FDA Warning Letters Week of 12/8/2019: CAPAs, Complaints, and Quality Systems

Enforcement this week included two drug GMP warning letters, both to firms in the US.  In the week prior, FDA posted and then removed a warning letter to a device manufacture that also functioned as a contract sterilizing service.  The letter has yet to be posted again.

DRUGS | Ohm Pharmaceuticals

Ohm Pharmaceuticals (Mineral Wells, TX) received a warning letter based on the outcome of an inspection ending May 23, 2019.  The firm manufactures both dietary supplements and drugs.

In addition to adulteration of dietary supplements, FDA cites some dietary supplements as misbranded.  FDA recommends the firm hire qualified consultant(s) to assist them in coming into GMP compliance.  Further, FDA notes that their quality systems are inadequate.

Drug GMP deficiencies (read the letter to find the deficiencies for dietary supplements) include but are not limited to:

• The facility was not maintained clean.  The investigators identified white residue in hallways and rooms although they were identified as “clean”.  The white powder residue was not identified.  Rooms and equipment were shared between drugs and dietary supplements.  Of particular concern are drugs intended for infants and children that may share equipment with potentially toxic ingredients including boric acid.
• Laboratory sampling plans and test methods are not scientifically sound.  Purified water was stored in plastic containers prior to use in manufacturing operations.  Further, the microbiological methods used to test water and final product lacked growth promotion evaluation of media, lacked method suitability, and test procedures lacked sufficient detail to determine how many units of finished product are to be used for microbiological testing.
• The manufacturing process is not validated.  Batch records are not complete, and reproducibility of manufacture cannot be ensured.

DRUGS | Teligent Pharmaceuticals

Teligent Pharmaceuticals (Buena, NJ) received a warning letter on November 26, 2019 based on the outcome of an inspection ending May 20, 2019.  The firm manufactures drug products.

FDA notes that this inspection cited similar deficiencies as were identified during the October 2017 inspection.  FDA states that “Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.”  Note that FDA asks for “comprehensive, independent assessment…” indicating they feel the company is incapable of doing an effective assessment on their own.

Deficiencies include but are not limited to:

• Investigations into OOS events are inadequate because they aren’t investigated in a timely manner, don’t have root causes identified, don’t include all potentially impacted lots, do not have CAPAs initiated and do not ensure the effectiveness of those CAPAs.
• The firm did not test stability samples within the timeframes of the stability protocol.
• The firm did not have adequate procedures for the management of customer complaints.  75 of 127 complaints received in 2018 and 2019 were open more than 30 days and at least 6 that were open more than 150 days.  Further, ~60% focused on product separation, lack of effect and adverse events.
• The firm failed to evaluate changes to the manufacturing process to ensure consistent manufacturing and drug quality.
• The firm failed to submit Field Alert Reports as required by the regulations.