What's new?

The following changes have been made to the GMP Guide:

• Chapter 4 - Documentation: The sections on "generation and control of documentation" and "retention of documents" have been revised, in the light of the increasing use of electronic documents within the GMP environment. The revised text takes effect 30 June 2011.
• Annex 11 - Computerised Systems has been revised in response to the increased use of computerised systems and the increased complexity of these systems. Consequential amendments are also proposed for Chapter 4 of the GMP Guide.The revised text takes effect 30 June 2011.
• Annex 14 - The Annex has been revised in the light of Directive 2002/98/EC and relevant implementing directives setting standards of quality and safety for the collection and testing of human blood and blood components for all uses, including the manufacture of medicinal products.The revised text takes effect 30 November 2011.

The following changes have been made to the GMP Guide. Part II has been amended to incorporate the principles of Quality Risk Management, in line with the ICH Q9 guideline on Quality Risk Management. A new section on Quality Risk Management (Section 2.19) has been incorporated alongside a minor change to Section 2.21, and the remaining sections of chapter 2 have been renumbered. The revised text takes effect 31 July 2010.

The following changes have been made to the GMP Guide:

• Annex 6 has been revised as a consequence of the restructuring of the GMP Guide and the need to modify the requirements of Part II of the Guide for applicability to medicinal gases. The revised annex takes effect from 31st July 2010.
• Annex 13 has been revised on a number of points, and takes effect from 31st July 2010:
  • Revised to reinforce the principle of independence between production and quality control functions in cases where the number of personnel is small
  • Changes to sections 36 and 37 to supplement, for investigational medicinal products, the guidance for reference and retention samples given in Annex 19
  • Clarification of the meaning of "reconstitution" as referred to in article 9.2 of Directive 2005/28/EC
  • Addition of the content of the Batch Certificate referred to in Article 13 of Directive 2001/83/EC, as Attachment 3 in the annex, following a separate public consultation.

The following changes have been made to the GMP Guide:

• Annex 3 has been revised in the light of new GMP requirements for active substances used as starting materials (GMP Part II) and updated for all relevant aspects of GMP for radiopharmaceuticals. The revised annex takes effect 1 March 2009.
• Annex 7 has been revised to specify application of GMP provisions for active substances used as starting materials (Part II) for the manufacture of herbal medicinal products and additional changes related to the new Directive 2004/24/EC on traditional herbal medicinal products. The revised annex takes effect 1 September 2009.

Both revised and current versions of these annexes are included.

The following changes have been made to the GMP Guide:

• Chapter 1 has been revised as an implementation measure related to the ICH Q9 guideline on quality risk management. Whilst quality risk management has always been a founding principle of GMP the amendments make it clearer that quality risk management should be an integral part of a manufacturer's quality system.
• A revised Introduction to the GMP guide provides background on the implementation of these revisions.
• Annex 1 has been revised which takes effect 1 March 2009 except for the provisions on capping of freeze dried vials, which come into operation by 1 March 2010. Both revised and current versions of this annex are included.
• A new Annex 20 (Quality Risk Management) is included, implementing the ICH Q9 guidelines.

This online version coincides with the publication of the 2007 print edition.

Since the previous (2002) print edition of Rules and Guidance for Pharmaceutical Manufacturers and Distributors (the “Orange Guide”) there have been many changes and additions to the detailed European Community guidelines on Good Manufacturing Practice (GMP). In addition, there is a new Directive dealing specifically with GMP and the Community code relating to medicinal products for human use (Council Directive 2001/83/EC) has itself been the subject of substantial revision, via amending Directive 2004/27/EC, and these changes have been transposed into UK domestic legislation.

The UK’s Code of Practice for Qualified Persons has been updated by the professional bodies in consultation with the MHRA; this is included.

Recommendations on meeting the important requirement to ensure the “proper conservation and distribution” of medicines requiring storage below ambient temperature (“cold-chain distribution”) have been developed between representatives of wholesalers and the MHRA. These were published originally in the Pharmaceutical Journal, were summarised in MAIL, and are reproduced here in updated form.

Finally, there is a new section on the activities and services of the Inspection and Standards Division of the MHRA, which will be of interest to manufacturers and wholesalers.

Although much of the text in this publication is available in its original form in other places, including various websites, the “Orange Guide” continues to satisfy a demand for information in one authoritative, searchable and convenient place.