Metacel Pharmaceuticals, LLCOzobax (baclofen) oral solution 1 mg/mL

NDA 208193

Food and Drug Administration Silver Spring MD 20993

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 1 mg/mL.

We also acknowledge receipt of your amendment dated October 14, 2016, which 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 reasons for this action below and, where possible, our recommendations to address these issues.

PRODUCT QUALITY

The proposed manufacturing and control strategy for Ozobax (baclofen oral solution) is inadequate to assure the identity, purity, strength, and quality of the commercial drug product. The strategy lacks sufficient controls over all of the identified critical quality attributes, at release and over the product shelf life. You will need to address the gaps in the control strategy outlined below. Note that any changes made to the product, manufacturing process used for registration batches, analytical procedures, or container closure system in order to address these deficiencies will require new stability studies.

Manufacturing Process

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Control of Drug Product (Validation)

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Control of Drug Product (Release and Stability Specifications)

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Drug Product Stability

Labeling 12. The dosage form and strength section contains the dosage si and identifying characteristics of the dosage form. However, it also contains information, which

is not appropriate for the dosage form and strength section. Remove this information.

13. The drug substance structure in the description section is blurry. Update the label with a clear structure.

14. The how supplied section does not contain the dosage form, strength of the dosage form,

or the identification of dosage form (e.g., color). It also does not have information for in- use storage. Update the how supplied section with this information.

PREA REQUIREMENTS

9, 2016, submission,

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For additional guidance on the timing, content, and submission of the PSP, including a PSP Template, please refer to the draft guidance for industry, Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Pediatric Study Plans at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U CM360507.pdf . In addition, you may contact the Division of Pediatric and Maternal Health at 301-796-2200 or email pdit@fda.hhs.gov. For further guidance on pediatric product development, please refer to:

http://www.fda.gov/Drugs/DevelopmentA pprovalProcess/DevelopmentResources/ucm049867.ht m.

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)(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, 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.

ADDITIONAL COMMENTS

We have the following comment that is not an approvability issue:

1. Certificates of analysis (CoAs) for three drug substance batches used for manufacture of the drug product were provided. The CoAs indicate that the related compound specification for any individual unspecified impurity is NMT""%. This is in contrast to specification of NUT Pay, proposed in 3.2.S.4.1. Furthermore, quantitative results for related substances were not reported, as the CoAs only indicate that the drug substance meets requirements. Please request updated CoAs from you supplier that reflect the specification proposed in 3.2.S.4.1, and include quantitative results for individual unspecified impurities.

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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 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 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.

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 01/11/2017

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