Novo Nordisk: NNC0148-0287

, which constituted a major amendment to this application and therefore extended the goal date by three months.

BLA 761326 provides for the use of NNC0148-0287 injection for the following indications which, for administrative purposes, we have designated as follows:

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to submission of your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies will be evaluated upon receipt of the complete response and may include re-inspection of the facility.

Although NNC0148-0287 allows for fewer weekly injections for patients over daily basal insulin products, this feature on its face does not offset the observed difference in clinically meaningful hypoglycemia in ONWARDS 6.

As a path forward, provide new clinical data to demonstrate favorable benefit-risk for NNC0148-0287 in subjects with type 1 diabetes.

We recommend that you request a post-action meeting to discuss a potential new glycemic control clinical study in participants with type 1 diabetes that would optimize the dosing and titration algorithm and assess other outcome(s) important to patients such as the patient experience with NNC0148-0287.

Health Service Act for NNC0172-2021 injection.

We also acknowledge receipt of your amendment dated April 19, 2023, which was not reviewed for this action.

(1) Despite fixed maintenance doses of NNC0172-2021 significant fluctuations in concentrations were noted in patients over the treatment period.

At the target exposure range of 200 - 4000 ng/mL, target-mediated drug disposition (TMDD) plays a dominant role in NNC0172-2021 clearance, leading to rapid drug elimination and a relatively shorter half-life at the proposed doses of 0.15 - 0.25 mg/kg.

NNC0172-2021 levels should be stressed in a Medication Guide, labeling and educational materials.

As stated in the Late-Cycle Meeting on March 9, 2023, the validation of the!"

NNC0172-2021 ELISA is inadequate to support the use of the assay in testing clinical specimens.

Conduct a dose-response study to determine at which concentrations these substances no longer interfere with the °NNC0172-2021 ELISA.

In the response received on February 21, 2023 to the Agency's information request (IR) comment 26 dated February 8, 2023, you described the control strategy for © in the NNCO172-2021 drug product (DP).

(13) In the response received on February 21, 2023 to the Agency's IR comment 18 dated February 8, 2023, you provided revised NNC0172-2021 primary reference material (PRM) and secondary reference material (SRM) stability protocols in section 3.2.S.5. These protocols are inadequate to ensure consistent control over stability of the reference materials.

(16) In the response received on February 21, 2023 to the Agency's IR comment 22 dated February 8, 2023, you revised section 3.2.P.3.3 with a description of the sampling for identity testing and how tracking is assured.

To comply with 21 CFR 610.14, revise section 3.2.P.3.3 to specify the physical characteristics that are used during tracking (e.g., cap color or markings) to ensure correct identity after all labeling operations.

(18) On March 7, 2023, we sent an IR requesting to include the EPRs (i.e., activation force, hold force, and injection time) of device constituents of the combination product in the DP release specifications.

(19) Following inspection of a manufacturing facility listed in this application, FDA conveyed deficiencies to the representative of the facility.

Denmark and provide the method validation results or method transfer results to support routine release and stability testing at each site if they have not already been provided in the BLA.

NNC0172-2021 impurity/purity profile during the in-use period of 4 weeks when stored below 30°C at the end of shelf-life is consistent with the product profile shown to be safe in clinical studies.

(17) In your resubmission, provide any updated batch analysis data for DS and DP as applicable for batches released since your original BLA submission.

The comments in this section are not intended to convey human factors (HF) approvability issues with your proposed product; however, it will be necessary for you to consider how any revisions to your proposed product to address the deficiencies outlined above will impact your user interface.

If your user interface is revised in response to the complete response, you should update your use-related risk analysis (URRA) to determine whether any new risks, including new critical tasks or failure modes are introduced by the changes.

If you determine that an additional HF study does not need to be submitted, submit your justification, updated URRA, comparative analyses such as a labeling comparison, a comparative task analysis, and a physical comparison between your revised user interface and the user interface that is the subject of the complete response.

We strongly recommend you submit this information to the Agency for review prior to resubmitting BLA 761315 to ensure the Agency agrees with your determination regarding the HF data need to support your revised user interface.

If you determine that you do need to submit the results of an additional HF validation study for your revised user interface, we recommend you submit your study protocol for feedback from the Agency before commencing your study to the IND, and prior to resubmitting BLA 761315. Note that submission of a protocol for review is not a requirement.

The results from the HF validation study indicate that there are additional labeling mitigations that can be implemented to address use errors that occurred with critical tasks.

'ake before the application may be approved.