Qualifying Notice for Keytruda
Biologics and Genetic Therapies Directorate
100 Eglantine Driveway
Address Locator #0601C
Dossier ID: HC6-024-e171468
Control #: 212388
Document #: 1351427
[employee name removed]
[employee title removed]
Merck Canada Inc.
16750 route Transcanadienne
Kirkland, QC H9H 4M7
Notice of Compliance with Conditions - Qualifying Notice
[employee name removed]
This Notice of Compliance with Conditions (NOC/c)-Qualifying Notice, issued in accordance with the Health Canada NOC/c Policy, is to advise you that information submitted in support of the Supplemental New Drug Submission (SNDS) for KEYTRUDA (pembrolizumab), Control Number 212388, indicated for adult and pediatric patients with relapsed or refractory Primary Mediastinal B-cell Lymphoma (rrPMBCL), qualifies to be considered for authorisation under the NOC/c policy. In keeping with the provisions outlined in the NOC/c policy, the following additional information is required to complete the assessment:
- A letter, signed by the Chief Executive Officer, or designated signing authority of Merck Canada Inc., indicating that you agree to have this submission considered under the NOC/c Policy. Please be reminded that in agreeing to accept an NOC under the NOC/c Policy, Merck Canada Inc. consents to the posting of the NOC/c-QN on Health Canada's website.
- A draft Letter of Undertaking signed by the Chief Executive Officer, or designated signing authority, of Merck Canada Inc., having a form and content satisfactory to Health Canada, as indicated in the Guidance Document: Notice of Compliance with Conditions (NOC/c), including commitments to provide the following:
- Submit, by the 4th quarter 2020 as an SNDS-c, the final Clinical Study Report for KETNOTE-170: A Phase II open-label, single arm study of pembrolizumab (MK-3475) in subjects with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL). The report will include the data from all study subjects and study endpoints with follow-up of 3 years.
- Submit by the 2nd quarter 2021, as an SNDS-c, the final report of the KN204 trial titled: “A Phase III randomized, open-label, active-controlled trial comparing pembrolizumab to brentuximab vedotin for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma”.
- Submit, as an SNDS-c, the completed study report for Keynote-051, titled: “A phase I/II study of pembrolizumab (MK-3475) in children with advanced melanoma or a PD-L1 positive advanced, relapsed or refractory solid tumour or lymphoma”. The study is designed to evaluate the Objective Response Rate (ORR), per RECIST v1.1 criteria, in pediatric patients with various types of solid tumour and the ORR per International Working Group Response Criteria in pediatric patients with lymphoma. The study is expected to enroll 310 participants and to be completed by the 4th quarter of 2022.
Progress Reports of Confirmatory Trials and Other Ongoing Trials
- On an annual basis, within 60 calendar days of the market authorization anniversary or a date agreed upon at the time of the issuance of the market authorization, status reports on the progress of ongoing confirmatory trials, as per section 3.2 and Appendix 4 of the Guidance Document: Notice of Compliance with Conditions (NOC/c). The details of the requirements for filing and termination of the annual status report as agreed upon by Merck Canada Inc. and Health Canada must be outlined in the Letter of Undertaking.
- Report all serious Adverse Reactions (AR) that occur in Canada and all serious unexpected ARs that occur outside of Canada within 15 days to the Marketed Health Products Directorate. Adverse Events (AE) and AR reports on marketed drugs occurring as part of confirmatory trials subject to clinical trial applications, as outlined in the Letter of Undertaking, must be sent to the Biologics and Genetic Therapies Directorate. Reporting must be conducted as per section 3.4.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c) and in accordance with current regulations and guidelines (e.g. Guidance for Industry: Reporting Adverse Reactions to Marketed Health Products and the Guidance for Clinical Trial Sponsors: Clinical Trial Applications).
- Periodic Safety Update Reports or Periodic Benefit-Risk Evaluation Reports-C for NOC/c Products (PSUR-Cs or PBRER-Cs) on an annual basis until such time as conditions associated with the market authorisation are removed. PSUR-Cs/PBRER-Cs should be prepared in accordance with the E2C(R1) and E3C(R2) ICH Guideline, including format and content, as per section 3.4.2 of the Guidance Document: Notice of Compliance with Conditions (NOC/c);
- Comply with the notification and reporting of specific issues of concern as outlined in Section 3.4.4 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
- In your response to NOC/c-QN, provide a copy of the most recent study protocol of the KN204 trial.
- Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to KEYTRUDA (pembrolizumab) authorized under the NOC/c policy as per section 5.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
- An outline of the agreed-upon advertising, labelling or distribution requirements, including a commitment to file revised Product Monographs under the appropriate submission type as information is made available as per section 4.3 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
- An up-to-date, complete listing of ongoing additional clinical trials related to KEYTRUDA (pembrolizumab), appended to the draft Letter of Undertaking, as per Section 4.5 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
- Copies of any marketing authorizations for KEYTRUDA (pembrolizumab) from major drug regulatory authority (FDA, EMA, TGA) as per Section 4.6 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
I wish to advise you that this Qualifying Notice is being issued in accordance with Health Canada's guidances on the Management of Drug Submissions and Notice of Compliance with Conditions, respectively. Sponsors are instructed to submit a complete response (refer to Guidance Document: Notice of Compliance with Conditions) to the outstanding information within 30 calendar days of the date of this letter.
Your response to the above should be submitted with a copy of this letter to the Office of Submissions and Intellectual Property. In order to facilitate and ensure proper processing of your response, please include a revised Submission Certificate, quoting the product name, assigned dossier ID, and control number of the original submission, and address your response to:
Director, Office of Submissions and Intellectual Property
Therapeutic Products Directorate
101 Tunney's Pasture Driveway
Address Locator 0201A1
Ottawa, Ontario, K1A 0K9
Attention: Office of Regulatory Affairs
Biologics and Genetic Therapies Directorate
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