Qualifying notice for Lucentis

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

Dossier ID: HC6-024-e134511
Control number: 233361

[Employee name removed]
Regulatory Affairs Specialist
Novartis Pharmaceuticals Canada Inc.
385 Bouchard Boulevard
Dorval, QC H9S 1A9

Dear [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 Lucentis (ranibizumab), Control Number 233361, indicated for retinopathy of prematurity, 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 Novartis, 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, Novartis 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 Novartis, 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 Study CRFB002H2301E1: RAINBOW extension study to confirm the clinical benefit following ranibizumab intravitreal treatment in ROP population. The visual acuity should be assessed using validated age appropriate tools by assessors who are blinded to the assigned treatment allocation. The safety profile should be comprehensively analysed, including developmental and neurodevelopmental effects to characterize any long-term safety issues of ranibizumab intravitreal treatment in preterm infants with ROP.

    The sponsor should acknowledge that the indication authorized under the NOC/c pathway for Lucentis under control # 233361 can be withdrawn or revised, pending the outcomes of Study CRFB002H2301E1. The decision by BRDD on the removal of the condition and/or modification of the current proposed indication will be based on that clinical outcomes can be confirmed and there are no long-term safety concerns of ranibizumab in the indicated patient population, and the risk/benefit analysis as determined by BRDD is positive.

    The sponsor should provide the approximate dates of completion of the Study CRFB002H2301E1, and should commit to approximate dates of filing of the SNDS-c submissions.

Progress reports of confirmatory trials and other ongoing trials

  1. 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 Novartis 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 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).
  2. Within 70 days of the Data Lock Point (DLP) date, submit 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). Additionally, within the PBRERs, submit safety analysis of the data collected from the study CRFB002H2301E1.
  3. Provide 5-yr safety analysis, including neurodevelopmental effects to characterize any long-term safety issues of ranibizumab IVT treatment in this population.
  4. 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).
  5. 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 Lucentis (ranibizumab) authorized under the NOC/c policy as per section 5.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
  2. 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).

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 the Office of Submissions and Intellectual Property.

Sincerely,

Celia Lourenco, Ph.D.
Director General

Page details

Date modified: