Diagnostic Preparedness Platform WHO R&D Blueprint for Priority Infectious Diseases with Epidemic Potential

Transcription

1 Diagnostic Preparedness Platform WHO R&D Blueprint for Priority Infectious Diseases with Epidemic Potential 2 nd round presentation Geneva July 21 st, 2016

2 Diagnostic Preparedness Platform Aim Surveillance and monitoring of pathogens with high epidemic potential in resource limited settings Capacities for fast ramp up of diagnostic testing in central lab settings of epicentres of an outbreak and at the point of need Strategy Early detection of onsets of outbreaks by diagnostic tools in decentralized settings Corresponding central lab based confirmatory tests Scalability of production and implementation of POC and central lab based tests by leveraging existing R&D and production capacities at Alere and altona Capacity building and training in epidemiological hot spots 2

3 Diagnostic Preparedness Platform 3

4 MH2 Diagnostic Preparedness Platform Alere Technologies Alere q and lateral flow POC system Proven applicability Decentralized testing Scalable in volume and number of assays CE IVD, WHO PQ Dxfor Alere q HIV1/2 Detect Proven compatibility between altona RealStar assays and Alere q Filovirus Detect altona Diagnostics RealStar product line for tropical infectious disease Proven high quality standardized real-time (RT)-PCR kits CE IVD, FDA EUA, WHO EUAL Proven fast response to outbreaks (SARS, MERS, flu, CHIKV, EBOV, ZIKV) AltoStarautomatedhigh thoughput central lab workflow Solution Extension of Alere q assay portfolio by tests for WHO listed pathogens Extension of existing RealStar real-time PCR assay portfolio to complete high priority list transfer to the AltoStar automated workflow Creation of a scientific network of reference laboratories on a global scale 4

5 Folie 4 MH2 I would make two slides out of this one Markus Hess;

6 Alere q Technology Multiple Assays add sample direct from patient Molecular POC Array based detection Connected Automatic: Extraction Purification, Amplification and detection Single use Cartridge Onboard device and assay controls 5

7 Alere q Cartridge Features No cold chain requirements Real multiplexing capabilities Enables for diagnostic test panels SNP Detection Integrated Cartridge Workflow Extraction Target Isolation Amplification Array Detection - Chemical lysis - Mechanical lysis -Heat lysis - Specific target capturing (e.g. RNA) using biotinylated probes on sepharose beads PCR Real time & end point, Melting curves CMA technology; high density arrays - Unspecific DNA binding on silica beads 6

8 altona RealStar Technology Laboratory high throughput altona RealStar / AltoStar RealStar: Open platform Application on commonly used real-time PCR instruments High throughput in centralised laboratories Flexible parallel testing for target organism and differential diagnostic Parallel testing of symptomatically similar pathogens: shared PCR profile, shared internal control AltoStar workflow: Automated NA extraction from different sample matrices and automated PCR set-up MH7 7

9 Folie 7 MH7 Automated NA extraction from different sample matrices and automated PCR set-up Markus Hess;

10 SD Bioline Ab RDT s Product Specification Sample Type : serum, plasma and whole blood Sample Volume : 10 ul Interpretation Time : min Nitrocellulose membrane Control line Gold Conjugate Pad Sample Pad Absorbent pad Test procedure Test line (1) Dispense 10 ul of specimen into the sample well(s). SD Color scale chart (2) Dispense 4 drops of assay diluent vertically into the assay diluent well. (3) Interpret test results in 15~20 minutes. *Score rating 1+ positive: G1~G8 2+ positive: G9~G14 3+ positive: G15~G20 8

11 DPP Assay Panels Assay panels for Nucleic Acid Testing 1. VHF panelmandatorily including Ebola and Marburg viruses, Lassa virus, Rift Valley fever virus, and CCHF virus Optionally: Zika virus, dengue virus, and chikungunya virus, as well as malaria 2. Respiratory panel, mandatorily including SARS-CoV, MERS-CoV Optionally: pandemic Influenza viruses, RSV, MPV, PIV 3. Encephalitis panel, mandatorily including Nipah virus Optionally: Japanese encephalitis virus, Enterovirus species, rabies virus, herpesviruses and measles virus The lateral flow assays: Malaria and dengue on market Zika and chikungunya IgM/IgG/Ag in development. Other LF tests will be evaluated case by case to ensure appropriate use of RDT s within their performance specifications. 9

12 DPP Assay Panels Assay strategy POC assays to be spatially multiplexed in a multianalyte cartridge covering clinically relevant pathogens Central lab assays to be designed to run in parallel using one sample preparation offering flexibility to include region specific pathogens in the panel testing Shared process controls for QC and proficiency testing Selected lateral flow assays to widen the diagnostic window 10

13 Platform Integration Pathway I Transfer of existingrealstar assays to multiplexed Alere q POC system Example: Filovirus CCHFV Rift Valley fever virus Advantage: Same controls and uniform post-market-surveillance, relatively low development risk 11

14 Platform Integration Pathway II In case of new pathogens or new genotype parallel development of lab based and POC system. Advantage: Faster availability of outbreak control measures on all levels. 12

15 DPP Advantages Validation Shared validation protocols for Alere q and RealStar assays Leveraging biobanks, strain collections and BLS4 capacities of existing network of reference laboratories for validation of panels with stored samples and viral cultures Employment of developed panels in reference labs and their outstations for usability testing Laboratory Collaboration Network (LCN) Production and Quality Control Utilisation of existing production capacities for Alere q cartridges, lateral flow assays and RealStar/AltoStar assays Establishment of quality control process for panels 13

16 altona s Capacity Supply Fast ramp up of production capacity Own oligonucleotide production Own enzyme production Independence of suppliers for main components Example of ramp up potential: Filovirus assay 14

17 altona Portfolio and Pipeline Panel Assay planed development verification validation launched regulatory status Respiratory SARS CoV CE-IVD MERS CoV CE-IVD, FDA EUA Influenza A/B virus CE-IVD Respiratory syncytial virus CE-IVD Parainfluenza virus CE-IVD Human metapneumovirus CE-IVD VHF Filoviridae CE-IVD, WHO EUAL, FDA EUA Lassa virus CCHF virus Rift Valley fever virus Malaria parasites Dengue virus Chikungunya virus Zika virus Hantavirus Yellow fever virus CE-IVD Research Use Only CE-IVD CE-IVD CE-IVD CE-IVD, WHO EUAL*, FDA EUA Encephalitis Nipah virus Japanese encephalitis virus West Nile virus Herpes simplex virus Varizella zoster virus Measles virus CE-IVD CE-IVD CE-IVD * submitted 15

18 Alere s Global Capability Leading global supplier of POC diagnostics Shipped over 1 billion tests in 2015 Highly automated, high throughput and scalable manufacturing across sites in NA, Asia and Europe encompassing both lateral flow and instrument-based POC assays ~1/3 of our business is in Infectious Diseases and this is spread very evenly between regions (Sub-Saharan Africa, Latin America, Asia Pacific, Europe and the Middle East and North America) Our global reach * Regional Distributors: 147 Regional Distributors : 124 Regional Distributors: ** * 113 Key: Commercial T. Support Manufacturing R&D * Excludes Contracted Workers (3582) ** Excludes Philippines Health Management Business (939) 16

19 Alere q Assay Portfolio Alere q HIV-1/2 Detect Qualitative HIV diagnosis test for whole blood and plasma samples (CE-IVD marked, WHO PQ review) Alere q Filovirus Detect Pan-Filovirusscreening assay panel for detection and discrimination of 6 known Ebola and Marburg virus species (in clinical validation) FILOatj01 SUDV FILOatj02 EBOV FILOatj03 BDBV FILOatj04 TAFV FILOatj05 MARV FILOatj06 RESTV Alere q HIV-1/2 VL Plasma Quantitative HIV monitoring test for plasma samples (in development) Alere q Carba Profile Qualitative test for the detection of 11 clinically most relevant carbapenemase genes from swab samples (in feasibility) other applications MRSA profile, Respiratory Panel, Fever Panel, STI Panel, Companion Diagnostics 17

20 Alere SD WHO Prequalified Product Pipeline Completed 7 Under progress 2 In development 18

21 Data Management and Epidemiology Incidence Tracking Geographic Mapping

22 The MOFINA Project Showcase The goals: Develop, validate and deploy a fully integrated, POC, molecular pan- Filovirus assay The project: Mobile Filovirus Nucleic Acid Test (MOFINA) The consortium: Technical/development: Alere Technologies and altona Diagnostics Evaluation/validation: BNITM, INMI Lazzaro Spallanzani, PHE, FIND The approach: Integrate widely used, CE-IVD, FDA EUA, WHO EUAL RealStar Filovirus assay with the Alere q analyzer and cartridge technology incorporating fully-integrated sample preparation, target amplification and detection The Status: Field validation in Sierra Leone, FDA EUA pre-submission complete With support from

23 The MOFINA Project Showcase The only POC Pan-Filovirusassay which detects and discriminatesall known Ebola species and detects both known Marburg species In-field (Sierra Leone) clinical testing completed with 69 samples FDA EUA pre-submission completed, WHO EUAL in process CE IVD submission in 2016 Product Development Validation & Clinical Support -MOFINA partners Molecular POC Multiplex Screen 6 Species in a Single Test FILOatj01 SUDV FILOatj02 EBOV FILOatj03 BDBV FILOatj04 TAFV FILOatj05 MARV FILOatj06 MARV Ravn FILOatj07 RESTV 21

24 The MOFINA Project Showcase The partnership Alere Technologies (an Alere Inc. company) altona Diagnostics Bernhard Nocht Institute for Tropical Medicine (BNITM) Istituto Nazionale Malatie Infettie(INMI) Lazzaro Spallanzani Public Health England Porton Down The Foundation for Innovative New Diagnostics (FIND) Assay development Led by Alereand altona based on existing technology (Alereq platform, altona Filovirus assay) Design inputs from all project partners Assay validation Some work in house with purified nucleic acids Live cultured virus by BNITM, INMI and PHE in BSL4 facilities Retained patient sample testing in Sierra Leone facilitated by FIND and PHE With support from

25 Laboratory Collaboration Network The strategy Partner with national and international scientific institutions Global footprint to cover genetic background, environmental and ethnical diversity Inclusion of most of the variety of strains and subspecies of the focal pathogens The management co-managed by Alere and altona The role Definition of design input, user specifications, product profiles Prototype testing, verification and validation, field data Focal points for piloting the deployment of technologies, training and pilot monitoring and surveillance programs

26 Laboratory Collaboration Network Currently existing laboratory network(to be extended) Bernhard-NochtInstitute for Tropical Medicine WORLD MAP to be added Which ones do we have?

27 DPP project structure

28 DPP project plan 1 Viral Hemorrhagic Fever Panel 1.1 Development Year 1 Year 2 Year 3 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 RUO RUO RUO 1.2 Verification 1.3 Validation 1.4 Technical documentation CE-IVD CE-IVD CE-IVD 1.5 deployment 2 Respiratory Panel RUO RUO RUO 3 Encephalitis panel RUO RUO RUO 4 process control panels 4.1 Development 4.4 Technical documentation * single target assay RealStar/ Altostar Alere q SD Bioline*

29 DPP Development Estimates Development cost and timelines Estimated 15,9 Mio. USD 3 years development and deployment project VHF panel CE IVD marked, respiratory and encephalitis panel RUO Duration of validation phase is highly dependent on access to isolates and specimens, Regulatory Authority requirements, appropriate ethical approval(s), logistics and financing. Deployment, training and field studies on VHF in several geographically distributed areas 27

30 Key DPP Development Challenges Access to isolates and clinical specimens Despite intentions by stakeholders to establish repositories and banks access to pathogen isolates and clinical specimens remains a major challenge for product developers Sustainability Lack of current business case for potential assay makes justifying R&D spend and occupying precious R&D time very difficult Support in form of external financing of R&D and/or assay volume guarantees need to be explored Develop and supply critical products Industry Implementers, multilaterals, academics Design inputs, surveillance information, samples and isolates 28