Celitrion, Inc.CT-P17

BLA 761219 COMPLETE RESPONSE

Celitrion, Inc.

c/o Parexel International

2520 Meridian Parkway Suite 200 Durham, NC 27713

Attention: Ryan Zettle, PharmD, MBA Manager, Regulatory Affairs

Dear Dr. Zettle:

Please refer to your biologics license application (BLA) dated and received November 24, 2020, and your amendments, submitted under section 351(k) of the Public Health Service Act for CT-P17.

We acknowledge receipt of your amendment dated May 27, 2022, which constituted a complete response to our November 24, 2021, action letter.

We have completed our review of this application, as amended, 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.

FACILITY INSPECTION DEFICIENCY

During a recent inspection of the ] manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility. Satisfactory resolution of these deficiencies is required before this application may be approved.

ADDITIONAL COMMENTS

We also have the following comment that is not an approvability issue:

Center for Devices and Radiological Health

FDA conducted an inspection of your contract manufacturing organization (CMO), ©® manufacturing facility for this application from a] During the inspection three device observations were noted. At the time of your response to this CR letter, provide an update on the corrections and corrective actions the CMO has taken to address all observations.

Reference ID: 5083004

BLA 761219 Page 2

PRESCRIBING INFORMATION

(1) We reserve comment on the proposed labeling until the application is otherwise adequate. 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. In addition, we encourage you to review the FDA guidance for industry Labeling for Biosimilar Products.

If you revise labeling, use the SRPI checklist to ensure that the Prescribing Information conforms with format items in regulations and guidances. Your response must include updated content of labeling [21 CFR 601.14(b)] in structured product labeling (SPL) format as described at FDA.gov.?

In addition, we encourage you to review the draft guidance for industry Labeling for Biosimilar Products.

CARTON AND CONTAINER LABELING

(2) We reserve comment on the proposed labeling until the application is otherwise adequate.

Please refer to correspondence dated, August 11, 2022, which addresses the proposed proprietary name, Yuflyma, in the current review cycle. Please resubmit the proposed proprietary name when you respond to the application deficiencies.

SAFETY UPDATE When you respond to the above deficiencies, include a safety update. The safety

update should include data from all nonclinical and clinical studies 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 and their relevance, if any, to whether there may be clinically meaningful differences between the proposed biosimilar product and the U.S.-licensed reference product.

‘https:/Avww.fda.gov/drugs/laws-acts-and-rules/prescription-drug-labeling-resources

? https:/Avww.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs- final-rule

3 http://www fda.gov/Forlndustry/DataStandards/StructuredProductLabeling/default. htm

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

Reference ID: 5083004

BLA 761219 Page 3

(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 clinical studies for the proposed indication using the same format as the original BLA submission.

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

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

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

(4) Provide case report forms and narrative summaries for each subject who died during a clinical study or who did not complete a study 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 BLA data.

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

(7) Provide a summary of worldwide experience on the safety of this product, including adverse events known to be associated with the use of the product and immunogenicity. Include an updated estimate of use for this product marketed in other countries.

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

OTHER

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.

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

Reference ID: 5083004

BLA 761219 Page 4

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

his 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 Biosimilar Biological Product Sponsors or Applicants.

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

If you have any questions, call Sadaf Nabavian, Regulatory Project Manager, at 301- 796-2777.

Sincerely, {See appended electronic signature page}

Nikolay P. Nikolov, MD

Director

Division of Rheumatology and Transplant Medicine Office of Immunology and Inflammation

Office of New Drugs

Center for Drug Evaluation and Research

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

Reference ID: 5083004

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.

NIKOLAY P NIKOLOV 11/23/2022 10:50:22 AM

Reference ID: 5083004