Metacel Pharmaceuticals, LLCOzobax (baclofen) oral solution Img/mL

NDA 208193 COMPLETE RESPONSE

Metacel Pharmaceuticals, LLC

Attention: Jeff Bryant, Chief Operating Officer 137 N. Broad Street, Suite E

Winder, GA 30680

Dear Mr. Bryant:

Please refer to your New Drug Application (NDA) dated January 9, 2016, received March 11, 2016, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Ozobax (baclofen) oral solution Img/mL.

We acknowledge receipt of your amendment dated January 1, 2018, which constituted a complete response to our January 11, 2017, 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.

PRODUCT QUALITY

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It was clearly stated in the January 11, 2017, Complete Response Letter, item #7, that if the identity, assay, or related substance method has to be modified to be fully validated, drug product samples may require retesting. If there are no samples available for retesting, drug product stability studies need to be repeated, since the current data would not reliable. Therefore, you should place an additional 2 batches of the drug product on stability, according to ICH Q1A (R2), and submit sufficient long-term stability data to support the proposed shelf life.

NONCLINICAL

oO@

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 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 (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(1)(1)()] in structured product labeling (SPL) format as described at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm

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. 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.

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

PROPRIETARY NAME Please refer to correspondence dated, March 30, 2018, which addresses the proposed proprietary name, Ozobax. 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.

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ADDITIONAL COMMENTS

We have the following comments/recommendations that are not approvability issues:

1. Product Quality

4 s ) e Perform a risk assessment screening we

e Provide batch analysis data on the drug product, batch C0412.

e Provide reference standard source information oy

2. Container Labels

e As currently presented, the format for the expiration date is not defined. To minimize confusion and reduce the risk for deteriorated drug medication errors, identify the format you intend to use. We recommend using a format like either DDMMMYYYY (e.g., 31JAN2013), MMMYYYY (e.g., JAN2013), YYYY-MMM-DD (e.g., 2013- JAN-31), or YYYY-MM-DD (e.g., 2013-01-31).

e The current temperature statements do not contain the temperature scale designation (Le., “°C” or “°F”) after each numerical value. We are concerned that this information could be misinterpreted and may pose a risk of drug degradation. We recommend you ensure that the degree symbol and temperature scale follows each numeric value denoting temperature ranges to increase clarity. For example, revise a

©® to read

ow

e The following cautionary statement is present on the container label ow

©® which mia mislead users In response to an Information Request sent to the Sponsor on June 3, 2016, the Sponsor submitted an amendment to its NDA on June 10, 2016. ms We recommend you remove the statement from the container label.

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.

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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 FDA Guidance for Industry, “Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products,” December 2017 at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM59054 1.

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, contact Taura Holmes, PharmD, MS, Senior Regulatory Project

Manager, at Taura.Holmes@fda.hhs.gov. Sincerely, {See appended electronic signature page} Eric Bastings, MD Deputy Director Division of Neurology Products

Office of Drug Evaluation I 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.

ERIC P BASTINGS 06/25/2018

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