FDA Warning Letters Week of 1/12/2020: CMO Quality

This week we cover three warning letters: two to pharma firms and one to a clinical investigator.

DRUG | Health Pharma USA LLC

Health Pharma USA LLC (Rahway, NJ) received a warning letter on Dec 18, 2019 based on the outcome of an inspection ending June 3, 2019.  The FDA reminds them that as a contract manufacturer they are responsible for the quality of drugs they produce and points them to the FDA guidance on the topic.  FDA recommends they hire a qualified consultant to assist them in coming into GMP compliance. FDA also stated, “Your firm’s quality systems are inadequate.”

Deficiencies include but are not limited to the following:

• The first deficiency states that the Quality Unit failed to adequately exercise their responsibilities because they lacked written procedures for many of their functions, products were shipped before Quality Unit review, and they failed to implement an adequate stability program, just to name a few.
• Batch records are missing critical information including, but not limited to, information regarding details on the tablet coating process, length of time that bulk material is blended, information on shipping boxes, lining, and labels.
• Process validation is not adequate because there are no procedures for process validation nor are impurities and content uniformity, for example, considered to be critical drug attributes. 
• The firm does not routinely perform identity testing for incoming components such as excipients or APIs.  Further, the firm does not adequately qualify suppliers to establish the reliability of the CoA.

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DRUG | Hualan Zongheng Bio-Tech Co., Ltd

Hualan Zongheng Bio-Tech Co., Ltd (China) received a warning letter on January 9, 2020 based on the outcome of an inspection ending July 5, 2019.  The firm manufactures OTC products and was placed on Import Alert 66-40 on November 8, 2019.  FDA recommended that the firm hire qualified consultants to assist them in coming into GMP compliance.  The firm is a contract manufacturer and FDA reminded them of their responsibilities in this area.  And finally, FDA expressed concerns about whether they are adequately testing the glycerin they use as an ingredient for the presence of diethylene glycol per FDA guidance.

Specific deficiencies include but are not limited to:

• OTC products intended for use by children were released without testing for identity and strength of the active ingredient.
• Incoming components including APIs were not tested for identity.  The firm’s response did not commit to perform identity testing of all components used in the manufacture of drug product.  Further, the firm did not test their retain samples to ensure they meet a specification for identity.
• The firm did not have a sufficient stability program to support the labeled 36-month expiry dating.  While the firm claimed to have stability data for “one identical drug product formula for another market” they did not provide these data to FDA in their response nor did they provide any data for their other product formulas.
• The firm failed to validate any, except for one product, manufacturing process.  The firm makes multiple products with multiple formulations.  In their response to the form 483, the firm failed to commit to validating the manufacturing process of ALL drug products.
• The firm has not adequately qualified the equipment used in the manufacture of drug product to ensure it operates consistently.  This deficiency is well redacted, but I think they are referring to the system for generation and distribution of water used in manufacture.

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CLINICAL INVESTIGATOR | James Findling MD

James Findling MD (Milwaukee, WI) received a warning letter on December 31, 2019 based on the outcome of an inspection ending August 2, 2019.  This inspection was conducted as part of FDA’s Bioresearch Monitoring Program.

Deficiencies include but are not limited to:

• Failure to conduct the study consistent with the clinical protocol.  The warning letter provides a litany of examples where the investigator failed to follow the protocol.