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Diagnostic Preparedness PlatformWHO R&D Blueprint for Priority Infectious Diseases with Epidemic Potential
2nd round presentation
GenevaJuly 21st, 2016
Diagnostic Preparedness Platform
2
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
Diagnostic Preparedness Platform
3
Diagnostic Preparedness Platform
4
Alere Technologies
• Alere® q and lateral flow POC
system
• Proven applicability
• Decentralized testing
• Scalable in volume and number
of assays
• CE IVD, WHO PQ Dx for 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)
• AltoStar automated high
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
MH2
Folie 4
MH2 I would make two slides out of this oneMarkus Hess; 18.07.2016
Alere q Technology
5
ConnectedMolecular POC
Multiple
Assays
add sample
direct from
patient
Single use
Cartridge
Array based
detection
Automatic:
Extraction
Purification,
Amplification
and detection
Onboard
device and
assay controls
PCR
Extraction Target Isolation Amplification
- Chemical lysis
- Mechanical lysis
- Heat lysis
Integrated Cartridge Workflow
Real time & end point,
Melting curves
CMA technology; high
density arrays
Alere q Cartridge Features
� No cold chain requirements
� Real multiplexing capabilities
� Enables for diagnostic test panels
� SNP Detection
- Specific target capturing (e.g. RNA)
using biotinylated
probes on sepharose beads
- Unspecific DNA binding on silica
beads
Array Detection
6
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
altona RealStar Technology
7
MH7
Folie 7
MH7 Automated NA extraction from different sample matrices and automated PCR set-upMarkus Hess; 18.07.2016
SD Bioline Ab RDT’s
8
� Product Specification
� Sample Type : serum, plasma and whole blood
� Sample Volume : 10 uL
� Interpretation Time : 15-20 min
� Test procedure
� SD Color scale chart
(2) Dispense 4 drops of
assay diluent vertically into
the assay diluent well.
(1) Dispense 10 uL of
specimen into the sample
well (S).
(3) Interpret test results
in 15~20 minutes.
*Score rating
1+ positive: G1~G8
2+ positive: G9~G14
3+ positive: G15~G20
Absorbent pad
Control line
Sample Pad
Gold Conjugate Pad
Nitrocellulose membrane
Test line
DPP Assay Panels
9
Assay panels for Nucleic Acid Testing
1. VHF panel mandatorily 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.
DPP Assay Panels
10
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
Platform Integration Pathway I
11
Transfer of existing RealStar assays to multiplexed Alere® q POC
system
Example:
Advantage: Same controls and uniform post-market-surveillance,
relatively low development risk
Filovirus
CCHFV
Rift Valley
fever virus
Platform Integration Pathway II
12
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.
DPP Advantages
13
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
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
altona‘s Capacity
14
altona Portfolio and Pipeline
15* submitted
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 CE-IVD
Rift Valley fever virus Research Use Only
Malaria parasites CE-IVD
Dengue virus CE-IVD
Chikungunya virus CE-IVD
Zika virus CE-IVD, WHO EUAL*, FDA EUA
Hantavirus
Yellow fever virus
Encephalitis Nipah virus
Japanese encephalitis virus
West Nile virus CE-IVD
Herpes simplex virus CE-IVD
Varizella zoster virus CE-IVD
Measles virus
Alere’s Global Capability
16
1716113906*20677**
210
0026184
| 16
80010*1654
R&DManufacturingCommercial T. SupportKey: * Excludes Contracted Workers (3582)
** Excludes Philippines Health Management Business (939)
Regional Distributors : 124Regional Distributors: 147 Regional Distributors: 50
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
Alere q Assay Portfolio
FILOatj01 – SUDV
FILOatj02 – EBOV
FILOatj03 – BDBV
FILOatj04 – TAFV
FILOatj05 – MARV
FILOatj06 – RESTV
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-Filovirus screening assay panel for detection and discrimination
of 6 known Ebola and Marburg virus species (in clinical validation)
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
Alere SD WHO Prequalified Product Pipeline
18
Completed 7 Under progress 2
In development
Data Management and Epidemiology
Incidence
Tracking
Geographic
Mapping
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
The MOFINA Project Showcase
21
The only POC Pan-Filovirus assay which detects
and discriminates all 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
Molecular POC
Validation & Clinical Support - MOFINA
partners
Product
Development
FILOatj01 – SUDV
FILOatj02 – EBOV
FILOatj03 – BDBV
FILOatj04 – TAFV
FILOatj05 – MARV
FILOatj06 – MARV Ravn
FILOatj07 – RESTV
Multiplex
Screen
6 Species in a
Single Test
The MOFINA Project Showcase
With support from
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 Alere and altona based on existing technology (Alere q 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
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
Laboratory Collaboration Network
Currently existing laboratory network (to be extended)
WORLD MAP to be added
Which ones do we have?
Bernhard-Nocht Institute
for Tropical Medicine
DPP project structure
DPP project plan
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
1 Viral Hemorrhagic Fever Panel
RUO
RUO
RUO
CE-IVD
CE-IVD
CE-IVD
2 Respiratory Panel RUO
RUO
RUO
3 Encephalitis panel RUO
RUO
RUO
4 process control panels
4.1 Development4.4 Technical documentation
RealStar/ Altostar
Alere q
SD Bioline*
* single target assay
1.3 Validation
1.4 Technical documentation
1.5 deployment
1.2 Verification
Year 1 Year 2 Year 3
1.1 Development
DPP Development Estimates
27
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
Key DPP Development Challenges
28
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
IndustryImplementers, multilaterals,
academics
Develop and supply critical products
Design inputs, surveillance
information, samples and isolates