Qualifying notice for Lynparza

Pharmaceutical Drugs Directorate
Holland Cross, Tower "B"
6th Floor, 1600 Scott Street
Address Locator #3106B
Ottawa ON K1A 0K9

Dossier ID: HC6-024-e167204
Control number: 265427

[name of employee removed]
[title of employee removed]
AstraZeneca Canada Inc.
1004 Middlegate Road, Suite 5000
Mississauga ON L4Y 1M4
Fax number: 905-275-6271

Dear [name of employee 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 Supplemental New Drug Submission for Lynparza (olaparib), Control Number 265427, for the indication in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA mutated (germline and/or somatic) metastatic castration resistant prostate cancer (mCRPC), whom chemotherapy is not clinically indicated. Patients must have confirmation of BRCA mutation before Lynparza treatment is initiated, qualifies to be considered for authorization in accordance with the above guidance document. In keeping with the provisions outlined in the Guidance Document: Notice of Compliance with Conditions (NOC/c), the following additional information is requested to complete the assessment:

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

Confirmatory studies

1. To confirm the clinical benefit in the BRCA mutant subgroup, submit the final efficacy analysis (end of Q4 2023) the Phase 3 PROpel study as a Supplemental New Drug Submission-Confirmatory (SNDS-C). The analyses should verify and describe the clinical benefit of olaparib plus abiraterone acetate and prednisone in terms of Overall Survival in the BRCA subgroup.

Progress reports of confirmatory 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 AstraZeneca Canada Inc and Health Canada should be outlined in the Letter of Undertaking.

Safety monitoring

3. Report(s) of 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 reported 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. Provision of Periodic Safety Update Reports or Periodic Benefit-Risk Evaluation Reports-C for 2 consecutive years following marketing of this new Lynparza (olaparib) indication in Canada. 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. 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). Please note that once all the commitments are fulfilled, Periodic Benefit-Risk Evaluation Reports-Pharmacovigilance (PBRER-PV) or Periodic Safety Update Reports-Pharmacovigilance (PSUR-PV) should be submitted as stipulated in the regulations (subsection C.01.018(4)), upon request or in situations where the Market Authorization Holder (MAH) identifies any negative safety findings and/or significant change in the product's overall benefit-risk and safety profiles.
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).

Additional information

6. Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to Lynparza (olaparib) as per section 5.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c). For more information on the regulatory requirements for advertising, please visit: https://www.canada.ca/en/health-canada/services/drugs-health-products/regulatory-requirements-advertising.html.
7. An up-to-date, complete listing of ongoing additional clinical trials related to Lynparza (olaparib), appended to the draft Letter of Undertaking, as per Section 4.5 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
8. Copies of any marketing authorizations for Lynparza (olaparib) from any other drug regulatory authority as per Section 4.6 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).

3. A draft of the Product Monograph that is consistent with the requirements in accordance with the Guidance Document: Product Monograph (2020) and the Product Monograph Master Template, disclosing the nature of the authorization granted for Lynparza (olaparib) and the need to conduct confirmatory trials.
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 Lynparza (olaparib) for the indication in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA mutated (germline and/or somatic) metastatic castration resistant prostate cancer (mCRPC), whom chemotherapy is not clinically indicated. Patients must have confirmation of BRCA mutation before Lynparza treatment is initiated

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 Applications and Notice of Compliance with Conditions (NOC/c), respectively.

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 directly to the Office of Submissions and Intellectual Property (OSIP) via the Common Electronic Submissions Gateway using Regulatory Enrolment Process.

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.

Yours sincerely,

Karen Reynolds
Director General
Pharmaceutical Drugs Directorate
KR/oh