The US Food and Drug Administration (FDA) has issued a Warning Letter dated February 17, 2017 to Morton Grove Pharmaceuticals, a subsidiary of Wockhardt, a Mumbai, India-headquartered biopharmaceutical company, for violations of current good manufacturing practices (cGMP) for finished pharmaceuticals. The violations were noted at Morton Grove’s drug manufacturing facility in Morton Grove, Illinois during an FDA inspection conducted from January 4 to February 5, 2016. The FDA reviewed the firm’s response on March 7, 2016 and acknowledged receipt of subsequent correspondence relating to this facility.
The FDA made several observations including: failure to thoroughly investigate unexplained out-of-specification (OOS) stability tests of a batch, whether or not the batch has already been distributed; failure to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards; and failure to follow written procedures applicable to the firm’s quality control unit. Other observations included: failure to establish and follow adequate control procedures on manufacturing output and validation; failure on the part of the firm’s quality control to test in-process materials during the production process; and failure to exercise appropriate controls over computer or related systems to assure data and IT integrity.
In response to this letter, the FDA requires the following of Morton Grove:
- That the company give details of its investigation and how it determined the root cause of the OOS stability tests; updated its efforts to identify cGMP violations and assess each one; detail actions that ensure all product/quality-related investigations are thorough, timely, and scientifically sound; and justify why the firm failed to take additional actions with respect to batches of potentially-affected products that were distributed and remain on the market.
- That the company provides scientific data supporting the validated status of its fluticasone propionate nasal spray USP manufacturing process; retrospectively reviews every instance where no in-process testing was conducted at the appropriate time; lists all OOS, invalidated OOS, unexpected, and out-of-trend in-process test results for products within expiration; investigates previous assessments of quality standards to determine the need for changes in drug product specifications, manufacturing, or control procedures; and explains why quality-related investigations were performed and documented without the quality unit’s oversight.
- Also, that the company list all its corrective and preventive actions (CAPAs) to ensure that all investigations and deficiencies from internal audits are overseen by the quality unit; list all quality-related investigations and CAPA generated during the last three years initiated as a result of an internal audit or any other mechanism, with reference to the procedure governing each of these investigations and CAPA; and justify why review was limited to only adulterated batches representing adulated finished drug products and did not extend to the active pharmaceutical ingredient and excipients.
- Furthermore, the company is to provide a detailed plan to ensure that each current and future employee will have a unique username and password to allow traceability of changes to electronic data back to specific authorized personnel; describe the specific changes made to software and electronic systems to ensure the effectiveness of the firm’s corrective actions; and include a detailed description of the role of the quality unit to ensure that the corrections are appropriately implemented and sustainable.
The FDA noted in the Warning Letter that, at this time, seven Wockhardt facilities (including Morton Grove) are considered out of compliance with cGMP.
Source: Food and Drug Administration