Risk Wise

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] 36

European Medicines Agency:

influenza pandemic preparedness

Ragini Shivji, Scientific Administrator and John Purves, Head of Sector, Quality of Medicines Sector; and Patrick Celis,

Principal Scientific Administrator, Regulatory Affairs and Organizational Support Sector, European Medicines Agency (EMEA)

he European Medicines Agency (EMEA) is a decentralized

body of the European Union (EU). Its main responsibility

is the protection and promotion of public and animal

health, through the evaluation and supervision of medicines for

human and veterinary use. All medicinal products for human

use derived from biotechnology and other high-tech processes,

including advanced-therapy medicines and products for some

clinical uses, must be approved via the centralized procedure.

EMEA carries out significant work on human medicines, includ-

ing dealing with applications for marketing authorizations for

influenza vaccines.

The EMEA is responsible for the scientific evaluation of applications

for European marketing authorization for medicinal products

(centralized procedure). Under the centralized procedure, compa-

nies submit a single marketing authorization (licence) application

to the EMEA. The EMEA conducts a single evaluation and adopts a

scientific opinion, recommending or refusing the granting of a

centralized (or ‘Community’) marketing authorization to the

European Commission. Once granted the marketing authorization

is valid in all European Union and European Economic Area (EEA)

states (Iceland, Liechtenstein and Norway).

The safety of medicines is monitored constantly by the agency

through a pharmacovigilance network. EMEA takes appropriate

actions if adverse drug reaction reports suggest changes to the

benefit-risk balance of a medicinal product.

Six scientific committees, composed of members of all EU and EEA

states, conduct the main scientific work of the agency. For vaccines

authorization, the main committees are the Committee for Medicinal

Products for Human Use (CHMP), and the Paediatric Committee

(PDCO). These committees are also supported by a number of working

parties, such as the Vaccine Working Party (VWP).

The agency brings together the scientific resources of the EU medi-

cines national competent authorities (NCAs) in 30 EU and EEA states

in a network of European experts. It contributes to the EU’s interna-

tional activities through its work with the European Pharmacopoeia,

the World Health Organization, US Food and Drug Administration

and the ICH trilateral (EU, Japan and US) conferences on harmo-

nization, involving other international organizations.

As part of its remit, the agency has been undertaking, for several

years, work in the area of influenza pandemic preparedness. There

follows some background regarding the influenza viruses causing

disease and an overview of the history and current status of EMEA

pandemic preparedness activities.

Influenza viruses and influenza pandemic

Influenza viruses that cause human disease are divided

into two groups: A and B. Influenza A has two subtypes

which are important for humans: A(H3N2) and

A(H1N1), of which the former is currently associated

with most deaths. Influenza viruses are defined by two

different protein components, known as antigens, on

the surface of the virus. They are spike-like features

called haemagglutinin (H) and neuraminidase (N)

components.

The genetic make-up of influenza viruses allows

frequent minor genetic changes, known as antigenic

drift, and these changes require annual reformulation of

influenza vaccines. Three times in the last century, the

influenza A viruses have undergone major genetic

changes mainly in their H-component, resulting in

global pandemics and large tolls in terms of both disease

and deaths. The most infamous pandemic was ‘Spanish

flu’, which affected large parts of the world population

and is thought to have killed at least 40 million people

in 1918-1919.

Most recently, limited outbreaks of a new influenza

subtype A (H5N1) directly transmitted from birds to

humans have occurred in Hong Kong Special

Administrative Region of China in 1997 and 2003.

Although H5N1 is presently the virus of greatest concern

to become a pandemic influenza virus, other avian

influenza viruses known to infect humans could also

cause a pandemic.

Early EU/EMEA pandemic preparedness activities

WHO has been leading pandemic preparedness activities

for a number of years. However, in 2001 the Health and

Consumers Directorate General of the European

Commission (DG SANCO, Health Threat Unit (HTU))

initiated the development of pandemic preparedness

plans in all EU member states that had not already

prepared pandemic plans.

This work has continued in

recent years, also in association with the European

Centre for Disease Prevention and Control (ECDC). All

EU member states now have a national influenza

pandemic preparedness plan.

During this initial work into pandemic preparedness,

to which EMEA contributed, it was recognized that the