FDA Warning Letters Week of 3/22/2020: OTC and HCT/P

In the areas we cover, FDA posted three drug GMP warning letters including one sent to a fertility clinic governed by HCT/P regulations. The other two letters were to firms that manufacture OTC products.

FDA also posted a warning letter to a firm in Ireland, Carahealth, for distributing unapproved and misbranded products related to coronavirus disease. Previously, FDA warned seven companies for distributing unapproved and unproven treatments for COVID-19 infections. FDA has started a website identifying the unapproved products and warning letters—expect this to expand in the near future.

BIOLOGICS, 21 CFR 1271 | California IVF Fertility Center

California IVF Fertility Center (Sacramento, CA) received a warning letter on February 26, 2020, based on the outcome of an inspection ending October 11, 2019.

Deficiencies include but are not limited to:

• Failure to test human specimens for evidence of infection of relevant communicable diseases.
• Failure to screen donor medical records for risk factors that provide insight into possible communicable diseases.  
• Failure to establish and maintain procedures for all steps in screening, testing, and determining donor eligibility, and complying with other donor documentation requirements.  

DRUGS | DermaPharm A/S

DermaPharm A/S (Denmark) received a warning letter on March 10, 2020, based on the outcome of an inspection ending September 19, 2019. The firm manufactures OTC products. FDA placed the firm on Import Alert 66-40 on March 9, 2020, and recommended that the firm hire a qualified consultant(s) to assist them in coming into GMP compliance.

Deficiencies include but are not limited to:

• The firm failed to test drug product for identity and strength of the active ingredient prior to release for distribution. The firm’s response to implement testing for assay/potency for future product release was not adequate because they did not address previously released product. The firm did not test reserve samples that represented drug currently in commercial distribution in the US. 
• Identity testing was not conducted on incoming raw materials and components. The firm also failed to establish the reliability of the supplier’s CoA at appropriate intervals. The firm stated that they only tested raw materials for “appearance” and “…because the supplier of this component is qualified; you did not perform incoming testing of this material.” This begs the question of how the material was “qualified.”
• The manufacturing process was not validated before the products were distributed for sale. During the inspection, the firm told the investigators that two batch sizes were manufactured and neither was validated.

DRUGS | Hangzhou Linkeweier Daily Chemicals Co., Ltd

Hangzhou Linkeweier Daily Chemicals Co., Ltd (China) received a warning letter on March 13, 2020, based on the outcome of an inspection ending September 17, 2019.

The firm contract manufactures OTC products. FDA placed the firm on Import Alert 66-40 on March 9, 2020, and recommends the firm hire a qualified consultant(s) to assist them in coming into GMP compliance.  And finally, FDA reminds them of their responsibilities as a contract manufacturer.

Deficiencies include but are not limited to:

• The firm failed to conduct testing for objectionable organisms prior to releasing product for distribution. The firm’s response to the 483 was not sufficient because the firm failed to justify their product specifications and did not perform a retrospective review and risk evaluation of drugs that are currently on the US market.
• The firm failed to test incoming materials and components but rather rely on the CoA from unqualified suppliers. In addition, the CoA for the purchased active ingredient does not include appropriate microbiological testing results. The firm’s response to the 483 was not adequate because it did not provide specifics about the firm’s supplier validation program nor did they commit to test each shipment of components received. And finally, they did not commit to perform a retrospective evaluation of products distributed in the US with components that had not been subject to adequate testing to ensure they met adequate specifications.
• The firm did not validate their manufacturing process, nor do they have an ongoing program of process monitoring. The firm’s response to the 483 was not adequate because it lacked detail about the proposed validation program. It also did not commit to evaluate previously manufactured lots to ensure they were manufactured with adequate controls.
• The firm does not have an adequate stability program to demonstrate chemical and microbiological stability through its expiry period. The firm’s response was inadequate because it did not provide stability protocols and it did not take any actions to ensure that product currently in the US market remains stable through its labeled expiry.
• The firm’s quality system and elements are inadequate.