Qualifying notice for HepaGam B

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

• Dossier ID: HC6-024-e137614
• Control #: 263971

KI Biopharma LLC
[employee name removed]
[employee title removed]
Proficio Scientific Affairs Inc.
3700 St-Patrick
Montreal QC H4E 1A2

Email: [employee email removed]

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 New Drug Submission (NDS) for HepaGam B (Hepatitis B Immune Globulin [Human] Injection), Control #263971, indicated for the prevention of hepatitis B recurrence following liver transplantation in adult patients with hepatitis B who have no or low prior levels of HBV replication, 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 KI Biopharma LLC, 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, KI Biopharma LLC 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 KI Biopharma LLC, 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 as Supplemental New Drug Submission- Confirmatory (SNDS-c):

Confirmatory studies

1. The final study report for the phase 3 clinical trial [study name/number has been removed], Hepatitis B immune globulin (NP-002) for prevention of graft re-infection in hepatitis B related liver transplant patients.
2. The final study report of the 1-year extension study to [study name/number has been removed], [study name/number has been removed].
3. The final study report for the [study name/number has been removed] study, examining the safety, pharmacokinetics and efficacy of HepaGam B in combination with antiviral therapy in the first year post-transplant.

Safety monitoring

4. 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).
5. Periodic Safety Update Reports or Periodic Benefit-Risk Evaluation Reports-C for NOC/c Products (PSUR-Cs or PBRER-Cs) on a semi-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);

• 3. A draft of the "Fact Sheet", outlining in lay language the risks, benefits, and side effects of the indication for HepaGam B.
• 4. A draft of the "Dear Heath Care Professional Letter" detailing the conditional approval of HepaGam B 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 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