Summary Basis of Reconsideration Decision (SBRD) Reconsideration of a Notice of Non-Compliance Withdrawal

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Contact: Biologics and Genetic Therapies Directorate

Published by authority of the Minister of Health

Date Issued: 2007/12/20

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) Révision de retrait suite à un avis de non-conformité

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 that allows stakeholders to be aware of decisions made, without disclosing potentially confidential information about a submission that may not have received authorization.

Summary Basis of Reconsideration Decision

Reconsideration Issue

The sponsor filed a New Drug Submission to the Biologics and Genetic Therapies Directorate. The drug product was intended for use in immunocompromised patients.

A Notice of Non-compliance (NON) was issued citing numerous deficiencies. The sponsor responded to the NON, but the clinical deficiencies identified previously during review of the NDS were not corrected and the responses were insufficient. Thus, the rationales in the sponsor's response did not comply with the requirements of the Food & Drugs Act and Regulations, and a Notice of Non-compliance - Withdrawal (NON/W) was issued on this basis.

Reconsideration Process and Decision

The sponsor filed a Request for Reconsideration of the NON/W. 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. The Director General of BGTD informed the sponsor that the reconsideration of the final decision issued would proceed as an internal reconsideration, as the reconsideration is of a regulatory nature.

In its Request for Reconsideration, the sponsor stated that the clinical development program and submission strategy for the product, including the design of the pivotal clinical trials, number of patients enrolled, and comparators used, were discussed with and agreed to by Health Canada prior to initiation and during the conduct of the pivotal clinical trials, and again prior to filing the NDS. The sponsor further claimed that there had been no substantial changes in the Food and Drugs Act and Regulations governing this type of therapy that would preclude authorization of the product. The sponsor stated that the results of the pivotal clinical trials were positive, demonstrating that the product was efficacious in the proposed indication and that the product was safe, with exposure to the subject numbers that Health Canada had stated would be required if no significant safety concerns were identified.

Upon reviewing the Request for Reconsideration, the Reconsideration reviewer concluded that the pivotal trials in the submission used a comparator whose dose and route did not comply with Health Canada requirements for pivotal trials, and that although "no substantial changes" have been made in legislation that would preclude the authorization of the product, the original trial designs were insufficient to prove safety and efficacy, and were therefore insufficient to support authorization. A thorough assessment of pivotal trials with a valid comparator and sufficient statistical analyses are required. Immunogenicity is typically a challenge with Biologics, and is not specific or proprietary to this agent; the sponsor's response regarding immunogenicity testing was insufficient.

The Director General of BGTD upheld the original decision on the basis of several instances of failure to comply with Health Canada Guidelines and Policies, as well as multiple deficiencies identified in meetings with the sponsor, the original submission review and the Request for Reconsideration analysis. It was reiterated that Health Canada does not 'agree upon a licensure strategy', but if requested by a sponsor, Health Canada advises if the current data support the submission and what would be required for a pivotal trial, but it is the onus of the sponsor to ensure the trial would be pivotal at completion.