Notice of Compliance With Conditions - Qualifying Notice

2007-01-19

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.

Contact: BGTD RAD Enquiries

Biologics and Genetic Therapies Directorate
200 promenade Tunney's Pasture Driveway
Address Locator #0701A
Ottawa, Ontario
KlA 0K9

9427-C1449\1-28

November 24, 2006

[employee's name removed]
Senior Regulatory Affairs Associate
Cangene Corporation
3403 America Drive
Mississauga, Ontario
L4V 1T4
Fax: 905-673-5123

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 New Drug Submission for HepaGam B^TM (Hepatitis B Immune Globulin [Human] Injection), Control # 089393, qualifies to be considered for approval, 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 Cangene Corporation, indicating that you agree to have this submission considered under the NOC/c policy.
2. A draft Letter of Undertaking, signed by the Chief Executive Officer or designated signing authority of Cangene Corporation, which should have form and content satisfactory to Health Canada, including commitments to supply the following:
   1. Updates to the results of Study HB-005, to be submitted to BGTD on an annual basis, as well as the completed study report, as soon as it is available.
   2. The final study report of the extension study, Protocol HB-006, to be submitted, as soon as it is available.
   3. In addition, the response to question #2 in our Clarifax dated October 31, 2006, states that 'In North America, the majority of patients are treated with antiviral therapy pre- LT, and are not eligible for the study', and only one patient from San Francisco has been enrolled to date. This response suggests that data on Canadian and North American (US) patients are unlikely to become available from the ongoing study HB-005, with few exceptions. BGTD considers the data on Canadian and/or US liver transplant patients, treated under a standard of care similar to the one currently used in Canada, to be essential for the evaluation of benefit and risk to our Canadian patients. Since the majority of patients are treated with antiviral therapy and the exclusion due to the use of antiviral therapy for hepatitis B appears to be the principal obstacle for obtaining the required data, a new comparative add-on superiority study comparing the efficacy and safety of anti-viral therapy alone, to HepaGam B^TM with antiviral therapy needs to be conducted. The margin of benefit expected when HepaGam B^TM is added to anti-viral therapy above and beyond the benefit that can be achieved with anti-viral therapy alone should be specified in the study protocol. The margin of benefit should represent a clinically meaningful improvement in the reduction of HBV recurrence and once specified, the study should be designed and powered accordingly.
   4. All the above studies and conditions must be completed within five years following the issuance of the NOC/C.
3. A draft of the "Fact Sheet", outlining in lay language the risks, benefits, and side effects of the indication for HepaGam B^TM.
4. A draft of the "Dear Health Care Professional Letter" detailing the conditional approval of HepaGam B^TM for the indication of prevention of hepatitis B recurrence following liver transplantation.

I wish to advise you that this Qualifying Notice is being issued in accordance with Health Canada's guidance and policy on the Management of Drug Submissions and Notice of Compliance with Conditions, respectively. Sponsors are instructed to submit a complete response (refer to "Guidance for Industry; Notice of Compliance with Conditions") to the outstanding information within 30 calendar days to the date of this letter.

In order to facilitate proper processing, please include a revised Submission Certificate with your response, quote the product name and control number, and address all correspondence to the Chief, Submission and Information Policy Division, Bureau of Operational Services, Therapeutic Products Directorate, Finance Building, 101 Tunney's Pasture Driveway, Address Locator 0201A1, Tunney's Pasture, Ottawa, Ontario, K1A 0L2.

Yours sincerely,

Original signed by

Dr. Pierre Charest
Director General