Cross-contamination: Topic of the Revisions of Chapters 3 and 5 EU GMP Guideline

As already published in the GMP-Newsletter dated 23 January 2013 the European Commission has revised numerous chapters of the EU GMP Guideline (Part 1). This revision concerns, inter alia, chapter 3 "Premises and Equipment" sub-point 3.6 as well as chapter 5 "Production" points 5.17 - 21.
An interesting point in chapter 3 is, that the controversial wording "particular medicinal products" for which dedicated facilities had been required has been deleted completely. It has been replaced by the relatively concrete requirement: dedicated facilities are required for medicinal products:

  • that present a risk which cannot be adequately controlled by operational and/ or technical measures (Quality Risk Management) 
  • for which no scientific proof for threshold values exists (dose/effect) such as sensitising materials (beta lactams are still mentioned) 
  • with threshold values below the levels of detection

Whereas the points number 2 and 3 are clear, there is certainly more need for discussion concerning the first one. Regarding the threshold values reference is made to the new EMA Guideline (see below).

In chapter 5 the necessity is emphasised to avoid cross contamination by an appropriate design of the processes, premises and equipment. Here, the Quality Risk Management approach is presented, too, in order to assess the potential risk for cross contamination and to derive the necessity for the use of dedicated premises. The list of measures that can be taken to minimise the risk of cross contamination has been greatly expanded. New are for example:

  • use of barrier systems (isolator) 
  • localised extraction of dust 
  • use of dedicated equipment including maintenance tools 
  • use of disposable equipment 
  • use of CIP systems (validated) 
  • use of air and surface samples taken outside the working area to demonstrate the efficiency of the measures chosen 
  • monitoring of the staff's working behaviour to ensure training effectiveness

Furthermore, it is proposed to carry out a cleaning verification after each product campaign instead of a cleaning validation. This point will surely lead to discussions.

The requirement that measures to prevent cross-contamination and their effectiveness should be checked periodically did not change. Only the chapter number was changed from 5.20 to 5.21.

As part of these changes the European Medicines Agency (EMA) has published a draft for a Guideline on scientifically sound exposure limits nearly at the same time (see also here). In addition to the changes in chapters 3 and 5 this guideline explains how pharmacological/toxicological data should become part of the risk assessment and the determination of exposure limits. 

Here you find the two new chapters of the EU GMP Guideline: Chapter 3, chapter 5.

Deadline for comments is 18 June 2013.

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