FDA blasts US API firm for lax response to mold contamination, data integrity failings

Regulatory NewsRegulatory News | 29 July 2022 |  By 

A US manufacturer of active pharmaceutical ingredients (API) was lambasted in a recent warning letter by the US Food and Drug Administration (FDA) for multiple good manufacturing practice (GMP) violations, one of which was a failure to adequately respond to mold contamination.
The firm also failed to maintain control over its computer systems to prevent unauthorized access to electronic data.
The warning letter was issued on 18 July to St. Louis-based manufacturer Jost Chemicals and posted on FDA’s website 26 July. It follows an inspection conducted in January 2022.
FDA said the firm failed to adequately investigate and resolve a complaint related to the discovery of mold contamination in its potassium sulfate API lots in August 2018. Subsequent retain testing showed a “gross mold failure.” The firm identified mold in two additional lots.
The company informed its clients that lots failed to meet specifications and gave instructions to return or destroy the failing lots yet did not initiate a formal recall.
Subsequent retests showed “pervasive” mold in three lots, yet the company failed to expand the scope of its investigation to include other potentially impacted lots.
FDA said the mold problem may have emanated from failures in the water system. “Notably, you reported that approximately that 83 percent of your microbial product failures were mold-related failures. Your current frequency of testing and water quality standards are inadequate to ensure control over your manufacturing processes. You are responsible for ensuring the water for equipment cleaning and manufacturing is of suitable quality and does not potentially contribute to contamination of microbes or microbial byproducts to API processes.”
Lax approach to equipment cleaning
FDA said the firm also lacked adequate equipment cleaning standards. “Your quality assurance personnel stated that equipment cleaning is performed between manufacturing campaigns which can vary in length … and between [redacted] lots. However, your cleaning validation (18PRO054) did not document or detail the campaign length evaluated for all equipment. Further, your cleaning procedures did not define the campaign length before cleaning,” FDA wrote.
The firm also failed to ensure that laboratory data was complete and attributable. For example, microbial test procedures did not include growth promotion studies to verify the adequacy of the media for its intended use. The firm also used microbial growth media prepared in-house and relied only on the original media vendor certificate of analysis (CoA) test results without further verification.
The identity of the analysts that inoculated the plates for microbial testing were not identified.
Investigators also found the firm lacked sufficient controls over its computer systems to prevent unauthorized access or changes to data. The firm lacked unique passwords for laboratory instruments.
FDA “strongly” recommended the firm hire a GMP consultant to help remediate these violations.
The firm was given 15 days to respond to the observations in the letter. FDA said failure to address these problems may cause the agency to withhold export certificates or withhold approval of new drug applications or supplements listing the firm as a manufacturer.
Warning letter


© 2023 Regulatory Affairs Professionals Society.

Tags: APIs, FDA, GMPs, letter, warning

Discover more of what matters to you