Laboratorios Farmacéuticos ROVI, S.A.Risvan (risperidone ISM) intramuscular injectable suspension

NDA 214835 COMPLETE RESPONSE

Laboratorios Farmacéuticos ROVI, S.A. c/o PharmaLex

Attention: Anna Perelka

Associate Director, Regulatory Affairs 1700 District Avenue, Suite 100 Burlington, MA 01803

Dear Anna Perelka:

Please refer to your new drug application (NDA) dated and received November 24, 2020, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Risvan (risperidone ISM) intramuscular injectable suspension.

We acknowledge receipt of your amendment dated January 27, 2023, which constituted a complete response to our July 15, 2022, 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 INSPECTIONS

Following pre-approval inspection of the Laboratorios Farmacéuticos ROVI, S.A. (FEI: 3010705046) manufacturing facility listed in this application, FDA conveyed deficiencies to the representative of the facility. Satisfactory resolution of these deficiencies is required before this application may be approved.

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

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

Reference ID: 5216371

NDA 214835 Page 2

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.

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.?

CARTON AND CONTAINER LABELING

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

MEDICATION GUIDE

Add the following bolded statement or appropriate alternative to the carton and

container labeling per 21 CFR 208.24(d): a

(@) (4)

PROPRIETARY NAME

Please refer to correspondence dated, April 19, 2023, which addresses the proposed proprietary name, Risvan. This name was found acceptable pending approval of the application 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 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 https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs- final-rule 3 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm

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

Reference ID: 5216371

NDA 214835 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 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.

OTHER

Within 1 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.

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

Reference ID: 5216371

NDA 214835 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 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.

If you have any questions, please email Simran Parihar, PharmD, at simran.parihar@fda.hhs.gov.

Sincerely, {See appended electronic signature page}

Bernard Fischer, MD

Deputy Director

Division of Psychiatry

Office of Neuroscience

Center for Drug Evaluation and Research

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

Reference ID: 5216371

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.

BERNARD A FISCHER 07/27/2023 02:23:23 PM

Reference ID: 5216371