Summary Basis of Reconsideration Decision (SBRD) Advance Consideration under the Notice of Compliance with Conditions Policy

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Contact: Biologics and Genetic Therapies Directorate

Published by authority of the Minister of Health

Date Issued: 2007/05/15

Health Products and Food Branch

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Health Products and Food Branch

Également disponible en français sous le titre : Sommaire des motifs de décision de révision (SMDR) Considération anticipée sous la notification de la conformité à la politique de conditions

Foreword

Health Canada's Summary Basis of Reconsideration Decision (SBRD) documents outline the scientific and regulatory considerations that factored into Health Canada's decision to grant or deny a Request for Reconsideration filed as per the Health Canada Guidance Document: Reconsideration of Final Decisions Issued for Human Drug Submissions. The SBRD has been prepared in such a way to inform stakeholders of decisions made, without disclosing potentially confidential information about a submission that may not have received authorization.

This document should be read in conjunction with the relevant sections of other applicable guidance documents.

Summary Basis of Reconsideration Decision

Reconsideration Issue

The sponsor filed a Request for Advance Consideration under Health Canada's Notice of Compliance with Conditions (NOC/c) Policy, in anticipation of filing a Supplemental New Drug Submission for a potential first line therapy in the treatment of acute intracerebral hemorrhage (ICH) to the Biologics and Genetic Therapies Directorate (BGTD). BGTD issued a Rejection letter to the sponsor, stating that the information provided for the preliminary analysis was insufficient to grant advance consideration under the NOC/c Policy. The provided information indicated that data to be submitted were limited to the results of a surrogate clinical endpoint from one single dose-finding study with a small number of patients. Available data to be submitted were found insufficient to demonstrate the required substantial evidence of an acceptable safety profile and potential to provide effective treatment of the disease. BGTD also had concerns that the ongoing trial proposed as a confirmatory study (to fulfil the potential conditions under the NOC/c Policy) was not sufficiently powered to demonstrate safety.

The sponsor filed a Request for Reconsideration of the Rejection of advance consideration under the NOC/c Policy. In the Request, the sponsor questioned the clarity of the phrase "lacks data on a statistically significant endpoint", asking whether it meant that the information package lacked "statistically significant" data on a clinical endpoint, or that the submission lacked data on a "relevant" clinical endpoint. The sponsor addressed both propositions, arguing that there were indeed statistically significant differences on relevant clinical endpoints.

Reconsideration Process and Decision

In consultation with the Reconsideration reviewer, the Office of Quality and Risk Management, BGTD recommended that the Request for Reconsideration proceed as an internal review as outlined in the Guidance for Industry Reconsideration of Final Decision Issued for Human Drug Submissions. Decisions which are based on an interpretation of policy are best suited for internal reconsideration. The Request for Reconsideration was reviewed by the Office of Science of the Therapeutic Products Directorate.

The Reconsideration reviewer stated that although the information provided indicated promising efficacy data in limiting early growth in ICH volume, in reducing the risk of mortality, and in improving modified Rankin Scale (mRS) without incurring an increase in severe disabilities in the survivors, information was still lacking for full interpretation of the efficacy result for optimal benefit in clinical application. The Reconsideration reviewer also stated that patient number at the proposed marketing dose did not provide adequate safety and effectiveness information for the targeted populations.

While ICH is recognized as meeting the disease condition of the NOC/c Policy, the efficacy and safety factors which need to result in an improved risk/benefit profile were not satisfactory within the limitations of the currently provided information. Therefore, the Director General of BGTD issued the Reconsideration Decision upholding the original denial of the Request for Advance Consideration under the NOC/c Policy for acute ICH. The sponsor was advised of the type of information which would support a future Request for Advance Consideration under the NOC/c Policy.