Strategic problem-solving for a complex Canadian New Drug Submission

Overview

A midsize pharmaceutical company based in the EU contracted ICON to support a New Drug Submission in Canada for a respiratory drug for chronic obstructive pulmonary disease (COPD).

ICON had previously partnered with the sponsor in other regulatory jurisdictions, though this was the first time the partnership operated in Canada. Drawing on ICON's local regulatory strategy expertise, an approach was proposed to mitigate the issue of an unapproved active comparator. Ultimately, ICON facilitated a comprehensive Canadian submission and responded to Health Canada questions during review, leading to a successful approval outcome.

Challenge

This NDS project first required a gap assessment of the EU dossier, including clinical, nonclinical and CMC components, to build a regulatory strategy for the regional requirements. The CMC dossier was complex as there were three active ingredients and a device component. In addition to extra time required for review of multiple components during submission preparation, it also involved challenges of clinical verses commercial product differences, equivalency determination and third-party data submissions during agency review. 

Significantly, ICON discovered in the gap analysis that the active comparator in the pivotal clinical studies was not approved in Canada, which could jeopardise the acceptability of the pivotal studies. To progress the project, the team had to demonstrate the comparator’s approvability to enable Health Canada’s review of the proposed product.

Solution

To address the challenge posed by the use of an unapproved active comparator in the pivotal study, ICON’s Regulatory Strategy teams planned the submission to essentially support the approval of both products—the proposed NDS and the active comparator. This required incorporating the available safety and efficacy data for the active comparator (owned by the sponsor) into Module 2 summaries. ICON engaged with Health Canada to confirm and agree on the approach during a pre-submission meeting to protect the sponsor’s time and resources.

ICON facilitated extensive authoring of the EU modules to include the requisite comparator data to demonstrate the comparator’s approvability to Health Canada. With this data, Health Canada could then accept the use of the comparator and focus on the safety and efficacy data obtained for the proposed product.

The complexity of preparing a quality CMC dossier for a product with three active ingredients and a device, required ICON CMC Regulatory team collaboration with the sponsor. ICON CMC Regulatory’s extensive experience in reviewing and authoring Module 3 to meet Canadian requirements helped complete the Module and dossier in a timely manner. ICON’s CMC team also supported in:

• Addressing clinical verses commercial comparability issues
• Confidentiality concerns in submitting third party vendor information to Health Canada
• Authoring to repurpose CMC content as per Health Canada requirements
• Importer change requirements during agency’s review process

Outcome

The complex NDS filed with Health Canada was comprehensive, with safety and efficacy data supporting the approval of two products (proposed product and the active comparator) and included drug substance and drug product for three active ingredients and the device and its components. The ICON Regulatory team assisted the sponsor throughout the NDS review, providing regulatory support and strategy in responding to Health Canada’s questions quickly and efficiently.

Multiple functions from ICON contributed to the regulatory strategy to accomplish:

• A gap assessment of the EU dossier
• Health Canada meeting activities, including preparation of the meeting package, attendance and minutes
• Submission authoring (Module 2, 3, regional Product Monograph, Risk Management Plan)
• Post-filing support (Canadian agent and submission contact, preparation of responses to Health Canada in collaboration with the sponsor)
• Publishing of documents
• eCTD build throughout the project 

As a result of close collaboration with the sponsor, the team achieved an issuance of the Notice of Compliance.