Last week, FDA posted two drug-related Warning Letters. One was issued to a drug packager and listed two cleaning validation issues. The other was issued to a manufacturing firm that received a 25-page Form 483 in April.

Drug Warning and Untitled Letters

KVK-Tech, Inc

KVK-Tech, Inc (Newtown, PA) received a Warning Letter on October 8, 2020, based on the outcome of an inspection ending March 13, 2020. Never a good thing, the firm also received a Warning Letter on February 11, 2020. The firm is identified as a drug packaging operation. In the October Warning Letter, FDA noted that similar GMP violations have been identified at other facilities owned by the firm, but did not reference the Warning Letter from February. “These repeated failures at multiple sites demonstrate that management oversight and control over the manufacture of drugs is inadequate,” FDA recommends the firm hire a qualified consultant(s) to assist them in coming into GMP compliance. FDA also acknowledges that the firm has suspended operations at the facility in question, and must notify the FDA before resuming operations. Deficiencies identified include but are not limited to:

Cleaning of non-dedicated equipment was not validated. Further, the firm has not established a worst-case scenario to support cleaning validation activities.
Batch records did not include complete information. The air pressure gauge was observed to read outside the acceptable range, though a conforming value was recorded in the batch record. In other instances staff failed to record accrual air pressure reading. The firm’s response was inadequate because they did not conduct a comprehensive review to determine the extent of inaccurate data recordings in production records.
Cleaning validation samples for one product were documented as being received in the incoming sample logbook as being received at a time approximately five hours after they were tested.

Shilpa Medicare Limited

Shilpa Medicare Limited (India) received a Warning letter on October 9, 2020, based on the outcome of an inspection ending February 25, 2020. FDA posted a 25-page, 14-observation Form 483 on the FDA website in April. In addition to the GMP violations, the firm also failed to submit Field Alert Reports within three working days of being made aware of an event covered in 21CFR314.81(b)(1)(ii). Eight specific examples were provided. FDA is making the point that this was not simply a one-off failure. FDA notes that the firm manufactures both sterile injectables and solid oral dose drug products. FDA recommends that the firm hire a qualified consultant to assist them in coming into GMP compliance. The warning letter identifies two deficiencies including but not limited to:

The firm did not conduct adequate OOS investigation and did not address an unknown chromatographic peak adjacent to a known impurity peak in an HPLC analysis.
The firm received multiple customer complaints for the presence of foreign particles. The firm also received complaints for sealing defects.
Failure to follow adequate procedures upon receipt of a customer complaint. FDA objected because the firm did not provide a scientific justification for not classifying the following as critical complaints: particulate contamination, coring, and seal integrity. These defect complaints were initially classified as minor, but in their response, the firm reclassified them as major.