IntelGenx Corp.Rizaport (rizatriptan) oral film | 10 mg

Dear Dr. Emanuele:

Please refer to your New Drug Application (NDA) dated March 26, 2013, received March 27, 2013, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Rizaport (rizatriptan) oral film | 10 mg.

We acknowledge receipt of your amendment dated October 1, 2018, which constituted a complete response to our January 21, 2014, 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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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

and 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

CARTON AND CONTAINER LABELING If you resubmit this application, include draft carton and container labeling revised as follows:

A. Container Labels

1. 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. FDA recommends that the human readable expiration date on the drug package label include a year, month, and non-zero day. FDA recommends that the expiration date appear in YY YY-MM-DD format if only numerical characters are used or in YYYY-MMM-DD if alphabetical characters are used to represent the month. If there are space limitations on the drug package, the human-readable text may include only a year and month, to be expressed as: YY YY-MM if only numerical characters are used or

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YYYY-MMM if alphabetical characters are used to represent the month. FDA recommends that a hyphen or a space be used to separate the portions of the expiration date.

2. The immediate container label lacks a barcode. The drug barcode is often used as an additional verification before drug administration in the hospital setting; therefore, it is an important safety feature that should be part of the label whenever possible. Therefore, we request you add the product’s linear barcode to each individual pouch as required per 21CFR 201.25(c)(2).

3. The layout of the strength is not consistent with our current guidance for the presentation of the proprietary name, established name, dosage form, and strength for drug products.* Relocate the strength statement to follow the established name on the principal display panel as this is the customary placement of the strength statement, and therefore the location most familiar to users. See example below:

RIZAPORT (rizatriptan) oral Of Film 10 mg

4. We note the container label lacks instruction on how to use the film, which poses risk of wrong technique administration errors. We recommend adding a statement such as “How to use: Use dry hands. Place film on tongue. Keep in place until film dissolves.” or any other relevant statements should be added to the container label to minimize the risk of wrong technique administration errors.

B. Carton Labeling

1. The net quantity statement (i.e., 18 Films, 12 Films, 6 Films) competes in prominence with the proprietary name, established name, and product strength and takes away from important product information.* Decrease the prominence of the net quantity statement (i.e., 18 Films, 12 Films, 6 Films).

C. References @ Guidance for Industry: Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Errors (lines 336-342). Food and Drug Administration. 2013. Available from http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance s/UCM349009.pdf

PROPRIETARY NAME The review of your proposed proprietary name has been terminated due to the deficiencies with

the application as described in this letter. Please resubmit the proposed proprietary name when you respond to the application deficiencies.

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FACILITY INSPECTIONS

During recent inspections of the Po drug substance manufacturing facility) and Intelgenx Corp., (FEI: 3005721224, drug product manufacturing facility) for this NDA, our field investigators conveyed deficiencies to the representatives of the facilities. Satisfactory resolution of these deficiencies is required before this NDA may be approved.

ADDITIONAL COMMENTS

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

Product Quality

1. Provide the full report for the elemental impurities risk assessment summarized in section 3.2.P.5.6 Justification of Specification. We note that this assessment was provided in the previous 3.2.P.2 Pharmaceutical Development document submitted October 31, 2017, which has been removed from the submission, but does not appear in the current version of this document submitted October 1, 2018.

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8. We request that you upload the original method validation reports for the assay and dissolution methods (ITG-17-0002, ITG-17-0004, resp.) into eCTD format.

9. In section 3.2.P.8.3, the long-term results for assay and impurities at approximately 2 months appear to be missing for the four batches manufactured at IntelGenx in 2018. Provide this data, if available, and update the application accordingly.

Clinical

You should develop (1! dosage strength of your product to support dosing and administration in pediatric patients age 6 through 11 years.

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 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 ZL.

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 Lana Chen, Regulatory Project Manager, at (301) 796-1056. Sincerely,

{See appended electronic signature page}

Eric Bastings, M.D. Deputy Director

Division of Neurology Products Office of Drug Evaluation I

Center for Drug Evaluation and Research

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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.

ERIC P BASTINGS 03/28/2019 03:42:19 PM

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