Implementation of Modern GMP Aspects: Revision of the Annex 2 of the EC GMP Guide as an Example

The GMP environment is currently changing. Not only the US Food & DrugAdministration modifies its GMP regulations, but also the European MedicinesAgency (EMEA) has taken up an ambitious revision programme for this year (seealso GMP-News from 2 November 2007). As an “outcome” the EMEA recentlyissued the drafted revision of the Annex 2 of the EC GMP Guide for (seealso GMP-News from 9 October 2007).

The draft clearly shows the modern GMP aspects incorporated –as, for instance, risk management. ICH Q9 (Quality Risk Management) is currentlydiscussed everywhere. The EC GMP Guide chapter 1 was modified accordingly, andthe Community Procedures are currently revised with regard to risk managementalso. ICH Q9 itself will supposedly be implemented as Annex 20.

The draft of Annex 2 now also reinforces the requirement for risk baseddecisions. This affects for example

• The access of personnel in the manufacture of biotechproducts,
• The management of aseptic processes and
• Tests with regard to cross contamination.

Other changes currently discussed apply to the EC GMP Guidechapters 3 and 5 concerning “dedicated facilities/dedicated equipment”. TheAnnex 2 draft requires e.g., to take “dedicated equipment/facilities“ intoaccount to be able to reproduce products and avoid cross contaminations. Riskmanagement is present here as well. It also addresses a possible conflict withrequirements regarding work safety. In the changes to the chapters 3 and 5themselves risk management will also be a main focus.

A well-known issue – validation/qualification – will still remain. For instance,the draft addresses validation-related requirements like

• Validation of decontamination,
• Validation of air vent filters (for their life span
• Processes validation (specifically mentioned are allergenand recombinant products, monoclonal anti bodies and gene therapeutics
• Validation of sterilisation, disinfection, virus removaland –inactivation
• Requalification of the irradiation
• Validation of hold time
• Validation of purification
• Cleaning Validation (specifically mentioned are genetherapeutics)

The Annex 2 draft can be used as indicator for “modern GMP”.The trend clearly goes toward risk based decisions which the authorities demandfrom pharmaceutical companies – however, paying attention tovalidation/qualification at the same time though.

Author:
Sven Pommeranz
On behalf of the European Compliance Academy (ECA)