Zhejiang Novus Pharmaceuticals Co. Ltd.Vancomycin Hydrochloride for Injection

NDA 210274 COMPLETE RESPONSE

Zhejiang Novus Pharmaceuticals Co. Ltd. c/o NSF Health Sciences

Attention: Andy Papas, PhD, MBA Vice-President, Regulatory Affairs

2001 Pennsylvania Avenue, NW, Suite 950 Washington, DC 20006

Dear Dr. Papas:

Please refer to your new drug application (NDA) dated and received March 10, 2017, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Vancomycin Hydrochloride for Injection, 500 mg/vial,

1 gram/vial, 5 gram/vial and 10 gram/vial.

We acknowledge receipt of your amendment dated May 29, 2020, which constituted a complete response to our June 15, 2018, 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 reason for this action below and, where possible, our recommendations to address the issue.

FACILITY INSPECTIONS

Following an evaluation of the last inspection performed at Zhejiang Novus Pharmaceuticals Co., Ltd. FEI: 3013567704 manufacturing facility at Zhejiang, China, for this application, our field investigator observed objectionable conditions at the facility and conveyed that information to the representative of the facility at the close of the inspection. Satisfactory resolution of the remaining objectionable conditions, and verification by the FDA, is required before this application may be approved. We recommend you contact the manufacturing facility if more information is needed.

We will continue to monitor the public health situation as well as travel restrictions. We are actively working to define an approach for scheduling outstanding inspections, once safe travel may resume and based on public health need and other factors.

For more information, please see the FDA guidances related to COVID 19. These guidances can be found at https://www.fda.gov/emergency-preparedness-and- response/coronavirus-disease-201 9-covid-19/covid-19-related-quidance-documents- industry-fda-staff-and-other-stakeholders

Reference ID: 4707904

NDA 210274 Page 2

PRESCRIBING INFORMATION

Submit draft labeling that addresses our proposed revisions in the attached labeling.

Your proposed Prescribing Information (Pl) must conform to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57. As you develop your proposed PI, we encourage you to review the labeling review resources on the PLR Requirements for Prescribing Information’ and Pregnancy and Lactation Labeling Final Rule? websites, which include:

e The Final Rule (Physician Labeling Rule) on the content and format of the Pl for human drug and biological products

e The Final Rule (Pregnancy and Lactation Labeling Rule) on the content and format of information in the PI on pregnancy, lactation, and females and males of reproductive potential

e Regulations and related guidance documents e Asample tool illustrating the format for Highlights and Contents, and

e The Selected Requirements for Prescribing Information (SRPI) — a checklist of important format items from labeling regulations and guidances.

e FDA's established pharmacologic class (EPC) text phrases for inclusion in the Highlights Indications and Usage heading.

Prior to resubmitting the labeling, use the SRPI checklist to correct any formatting errors to ensure conformance with the format items in regulations and guidances. In addition, submit updated content of labeling [21 CFR 314.50(I)(1)(i)] in structured product labeling (SPL) format as described at FDA.gov.?

To facilitate review of your submission, provide a highlighted or marked-up copy that shows all changes, as well as a clean Word version. The marked-up copy should include annotations that support any proposed changes.

CARTON AND CONTAINER LABELING

In any resubmission of this application, please submit revised draft carton and container labeling that contains the following revisions:

1 http://www.fda.gov/Drugs/GuidanceComplianceRequlatory|nformation/LawsActsandRules/ucm08415 9.htm 2 http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm09330 7.htm 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: 4707904

NDA 210274 Page 3

(1) (2)

Revise the storage statement to read, “Prior to reconstitution, store at 20°C to 25°C (68°F to 77°F)...”.

Revise the proposed container labels and carton labeling strength statements (i.e., 4) ) to read “5 g*/Pharmacy Bulk Package” and “10 g*/Pharmacy Bulk Package.”

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) (2)

(6)

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

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.

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.

Provide case report forms and narrative summaries for each patient 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.

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.

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

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

Reference ID: 4707904

NDA 210274 Page 4

(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.

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 ‘ake 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 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 Sheel Shah, PharmD, Regulatory Project Manager, at 240-402-3968.

Sincerely, {See appended electronic signature page}

Sumathi Nambiar, MD, MPH

Director

Division of Anti-Infectives

Office of Infectious Diseases

Center for Drug Evaluation and Research

ENCLOSURE: ¢ Content of Labeling o Prescribing information

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov 47 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately Reference ID: 4707904 following this page

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.

SUMATHI NAMBIAR 11/27/2020 09:44:15 AM

Reference ID: 4707904