Massachusetts Company Receives Warning Letter

FDA sent a warning letter dated March 14, 2019 to Pharmasol Corporation after inspections of two of the company’s facilities found violations of current good manufacturing practices (CGMP). Violations found ranged from a failure to investigate batch failures and inadequate quality control units.

Pharmasol’s South Easton, MA facility was inspected from July 23–August 20, 2018. Inspectors found that investigations into out-of-specification (OOS) stability test results were not thoroughly conducted. Lots were rejected because of leaking in stability units for three validation lots; however, despite a change in the container-closure system, the stability samples were still leaking. “In your response, you suggested that the leaking did not compromise the quality of the drug product. You proposed to stop placing stability samples in a horizontal position, adding ‘upward arrows’ to the shipping cartons, evaluating shipping containers for the necessity of additional dividers, and providing shipper instructions to ‘keep product upright.’ Your response was inadequate in that you did not identify a root cause or suggest a corrective action for the leakage,” the agency stated in the letter. The agency requested the company provide root-cause investigations into the leaking containers, a corrective action and preventive action (CAPA) plan, an improved risk-assessment process, and an assessment of the company’s overall investigating system.

According to FDA, the company also lacked an adequate quality control unit. The quality unit that was in place did not review, approve, or close investigations and CAPA in reasonable time limits. “These open investigations included significant drug product quality issues, such as leaking containers, deviations from key production parameters (e.g., mixing speeds), and OOS solvent assay results in finished drug product release testing. During our inspection, you explained that you believed that lapses in quality system performance were due to the strained quality system, your firm’s cumbersome procedures, and inefficient management of resources,” the letter stated. The agency requested the company provide a retrospective, independent review of all invalidated OOS results, a review of its system for investigating OOS results, and a CAPA assessment.

An adequate written testing program to assess stability characteristics of products was also lacking, according to FDA. The agency requested the company provide a comprehensive assessment and CAPA plan for ensuring an adequate stability program.

According to FDA, similar observations were found at the South Easton facility during inspections in 2013, 2014, and 2015.

The company’s Stoughton, MA facility was also cited in the letter for failure to thoroughly investigate batch failures. Improperly discarded worksheets with OOS results were found in the recycling bin by inspectors. The company stated an ex-employee created the records and the components passes upon reexamination. “You also reported that you updated your 'good documentation practices' procedure and your procedure for sampling and releasing components. Your response was inadequate, because it did not provide the re-examination results (including raw data and worksheets) for the bottles and caps to show they met your acceptance criteria,” the letter stated. The agency asked for copies of the original raw data and worksheets documenting the reexamination and measurements as well as an assessment and review of its documentation system.

Source: FDA