The US Food and Drug Administration (FDA) has cited an insulin manufacturing facility in Malaysia of Biocon, a Bangalore, India-based pharmaceutical company, following a pre-approval inspection. Biocon announced the FDA’s citations in a February 2018 company statement.

“The US FDA has completed a pre-approval inspection of our manufacturing facility in Malaysia and issued a Form 483 with six observations,” Biocon said in its statement. “As per the normal expectations of the agency, we intend to respond with a corrective and preventive action plan in a timely manner.” Biocon did not explain the nature of the observations in its statement.

An FDA Form 483 is issued to company management at the conclusion of an inspection when an investigator(s) has observed any conditions that in their judgment may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related acts. Observations are made when in the investigator’s judgment, conditions, or practices observed would indicate that any food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health, according to information from the FDA.

Mylan and Biocon are currently advancing a biosimilar to Sanofi’s diabetes drug, Lantus (insulin glargine) called Semglee (insulin glargine). Lantus is one of Sanofi’s top-selling drugs with 2017 sales of EUR 4.62 billion ($5.64 billion). Biocon and Mylan are exclusive partners on a broad portfolio of biosimilars and insulin analogs. Glargine is one of the three insulin analogs being co-developed by Mylan and Biocon. Mylan has exclusive commercialization rights for insulin glargine in the US, Canada, Australia, New Zealand, the European Union, and European Free Trade Association countries. Biocon has exclusive rights for Japan and a few emerging markets, and co-exclusive commercialization rights with Mylan in the rest of the world. In January 2018, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended approval of Semglee as a long-acting insulin analog for treating diabetes mellitus in adults, adolescents, and children aged two years and above. The CHMP positive opinion will be considered by the European Commission. The European Commission decision on the approval is expected in April of this year.

Biocon’s Malaysia facility was commissioned in 2015 and started commercial operations in 2017. Biocon invested approximately $275 million to build the integrated insulins manufacturing facility, which is located at the BioXcell Biotech Park in Johor, Malaysia.

Biocon is partnered with Mylan for the development, manufacturing, supply, and commercialization of up to six proposed biosimilars, which includes insulin analogs, trastuzumab, and pegfilgrastim. Trastuzumab is the active ingredient in the reference product, Roche’s Herceptin, a drug for treating HER2-positive breast and gastric cancers. It had 2017 global sales of CHF 7.01 billion ($7.5 billion). Pegfilgrastim is the active ingredient in Amgen’s Neulasta, a leukocyte factor for treating neutropenia, or low white blood cell count, in patients with certain types of non-myeloid cancers. Neulasta is one of Amgen’s top-selling drugs with 2017 sales of $3.9 billion.

The manufacturing issue at the Malaysia plant follows other manufacturing issues at Biocon facilities, which are producing biosimilars from Mylan and Biocon. In October 2017, the FDA issued a Complete Response Letter (CRL) to Mylan and Biocon, for their biologics license application (BLA) for a proposed biosimilar to Amgen’s Neulasta (pegfilgrastim). The CRL related to the pending update of the BLA with certain chemistry, manufacturing, and controls data from facility requalification activities post recent plant modifications. At the time of the CRL in October 2017, Biocon said it did not expect the CRL to impact the time of commercial launch for the product.

In July 2017, Biocon was cited by French regulatory authorities for good manufacturing practice deficiencies in a drug-product manufacturing plant that was to make pending biosimilars, including trastuzumab and pegfilgrastim. While European regulatory authorities approved the drug-substance facilities for manufacturing trastuzumab and pegfilgrastim, regulators informed the company that there was a need for a reinspection of its drug-product manufacturing facility. Biocon’s subsequent resubmission of its applications for the drugs to the European Medicines Agency, which accepted the submissions in December 2017, follows an earlier withdrawal of both applications in response to the earlier inspection of Biocon´s drug-product manufacturing facility. Biocon completed the corrective and preventive actions (CAPAs) outlined as a result of the observations. The CAPAs will be confirmed during reinspection, which will be completed as part of the regulatory review process.

Source: Biocon