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Marsam Pharmaceuticals Fails FDA Inspection, Receives Warning Letter and 483

Strategic Insights

— 1 min read

In a span of nearly four months, from March to July 1999, Marsam Pharmaceuticals, a subsidiary of Schein Pharmaceuticals, was inspected by the New Jersey District Investigators Denise DiGiulio, Joseph McGinnis, and Regina Brown, along with chemist Jean Blackston-Hill. The inspection revealed numerous discrepancies and critical issues, leading to a 27-page 483 and a warning letter. The FDA cited concerns regarding the accuracy and reliability of impurity test results for Cefazolin and Cefuroxime, with a significant percentage of lots failing to meet impurity specifications. The agency also raised concerns about the production process, including the evaluation of product potency and the lack of impurity specifications for finished dosages.

Key Takeaways:

  • Marsam Pharmaceuticals received a 27-page 483 and a warning letter due to numerous critical issues and discrepancies during a four-month inspection period.
  • The FDA cited concerns regarding the accuracy and reliability of impurity test results for Cefazolin and Cefuroxime, with a significant percentage of lots failing to meet impurity specifications.
  • The agency found issues with the production process, including the evaluation of product potency and the lack of impurity specifications for finished dosages.
  • The FDA raised concerns about the firm's cleaning validation for equipment used in processing multiple drugs, including the failure to conduct solubility studies of active and inactive ingredients.
  • The agency found that the computer system in the chemistry lab lacked adequate controls, allowing unauthorized users to access and manipulate data.
  • The firm's software validation failed to address volume, boundary conditions, and system revalidation subsequent to modifications or changes.
  • Marsam Pharmaceuticals failed to maintain adequate documentation of the computer system, including the original system configuration and changes implemented.

Statistics:

  • The inspection period spanned five days in March 1999, 17 days in April, 14 days in May, and nine days each in June and July.
  • A significant percentage of lots (exact percentage not specified) failed to meet impurity specifications for Cefazolin and Cefuroxime.
  • The agency noted that impurity specifications had not been established for the finished dosage of Cefazolin and Cefuroxime.
  • The firm's computer system lacked an independent audit trail, which the FDA required for data integrity.
  • System revalidation was not conducted subsequent to modifications or changes to system software and hardware.

Sources:

  • Warning Letter (Doc. 8615W, see March 27 issue of Warning Letter Bulletin)
  • Marsam Pharmaceuticals' inspection report (Doc. 108806)
  • Warning Letter issued to Marsam Pharmaceuticals (March 2, 1999)
  • 483 issued to Marsam Pharmaceuticals (July 29, 1999)

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