentralized sustainable lot testing of malaria RDTs Evaluation of RDTs with panels of recombinant proteins: Cheaper and simpler than sample collection Standard commercially available reference materials Cost covered by users (country budgets) to avoid dependence on donor funding Piloting lot testing in 2 countries: Capacity building in reference laboratories Testing after shipment and before distribution Confirmatory testing of lots failing in the field ASTMH meeting Philadelphia October 28th, 205 8

10 Overall structure of a global sustainable QA programme for malaria RDTs Internal QC Manufacturer QC Lab by manufacturer. PRODUCT TESTING directly overseen by central oversight agrncy (COA) Central Reference Lab 2. LOT TESTING directly overseen by MoH [+ TECHNICAL SUPPORT from COA] 3. Field QC [PCW] directly overseen by MoH [+TECHNICAL SUPPORT from COA] National Ref. Lab National Ref. Lab National Ref. Lab RDT lot failure RDT failure with PCWs ASTMH meeting Philadelphia October 28th, 205 9

11 Conclusions Quality control and quality assurance of malaria RDTs are necessary to ensure access of patients to adequate diagnosis and treatment Implementation of a QC/QA programme for malaria RDTs has positively affected the market: procurement agencies are selecting good products and manufacturers are improving their RDTs Every country using malaria RDTs should have the capacity to ensure quality of lots being deployed in their endemic settings Malaria RDTs should have adequate positive controls in order to facilitate QC after distribution and to increase confidence of endusers in RDT results ASTMH meeting Philadelphia October 28th, 205 9

12 Acknowledgments FIND Geneva: Sandra Incardona Nora Champouillon (David Bell) FIND Uganda: Daniel Kyabayinze Global Malaria Programme (WHO/GMP): Jane Cunningham Andrea Bosman Centers for Disease Control (CDC): Jeffrey Glenn John Barnwell Hospital for Tropical Diseases (HTD) in London: Roxanne Rees-Channer Peter L. Chiodini University of Queensland, Australia: Michelle Gatton Australian Army Malaria Institute: Qin Cheng Institut Pasteur du Cambodge: Sina Nhem Didier Ménard Research Institute for Tropical Medicine (RITM), Philippines: Jennifer Luchavez University of Lagos, Nigeria: Wellington Oyibo Universidad Peruana Cayetano de Heredia, Peru: Dionicia Gamboa Katherine Torres 2

13 Backup slides ASTMH meeting - Philadelphia October 28th, 205 3

14 Interactive guide for selection of RDTs ASTMH meeting Philadelphia October 28th, 205 4

15 Long term testing Initial Testing Initial QC testing (Combination tests)* Pf A P. falciparum P. vivax Pf B Pf C Pf D Pv E Pv F Pv G Pv H Negative I J K L M N O P Q R * Initial QC testing : Use 48 RDTs, and use QC samples from 4 different Pf cases (A, B, C, D), 4 different Pv cases (E, F, G, H) and 0 different malaria parasite negative cases (I-R). Long-term QC testing (Combination tests) P. falciparum P. vivax Pf Pf Pv Pv Negative A B E F Long term QC testing : Use only 8 RDTs, and use QC samples from 2 different Pf cases (A, B), 2 different Pv cases (E, F) and 2 malaria parasite negative cases (I,J) used in the initial QC testing (if possible). 5