New FDA Term in the Field of Equipment

A Canadian drug manufacturer received a warning letter due to its GMP deficiencies. Among other things, deviations from 21 CFR 211.67 (a) were found. What did the FDA criticise?

The finding was listed as follows in the warning letter: "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))"

Insufficient maintenance was criticised. During the inspection, white particle deposits were found on the surfaces of production equipment used to manufacture spray drug products for the US market. The source and nature of the contamination were determined. Particles were also found along a conveyor belt that transports closure components for filling.

Almost a year before the FDA came to inspect, the company purchased equipment with an improved design. However, they continued to work with the old equipment, which generated particles. This was criticised by the FDA as a deficient maintenance programme.

In its warning letter, the FDA demanded an "effective equipment management programm". This term can not be found in 21 CFR 210/211 (US GMP regulations). The warning letter shows what the FDA means by ‘current’. It calls for a proactive life cycle approach with systematic monitoring, maintenance and, if necessary, prompt replacement to ensure long-term process capability. As part of the pharmaceutical quality system, data on equipment performance, maintenance trends and risk assessments must be included to enable timely CAPA measures. A separate news article will deal explicitly with the CAPA deficiencies in detail.

FDA-Expectations

Following the warning letter, the FDA expects:

A comprehensive, independent retrospective assessment of cleaning effectiveness to evaluate the extent of cross-contamination hazards. This includes:

• the identification of residues,
• other production equipment that may not have been cleaned properly and
• an assessment of whether cross-contaminated products may have been released for distribution.

The assessment should identify any shortcomings in cleaning procedures and practices and cover all production facilities used to manufacture more than one product.

Conclusion: With this warning letter, the FDA is making clear what it expects in terms of cGMP for equipment – an effective equipment management system as a proactive life cycle approach with systematic monitoring, maintenance and, if necessary, prompt replacement to ensure long-term process capability.

You can find the entire warning letter on the FDA website.