Mylan GmbH – FDA CRL

The FDA issued a Complete Response Letter (CRL) to Mylan GmbH for its New Drug Application (NDA) 210605 for insulin glargine injection 100 units/mL, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The application cannot be approved in its current form due to several significant deficiencies.

Key clinical issues include the need for additional safety and efficacy bridging data, including immunogenicity assessment, because the proposed commercial product (Process VI, Malaysia facility) differs from the product used in Phase 3 trials (Process V, India facility). Bridging pharmacokinetic/pharmacodynamic data is also required for the vial presentation to demonstrate equivalence with the cartridge presentation.

Product quality deficiencies involve unsatisfactory observations from a recent inspection of the manufacturing facility, Biocon Sdn. Bhd., which require resolution. Furthermore, Mylan must provide complete method suitability data for endotoxin, sterility, and antimicrobial effectiveness testing, and submit antimicrobial effectiveness data supporting the product's expiry from stability studies.

Human factors deficiencies were identified, noting an insufficient number of untrained pediatric patients in the validation study and issues with the Instructions for Use (IFU) that could lead to medication errors. Mylan must revise the IFU, conduct a new validation study with more pediatric patients, and modify carton and container labeling to improve product differentiation, followed by a new differentiation study. Additionally, the proposed prescribing information requires revisions to comply with regulatory content and format. Mylan GmbH must address all cited deficiencies before resubmission for potential approval.