Warning Letter Issued to Watson Laboratories Despite Recommendation for Approval

Watson Laboratories, a generic drug maker based in Corona, California, faced a critical inspection in December 1998, which resulted in a recommendation for approval. However, a warning letter was issued in January 1999, demonstrating the complexities of the regulatory environment in the pharmaceutical industry. The inspection, conducted by investigators Virgilio Pacio and Caryn Everly, evaluated the company's practices for a site change of Dilacor XR (diltiazem HCl) extended-release capsules and post-approval audits of four other generics. The FDA raised concerns about several issues, including inadequate investigation into product contamination, uncontrolled logbooks, and insufficient training of personnel.

Key Takeaways:

• Watson Laboratories faced a four-page 483 and a warning letter in January 1999, despite a recommendation for approval in December 1998.
• The inspection raised concerns about inadequate investigation into product contamination, which was primarily related to documentation.
• Watson's practice of conditionally releasing in-process blends for further processing while awaiting blend uniformity test results was identified as a concern, which the firm agreed to change.
• Several blend uniformity failures were attributed to inexperienced employees, highlighting the need for adequate personnel training.
• Watons received a warning letter for validation deficiencies, including conducting validation studies without three consecutive successful lots.
• The company was also criticized for insufficient chromatographic review, insufficient stability sample accountability, and missing manufacturing process controls from batch records.

Statistics:

• 4-page 483 issued to Watson Laboratories in January 1999.
• 1 warning letter issued to Watson Laboratories in January 1999, the company's second in a year.
• 4 generics evaluated in the post-approval audit: estradiol, in-apamide, hydrocodone bitartrate/acetaminophen, and mexilitine.
• 1 November 1997 inspection resulted in a January 1998 warning letter.
• $21 plus retrieval fee for inspection report (Doc. 108642M).

Sources:

• Watson Laboratories, Corona, CA, Los Angeles District. A combination pre-/post-approval and process validation audit of generic drug maker Watson Laboratories ended in December with a recommendation for approval, despite a four-page 483. (Doc. 7262W)
• FDA inspection report (Doc. 108642M, $21 plus retrieval fee), dated 12/7-18/98.