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FDA warns companies for GMP violations, conducting trial without IND

Posted 13 October 2021 | By Jeff Craven 

FDA warns companies for GMP violations, conducting trial without IND

A contact testing laboratory found in violation of Current Good Manufacturing Practice (CGMP) regulations and a nutritional supplement company conducting a clinical investigation without an investigational new drug application (IND) have been sent warning letters by the US Food and Drug Administration (FDA).
 
FDA sent Missouri Analytical Laboratories Inc. a warning letter on 30 September due to “significant violations” of CGMP and “significant deviations from CGMP" for active pharmaceutical ingredients (API) observed during an inspection. On the same day, FDA issued a warning letter to RAAS Nutritionals, LLC/Rare Antibody Antigen Supply, Inc. for failing to submit an IND for clinical investigations of dietary supplements.
 
Both companies have 15 days to respond to the warning letters and describe what they have done to address the violations and how they plan to prevent them in the future.
 
 
Missouri Analytical Laboratories, Inc.
 
In its warning letter to Missouri Analytical Laboratories, FDA said the company failed to adequately explain and investigate discrepancies and out-of-specification results for batches. API deviations were also not documented and explained, the agency said. In addition, Missouri Analytical Laboratories did not ensure appropriate controls were in place that would allow only authorized personnel to make master production and record changes, according to the letter.
 
Data integrity and compliance was another issue raised by FDA in the warning letter. In a section on data integrity remediation, FDA said the company’s current system “does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you test,” and that a detailed data integrity investigation, risk assessment, and management strategy should be conducted that includes a corrective action plan.
 
FDA took special note to highlight Missouri Analytical Laboratories’ role as a contract testing lab in the warning letter.
 
“FDA considers contractors as extensions of the manufacturer’s own facility. Your failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs you test for your clients. It is essential that you understand your responsibility to operate in full compliance with CGMP, and that you inform all your customers of any OOS results or significant problems encountered during the testing of these drugs,” FDA wrote.
 
 
RAAS Nutritionals, LLC
 
FDA’s warning letter to RAAS originated from a failure by the company to submit an IND application for one or more dietary supplements before conducting investigative trials. The agency said the company had previously written to FDA in April expressing its opinion that an IND was not needed before starting a clinical investigation “because the articles under study are dietary supplements and not drugs.”
 
“RAAS stated that it proceeded without an IND because it believed that if it was legally able to sell its nutritional supplements to the general public, it should be able to test and observe the effects of those supplements without an IND,” FDA wrote. “RAAS believed that as long as it did not advertise in direct conjunction with a product sold in the market, the products could continue their designation as dietary supplements.”
 
While the details of each trial were redacted in the warning letter, at least one trial being conducted by RAAS was evaluating the safety and efficacy of an investigational product in relation to COVID-19. In a response on an FDA form for one investigational product, RAAS wrote that “our hopes were that the botanicals could have drug-like impact on the participant’s health (i.e., curing or preventing disease).”
 
The company noted it had sent previous communications about its “non-pharmaceutical products” to the National Institutes of Health (NIH), the Biomedical Advanced Research and Development Authority, and former FDA Commissioner Stephen Hahn, which they said supported their argument that an IND was not needed. RAAS also “claims that the FDA explicitly indicated that the sponsor did not need to proceed with an IND,” which the agency said was an NIH communication erroneously attributed to FDA and “did not suggest that RAAS’s product was not considered a drug for purposes of the FD&C Act, or that an IND was not required.”
 
FDA explained that whether an investigational product is considered a dietary supplement or drug “depends on the intent of the investigation,” and that RAAS’s products designated as dietary supplements are not exempt from needing an IND for trials where they are being investigated as a drug.
 
While FDA said RAAS acknowledged in a response that the company would “comply with the recommended use of IND…guidelines in the future,” RAAS also did not provide a corrective action plan explaining how they would comply with IND requirements.
 
“Without this information, we are unable to determine whether RAAS’s stated intent to comply with IND regulations is adequate to prevent similar violations in the future,” FDA said.
 
 
FDA warning letter to Missouri Analytical Laboratories Inc.
 
FDA warning letter to RAAS Nutritionals, LLC/Rare Antibody Antigen Supply, Inc.

 

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