Diagnostic Preparedness Platform

WHO R&D Blueprint for Priority Infectious Diseases with

Epidemic Potential

2nd round presentation

Geneva
July 21st, 2016
 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
Diagnostic Preparedness Platform

3
MH2

Diagnostic Preparedness Platform

Alere Technologies altona Diagnostics

• 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
• 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
4
Folie 4

MH2 I would make two slides out of this one

Markus Hess; 18.07.2016
Alere q Technology

add sample
Multiple
direct from
Assays patient

Single use
Molecular POC Connected Cartridge

Automatic:
Extraction Onboard
Purification, device and
Array based Amplification assay controls
detection and detection

5
 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 - Specific target Real time & end point,
capturing (e.g. RNA) Melting curves
- Mechanical lysis using biotinylated
PCR CMA technology; high
probes on density arrays
- Heat lysis
sepharose beads
- Unspecific DNA
binding on silica
beads

6
 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
MH7
• AltoStar workflow: Automated NA extraction from different sample matrices
and automated PCR set-up

7
Folie 7

MH7 Automated NA extraction from different sample matrices and automated PCR set-up
Markus Hess; 18.07.2016
 SD Bioline Ab RDT’s
Product Specification Absorbent pad
Nitrocellulose membrane
Control line
Sample Type : serum, plasma and whole blood
Sample Volume : 10 uL Gold Conjugate Pad

Interpretation Time : 15-20 min Sample Pad

Test procedure Test line

(1) Dispense 10 uL of (2) Dispense 4 drops of (3) Interpret test results

specimen into the sample assay diluent vertically into in 15~20 minutes.
well (S). the assay diluent well.

SD Color scale chart

*Score rating
1+ positive: G1~G8
2+ positive: G9~G14
3+ positive: G15~G20

8
 DPP Assay Panels

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.
9
 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
 Platform Integration Pathway I

Transfer of existing RealStar 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
 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
 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
 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
 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 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
* submitted
15
 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

80 210 1716
54 16 10* 0 184 26 0 0 677** 20 906* 113
Regional Distributors: 147 Regional Distributors : 124 Regional Distributors: 50
* Excludes Contracted Workers (3582)
Key: Commercial T. Support Manufacturing R&D
** Excludes Philippines Health Management Business (939) | 16
 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 FILOatj01 – SUDV

FILOatj02 – EBOV
Pan-Filovirus screening assay panel for detection and discrimination FILOatj03 – BDBV
FILOatj04 – TAFV
of 6 known Ebola and Marburg virus species (in clinical validation) 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
Alere SD WHO Prequalified Product Pipeline
Completed 7 Under progress 2

In development

18
 Data Management and Epidemiology

Incidence Geographic
Tracking 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

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
Product Validation & Clinical Support - MOFINA
Development partners

Multiplex FILOatj01 – SUDV

FILOatj02 – EBOV
Screen FILOatj03 – BDBV
6 Species in a FILOatj04 – TAFV
FILOatj05 – MARV
Molecular POC Single Test FILOatj06 – MARV Ravn
FILOatj07 – RESTV
21
 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 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

With support from

 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)

Bernhard-Nocht Institute
for Tropical Medicine

WORLD MAP to be added

Which ones do we have?

DPP project structure
DPP project plan

Year 1 Year 2 Year 3

Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
1 Viral Hemorrhagic Fever Panel
RUO
1.1 Development RUO
RUO

1.2 Verification

CE-IVD
1.3 Validation CE-IVD
CE-IVD

1.4 Technical documentation

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

RealStar/ Altostar
Alere q
SD Bioline*
* single target assay
 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
 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

Implementers, multilaterals,
Industry
academics

Design inputs, surveillance

information, samples and isolates 28