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 & Drug Administration modifies its GMP regulations, but also the European Medicines Agency (EMEA) has taken up an ambitious revision programme for this year (see also GMP-News from 2 November 2007). As an “outcome” the EMEA recently issued the drafted revision of the Annex 2 of the EC GMP Guide for (see also 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 currently discussed everywhere. The EC GMP Guide chapter 1 was modified accordingly, and the Community Procedures are currently revised with regard to risk management also. ICH Q9 itself will supposedly be implemented as Annex 20.

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

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

Other changes currently discussed apply to the EC GMP Guide chapters 3 and 5 concerning “dedicated facilities/dedicated equipment”. The Annex 2 draft requires e.g., to take “dedicated equipment/facilities“ into account to be able to reproduce products and avoid cross contaminations. Risk management is present here as well. It also addresses a possible conflict with requirements regarding work safety. In the changes to the chapters 3 and 5 themselves 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 allergen and recombinant products, monoclonal anti bodies and gene therapeutics
• Validation of sterilisation, disinfection, virus removal and –inactivation
• Requalification of the irradiation
• Validation of hold time
• Validation of purification
• Cleaning Validation (specifically mentioned are gene therapeutics)

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

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