Revision of the Directive 91/356/EEC

Revision of the Directive 91/356/EEC

In the subordinate document "EC Guideline for a Good Manufacturing Practice for Medicinal Products" with its now 18 Annexes, comprehensive guidelines are presented and sometimes revised in order to take the technical and scientific progress into account. A recent revision concerned Annex 13, which deals with the "Manufacture of Investigational Medicinal Products" (see News of 8 March 2002). The modifications that are suggested in the document and have been released for comment regard a stricter implementation of the GMP principles to the manufacture of investigational medicinal products and correspond to the requirements of the Directive 2001/20/EC on the implementation of GCP in the conduct of clinical trials. These regulations have now been included in analogy into the GMP Directive. The thus created revision of the 91/356/EEC document was published as Draft Proposal on 2 May 2002 and released for comment until 2 August 2002.

In the following you will find some characteristic examples of the changes.
In order to clarify expressly how one has to proceed in the manufacture of investigational medicinal products, additional formulations have been inserted, requiring e.g. validated processes and data processing systems.
Furthermore the text requires that "the function of quality control shall be established and maintained distinct from other functions." The responsibility shall lie with a person who is independent of production.
The retention period for samples (bulk formulated products, finished drug products, packaging components for finished drug products) is clearly defined.
Different passages of the document contain detailed regulations for the triangle constituted by manufacturer, importer and sponsor, above all in view of complaints or recalls during clinical trials.

The draft revision of the Directive is embedded in a modified network of regulations some of which have been published only recently.
The two most important new Directives to which the document refers continually are the

"Directive 2001/83/EC ... of 6 November 2001 ... on the Community code relating to medicinal products for human use"

and the already mentioned

"Directive 2001/20/EC ... of 4 April 2001 ... relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use."

The second Directive regulates the conduct of clinical trials, the first one strives for a harmonisation of the different regulations of the individual states in the European Economic Area regarding all categories of medicinal products for human use, and thus also investigational medicinal products.

This revision of the Directive 91/356/EEC is the consequence of both the "GCP Directive" 2001/20/EC and the revision of Annex 13 to the GMP Guideline. This shows very clearly that the manufacture of investigational medicinal products is the focus of GMP attention and that any grey zones in the manufacture of investigational medicinal products have been eliminated in the corresponding regulations.

The revised draft directive can be downloaded here:
http://pharmacos.eudra.org/F2/pharmacos/docs/Doc2002/may/amend91356_2c.pdf

The Revision of Annex 13 can be downloaded from this address:
http://pharmacos.eudra.org/F2/eudralex/vol-4/pdfs-en/an13_draft1.pdf

Would you like to get more information on this topic?

Seize the opportunity to discuss your questions directly with Annex 13 Rapporteur David Cockburn, MCA! The Education Course "EU GMP and FDA Compliance in Pharmaceutical Development" takes place in Madrid on 17 and 18 October 2002. The speakers - David Cockburn, Dr Norman Franklin (former ICH Q7a member), Dr Gert Brandl (Schering AG), and Jef van Schuerbeek - will deal among others with the manufacture of investigational medicinal products. Click here in order to read the programme.

Writer: 
Dr Gerhard Becker
CONCEPT HEIDELBERG