U.S. FDA Flags Eight Lapses At Biocon’s Insulin Facility In Malaysia

The U.S. drug regulator has flagged eight lapses at Biocon Ltd.'s insulin manufacturing facility in Malaysia.

The lapses were related to biologic drug substances, drug product units, quality control laboratories, and delivery device units at the above-mentioned facility, the company said in an exchange filing.

"The U.S. Food and Drug Administration conducted two cGMP (current good manufacturing practises) inspections at Biocon Sdn. Bhd’s insulins manufacturing facility in Malaysia ... These inspections were conducted between July 10 and July 20, 2023," the company said in an earlier exchange filing on July 21.

"At the conclusion of these inspections, the agency issued a Form 483, with six observations for drug substances, drug product units, and quality control laboratories, as well as two observations for the delivery device unit."

These observations primarily relate to enhancing operational procedures and strengthening training programmes, the company said. The inspections did not identify any data integrity breaches or systemic non-compliance.

A Form 483 is issued when investigators have observed any condition that, in their judgement, may constitute a violation of the Food, Drug, and Cosmetic Act and Related Acts.

BQ Prime has obtained a copy of the observations from the administrator. One of them is a repeat observation.

These are the observations that were made:

• Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established and followed. This is a repeated observation.

• Failure to thoroughly review the failure of a batch or any of its components to meet specifications, whether or not the batch is distributed.

• Failure to review any unexplained discrepancy, whether or not the batch has already been distributed. Four instances were observed where the assigned root causes for laboratory out-of-spec results were not scientifically justified, and four instances of inadequate deviation investigations of leaks and physical defects post-completion of aseptic batches were identified.

• Failure to have written procedures on what corrective actions are to be performed when aseptic areas have a loss in differential pressure to return to a state of cleanliness that is suitable for the resumption of aseptic operations.

• Failure to establish and document the accuracy, sensitivity, and reproducibility of test methods. Certain test methods for vials and stoppers used are deficient to assure product quality and patient safety. Two instances were noted.

• Employees engaged in the manufacturing and processing of drug products lack the training required to perform their assigned functions. There is a lack of CGMP refresher training for process research and development personnel.

• Risk analysis is inadequate for devices. The risk management report does not address the control of the injection force of the finished product. No activities were identified for testing injection force for each lot of finished product released.

• Corrective and preventive action activities and results related to devices have not been adequately documented. One instance related to November 2022 was noted.

"We remain committed to global standards of quality and compliance and look at this as an opportunity to further strengthen our processes," a company spokesperson told BQ Prime.

The company's new product approval for generic Insulin Aspart was expected from this facility. When asked if the inspections would affect the timeline for the drug, the spokesperson said they did not have anything to do with Insulin Aspart.

"We have already submitted a comprehensive Corrective and Preventive Action Plan to the FDA in response to their site inspection observations issued during their inspection of our Malaysia facility last year. This CAPA plan has been accepted by the agency. In terms of timeline, we cannot comment on behalf of the agency," the spokesperson said.

The company's Insulin Aspart from the same facility has been approved in several global markets including EMA and was launched in Canada in FY23, the person said.

"We are hopeful that once approved by the U.S. FDA, we will be able to expand our Insulins portfolio for people with diabetes in the U.S., by introducing our biosimilar Aspart, a rapid acting insulin analog."

Shares of Biocon were trading 0.31% lower at Rs 255.65 apiece, as compared with a 0.23% rise in the benchmark Sensex at 3 p.m. on Monday.