FDA rejects Mylan and Biocon’s insulin glargine again

The US FDA has issued a second complete response letter for a follow-on insulin glargine product referencing Lantus made by Biocon at its facility in Malaysia.

In June 2018, the US Food and Drug Administration (FDA) issued a complete response letter (CRL) to Mylan and its manufacturing partner Biocon rejecting their insulin glargine product submitted through the 505(b)(2) regulatory pathway as a follow-on biologic referencing Sanofi’s Lantus.

Just over a year later and the firms have reported a second CRL has been received from the agency.

Image: iStock/Andranik Hakobyan

“The CRL has been issued pending completion of the Corrective and Preventive Actions (CAPAs) submitted to the US FDA in response to the observations made at the conclusion of the pre-approval inspection of our insulin manufacturing facility in Malaysia in June 2019,” a Biocon company spokesperson said in a statement.

In January 2019, the firm told stakeholders it expects to launch the insulin glargine product in the US from March 2020.

This latest rejection questions whether Biocon and its commercialization partner Mylan will still be able to uphold this proposed launch timeline. According to the spokesperson: “We remain confident of the quality of our application and do not anticipate any impact of this CRL on the commercial launch timing of our Insulin Glargine in the US.”

Regulatory actions

The original CRL asked Biocon and Mylan to provide additional clinical data in support of the manufacturing site change from Bangalore to Malaysia.

Since then an FDA inspection between June 24 and July 5 2019 at the plant resulted in a Form 483 with 12 observations.

At the time, Biocon chairperson and managing director Kiran Mazumdar-Shaw told this publication the observations were “largely procedural, aimed at continuous improvement and will help us strengthen our quality management system.” The firm has turned to digital solutions in a move away from a paper-based Quality Management System (QMS) to address these issues.

While still under scrutiny from US regulators, their European counterparts recently gave the Malaysian facility the nod of approval, issuing the plant a Certificate of GMP compliance.

Mylan and Biocon’s insulin glargine is approved in Europe and other regions as a biosimilar to Sanofi’s Lantus, under the name Semglee.

Bangalore 483

In related news, the FDA has issued Biocon a Form 483 following an inspection at its biologics drug product plant in Bangalore, India in August.

“The inspection concluded with four observations which we believe will not impact supplies from this facility,” a Biocon spokesperson said.

“We are confident of addressing these observations through a Corrective and Preventive Action plan in a timely manner.”