Qualifying Notice for Folotyn

Therapeutic Product Directorate
Holland Cross, Tower "B"
6th Floor, 1600 Scott Street
Address Locator #3106B
Ottawa, Ontario
K1A 0K9

September 10, 2018
Dossier ID: E196129

[employee name removed]
[employee title removed]
Servier Canada Inc.
235 Armand-Frappier
Laval, Quebec
H7V 4A7

Notice of Compliance with Conditions – Qualifying Notice

Dear [employee name removed]:

This Notice of Compliance with Conditions Qualifying Notice (NOC/c-QN), issued in accordance with the Health Canada Guidance Document: Notice of Compliance with Conditions (NOC/c), is to advise you that information submitted in support of the New Drug Submission for FOLOTYN (pralatrexate), control number 207545, indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), qualifies to be considered for authorization in accordance with the NOC/c Guidance. In keeping with the provisions outlined in the NOC/c Guidance, the following additional information is requested to complete the assessment:

1. A letter, signed by the Chief Executive Officer or designated signing authority of Servier Canada Inc., indicating that you agree to have this submission considered under the NOC/c Guidance. Please be reminded that in agreeing to accept a Notice of Compliance (NOC) under the NOC/c Guidance, Servier Canada Inc. consents to the posting of this NOC/c-QN on Health Canada's website once market authorization has been received.
2. A Letter of Undertaking signed by the Chief Executive Officer or designated signing authority of Servier Canada Inc., having a form and content satisfactory to Health Canada, as indicated in NOC/c Guidance, including commitments to provide the following:

   Confirmatory Trials

   1. [trial identifier removed] Phase 3 randomized clinical trial comparing [specific trial information removed]. A complete clinical study report (CSR) based on a pre-specified data cutoff date should be submitted with all supporting datasets. The CSR should permit the confirmation of objective response rate (ORR) and contain reliable estimate of time to event endpoints, for example (e.g.) duration of response (DOR), progression-free survival (PFS) and overall survival (OS).

   Post Market Safety Monitoring

   1. Provision of annual Periodic Benefit-Risk Evaluation Reports (PBRER-Cs) or Periodic Safety Update Reports (PSUR-Cs) in a manner deemed consistent with E2C ICH Guidelines, until such time as all conditions for market authorization under the NOC/c Guidance have been removed. The annual PBRER-Cs or PSUR-Cs should include cumulative data on relevant unlisted Adverse Reactions (ARs) from the date of marketing to the time of the report.
   2. Notification and reporting on specific issues of concern, as outlined in Section 3.4.4, Post-Market Commitments: Notification and Reporting of Specific Issues of Concern, of the Health Canada NOC/c Guidance.
   3. Report(s) of all serious adverse drug reactions (ADRs) that occurred in Canada and all serious unexpected ADRs that occurred outside of Canada should be forwarded within 15 days to the Marketed Health Products Directorate, in accordance with the current Food and Drug Regulations (C.01.017) and guidance documents.
   4. Implement and maintain the Risk Management Plan (RMP) in accordance with the published Health Canada Guidance.
3. A draft of the Product Monograph (PM) that is consistent with the requirements outlined in section 5.2.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c). Please note that boxed text should appear on the cover page as well as at the beginning of each major section of the Product Monograph (Parts I, II and III, as applicable), disclosing the nature of the authorization granted for FOLOTYN for the indication of “for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL)”.
4. A final mock-up of the Package Insert (if applicable), in line with the requirements outlined in Health Canada's Guidance Document, Questions and Answers: Plain Language Labelling Regulations (Q&A: PLL), containing boxed text disclosing the nature of the authorization granted for FOLOTYN.

I wish to advise you that this Qualifying Notice is being issued in accordance with Health Canada's guidance documents on the Management of Drug Submissions and Notice of Compliance with Conditions. Sponsors are instructed to submit a complete response [refer to "Guidance Document: Notice of Compliance with Conditions (NOC/c)”] with the requested information within 30 calendar days of the date of this letter.

In order to facilitate and to ensure proper processing, please include a revised Submission Certificate with your response, quote the product name and control number, and address all correspondence to:

Office of Submissions and Intellectual Property
Therapeutic Products Directorate
Health Canada
Finance Building Address Locator 0201A1
101 Tunney’s Pasture Driveway,
Ottawa, Ontario
K1A 0K9

Yours sincerely,

Dr. J. Patrick Stewart, MD, CCFP(EM)
Director General
Therapeutic Products Directorate
JPS/oh