Harmonisation, Standardisation and approval of diagnostic kits

Manufacturers point of view on validation of veterinary diagnostics – Seeking an efficient harmonised regulation

EMVD - EuropeanManufacturers of Veterinary Diagnostics

EMVD History – Who are we? Members Animal Health diagnostics, Why? Achievements Existing Regulations…. Priorities Products 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:

Most members have global presence Concentration of this market in EU

( “Diagnosis Approach” vs. “Vaccination Approach”)

Pre

sen

ce E

MV

D M

emb

ers

Board members Secretary: Annita Ginter, BioX Diagnostics, Belgium

Tresurer: François Merit, IDEXX, France

Vice President: Liesbeth Jacobs, Prionics, Netherlands

Vice President: Jacques Delbecque, Ingenasa, Spain

Vice President: Jean-Luc Troch, IDEXX, Europe

Chair: Johanna Koolen, Life Technologies, France

Secretariat: SIMV, France

Web site: www.aefrv.eu

Animal Health Diagnostics…. Why?

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)

What can we do for you? We bring highly innovative products on the market:

SMEs l

ed b

y vet

erina

rians

which

prov

e gr

eat

reac

tivity

and

flexib

ility f

or

deve

lopm

ent o

f new

prod

ucts

Knowledge on technology

and regulatory requirements

(veterinary, food safety and

human diagnostics)

LEADERS in

Biotechnology, key

players in the Life

Science market ,

possibilities to provide

“high-tech” solutions

Collab

orati

ons w

ith an

imal

healt

h vac

cine a

nd

phar

maceu

tical

compa

nies a

s well

as

impo

rtant

opini

on le

ader

s

Our know-how

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

EMVD Priorities

Dia

log

with

EU

com

mis

sion

: F

ind

supp

ort

for

an

AH

IV

D d

irect

ive

Promote mutual recognition of batch control byEU Member States

Express need for Harmonization

to regulate veterinary Diagnostics in the EU

Denounce Unfair competition from public laboratories

Dialo

g w

ith IGO

s (OIE

, FA

O, ..):

converge interests support initiatives for harm

onisation

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 be- used in complement (antigen and antibody detection)

ELISA principles

PCR principle

95 °C

Usually about 40 cycles

50-60°C

Denaturation

Displacement of the probe and release of signal

1

2

3

Probe/Primer Annealing

Sample DNA

RQ

R

Q

QR

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 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

Quality control process

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

Harmonize Validation/Registration processes of these tools

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)