Italian Manufacturer receives FDA Warning Letter for Hygiene Issues

Recommendation

18/19 June 2024
Copenhagen, Denmark

Environmental Monitoring
Compliant and Reasonable

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:

• A plan and a timeline of the measures taken to replace the floors with GMP-compliant floors. The plans should be submitted to the FDA before installing the new floors. The sanitisation plan should include details about the use of cleaners, sporicidal agents, and methods used to remove moisture.

• A plan on the requalification of the facility after construction which should also contain environmental monitoring and media fill strategy.

• The FDA requires photographs of the new floors as demonstration that the facility then meets the GMP standards.

"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.

 Source: FDA Warning Letter for Corden Pharma Latina S.p.A,