The GMP/GDP Inspectors Working Group already observed in 2005 the lack of clarity in the existing guides with respect to when a medicinal product should be manufactured in the shared or in dedicated facilities. A Concept Paper published in 2005 describes the need to revise chapters 3.6, 5.18 and 5.19 of the EU GMP Guide. Risk management methods (ICH Q9) should be integrated in the development of any guidance. Though, the Inspectors Working Group could notice missing toxicological expertise and therefore referred this aspect to the Safety Working Group.
The short Concept Paper presents the core problem as follows: at the moment, there is no defined approach to derive acceptable exposure limits for cross contamination between products manufactured using shared facilities. Both the pharmaceutical industry and the national GMP authorities face this problem. Depending on where a medicinal product has been manufactured, this may result in different requirements with financial impacts and potential impacts on the drug quality which may adversely affect patients’ health.
Limits such as 1/1000dose or the 10 ppm criterion are often used for cleaning validation. These limits are being questioned though, because they don't take account of the available pharmacological/ toxicological data and possible duration of exposure and may therefore be too restrictive or not restrictive enough. A more scientific approach to define exposure limits should be established in cooperation with the two working groups. The objective is to develop a new guidance to be used in the risk-identification stage to determine whether a medicinal product should be manufactured in dedicated facilities or not. The new guidance should then be integrated as an Annex to the EU GMP Guide. The final text should be finished in February 2013 and published in March 2013 with a 6 month implementation deadline.
For more details please also see the EMA Concept Paper on the development of toxicological guidance for use in risk identification in the manufacture of different medicinal products in shared facilities.
Dr Robert Eicher (CONCEPT HEIDELBERG a service provider entrusted by the ECA Foundation)