The discussion about dedicated facilities and whether the requirements in the GMP Guide are sufficient for the handling of highly toxic compounds was initiated with a concept paper from the European Medicines Agency (EMA) published in February 2005. Even though here a risk-based approach according to ICH Q9 was already mentioned in order to determine if product has to be manufactured in a dedicated facility, this paper rocked the boat. The reason for this was the question if product categories for which a dedicated facility is mandatory should be defined. This would make it impossible for the pharmaceutical operator to opt for a risk-based approach with regard to certain products. An exact definition is still to be made. The chapters of the EC GMP Guide that will be affected by the change are 6,3 and 5, 18-19.
In the meantime, the competent working group consisting of GMP/GDP inspectors have come to the conclusion that the manufacture of beta-lactam antibiotics has to take place in dedicated facilities. This shall also be mandatory for the handling of living pathogenic organisms. Details are intended to be included in the new Annexes 2 (biologics) and 4 (veterinary medicinal products) of the EC GMP Guide, which are expected to be published for commenting by the public in the first quarter of 2010.
Before further requirements are laid down in writing, manufacturers who do not interpret the manufacture of a toxic/active product as "dedicated" shall rely on risk assessment. This risk assessment shall take account of the corresponding product characteristics and be conducted with the help of a toxicologist. In case the product is additionally known to have a highly active/highly toxic or sensitising effect, the competent supervisory authority shall furthermore be consulted.
The new EMA document can be found here.
Dr Robert Eicher
On behalf of the European Compliance Academy (ECA)