16/17 November 2021
With the publication of EMA's guideline on Shared and Dedicated Facilities and the revision of Annex 15, the topic of cleaning validation has gained new attention. The PDE concept is now the determining factor. But what about the FDA?
A current Warning Letter addressed to a Chinese manufacturer provides some information about this. Referring to 21 CFR 211.67 (b) on "written procedures for cleaning and maintenance of equipment", the FDA criticized the lack of adequate cleaning validation studies. Production takes place in non-dedicated facilities, where products that are not medicinal products are also manufactured.
In its response to the FDA, the company assured to perform cleaning validation retrospectively. However, the FDA would like additional documentation regarding the CAPA activities proposed by the company. For the FDA, the production of medicinal products and non-medicinal products in the same equipment is "unacceptable". If the company wishes to continue manufacturing both product groups, it should submit a plan to the FDA showing how dedicated lines will be arranged in the premises.
In addition, the FDA requires a risk assessment for specific product changes with regard to potential (cross-)contamination. The risk analysis should include plans for product quality and patient safety risks with regard to products already on the market, including possible recalls.
But these were not the only deviations. Referring to 21 CFR 211.22(a), the FDA also criticized that products have been released without QA integration even though their specifications were not correct. Moreover, batches have been released before the content values have been determined.
Some tests that were specified were generally not performed and the stability programme did not include any assays.
These very serious deficiencies led to an import alert for this company. As is almost always the case with such violations, the FDA ("strongly") recommends hiring a GMP consultant.
The Warning Letter can be viewed on the FDA website.