Chlordiazepoxide Hydrochloride/Clidinium Bromide

A generics manufacturer has received a warning letter from the FDA over several issues surrounding supervision and quality control. Bi-Coastal Pharma International’s drug manufacturing facility in Shrewsbury, New Jersey initially received a Form 483 earlier this year. But according to another letter dated June 30, the FDA has found some flagrant issues with the company’s responses. The letter initially stated that Bi-Coastal had failed to establish and follow written procedures around the handling of written and oral complaints for drug products. The FDA found that the company had not investigated a complaint about an adverse reaction after taking Chlordiazepoxide Hydrochloride (HCl) and Clidinium Bromide (Br), 5 mg/2.5 mg, which was discovered and distributed by the company. No investigation was initiated to evaluate the manufacturing and packaging of Chlordiazepoxide HCl and Clidinium Br, according to the letter. In addition, the FDA said Bi-Coastal didn’t attempt to obtain samples of the drug or more information from the complainant. Bi-Coastal said that its CMO was no longer in business and was unable to share the complaint with the CMO for further investigation. However, the FDA argues that as the product owner, Bi-Coastal is still responsible for ensuring control over outsourced activities. While the company said it would revise the process for handling complaints, the FDA found the response inadequate. Regulators also accused Bi-Coastal of failing to write down and follow procedures. No details of its interim controls were supplied to the FDA, or an evaluation of its agreements with the CMOs. The FDA also found that the QA manager lacked experience and training in quality assurance and the sciences, despite being responsible for overseeing CMOs and batch release. The manager was also “unaware of GMP stability testing and process validation requirements for drug products manufactured by CMOs.” In response, Bi-Coastal said its vice president and general manager will help ensure proper adherence to procedures while it finds a new manager. “This response is inadequate. You failed to provide evidence showing this individual is qualified to provide oversight of CGMP activities. In addition, you have not provided details as to how you will ensure the new quality assurance manager will have the appropriate combination of training, education, and experience to perform the job adequately,” the letter said. The company had 15 days from June 30 to respond to the FDA to fix these issues. If the issues remain unaddressed, the FDA may withhold the issuance of export certificates, or the approval of new applications or supplements until the company complies.