Bausch Health Ireland Limitedfluorescein sodium and benoxinate hydrochloride ophthalmic solution

NDA 211039 COMPLETE RESPONSE

Bausch Health Ireland Limited c/o Paragon BioTeck Inc. Attention: Patrick Witham President and CEO 4640 SW Macadam Avenue, Suite 80 Portland, OR 97239

Dear Mr. Witham:

Please refer to your new drug application (NDA) dated and received

September 24, 2018, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for fluorescein sodium and benoxinate hydrochloride ophthalmic solution.

We have completed our review of this application, as amended, and have determined that we cannot approve this application in its present form. Specifically, the methods to be used in, and the facilities and controls used for, the manufacture, processing, packing, or holding of the drug substance do not comply with the current good manufacturing practice regulations in parts 210 and 211. During a recent inspection of © manufacturing facility, 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 observations is required before this NDA may be approved and all facilities used for the manufacture, processing, packing, or holding of the drug substance and drug product will need to be in compliance with the current good manufacturing practice regulations in parts 210 and 211.

When you respond to the above deficiency, 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.

In addition, we have the following comments/recommendations that are not approvability issues:

Manufacturing Process: (1) We acknowledge your responses dated June 4, 2019. However, you did not

provide the data requested for the two process deficiencies sent on May 22, 2019. We remind you that process validation is to confirm the process design

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NDA 211039 Page 2

and demonstrate that the commercial manufacturing process performs as expected (Guidance for Industry Process Validation: General Principles and Practices (2011

leficiencies sent on May 22, 2019.

b) Please ~ the ~ ~ to establish the control oe om

(2) The information request responses received by the Agency on 24 May 2019

. Alternately, provide a Letter of granting access to a Drug Master File (DMF) that includes the location in the DMF where the relevant information can be found.

(3) The Agency acknowledges the validation information and data provided for

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

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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 the deficiency 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 deficiency 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.

U.S. Food and Drug Administration

Silver Spring, MD 20993 www.fda.gov

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

If you have any questions, call Derek Alberding, Regulatory Health Project Manager, at (240) 402-0963.

Sincerely,

{See appended electronic signature page}

Wiley A. Chambers, M.D.

Deputy Director

Division of Transplant and Ophthalmology Products

Office of New Drugs Center for Drug Evaluation and Research

ENCLOSURE: Labeling

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.

WILEY A CHAMBERS 07/19/2019 02:49:39 AM

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