Restructuring the EG GMP Guide

GMP News No. 572

GMP News
4 July 2005
 

Restructuring the EG GMP Guide

 
In our GMP News of 11 March 2005 , we had already reported about the revision of EU GMP requirements. In the following we inform you about further changes resulting among others from the new Concept Paper of the Ad Hoc GMP Inspection Group of EMEA.  

The 2001 review of the European legislation (Directive 2001/83/EC as amended, (1)) will come into force in October 2005. From then on MA holders are obliged to use as starting materials only active substances that have been manufactured in accordance with the detailed guidelines on GMP for starting materials (see Article 46f of Directive 2001/83/EC as amended by Directive 2004/27/EC and Article 50f of Directive 2001/82/EC as amended by Directive 2001/82/EC as amended by Directive 2004/28/EC; 2, 3). This obligation has to be fulfilled by MA holders for human medicinal products as well as for veterinary medicinal products.

Please find the text of the relevant articles of these directives summarized below:
 

Article 46f Directive 2001/83 as amended by Directive 2004/27/EC
(relating to human medicinal products)
and
Article 50f of Directive 2001/83/EC as amended by Directive 2001/82/EC as amended by Directive 2004/28/EC
(relating to veterinary medicinal products)

"(…) to comply with the principles and guidelines of good manufacturing practice for medicinal products and to use as starting materials only active substances, which have been manufactured in accordance with the detailed guidelines on good manufacturing practice for starting materials (…)"

 
These 'principles and guidelines of GMP for active substances used as starting materials' were published as Annex 18 to the EU GMP Guide in November 2000. While Annex 18 in its current version applies to the manufacture of APIs for use in human drug (medicinal) only, these 'principles and guidelines' shall be adopted in the form of detailed guidelines that apply to human medicinal products as well as for veterinary medicinal products (2,3). Please find the text of the relevant articles of these directives summarized below:
 

Article 47 Directive 2001/83/EC as amended by Directive 2004/27/EC
(relating to human medicinal products)

"(…) 'The principles of good manufacturing practice for active substances used as starting materials referred to in point (f) of Article 46 shall be adopted in the form of detailed guidelines (…)".

Article 51 of Directive 2001/83/EC as amended by Directive 2001/82/EC as amended by Directive 2004/28/EC
(relating to veterinary medicinal products)

"(…) The principles of good manufacturing practice as regards the manufacturing of active substances for use as starting materials as referred to in Article 50(f) shall be adopted in the form of detailed guidelines (…)".

 
In order to fulfil these requirements the Member States have now agreed – after discussion at EMEA's ad hoc GMP inspection Services group - that "(…) Annex 18 will no longer be considered as annex, but it will form a new, Part II of the EU GMP (…)" (4). With this restructuring the EU GMP Guide will now be presented in 2 Parts:

  • Part I dealing with finished products 
  • Part II dealing with active substances used as starting materials (applicable for medicinal products for both human and veterinary use)

As the current Annex 18 is foreseen to become Basic Requirements Part II of the EG GMP Guide, a Draft revision of the introductory section of the current GMP annex 18 has been published (5). While Annex 18 in its current version is applicable to the manufacture of APIs for use in human drug (medicinal) only, the foreseen Part II of the EU GMP guide will "(…) apply to the manufacture of active substances for medicinal products for both human and veterinary use with the exception of ectoparaciticides (…)" (see 1.2 Scope of the revised introductory section of the current GMP annex 18, (5)).

Furthermore it will be necessary to amend some of the remaining annexes to the EU GMP Guide "(…) to ensure they provide appropriate supplementary guidance to the new Part II and to deal with any gaps and overlaps. At the same time the opportunity will be taken to update the annexes in the light of scientific and technical progress. (…)" (4). For this reason, the Concept Paper written by the Ad Hoc GMP Inspection Services Group lists changes to Annex 2 (Biologics), Annex 3 (Radioactive Drugs), and Annex 6 (Medical Gas), which have to be updated. Besides, Annex 2 and 6 as well as Annex 7 (Herbal Medicinal Products) have overlaps that should be corrected.

Comments on the Concept Paper can be handed in until 31 August 2005 (4).
  

The consequences of the EU's new GMP requirements on API manufacture are one of the focus topics of the 8th European Conference on Active Pharmaceutical Ingredients, which takes place in Berlin from 12 to 14 October. High-level speakers, among others from the EU and FDA, as well as more than 200 participants from Europe and overseas are expected. Please register in good time as this APIC conference will in all probability be booked up.

We would also like to recommend you the following events concerning API manufacture in GMP Compliance:

 
Author:
Dr B. Jentges, CONCEPT HEIDELBERG

List of Abbreviations

  • EMEA European Medicines Agency
  • EU European Union
  • GMP Good Manufacturing Practices
  • MA Marketing Authorisation

Literature

  • Directive 2001/83/EC DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 6 November 2001 on the Community code relating to medicinal products for human use;
    http://dg3.eudra.org/F2/eudralex/vol-1/DIR_2001_83/DIR_2001_83_EN.pdf
  • DIRECTIVE 2004/27/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
    of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use;
    http://dg3.eudra.org/F2/eudralex/vol-1/DIR_2004_27/DIR_2004_27_EN.pdf
  • Directive 2004/28/EC OF THE EUROPEAN PARLIAMENT AND OF THE
    COUNCIL of 31 March 2004 amending Directive 2001/82/EC on the Community code relating to veterinary medicinal products;
    http://dg3.eudra.org/F2/eudralex/vol-5/DIR_2004_28/DIR_2004_28_EN.pdf
  • Ad Hoc GMP Inspections Services, Concept Paper on the revision of some annexes to the European GMP Guide in the context of the GMP for active substances, May 2005;
    http://www.emea.eu.int/Inspections/docs/CP%20A2to7.pdf
  • Draft revision of the introductory section of the current GMP annex 18:
    Medicinal Products for Human and Veterinary Use: Good Manufacturing Practice
    Basic Requirements Part II: The Principles of Good Manufacturing Practice for Active
    Substances used as Starting Materials, 4 March 2005;
    http://dg3.eudra.org/F2/eudralex/vol-4/pdfs-en/anx18en_introduction_draft.pdf
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