Measures for contamination control are one of the basic requirements for the manufacturing of medicinal products. Manufacturing of pharmaceuticals warrants a dedicated and valid system to avoid contamination as well as a clear disaster strategy to handle microbiological deviations.
Preventive measures like suitable rooms, ventilation and equipment and a validated cleaning and disinfectant process for these rooms and the equipment are the first part of such a system. The second part are controlling measures like environmental monitoring, IPC and last but not least the handling of deviations and the following CAPA. Normally we should expect that these should be well known by the manufacturers and their responsible employers.
Previous inspection reports of the responsible authorities demonstrate this: between 1995 and 2005, the potential risk of microbiological contamination was the No 2 Critical GMP Deficiency and the No 1 Major GMP Deficiency observed during inspections ordered by CHMP/CVMP. A detailed analysis of the annually published FDA Inspectional Observation Summaries (483s) also showed that issues like hygiene, cleaning and disinfecting were still frequent reasons of deviations. More than 120 entries in the FY 2010 Inspectional Observation Summaries clearly demonstrate this.
In the following years, the analysis of the FDA Warning Letters indicated that the situation had improved. In 2013 section 211.113 of the Code of Federal Regulations (CFR) did not show any respective citations in the top 10 of the ranking list of the most frequent GMP deviations. Expectations that this development would go on showed to be wrong, though.
An analysis of the FDA Warning Letters of Fiscal Year 2014 shows that the No. 1 of 21 CFR 211 Citations - Top Ten List of Finished Pharmaceuticals is topic § 211.113 - Control of microbiological contamination. Additionally, as No.8 on the Top Ten List you can find § 211.67 - Equipment cleaning and maintenance and, as No.9 § 211.56 - Sanitation.