Harmonisation, Standardisation and approval of diagnostic
kits
Manufacturers point of view on validation of
veterinary diagnostics – Seeking an efficient
harmonised regulation
EMVD - European
Manufacturers of Veterinary Diagnostics
EMVD

History – Who are we?

Members

Animal Health diagnostics, Why?
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Achievements
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Existing Regulations….
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Priorities
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Products
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What do we do before marketing a product?

Objectives
A bit of History…
First official meeting in March 2006 in Brussels
 Defend the interests of manufacturers of Diagnostics for Animal Health
 Headquarters based in Paris
 Many small or medium sized companies, some large companies but with
small veterinary activity
 Our members operate under ISO 9001 (at least)
 Together we represent the majority of veterinary diagnostics producers in
the world:
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Most members have global presence

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Concentration of this market in EU
( “Diagnosis Approach” vs. “Vaccination Approach”)
Presence EMVD Members
Board members

Secretary: Annita Ginter, BioX Diagnostics, Belgium
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Tresurer: François Merit, IDEXX, France
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Vice President: Liesbeth Jacobs, Prionics, Netherlands
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Vice President: Jacques Delbecque, Ingenasa, Spain
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Vice President: Jean-Luc Troch, IDEXX, Europe
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Chair: Johanna Koolen, Life Technologies, France
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Secretariat: SIMV, France
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Web site: www.aefrv.eu
Animal Health Diagnostics…. Why?
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Human and animal health are closely related and should be considered as one

Some facts:

75% or more of emerging diseases originate from animals

Neglected zoonosis continue to threat human health:

Tuberculosis: 1.4 M deaths in 2010 (source WHO); Rabies: 55 K deaths in
2010 (note 50% are children); Brucellosis; Anthrax
Improved Animal Health provides possibilities for poverty alleviation (necessary to meet
the Millennium goals):


Animals are protein providers through milk or meat, and provide work force

Example: Worldwide Rinderpest eradication considerably improved welfare
Economic reasons: International Trade of animals becomes impossible when some
diseases are present (Food and Mouth Disease…)

Achievements
We became a recognised stakeholder on an international level (because of our global
presence) for international organizations such as OIE



“Observer” in the OIE ad hoc group on Validation of diagnostic assays
Representation in IAEA/FAO/OIE joint meetings on the validation of
diagnostics
We became a recognised stakeholder on an EU level towards regulators, committees,
veterinary health industry



Animal Health Advisory Committee AHAC (DG Sanco)
Executive board of the European Technology platform for global animal
health

Project Management Board of Discontools

Request was formulated to DG Sanco for a suitable regulatory framework

Participation to EPRUMA (European Platform for the Responsible Use of
Medicines in Animals)

Our know-how
What can we do for you? We bring highly innovative products on the market:
highly
innovative
products
What
can
we
offer?
Regulatory situation in Europe for
Animal Health Diagnostic Products
Regulation per disease by EU directives, such as Aujeszki’s Disease,
tuberculosis, Brucellosis, etc. for which many countries have reached the
“disease free status” now


28 different ways to interpret an EU directive…
Some countries have registration process (Germany, Spain), or apply norms
(AFNOR in France) Result: burdensome situations where products need
marketing authorisations in some countries, or batch liberation in others, or
both…

OIE published a procedure providing harmonisation opportunities.
Unfortunately it is not considered an alternative procedure by countries with
registration procedures



The EMVD supports the harmonization effort
Mutual recognition is necessary in order to lighten the regulatory
administrative burden
Find support for an
AH IVD directive
Express need for
Harmonization
to regulate veterinary
Diagnostics in the EU
Denounce Unfair
competition
from public
laboratories
Promote
mutual recognition
of batch control by
EU Member States
Dialog with IGOs (OIE, FAO, ..):
converge interests
support initiatives for harmonisation
Dialog with EU commission:
EMVD Priorities
Our products in a flash…
The following is a non-exhaustive listing of the different veterinary diagnostic
products we offer:


Many different techniques are available to demonstrate the
presence of antibodies:


ELISA techniques are the most commonly used today but
other techniques such as: Agglutination tests; Complement
Fixation tests; Slow agglutination test (Wright) are still used
and available
The following techniques are used to demonstrate the presence
of antigens:

Nucleic acid detection methods, mostly PCR techniques

ELISA techniques (capture, or sandwich)

Classical techniques such as culture and staining
The above techniques are not exclusive but can -and sometimes should beused in complement (antigen and antibody detection)
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ELISA principles
R
Q
PCR principle
Sample DNA
R
Q
Displacement of the probe and
release of signal
3
R
Usually
about 40 cycles
1
Denaturation
Q
95 °C
50-60°C
Probe/Primer
Annealing
2
PCR principle
Source: www.ugent.be
What do manufacturers do before
marketing a veterinary diagnostic?

Emergence of a “need” (epidemic, eradication plan, etc.)
Partner with disease expert(s) – Control of the IP (Patents,...) – Market and
RA overview


Develop prototype “kit” – Feasibility - Cost of Production (Raw Materials)

Initial validation on limited number of samples

Design verification /optimisation
First batches of products, used for Validation studies : sensitivity, specificity,
sample treatment if applicable, robustness, external validation with
collaborators, QC procedure and QC panel, etc.


Results are documented (QA system, validation and/or registration dossier)
Registration where necessary, with registration dossier and samples for
testing

Quality control process
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Quality controls are performed in various stages of the production process
Critical ingredients are submitted for acceptation before entering the
production process

Quality control standards are used throughout the process to guarantee that
components fit the specifications

Individual components are tested and compared with former batches, and
final batch control is performed with a control panel for release testing


Our procedures are designed to minimize batch to batch variations

If required, the batch is sent for release to the relevant authorities
Why are products used for eradication in
Europe interesting for other markets?
Commercial veterinary diagnostic products have been on the
market since more than 20 years and have proved their
effectiveness in disease eradication
 They are available for markets outside of Europe where the
disease prevalence is higher and are reasonably priced (ex.
Brucellosis ELISA, )
 New techniques are available (PCR) and well adapted for Antigen
detection, providing rapid confirmation ((para)tuberculosis).
The EU has an interest to stimulate the improvement of herd-health
status of countries close to Europe to prevent reintroduction of
eradicated diseases

Objectives for the future

Continue to develop kits for emerging diseases
Continue to propose (new) well validated Kits (ELISA, PCR, ….) to the final
costumers

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Harmonize Validation/Registration processes of these tools
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Needs internationally recognised standards

Could OIE lab network help?

World wide acceptance of technologies :


ELISA technologies used since decades and successfully used
for disease eradication
PCR real time technology provides reliable assays for detection
of targets in various matrices (microorganisms in patient or
environmental sample material)