SCRIP World Pharmaceutical News, 01. Juni 2010

Ressort: Policy & Regulation

Author: Vibha Sharma


The European Medicines Agency has issued for public consultation a reflection paper that considers how to better monitor clinical trials conducted in third countries (ie outside the European Economic Area (EEA)) and used to support marketing authorisation applications submitted to the agency.

The reflection paper looks at how the agency can ensure that such trials meet all ethical and good clinical practice requirements that apply in the EEA. It "proposes a series of measures to ensure a robust framework for the oversight and conduct of clinical trials, no matter where in the world investigators' sites are located and patients are recruited".

The paper was developed by the EMA's "working group on third country clinical trials", which was set up last year to come up with practical proposals to further the agency's overall strategy on the acceptance of clinical trials conducted in third countries.

Written comments to the consultation will be accepted until 30 September; as part of the consultation process, the EMA will hold a workshop on 6-7 September to review and discuss feedback.

international co-operation

The purpose of the reflection paper, the agency clarifies, is not to establish a new, or additional, set of principles, but rather to describe the current regulatory processes of the EMA that can be used to ensure that third country clinical trials are conducted in accordance with principles equivalent to the ethical and GCP requirements applied to clinical trials in the EEA.

As part of the exercise, the EMA will seek to build and extend its relationship with drug regulators around the world and with related international organisations. It will first give priority to nations that recruit a large number of patients, followed by countries whose clinical trial regulatory systems are limited or underdeveloped.

According to data on pivotal trials included in marketing authorisation applications submitted to the EMA between January 2005 and December 2009, certain non-EU countries (excluding the US, Canada and the European Free Trade Association) contributed about 26% of patients.

These include, among others, Russia (2.9%), South Africa (2.6%), Brazil (2.6%), Argentina (2.2%), India (1.5%), Israel (1.3%) and Australia (1.2%). Some of these countries, the paper says, should be considered as a priority. To accord priority to international partnerships on the basis of the type of regulatory system in place, the EMA will undertake a high-level "mapping" to identify the current strengths and weaknesses of the national systems in third countries.

There are six definite goals that the EMA's global co-operation and capacity building initiative will seek to achieve. These include establishing: truly independent ethics committees; follow-up systems

with the power to suspend/stop trials when needed; the use of GCP inspections by the national regulatory authority; and sanctions against any non-compliance.

Such an approach, the paper says, will promote confidence among ethics committees and regulatory authorities, avoid unnecessary duplication and multiplication of site inspections and allow exchange of valuable information. To fulfil this long-term objective, the EMA said it would proceed in a phased manner by focusing its attention on third countries based on priority.

drug development and marketing authorisation phase

Prior to commencing a trial in a third country, the EMA says the company should discuss with EEA regulators the trial's design and related ethical considerations. The company should clearly explain why data from the patient populations selected are applicable to the EEA population, unless the product is intended to be used outside the EEA.

The marketing authorisation evaluation should ensure that GCP principles have been applied to all submitted clinical trials and that ethical guidance is sought if required. As part of the review of the MA application, the assessors should confirm in their assessment report, among other things, that they have not identified any ethical issues in their assessment of the studies, that the studies have been approved by the concerned ethics committee and by the national regulatory authority. Where the assessors are concerned that a study may not have been conducted ethically, they should seek further clarification from the applicant, who should be given the opportunity to justify their position. In addition, the paper recommends establishing a pool of experts to advise the EMA's scientific advisory body, the CHMP, in its assessment of ethical aspects of clinical trials.