Seikagaku Corporation

BLA 761393 COMPLETE RESPONSE

Seikagaku Corporation

c/o PAREXEL International

2520 Meridian Parkway, Suite 100 Durham, NC 27713

Attention: Katherine Fertal US Agent Dear Katherine Fertal: Please refer to your biologics license application for injection. We have completed our review of this amended application and have determined that we cannot approve this application in its present form. We have described our reasons for this action below and, where possible, our recommendations to address these issues. EACILITY INSPECTIONS 1. Following pre-license inspection of isted in this application, conveyed leficiencies to the representative of the facility. Satisfactory responses from the

facility are needed before this application can be approved. Work with the facility in resolving the related deficiencies.

PRODUCT QUALITY MICROBIOLOGY

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U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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PRESCRIBING INFORMATION

We intend to convey our comments on your proposed package insert following this action. Prior to resubmitting the labeling in your resubmission, we encourage you to review the labeling review resources on the Prescription Drug Labeling Resources! and Pregnancy and Lactation Labeling Final Rule? websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPI) - a checklist of important format items from labeling regulations and guidances.

PROPRIETARY NAME

The review of your proposed proprietary name has been terminated due to the deficiencies with the application as described in this letter. Please resubmit the proposed proprietary name when you respond to all of the application deficiencies that have been identified in this letter.

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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SAFETY UPDATE

When you respond to the above deficiencies, include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and clinical studies/trials of the product under consideration regardless of indication, dosage form, or dose level.

(1) Describe in detail any significant changes or findings in the safety profile.

(2) When assembling the sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, incorporate new safety data as follows:

e Present new safety data from the studies/clinical trials for the proposed indication using the same format as in the original submission.

e Present tabulations of the new safety data combined with the original application data.

e Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies described in the bullet above.

e For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in Clinical trials.

(3) Present a retabulation of the reasons for premature trial discontinuation by incorporating the drop-outs from the newly completed trials. Describe any new trends or patterns identified.

(4) Provide case report forms and narrative summaries for each subject who died during a Clinical trial or who did not complete a trial because of an adverse event. In addition, provide narrative summaries for serious adverse events.

(5) Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data.

(6) Provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).

(7) Provide a summary of worldwide experience on the safety of this product. Include an updated estimate of use for product marketed in other countries.

(8) Provide English translations of current approved foreign labeling not previously submitted.

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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ADDITIONAL COMMENTS

We have the following comments/recommendations that are not approvability issues:

Product Quality

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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(b) (4)

OTHER IMPORTANT INFORMATION

Within one year after the date of this letter, you are required to resubmit or take other actions available under 21 CFR 601.3(b)). If you do not take one of these actions, we may consider your lack of response a request to withdraw the application under

21 CFR 601.3(c). You may also request an extension of time in which to resubmit the application.

A resubmission must fully address all the deficiencies listed in this letter and should be clearly marked with "RESUBMISSION" in large font, bolded type at the beginning of the cover letter of the submission. The cover letter should clearly state that you consider this resubmission a complete response to the deficiencies outlined in this letter. A partial response to this letter will not be processed as a resubmission and will not start a new review cycle.

You may request a meeting or teleconference with us to discuss what steps you need to take before the application may be approved. If you wish to have such a meeting, submit your meeting request as described in the draft guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products.

The product may not be legally marketed until you have been notified in writing that this application is approved.

(b) (4)

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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Sincerely,

{See appended electronic signature page}

Center for Drug Evaluation and Research

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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Signature Page 1 of 1

This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.

(b) (4)

03/11/2025 10:29:02 AM

Reference ID: 5546729