The "Commission Directive 91/356/EEC of 13 June 1991 laying down the
principles and guidelines of good manufacturing practice for medicinal
products for human use" formulates - as can be gathered from the
slightly long-winded title - the basic framework for the Good
Manufacturing Practice for human drugs. It entered German law as German
Operation Ordinance for Pharmaceutical Entrepreneurs
(Pharmabetriebsverordnung) in 1994.
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
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