This week, there were a total of five issued warning letters: three were issued to drug manufacturers, one to a compounding pharmacy, and one to a device manufacturer. The first one issued to Deva Holdings addresses severe penicillin cross-contamination.

DRUGS | Deva Holding AS Cerkezkoy Subesi

Deva Holding AS Cerkezkoy Subesi (Istanbul, Turkey) received a warning letter on August 6, 2019 based on the outcome of an inspection ending February 15, 2019. FDA placed the firm on import alert 66.40 on July 1, 2019. Further, the FDA recommends the firm hire qualified consultant(s) to assist in bringing them into GMP compliance. Deficiencies focus on the facility/product cross-contamination by penicillin.

The FDA website lists this as having been posted on August 13, 2019 and this clearly was not posted by end of the day on Friday, the 16th because I recheck the warning letters before finalizing the weekly newsletter I compile and author. This is the second time this has happened. So, for those of you who do similarly, don’t necessarily trust the posting date, they appear at least twice to have been backdated.

Now, onto the deficiencies which include but are not limited to:

  • Penicillin was detected throughout the facility and outside the facility. The firm has two campuses approximately ¼ mile apart. Both campuses manufacture penicillin and non-penicillin products. The firm’s controls for preventing cross-contamination of other products with penicillin are inadequate. Further, the firm did not adequately monitor the areas where non-penicillin products are manufactured. 
  • The firm failed to test non-penicillin products when there is a reasonable possibility they may be contaminated.
  • The firm lacks data to demonstrate effectiveness of decontamination of surfaces that might contain penicillin. The firm has decided to recall all products from the US market due to the potential for cross-contamination.

DRUGS | Ningbo Huize Commodity Co., Ltd.

Ningbo Huize Commodity Co., Ltd. (Zhejiang, China) received a warning letter on August 2, 2019 based on the outcome of an inspection ending March 22, 2019. The drugs mentioned in the warning letter are sunscreens, so OTC rather than prescription drug manufacture. The firm recalled products from the US market and was placed on import alert on June 13, 2019.

The warning letter recommends the firm hire a GMP consultant to help them come into compliance. FDA also notes “Your firm’s quality systems are inadequate.” And finally, they are required to respond to FDA’s data integrity remediation requests, along with a suggestion that a qualified consultant help them in this area. The warning letter included only one deficiency associated with a lack of trustworthiness of the records and apparent fraudulent activity. FDA also published a release about this warning letter.

The deficiency identified included:

  • Upon being questioned by the investigator after review of certain documents, “Your General Manager and Quality Manager, then stated that multiple documents provided were in fact falsified ‘for the purpose of this inspection.’” The falsified documents included cleaning validation reports, batch records, and annual product review.
  • The firm could not provide basic GMP records such as equipment qualification, raw material qualification, and API testing, finished product testing, batch records, and process validation.

DRUGS | TG United, Inc.

TG United, Inc. (Brooksville, FL) received a warning letter on August 1, 2019 based on the outcome of an inspection ending February 15, 2019. The firm manufactures OTC drugs. As well as being cited for GMP violations, FDA deems they are making and selling unapproved new drugs that do not have labeling that meets current requirements. FDA recommends they hire a qualified consultant to assist them in coming into compliance with GMPs.

They also note that FDA cited similar CGMP violations during inspections in 2010, 2012, 2014, and 2017. They received an untitled letter in 2011 followed by a regulatory meeting in December 2012, but it appears they have yet to fully grasp and implement requirements. FDA states “This repeated failure to correct brings into question your firm’s ability to manufacture drugs according to CGMP.”

Current deficiencies include but are not limited to:

  • Investigations into OOS results and water system monitoring failures are inadequate or not conducted.
  • The firm has not established that the water systems are adequately designed and controlled, maintained, and monitored to ensure they can meet USP water and appropriate microbial limits.
  • The firm failed to demonstrate that cleaning practices remove residue from shared equipment. Cleaning is only assessed by TOC analysis of rinse water. Further, there was no demonstration that hoses and utensils were adequately cleaned.
  • The firm cannot demonstrate that the OTC products are stable thru their labeled expiry. Test method validation has not been completed. In response to a request to review validation of impurity test methods, the firm provided the investigator “…with a cart full of raw data that had not been reviewed by the Quality Unit.”

DEVICE | Polymer Technology Systems, Inc.

Polymer Technology Systems, Inc. (Indianapolis, IN) received a warning letter on July 31, 2019 based on the outcome of an inspection ending February 15, 2019. The firm manufactures in vitro diagnostic devices for a variety of medical conditions.

Deficiencies include but are not limited to:

  • The firm has not established mixing speeds to ensure maintenance of a homogeneous solution during filtration.
  • The firm did not adequately validate manufacture of the test strips.
  • Failure to validate design changes were effective prior to being implemented.
  • Failure to ensure that purchased products or services conform to requirements. Tolerances were removed without justification.
  • Investigations into the non-conformance of a purchased good were not initiated until requested by the inspector.
  • Failure to comply with medical device reporting requirements, multiple examples provided.

COMPOUNDING PHARMACY | Promise Pharmacy, LLC

Promise Pharmacy, LLC (Palm Harbor, FL) received a warning letter on July 29, 2019 based on the outcome of an inspection ending October 25, 2019.