FDA Warning Letter: Product Mix-Ups and Insanitary Conditions at US Repackager

The U.S. Food and Drug Administration (FDA) has issued a Warning Letter dated 03 October 2022 to a drug manufacturing facility in Missouri. The Warning Letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. It was preceded by a Form FDA 483. However, the response to this and the measures taken and planned were assessed by the FDA as inadequate.

Product Mix-Ups

The company repacks and relabels numerous finished drug products intended to treat various conditions. Obviously, product mix-ups occurred repeatedly during this process. The FDA says that the company "failed to adequately investigate the presence of foreign tablets" in the drug products.

Referring to two investigations of documented product mix-ups performed by the company, the FDA writes: "Both investigations indicated potential equipment design flaws, inappropriate cleaning, and ineffective line clearance. While you identified some corrective actions and preventive actions (CAPA) to address equipment design and cleaning, you did not extend the investigation to determine whether other batches in the same packaging line or within the same facility may also have been impacted."

Insanitary Conditions

During an FDA inspection, one operator was observed to pick up individual tablets off of the floor and place them directly into the feed hopper. However, even this obvious GMP violation was not addressed seriously by the company, neither immediately after the incident nor in the further course of the investigations. It was not evaluated how to prevent such violations in the future.

With reference to the company's written response to FDA, the agency states that the company "did not evaluate the impact on product quality for the lot where individual tablets were picked up off of the floor, did not provide assurance that material which comes into contact with the floor will not be re-introduced into any batches, did not extend the investigation to other batches, and did not conduct any risk assessment or retrospective review to evaluate the impact on the quality of other batches."

Further Violations

In addition to the violations mentioned above, the FDA also has other aspects to complain about:

  • Non-contemporaneous documentation;
  • General documentation deficiencies;
  • Ineffective line clearance.

FDA Calls for Measures

The FDA now expects the company to take a whole series of measures, such as:

  • A comprehensive, independent written evaluation of packaging and labeling operations;
  • An assessment of the company's overall system for investigating deviations, discrepancies, complaints, out-of-specification (OOS) results, and failures;
  • A comprehensive audit of the entire operation for CGMP compliance.

For more detailed information, please see the complete FDA Warning Letter to Legacy Pharmaceutical Packaging LLC.

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