On 20 May 2016, the FDA issued a Warning Letter to the Italian manufacturer Corden Pharma Latina S.p.A. because of major GMP violations in the manufacture of finished medicinal products and deficiencies in the production of APIs. Concerning the manufacture of finished medicinal products, violations were observed in premises design and cleaning procedures.
"Your firm failed to have facilities used in the manufacture, process, packaging and holding of drug products of appropriate construction to facilitate cleaning, maintenance, and proper operations (21 CFR 211.160(b))"
There were floor tiles in the manufacturing area which were filthy throughout the aseptic area. Some tiles were cracked and had been inadequately repaired which caused even more filthy gaps. The company responded with the repair of the cracked tiles and damaged seals as well as the replacement of the flooring in the area of the aseptic filling machine - which was inappropriate for the FDA. The FDA has considerable doubts that repairs would enable the achievement of a GMP-compliant stand. In fact, the FDA requires the following measures:
"Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a))"
On this point, the FDA criticised the cleaning procedure. Water had been sprayed throughout the aseptic area which led to stagnant water collects underneath the filling machine. The FDA considered this as a potential source of microbiological contamination. The company’s response was to use a mop after cleaning to remove stagnant water. Moreover, the company wanted to evaluate alternative disinfecting agents which would not require removal with water. However, the FDA wanted the demonstration that the use of a new disinfectant agent and the mop is adequate for cleaning and sanitising the floors.
Overall, the FDA expects from the company the sanitisation and the adaptation of the cleaning procedures to avoid microbial and particles contamination.