Qualifying notice for Tepadina

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

Dossier ID: E151892
[employee name removed]
[employee's title removed]
[name of company removed]

Dear [employee name removed]:

This Notice of Compliance with Conditions-Qualifying Notice (NOC/c-QN) is to advise you that information submitted in support of the New Drug Submission for Tepadina (thiotepa), control number 168816, for the indication in combination with other chemotherapeutic products as part of a high-dose chemotherapy (HDCT) consolidation regimen followed by autologous stem cell transplantation (ASCT) for adult patients with central nervous system (CNS) lymphoma, qualifies to be considered for authorization under the Notice of Compliance with Conditions (NOC/c) Policy. In keeping with the provision outlined in Part C, Section C.08.002.1 (3) (d) of the Food and Drug Regulations, the following additional information is required to complete the assessment:

1. A letter, signed by the Chief Executive Officer, or designated signing authority of [name of company removed], indicating that they agree to have this submission considered under the NOC/c Policy. [name of company removed] should be reminded that in agreeing to accept a Notice of Compliance (NOC) under the NOC/c Policy, [name of company removed] consents to the posting of this NOC/c-QN on Health Canada's website once market authorization has been received.
2. A Letter of Undertaking signed by the Chief Executive Officer, or designated signing authority of [name of company removed] having a form and content satisfactory to Health Canada to provide the following:

Confirmatory Trial

1. A multi-centre, prospective, observational, post-authorisation long-term study of the use of thiotepa as part-of a high-dose chemotherapy regimen followed by hematopoietic stem cell transplantation (HSCT) in Canadian and American patients.

Post Market Safety Monitoring

1. Provision of bi-annual Periodic Safety Update Reports (PSUR-Cs) or Periodic Benefit Risk Evaluation Reports (PBRER-Cs) in a manner deemed consistent with E2C ICH Guidelines, until such time as all conditions for the Canadian Reference Product market authorizations under the NOC/c policy have been removed. The bi-annual PSUR-Cs or PBRER-Cs should include cumulative data on relevant unlisted Adverse Reactions (ARs) from the date of marketing to the time of the report.
2. Notification and reporting on specific issues of concern as outlined in Section 3.4.4, Post-Market Commitments: Notification and Reporting of Specific Issues of Concern, of the Health Canada NOC/c revised policy dated June 30, 2011.
3. Reports of all serious ARs that occurred in Canada and all serious unexpected ARs that occurred outside of Canada should be forwarded within 15 days to the Marketed Health Products Directorate, in accordance with current Food and Drug Regulations (C.01.017) and Guidelines (Guidelines for Reporting Adverse Reactions to Marketed Drugs, March, 2011).

3. A draft of the Product Monograph (PM) which is consistent with the requirements outlined in Sections 5.2.1 of the Guidance for Industry, Notice of Compliance with conditions. Please note that a boxed text must appear on the cover page, at the beginning of each major section of the PM (Parts I, II and III, if applicable), disclosing the nature of the authorization granted for Tepadina, and the need to complete confirmatory studies by the innovator for the conditions to be lifted.

I wish to advise you that this letter is being issued in accordance with Health Canada's Notices to Stakeholder dated April 2nd, 2008 and March 17, 2009. You are instructed to submit a complete response (refer to Guidance for Industry; Notice of Compliance with Conditions, similar to the innovator) to the outstanding information within 30 calendar days of the date of this letter.

In order to facilitate and to ensure proper processing, please include a revised Submission Certificate with your response, quote the product name and control number, and address all correspondence to the:

Office of Submissions and Intellectual Property
Therapeutic Products Directorate
Finance Building
101 Tunney's Pasture Driveway
Address Locator 0201A1
Tunney's Pasture
Ottawa  ON K1A 0K9

Sincerely,
[employee name removed]
[employee title removed]
ML/oh