FDA Warning Letters Week of 11/17/2019: Torrent (Again) and Failing Water Systems

Enforcement was again busy in both the US and worldwide.  WHO published seven reports of inspections including one conducted for a bioequivalence study.  Europe published four reports of GMP non-compliance; one company had two sites inspected on the same day and the deficiencies identified were identical. 

Here we cover the three FDA warning letters published including the second one to Torrent Pharmaceuticals in October 2019.

DRUGS | Torrent Pharma Inc.

Torrent Pharma Inc (Levittown, PA) received a warning letter on October 28, 2019 based on the outcome of an inspection ending April 9, 2019.  This is the only US site for Torrent and is the second warning letter issued to the firm in October 2019—the earlier warning letter was sent to Torrent Pharmaceuticals Limited regarding operations at the site in Ahmedabad Gujarat, India.

In addition to adulteration, the FDA also identified in this recent warning letter that the firm is manufacturing unapproved drug products and misbranded drug products.  The firm manufactures finished drug products.  FDA recommends that the firm should employ a qualified consultant(s) to assist them in coming into GMP compliance.

Deficiencies include but are not limited to:

• The firm’s water system is not adequately designed, controlled, maintained or sampled.  The system has multiple dead legs and threaded pipe connections.  This system has been identified as the source of the isolated Burkholderia cepacia from equipment rinse samples.  The firm agreed to decommission and replace the water system.
• The firm did not adequately investigate failing microbial test results from samples taking from the water system.  The firm notes they recalled all products that remained on the market.

DRUGS | A.P. Deauville LLC

A.P. Deauville LLC (New Brunswick, NJ) received a warning letter based on the outcome of an inspection ending May 2, 2019.  The firm manufactures OTC products.

The FDA states they identified similar CGMP observations in the two previous inspections.  The repeated failures “demonstrate that your facility’s oversight and control over the manufacture of drugs is inadequate.”

Deficiencies include but are not limited to:

• The firm failed to investigate multiple test failures in the water system that failed to meet chemical and microbial limits.  Despite microbial values exceeding limits, the water was still used in the manufacture of drug products.  The firm also failed to investigate multiple customer complaints and adverse events.  FDA suggests that the firm hire a qualified consultant to assist them in coming into GMP compliance.
• The Quality Unit failed to identify and investigate deviations associated with batches released for distribution.  The Quality Unit does not have adequate written procedures associated with their responsibilities, change controls and investigations of OOS events, deviations and complaints.
• The manufacturing process is not adequately controlled and the process is not validated and there is no program for ongoing monitoring of process controls.  The firm does not have an adequately controlled water system and lacked routine monitoring data to establish that it operated in a state of control.
• The firm has not conducted cleaning validation, and the investigators noted product residue and a general lack of maintenance and cleaning of equipment and facility. 

DRUGS | Apothecus Pharmaceutical Corp.

Apothecus Pharmaceutical Corp. (Hicksville, NY) received a warning letter on November 8, 2019 based on the outcome of an inspection ending April 30, 2019.  The firm is reminded that the firm is responsible for the quality of their drugs even though they are manufactured by a contract manufacturer.

Deficiencies identified in the warning letter include but are not limited to:

• The firm did not adequately investigate complaints of product manufactured by a contract manufacturing organization.  The firm did not determine root cause of implement effective corrective actions.  While the firm indicated during the inspection that they would recall two lots, FDA notes that they have not yet taken any action.
• The firm does not have an adequate Quality Unit, and lacked control over manufacturing operations.
• Computer systems did not have adequate controls to ensure only authorized personnel have access.  Data on HPLC systems could be deleted or altered without documentation or justification.  The lab manager had administrator access though he also performs HPLC analyses.  Data on stand-alone systems are not backed up, and there is no procedure that requires a quality unit review of audit trails.