Bavencio - Notice of Compliance with Conditions - Qualifying Notice

Biologics and Genetic Therapies Directorate
100 Eglantine Driveway
Address Locator #0601C
Ottawa, Ontario
K1A 0K9

employee name removed
[Employee's title removed]
EMD Serono, A Division of EMD Inc., Canada
200 - 2695 North Sheridan Way
Mississauga, ON L5K 2N6

Dossier ID: HC6-024-e196892
Control #: 225974

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 BAVENCIO (avelumab), Control Number 225974, indicated for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC), 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:

  1. A letter, signed by the Chief Executive Officer, or designated signing authority of EMD Serono, 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, EMD Serono consents to the posting of the NOC/c-QN on Health Canada's website.
  2. A draft Letter of Undertaking signed by the Chief Executive Officer, or designated signing authority, of EMD Serono, 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:
    • Confirmatory Studies
      1. Submit, as an SNDS-c, the final report for the confirmatory study EMR100070-003 Part B entitled “A single arm, multi-center study to investigate efficacy and safety of avelumab in previously untreated adults with metastatic MCC”, with the primary analysis being conducted a minimum of 15 months after the last patient has received the treatment. The final report should be submitted by no later than January 30, 2020.
      2. The sponsor should acknowledge that they are aware that the indication authorized under the NOC/c pathway for BAVENCIO (avelumab) under control #225974 can be withdrawn if the final report of Study EMR100070-003 Part B fails to demonstrate that the overall risk/benefit assessment is favourable as determined by the Biologics and Genetic Therapies Directorate (BGTD).

        Submit along with the final report of Study EMR100070-003 Part B, a validated assay for avelumab neutralizing antibody testing.

    • Progress Reports of Confirmatory Trials and Other Ongoing Trials
      1. Submit 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 EMD Serono and Health Canada must be outlined in the Letter of Undertaking.
    • Safety Monitoring
      1. 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).
      2. Submit the Post-Market Benefit Risk Evaluation Reports-C (PBRER-C) for BAVENCIO to BGTD with the following submission schedule:
        • Every 6 months during the first 2 years following the initial marketing authorization;
        • Annually for following 2 years;
        • Every 3 years thereafter interval until such time as conditions associated with the market authorization are removed. 

        Include, in each PBRER, an analysis of all Adverse Events as per the Pharmacovigilance Plan as well as safety updates including immunogenicity from all ongoing and future clinical trials with BAVENCIO. 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).

      3. 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).
      4. Implement the Risk Management Plan (RMP) in Canada and provide any updates to the RMP whenever available.
    • Additional information
      1. Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to BAVENCIO authorized under the NOC/c policy as per section 5.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
      2. Provide 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).
      3. Prior to authorization, the sponsor must prepare for distribution educational material including a Dear Health Care Professional Letter.
      4. Provide an up-to-date, complete listing of ongoing additional clinical trials related to BAVENCIO, appended to the draft Letter of Undertaking, as per Section 4.5 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
      5. Submit copies of any marketing authorizations for BAVENCIO from any other drug regulatory authority as per Section 4.6 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
      6. Submit to Health Canada any other analyses that have been designated as post-marketing commitments to other international authorities (FDA, EMA and TGA).

I wish to advise you that this Qualifying Notice is being issued in accordance with Health Canada's guidance 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
Finance Building
101 Tunney's Pasture Driveway
Address Locator 0201A1
Ottawa, Ontario, K1A 0K9

Attention: Office of Regulatory Affairs
Biologics and Genetic Therapies Directorate

Sincerely,

Celia Lourenco, Ph.D.
Director General
Biologics and Genetic Therapies Directorate

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