Biocon’s Biosimilar insulin Aspart receives Complete response letter (CRL); require resolution of inspection deficiencies at Malaysia facility Read More

In a company announcement, Biocon informed that it has received a CR (Complete response) letter for its biosimilar version of insulin Aspart. The CRL references requirement of satisfactory resolution of deficiencies observed during the August 2022 PAI (pre approval inspection) at the Biocon Malaysia facility. There are no outstanding scientific issues with the product in the CRL.

Biocon Malaysia was inspected in August 2022 by USFDA inspectors Richard Ledwidge, Anjali Shukla, Hamet Toure, Santos E. Camara. Major deficiencies include 1) deficient procedures to control microbial contamination of sterile drug products, deficiencies in aseptic simulation studies vis a vis routine aseptic operations, and poor aseptic practices by operators 2) deficient investigation of deviations and establishment of root cause and CAPA – failure to identify source of glass particulates in vials, root cause for clogging of filters during manufacture.

Other issues cited in the FDA 483 include 3) deficiencies in cleaning and cleaning verification –  non contact surfaces inside the RABS are cleaned manually and there is no cleaning verification 4) Inadequate Quality oversight over GMP and laboratory operations – deficient procedures for tracking pharmacopeia standard lots and others, 5) lack of assurance of suitability of water used in drug substance, fermenter media – do not meet USP criteria for conductivity, TOC & risk assessment of additives used in water do not fully assess level of additives in process and ability of process to eliminate the additives 6) numerous correction foot notes in batch records. Biocon has submitted a comprehensive CAPA plan to FDA, and is found adequate by FDA; however it would require a re-inspection of the Malaysia facility.

1. Company Announcement
2. USFDA 483 – Biocon Malaysia (August 2022).