The FDA observed GMP deficiencies in an inspection of a Legacy Pharmaceuticals Switzerland facility, including problems with sterility, maintenance and discrepancy investigations.

The agency issued a Form 483 with six observations following a July 2017 inspection. The firm’s cleaning and maintenance written procedures did not adequately describe the methods, equipment and materials involved. For example, parameters like volume of water, time, pressure and water temperature, as well as exact equipment used, were not properly defined to ensure consistent and effective cleaning results.

The facility did not take representative samples of components, drug product containers and closure shipments for each lot. It also failed to take samples of stoppers and vials used in packaging to check for conformity to specifications and representative sampling, instead having samples sent with shipments taken by suppliers.

A manufacturing system at the facility was not fully protected from non-circulating materials and stagnant flow. The firm also did not fully test for microbial guideline compliance and did not adequately sanitize certain filters to control the spread of microbes and manage a potential source of endotoxins.

The facility also lacked a root cause analysis for out of specification results. The agency observed that “a new sample was analyzed and these conforming results [were] reported as the final data without a scientific basis for invalidating the original OOS results.” The detection of gram negative bacteria also did not result in timely action to ensure the bacteria did not spread.

In addition, the firm did not formulate all batches to give 100% of the labeled active ingredient, and its batch records did not provide for calculation of the API. The facility also failed to validate software used with high-performance liquid chromatography.