Megan Bettle
Director
Regulatory Review of Drugs and Devices
Health Canada

s a smaller market, Canada is often not the place of first submission of a new product; CIRS data show a consistent submission gap with larger jurisdictions, such as Europe or the US. How can the Canadian regulator adapt to decrease this gap? Is it even possible?

Key Takeaways

• Canadian regulatory modernization aims to create agile new pathways by which products can come to market.
• International work-sharing, parallel advice with health technology assessment (HTA) organizations to support early product development, and, where appropriate, relying on the decisions of regulatory partners are some of the tools now being developed.
• However, there are multiple factors which affect business decisions and the timing of drug submissions to a smaller marker like Canada, not all of which might be addressed by ongoing initiatives.

Can Early Scientific Advice Support Future Success?

Many regulators have early interactions with drug sponsors to provide technical and regulatory advice. Health Canada similarly runs an active program of pre-clinical trial application and pre-submission meetings. However, since Canada is not the site of first filing, pre-submission advice meetings are often used by sponsors to present the almost-complete clinical trial program which may have already been shaped by the advice of larger regulators such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).

While Canada aims to harmonize internationally, there are times when earlier discussion could highlight aspects of the Canadian clinical context which may be relevant, or where the views of additional regulators may be useful in planning a global development program. Additionally, advice which could support later recommendations for publically funded drug plans could be critical for timely access to a product.

As part of the work aimed at improving domestic collaboration and support access to drugs, Health Canada is partnering to provide early parallel scientific advice with the Canadian Agency for Drugs and Technologies in Health (CADTH), the HTA agency that provides funding recommendations for all but one of the provincial/territorial drug plans, as well as federally-funded drug plans (e.g., for military and First Nations people).

While still in the initial pilot stages, regulator-HTA early advice is expected to be attractive to companies looking to enter the Canadian market, particularly with expensive drugs for rare diseases, or development programs relying on adaptive clinical trial designs or Real World Evidence collection that will challenge the regulatory and reimbursement assessments.

How Can International Work-Sharing Be Optimized?

International work-sharing can be an important contributor to regulatory alignment and to creating access to larger markets. Centrally-authorized procedures in the European Union are the best example of how work-sharing can be leveraged to create efficiencies.

On a smaller scale, Canada has been building partnerships that would allow work-sharing, including the Australia-Canada-Singapore Switzerland (ACSS) consortium. Through recent work, this group has developed processes to share review workload, first for a generic product, and more recently, for an innovative product. The innovative product submission was shared between Canada and Australia, with the other partners as observers.

Significant time zone challenges aside, this was a valuable learning experience for all involved. Building from this experience, a number of other products have been proposed by sponsors or otherwise identified as candidates for shared reviews. While still too early to quantify any efficiencies gained, this exercise is expected to share review expertise and to further increase international alignment.

Relying on the Decisions of Others

Despite the submission gap described above, most new products do eventually come to Canada. However, there are a range of products that will not, especially where the market share is quite small. This can include very old products as well as innovative ones. Many of these products can be made available through the Special Access Programme, which provides emergency access to unauthorized drugs for individual patients on the request of their prescriber. In such circumstances, incentives that will bring a product into a regulated pathway may be useful. For this reason, a regulatory reliance pathway that would allow Health Canada to accept the approval of specified regulators in order to grant a Canadian authorization with minimal review is being proposed. Draft regulations are expected to be available for comment within the next few months.

Factors Affecting Filing Timing in Canada

The industry perspective in this session discussed a number of elements that may affect filing timing in Canada. Survey data gathered from companies who bring products to Canada reported the perception that Canada is more conservative and less likely to approve simultaneous filings first, compared to the EMA or FDA, and often with more restrictive labelling. The inability to add additional data during the review process, time delays to acceptance of accelerated review requests, and requirements related to labelling and manufacturing site licensing were seen as Canadian-specific barriers.

Discussions revealed that proposals for early advice, work-sharing, and using foreign decisions may be useful, but that other harmonization aspects may also need to be considered in order to bring products to Canadian markets sooner. Concern was also expressed about the number of different regulatory initiatives in play, and what the overall business impacts would ultimately be.