Qualifying notice amendment for Opdivo

Biologic and Radiopharmaceutical Drugs Directorate
100 Eglantine Driveway
LCDC Building
Tunney's Pasture, A.L. 0601C
Ottawa ON  K1A 0K9

Dossier ID: HC6-024-e177442
Control #: 259148

[employee's name removed]
[employee's title removed]
Bristol-Myers Squibb Canada
2344 Alfred-Nobel, Suite 300
Montreal, QC H4S 0A4
Email: [employee email removed]

Dear [employee's 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) – Confirmatory for Opdivo (nivolumab for injection), Control Number 259148, indicated for the treatment of patients with classical Hodgkin Lymphoma (cHL) after failure of autologous stem cell transplantation (ASCT), 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 Bristol-Myers Squibb Canada, 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, Bristol-Myers Squibb Canada 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 Bristol-Myers Squibb Canada, 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 a SNDS-c, the final Clinical Study Report for [study name/number has been removed]. The timelines should be included in the Letter of Undertaking, including the earliest anticipated availability of the data.

   The sponsor should acknowledge that they are aware that the indication authorized under the NOC/c pathway for Opdivo under Ctrl #203286 can be withdrawn if [study name/number has been removed] fails to demonstrate a favourable benefit-risk as determined by the BRDD.

Progress reports of confirmatory trials and other ongoing trials

2. 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 the Bristol-Myers Squibb Canada and Health Canada must be outlined in the Letter of Undertaking.

Safety monitoring

3. Commit to implement safety monitoring as per requirements of the Guidance Document: Notice of Compliance with Conditions (NOC/c). 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 Biologic and Radiopharmaceutical Drugs 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).

4. 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 authorization 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);

5. 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).

6. Implement the Risk Management Plan (RMP) in Canada and provide updates to the RMP whenever available.

Additional information

7. Submit the Clinical Study Reports for the following on-going and planned studies in accordance with Health Canada's guidance document entitled Post-Notice of Compliance (NOC) Changes: Safety and Efficacy Document:

   1. Safety study to characterize complications after allogeneic hematopoietic stem cell transplantation (HSCT) following nivolumab therapy. The Final Report by December 2022.

   2. [Study name/number has been removed]. The final CSR by May 2024.

8. Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to Opdivo (nivolumab) authorized under the NOC/c policy as per section 5.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).

9. 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).

10. An up-to-date, complete listing of ongoing additional clinical trials related to Opdivo (nivolumab), appended to the draft Letter of Undertaking, as per Section 4.5 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).

11. Copies of any marketing authorizations for Opdivo (nivolumab) from any other drug regulatory authority 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 quote the product name, assigned dossier ID, and control number of the original submission, and send directly to the Office of Submissions and Intellectual Property (OSIP) via the Common Electronic Submissions Gateway (CESG) using the Regulatory Enrolment Process (REP).

Sincerely,

Celia Lourenco, Ph.D.
Director General