Overview of the Transition, progress so far and normative guidance

Transcription

1 Overview of the Transition, progress so far and normative guidance Dr Raman Velayudhan Coordinator Vector Ecology and Management Dept. of Control of Neglected Tropical Diseases World Health Organization, Geneva, Switzerland

2 Outline Transition GLP accreditation Vector Control Advisory Group Equivalence Future work..

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4 GLP accreditation GMP & NTD October 2016 Geneva, Switzerland

5 I2I grant GLP accreditation WHO Criteria for selection of countries & research institutions 1. Existing WHO collaborating institutions engaged on pesticide product testing and other potential research institutions 2. Geographical representation of sites 3. Diversity of vectors to be tested Susceptible Resistant 4. Feasibility to evaluate a range of pesticide products 5. Institutional commitment and resources

6 WHO & IVCC sites for GLP accreditation Current testing capabilities: Region Site Products Phases Institut Pierre Richet (IPR), Institut National de Santé Publique, Cote d Ivoire LLIN IRS IVCC to lead WHO to lead West Africa East Africa America s Western Pacific SEA Institut de Recherche en Sciences de la Santé (IRSS) Centre Muraz, Bobo Dioulasso, B.F. LLIN IRS CREC, Cotonou (in collaboration with LSHTM), Benin LLIN IRS Centre Suisse de Recherches Scientifiques en Cote d Ivoire, CSRS, Cote d Ivoire LLIN Kilimanjaro Christian Medical University College, Moshi, Tanzania LLIN IRS Ifakara Health Institute, Bagamayo Research & Training Centre, Tanzania LLIN 2 3 Brazil & any other Latin American institution (TBD) SS Larv 2 3 Centro Regional de Investigación en Salud Pública, Tapachula, Mexico IRS 2 3 Vector Control Research Unit, Universiti Sains Malaysia, Penang, Malaysia SS Larv 2 3 Institute for Medical Research, Kuala Lumpur, Malaysia LLIN IRS SS 2 3 WHO CC - Centre for Disease Control, Beijing, China SS Larv 2 3 WHO CC - National Institute of Malaria Research (NIMR), Delhi, India LLIN IRS Larv WHO CC - Vector Control Research Centre, Puducherry, India LLIN IRS 2 3 Europea n WHO CC IRD, Montpellier, France LLIN IRS Larv 1

7 STEPS Baseline facility audit / onsite inspection, gap audit VCRC NIMR CCDC IMR VCRU IRD C C C C C P GLP Training Workshop C C C C C P Development of SOPs and Quality Management Systems O O O O O P Off site mentoring O O O O O P Progress reporting ( / Skype) O O O O O P Infrastructure improvements for GLP compliance purposes O O O O O P Training of Quality Assurance Manager P P P P P P Self-audit P P P P P P Development of GLP Training Manual C C C C C P Follow-up visit for facility audit P P P P P P ACCREDITATION PHASE Capacity building for GLP Inspectors (GLP CP) Application for GLP accreditation First visit of GLP Body Follow-up visit by GLP Body Accredation Granted FULLY ACCREDITED 7 C =completed O= ongoing P = planned

8 Vector Control Advisory Group (VCAG) on New Tools for Vector Control GMP & NTD & PQ October 2016 Geneva, Switzerland

9 VCAG repositioning and scheduled activities Revision of TOR functions: To assess the evidence for new vector control tools / approaches; To advise WHO on proof of principle of such tools; To discuss and finalize the Target Product Profiles; To advise WHO on product development plans including data requirements for accelerated recommendations. Membership comprising of 2 groups: A core group of 7, including chair, term of 3 years A flexible group of experts (max 8) invited as needed

10 VCAG repositioning and scheduled activities Special meeting on vector control pathways (19 Sept 2016) As multiple new innovative tools & approached have been reviewed, there is need to map out pathways for new vector control products and expected evaluation methods Selected VCAG, MPAC and STAG members, plus other experts with experience in public health product development and evaluation Output: expert advice to WHO on data requirements for new tools/approaches in Vector control 5 th VCAG meeting (2-4 Nov 16) Focus gene drive system (two ideas) and SIT for vector control Update on progress for other tools already reviewed by VCAG

11 Paradigm Paradigm in vector control is a category of intervention that share a common entomological mechanism of actionto reduces infection/ vector borne diseases. Paradigm is the same as a class of product category. It requires evidence of epidemiological efficacyas a proof of concept to confirm the product claim has impact on disease. A new paradigm requires a tailor made or specific set of evaluation and guidance for deployment.

12 Steps Pathway: LLIN Extension of claim to efficacy against insecticide resistance populations: New types of mixture/combination LLINs NOT previously reviewed(whopes& VCAG) Outcome expected 1 Manufacturer undertakes pre-submission meeting (participants: GMP, NTD and PQ) 2 Standard LLIN Efficacy(WHOPES Efficacy I/ II), Safety and Specifications 3 Demonstrate claims of efficacy against resistant populations (Laboratory and small scale field testing of IR claims VCAG guidelines) 4 Full demonstration of IR efficacy claims through field trials in areas of moderate to high pyrethroid resistance. The end points will be: VCAG/ERG to assess the data and the claim VCAG recommendation on IR efficacy 1. Community RCT with epidemiological endpoints (comparing standard LLIN vs new LLIN(PY+newAI)oneseasontrialand 1. Entomological end points, Proof of concept will require one trial, to validate the product does biologically what it claims todo (PQ listing on product claim.) 5 FulldemonstrationofLLINefficacythroughlargescalefieldtrials(WHOPESEfficacyIII) PQ Dossier Review and Listing(proceduresand timing defined by WHO PQ) Potential Outcome Pathway (1) VCAG endorses the proven efficacy claims against insecticide resistance (qualification of the claim, type of resistance mechanism required); publication of assessment via VCAG report (2) PQ listing and public assessment report leading to registration of products by countries (3) WHO Disease programmes (GMP) recommends where and how such LLINs can be used / deployed and develops operational guidance. Additional trial data may be needed for policy recommendation(gradual process) (4) Final Step:- Policy recommendation to be considered by MPAC. (5) Subsequent products in same category with resistance management claim will go through PQ for review

13 Steps Pathway 3: New Intervention Concept Biological Wolbachiainfected Mosquitoes specific for dengue/zika, Outcome so far for Wolbachia and Oxitec 1 Pre-submission meeting / Review LOI Completed 2 VCAG Initial Concept Review (Advice on any needed data for disease programme policy making) Completed 3 EAG/ERG to assess risk / safety and guide efficacy trials Completed 4 Entomological and Epidemiological efficacy data generated manufacturer generates data and dossier Reviewed 5 Specifications / Quality control criteria developed In progress 6 VCAG Data Review for Concept (answers the question: is the intervention effective against vectors? Against disease?) (CRT starting in 2017) 7 EAG for disease programme policy making (answers the question: what (if any) place does the intervention have in vector borne disease programmes?) 8 Policy Decision by WHO (advised by STAG) Potential Outcome Pathway Pilot deployment (with conditions) EAG/NTD (1) VCAG endorses the proven efficacy claims for the new intervention concept, publication of VCAG report (2) WHO Disease programme (VEM/NTD) recommends where and how these interventions can be used / deployed and develops operational guidance. Additional trial data and assessment via EAG may be needed for policy recommendation. (3) Final Step:- Policy recommendation to be considered by STAG.

14 Steps Pathway: New types of IRS AI previously not reviewed(whopes& VCAG) Outcome expected 1 Manufacturer undertakes pre-submission meeting (participants: GMP, NTD and PQ) 2 Standard IRS Efficacy (WHOPES Efficacy I/ II), Safety and Specifications 3 Demonstration of claims of efficacy against resistant populations (Laboratory and small scale field testing of IR claims VCAG guidelines) 4 Full demonstration of IR efficacy claims through field trials in areas of moderate to high pyrethroid resistance. The end points will be: ERGtoassessthedataandtheclaim VCAG recommendation on IR efficacy 1. Community RCT with epidemiological endpoints (comparing standardirsvsnewirsand 1. Entomological end points(proof of concept), Proof of concept will require one trial, to validate if the product does biologically what it is supposed to do, based on which guidance on deployment conditions will be issued 5 Full demonstration of IRS efficacy through large scale field trials (WHOPES Efficacy III) PQ Dossier Review and Listing (full) Potential Outcomes (1) PQ Interim Review, Listing and Public Assessment Report leading to country registration (2) VCAG endorses the efficacy claims for the AI, publication of VCAG report (3) PQ full review including efficacy against IR (4) WHO Disease programmes(gmp) recommends where and how IRS can be used/ deployed and develops guidance (5) Final Step:- Policy recommendation to be considered by MPAC.

15 Overview: new vector control tools in process and predicted timelines for policy development POLICY DEVELOPMENT PIPELINE New Category Prototype Step 1: Concept Step 2: Efficacy (Ento) Step 3: Efficacy (Epi) Risk Assess. Policy Review Specifications Operational Guidance Resistance targeting products PermaNet 3.0 LN X X not applicable X X MPAC 3 / 2015 ERG 9 / 2015 Microbial Control Wolbachia X X In progress ongoing ongoing Spatial Repellents Transfluthrin passive emanator X X In progress planning Vector traps for disease management A LOT / TNK / AGO / In2Trap X X In progress planning Systemic insecticides Rodent bait X X In progress Lethal House Lures Eave tubes and bricks X X in progress Genetic manipulation OX513A Aedes aegypti X X in progress ongoing ongoing Attract and kill baits Attractive Toxic Sugar Bait X X in progress (IVCC) Insecticide treated materials for specific risk groups none X stalled due to prototype Operational

16 PresubmissionGuidance (GMP/NTD/PQT) Based on LOI What is the label claim Data requirement Trial diversity (Geographic, vectors) QA assessment PQ dossier Does it need an ERG New paradigms REFER to VCAG Robust and complete guidance including time line

17 Equivalency October 2016 Geneva, Switzerland

18 Objectives: To discuss outcomes of the WHO informational session on determination of equivalence for pesticide-based vector control products, 1 2 February 2016; To further understand the perspectives of pesticide manufacturers on the current FAO/WHO equivalence criteria and procedures; and To advise on the FAO/WHO criteria, procedures and data requirements for determination of equivalence for public health pesticide products.

19 Evaluation parameters for reference LN 1. Human exposure risk assessment (HRA) 1. Regeneration time 2. Wash resistance index (WRI) for at least 20 laboratory washes 3. Active ingredient chemical content (within ±25% tolerance limit of the specification) 4. For new AI with knockdown/killing action: - Intrinsic insecticidal activity (lethal dosage; lethal concentrations) - Excito-repellent or irritant properties -Cross-resistance to other insecticide classes/ mechanisms - Discriminatory concentration. LLIN Evaluation parameters for generic LN Current criteria Changes proposed 1. No HRA None required 1. Regeneration time 1. The regeneration time 2. WRI for at least must be shorter or equal to 20 laboratory that of the reference LN. washes 2. The wash resistance index 3. Chemical shouldbe same, as for the content reference LN. 3. Same specification for chemical content (±25%) this involves parallel comparison between innovative versus generic LN. 4. Conduct cone, and if required tunnel test, on nets washed at least 20 times following the same wash procedure as for experimental hut trials. Use existing efficacy criteria for cone/tunnel test.

20 IRS Evaluation parameters for reference IRS products 1. Human exposure risk assessment (HRA) Tests for the new AI with knockdown/killing actions: 1. Intrinsic insecticidal activity (lethal dosage; lethal concentrations) 2. Excito-repellent or irritant properties 3. Cross-resistance to other insecticide classes/ mechanisms 4. Discriminatory concentration. 5. Efficacy and residual activity of the formulated product on relevant substrates (e.g. mud, cement, wood). 6. Quality control testing of the formulated product for compliance with WHO/ manufacturer's specification. Evaluation parameters for generic IRS products Changes Current criteria proposed 1. HRA not 1. None required 2. None of 1. Comparative insecticidal the tests efficacy and residual activity of are the formulated product on required relevant substrates (generic versus reference products). Residual activity and efficacy of generic products should be same or longer than the reference product. 2. Quality control testing of the formulated product for compliance with WHO/ manufacturer's specification.

21 Larvicides Evaluation parameters for reference mosquito larvicides 1. Human exposure risk assessment (HRA) 1. Biopotency of the technical material (lethal dosage and concentrations) 2. Diagnostic concentration of technical material 3. Cross-resistance to other insecticide classes 4. Biological activity of the formulated product. 5. Assessment of cross-resistance 1. Efficacy under different ecological settings 2. Method and rate of application 3. Initial insecticidal and residual activity 4. Effect on non-target organisms Evaluation parameters for generic mosquito larvicides Current criteria Changes proposed 1. HRA not 1. None required 1. No test 1. None required 1. No test required 1. Simulated efficacy evaluation under laboratory condition 2. Test 2, 3 & 4 not required for generic products

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23 Thank you!

24 Wolbachia could be a revolutionary form of protection against mosquito-borne disease. It s affordable, sustainable, and appears to provide protection against Zika, dengue, and a host of other viruses. We re eager to study its impact and how it can help countries, said Dr Trevor Mundel, president of the global health division of the Bill and Melinda Gates Foundation. There are great hopes for Wolbachia but it is too soon to suppose this is the answer to the Zika and dengue epidemics. I m in equipoise. I really hope it will work, but I d like to see the evidence at scale. Jeremy Farrar, director of the Wellcome Trust 26 October 2016