Mylan GmbH: insulin glargine

Please refer to your new drug application (NDA) dated and received April 27, 2017, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for insulin glargine injection 100 units/mL.

We note that this is the second Complete Response letter for this NDA that has identified inspectional observations at this manufacturing facility as a deficiency.

We recommend that you work with this manufacturing facility for your insulin glargine product and apply the necessary resources to address these inspectional observations in a timely manner.

Please note that we consider this to be a major change to the IFU, which was validated by the Human Factors study.

Therefore, please revert to the prior sub-bullet letter designations (A, B, C, etc.) under each numbered step that were used in the Human Factors study.

Submit draft carton and container labeling that is identical to the carton and container labels submitted on August 28, 2019.

Time (EDT)) on Friday, March 20, 2020, because the NDA for the listed drug relied upon will no longer exist at midnight on Monday, March 23, 2020."

Act for insulin glargine injection 100 units/mL.

We also acknowledge receipt of your amendment dated May 11, 2018, pertaining to antimicrobial effectiveness testing, which was not reviewed for this action.

1. Your 505(b)(2) application requests approval of your proposed insulin glargine product manufactured using Process VI at a facility in Malaysia (i.e., Process VI product), while the proposed insulin glargine product studied in the phase 3 clinical trials was manufactured using Process V at a different facility in India (i.e., Process V product).

Informal Conference held on August 15, 2017. Submit the results from the proposed study (Study MYL-1501D-1004) to address this deficiency.

CMC microbiology review noted the following deficiencies:

It is stated in your March 19, 2018 response that sterility testing method suitability was performed for the 10 mL drug product presentation including polysorbate 20 and the 3 mL cartridge drug product presentation.

You may also consider additional labeling changes as necessary.

Once you finalize your proposed to-be-marketed IFU, you should conduct an additional human factors validation study with 15 untrained injection naive pediatric patients.

Our review of the proposed carton and container labeling (see CARTON AND CONTAINER LABELING below) identified multiple areas that should be modified to enhance product differentiation.

Therefore, you should implement these modifications, in addition to any other labeling changes that you consider to be necessary, finalize your proposed to-be-marketed carton and container labeling, and conduct a differentiation study with all the intended user populations for the product with at least 15 users in each distinct user group.

We reserve additional comments on the proposed labeling until the application is otherwise adequate.