Accord Healthcare Inc.bendamustine hydrochloride injection

NDA 216987 COMPLETE RESPONSE

Accord Healthcare Inc.

Attention: Sabita Nair, RAC, ASQ-CPGP Vice President-Regulatory Affairs

8041 Arco Corporate Drive, Suite 200 Raleigh, NC 27617

Dear Mrs. Nair:

Please refer to your new drug application (NDA) oe

for bendamustine hydrochloride injection.

We acknowledge receipt of your amendment dated)

complete response to our oe , action letter.

, which constituted a

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 INSPECTIONS

1. Following a CGMP inspection of oe

), listed in this application, FDA conveyed deficiencies to the representative of the facility. The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response. The facility's satisfactory responses are dependent on FDA’s determination that the facility has come into compliance with CGMP and may require re-inspection of the facility. The deficiencies identified during the inspection may not be specific to your application. Therefore, you should coordinate with the facility for timely resolution. Your complete response should include the date(s) of the facility’s response(s) to the FDA Form 483. Please refer to Compliance Program CP 7356.002 for guidance on post inspection activities. Following resolution of the CGMP inspection, FDA may need to conduct a PAI/PLI of the facility. Satisfactory outcomes of both the PAI/PLI and the CGMP surveillance inspections will be needed prior to an approval of the application.

Reference ID: 5690700

NDA 216987 Page 2

2. Following a CGMP inspection of

(b) (4)

, listed in this application, FDA conveyed deficiencies to the representative of the facility. The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response. The facility’s satisfactory responses are dependent on FDA’s determination that the facility has come into compliance with CGMP and may require re-inspection of the facility. The deficiencies identified during the inspection may not be specific to your application. Therefore, you should coordinate with the facility for timely resolution. Your complete response should include the date(s) of the facility’s response(s) to the FDA Form 483. Please refer to Compliance Program CP 7356.002 for guidance on post inspection activities. Following resolution of the CGMP inspection, FDA may need to conduct a PAI/PLI of the facility. Satisfactory outcomes of both the PAI/PLI and the CGMP surveillance inspections will be needed prior to an approval of the application.

Following a CGMP inspection of om

) listed in this application, FDA conveyed deficiencies to the representative of the facility. The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response. The facility's satisfactory responses are dependent on FDA’s determination that the facility has come into compliance with CGMP and may require re-inspection of the facility. The deficiencies identified during the inspection may not be specific to your application. Therefore, you should coordinate with the facility for timely resolution. Your complete response should include the date(s) of the facility’s response(s) to the FDA Form 483. Please refer to Compliance Program CP 7356.002 for guidance on post inspection activities. Following resolution of the CGMP inspection, FDA may need to conduct a PAI/PLI of the facility. Satisfactory outcomes of both the PAI/PLI and the CGMP surveillance inspections will be needed prior to an approval of the application.

PRESCRIBING INFORMATION

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.

1 https:/Awww.fda.gov/drugs/laws-acts-and-rules/prescription-drug-labeling-resources 2 https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs-

final-rule

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

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NDA 216987 Page 3

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 314.50(I)(1)(i)] in structured product labeling (SPL) format as described at FDA.gov.3

CARTON AND CONTAINER LABELING

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

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 drug 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.

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

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

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NDA 216987 Page 4

(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 drug. Include an updated estimate of use for drug 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 314.110. 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 314.65. 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.

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

If you have any questions, contact oe

Sincerely,

{See appended electronic signature page}

(b) (4)

Center for Drug Evaluation and Research

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

Reference ID: 5690700

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)

11/06/2025 01:12:06 PM

Reference ID: 5690700