FDA Warning Letters Week of 1/26/2020: HCT/P and OTC Products

It was a busy week on the warning letter front with one warning letter issued to an HCT/P firm and three issued to OTC manufacturers located outside the US. Along with these warning letters which we cover below, the Center for Tobacco Products cited Smart Toothpicks, LLC in Tempe, AZ, for sale of dissolvable nicotine infused toothpicks based on information from their website.

DRUG | Baha Fur S.A. de C.V

Baha Fur S.A. de C.V (Tijuana, Mexico) received a warning letter on December 13, 2019, based on the outcome of an inspection ending July 12, 2019. The warning letter was sent to the CEO in the City of Industry, CA regarding this site. The firm manufactures OTC products. FDA advises the firm to hire a qualified consultant to assist them in coming into compliance.

Deficiencies include but are not limited to:

• The firm did not adequately investigate microbiological test results that were OOS. Even though the lot(s) were rejected, the firm should have conducted an investigation to identify the root cause and implement corrective actions to prevent this from happening in the future. The incubation parameters for microbiological tests performed at the contract laboratory differ from USP<61>. FDA also deems the firm’s response inadequate because the investigation did not consider distributed products that may be impacted by microbiological contamination.
• Batch records lack adequate detail including, for example, identification of each step in the filling operation and identification of the person who performed each significant step. The firm’s response was deemed inadequate because the firm did not provide details of how they would confirm compliance with batch records or other control records. Further, it did not provide information regarding review, evaluation, or identification of significant process parameters that apply to the drug product packaging and labeling operations.
• The firm did not adequately validate cleaning procedures for shared equipment. The cleaning is inadequate to prevent cross-contamination among products. The response to the observation was inadequate because it failed to determine the risk of potential cross-contamination and its impact on product quality for marketed products.

DRUG, HCT/P | R & B Medical Group Inc

R & B Medical Group Inc (Van Nuys, CA) received a warning letter on January 15, 2020, based on the outcome of an inspection ending September 25, 2019. The firm is a contract testing laboratory that tests for communicable diseases for fertility clinics and medical practices. Their data is used to determine donor acceptability for oocytes and semen. Thus, they are governed by 21 CFR 1271.

Deficiencies identified include but are not limited to the following:

• Donor screening tests were not used consistent with manufacturer’s instructions nor were all data, particularly data that were positive for a communicable disease, reported to the firm providing the sample. Screening test results are not reported, but only confirmatory or additional test results are communicated. In addition, samples were stored longer than allowed by the test kit manufacturer’s instructions.
• The firm has not “established and maintained” procedures for all steps they perform. FDA says that “Establish and Maintain” means “define, document, and implement; then follow, review and…revise on an ongoing basis.” The firm has failed to develop procedures for, among other activities, documentation of test kit numbers, identification of equipment used during testing, incubation times, steps in reporting results to clients, and calibration/maintenance of testing equipment.
• The firm does not have procedures to complain about management and their investigation.
• The firm does not have a quality program that includes investigation and documentation of deviations.
• The FDA investigators identified numerous incomplete records, missing documentation of lot number, and missing documentation of who performed the test.
• The agency expressed concern about the representation of screening test results as negative after performing confirmatory tests. The confirmatory test may not be as sensitive as screening tests. Note that within deficiency #1 the firm does not communicate the screening results which were positive for disease detection if the confirmation test was negative.

DRUG | Dental-Kosmetik GmbH & Co. KG

Dental-Kosmetik GmbH & Co. KG (Dresden, Germany) received a warning letter on January 16, 2020, based on the outcome of an inspection ending July 19, 2019. The firm’s products contain glycerin and FDA is concerned they may not be adequately tested for diethylene glycol. FDA also states that the firm’s quality systems are inadequate, and they should engage a consultant to assist them in coming into GMP compliance. FDA also placed the firm on Import Alert on January 10, 2020. The firm manufactures OTC drug products.

Deficiencies include but are not limited to:

• The firm has not validated their manufacturing process and states that “due to the variability the production process cannot be validated…” FDA found that unacceptable and justifies why process validation is important.
• While the deficiency is well redacted it appears that the firm’s water system is not adequately designed, controlled, maintained, and monitored.
• The stability program is not adequate to ensure the product meets specifications through their labeled expiry period. There are no long-term data; the only batch on stability is an R&D batch and what appears to be one commercial batch.
• The firm did not test incoming API for identity, purity, or other quality attributes, nor have they established the reliability of the results on the vendor’s certificate of analysis. The firm relies on the CoA to verify identity.

DRUG | Sunstar Guangzhou Ltd

Sunstar Guangzhou Ltd (China) received a warning letter on January 22, 2020, based on the outcome of an inspection ending June 28, 2019. The firm manufactures OTC drug products. FDA placed the firm on Import Alert on January 21, 2020. FDA recommends the firm engage a qualified consultant to assist them in coming into compliance with GMPs. FDA also has concerns about whether glycerin used by the firm is adequately tested for diethylene glycol.

Deficiencies include but are not limited to the following:

• The firm released some drug products without testing for the identity and strength of the active ingredient. The firm’s response was inadequate because they did not test reserve samples to ensure they met specifications for identity and strength.
• The firm does not test incoming products to confirm their identity, including the active ingredients.
• The firm does not consistently perform growth promotion testing on the in-house media prepared by microbiological testing.
• The quality unit does not have adequate procedures and does not provide adequate oversight over manufacturing operations. The firm does not have adequate control over the issuance, use, and reconciliation of manufacturing batch records and equipment maintenance sheets; raw data for laboratory test standard curves could not be located; scrap paper was used to record data; uncontrolled copies of batch records were pre-printed and maintained in an unsecured location.