Fera Pharmaceuticals, LLCAvaclyr (acyclovir ophthalmic ointment)

NDA 202408

Food and Drug Administration Silver Spring MD 20993

COMPLETE RESPONSE

Fera Pharmaceuticals, LLC Attention: John D’Angelo, M.S., R.Ph. Vice President Regulatory Affairs 134 Birch Hill Road Locust Valley, NY. 11560

Dear Mr. D’Angelo:

Please refer to your New Drug Application (NDA) dated May 31, 2013, received May 31, 2013, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Avaclyr (acyclovir ophthalmic ointment) 3.0%.

We acknowledge receipt of your amendment dated December 24, 2015, which constituted a complete response to our March 31, 2014, action letter.

We also acknowledge your amendment dated June 22, 2016. This amendment was not reviewed for this action. You may incorporate applicable sections of the amendment by specific reference as part of your response to the deficiencies cited in this 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 this issue.

You have not provided a sufficient scientific bridge between your product and the one used in the published clinical studies. While we acknowledge you have addressed a number of the items requested in our March 31, 2014, Complete Response letter, you need to address the following remaining items or follow other options, such as conducting a controlled clinical trial with Avaclyr.

Quality and Performance Tests/In Vitro Release Testing

1. We acknowledge that you have developed an in vitro release testing (IVRT) procedure |

™® as described in USP<1724>, in an attempt to demonstrate the suitability of the [VRT method and to establish the scientific bridge between your drug product and the comparator product (Zovirax) (In-Vitro Release Testing Report to Support Acyclovir Release Rate Comparisons from Acyclovir Ophthalmic Ointment Formulations). However, based on the data provided, the [VRT method is found to be inadequately validated for the following reasons:

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a. The method failed

based on any improvements.

b. Provide a full validation report of the final IVRT method, after addressing (a). Close attention should be paid to the sensitivity of the method, which is the ability to detect changes in the release rate as a function of drug concentration in the formulation.

c. Itis unclear if polymorphism of the drug substance has an influence on the IVRT results (refer to Comment #2). Provide solubility data as well as intrinsic dissolution rate (as per USP <1087> Apparent Intrinsic Dissolution) for acyclovir drug substance used in your product, in Zovirax and in the 7° formulations. Compare this data to the literature reports, if available, for the various polymorphs of acyclovir.

Acyclovir Polymorphisms

2. We acknowledge you Finding illlllltlnnyygyy™’ between your drug product and the currently marketed UK Zovirax.

1 Lutker, K.M. et al. Polymorphs and Hydrates of Acyclovir. J. Pharm.Sci. 2011;100 (3): 949-963.

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Other Options

Alternatively, you may also propose other options, such as conducting a controlled clinical trial using your Avaclyr (acyclovir ophthalmic ointment) 3%. We encourage you to request a meeting with the division to discuss further development of your product.

LABELING

We reserve comment on the proposed labeling until the application is otherwise adequate. We encourage you to review the labeling review resources on the PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPJ) — 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(1)(1)(i)] in structured product labeling (SPL) format as described at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm

PROPRIETARY NAME

Please refer to correspondence dated, April 8, 2016 which addresses the proposed proprietary name, Avaclyr. 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 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 the original NDA submission.

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

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

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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 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.

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 NDA 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. 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 FDA Guidance for Industry, “Formal Meetings Between FDA and Sponsors or Applicants,” May 2009 at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U CM153222.pdf.

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

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If you have any questions, call Lois Almoza, M.S., Regulatory Project Manager, at (301) 796-1600.

Sincerely, {See appended electronic signature page}

Renata Albrecht, M.D.

Director

Division of Transplant and Ophthalmology Products

Office of Antimicrobial Products

Office of New Drugs

Center for Drug Evaluation and Research

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This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature.

RENATA ALBRECHT 06/24/2016

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