New EU GMP Cleaning Validation guidelines for the manufacture of medicinal products in shared facilities

The new version of Annex 15 EU GMP which comes into operation 1st of October 2015 lists significantly updated approach for the Cleaning Validation. The most important change is that from October, the before accepted levels of carry-over of product residues after cleaning (the most strict of: visually clean, or 1/1000 of normal therapeutic dose, or 10 ppm of any product) are no longer valid as is. Moreover, the “visually clean” will be the important criterion, but not acceptable when used alone. The companies undergoing cleaning validation will soon have to provide the sound scientific proof of the carry-over safety via the toxicological evaluation.The European Medicines Agency has issued the guideline on setting health based exposure limits. This guideline is referred to in the Annex 15. To establish the permitted daily exposure (PDE) limits for the carry-over APIs, companies now need to, among other routines, identify hazards by reviewing all relevant data, which include“all available animal and human data…for each compound”,i.e.“non-clinical pharmacological data, repeat-dose toxicity studies, carcinogenicity studies, in vitro and in vivo genotoxicity studies, reproductive and developmental toxicity studies as well as clinical data (therapeutic and adverse effects).”“The search strategy and the results of the search must be clearly documented” and reviewed by/discussed with the expert to choose the doses for the calculation of the PDE.What does it mean for the companies? Every compound data will have to be evaluated (if not also gathered) by the expert toxicologist, and it’s a lot of additional expenses which makes the survival of a small medicinal products producing start-up clearly questionable.If your company needs to validate the cleaning procedure in the medicinal products production or if you need help in assessing the risks for your cleaning activities or to perform a cleaning validation—please contact us. We have all the expert knowledge in the field to help you perform it with highest expertise and efficiency.ReferencesEudraLex – Volume 4 Good manufacturing practice (GMP) Guidelines. Annex 15 Qualification and validation (Deadline for coming into operation: 1 October 2015)EMA Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities