CADTH Pharmaceutical Reviews Update — Issue 31

See Pharmaceutical Reviews Update ― Issue 31 for important news and information regarding the Canada's Drug Agency drug review programs. Highlights from this issue include:

• changes to filing new information during the review and recommendation phases
• revised instructions for the reconsideration request template
• revised application templates
• notifying Canada's Drug Agency regarding regulatory status changes
• update on the Interim Plasma Protein and Related Product (PPRP) Review Process.

Canada's Drug Agency Program Updates

Canada's Drug Agency is introducing procedural revisions for its reimbursement review process as a result of the following circumstances:

• Canada's Drug Agency is committed to initiating and completing reviews within the target time frames while submission volumes are growing.
• Sponsors are frequently filing new information during the review and reconsideration phases, which can impact review timelines and may require extending expert committee meetings to ensure a comprehensive review of each file.
  • Sponsors are frequently filing new information during the evidence review phase, which requires substantial revisions to Canada's Drug Agency reports that are often complete or near complete at the time the data are filed.
  • Canada's Drug Agency has noted that sponsors are also filing new information during the reconsideration phase of the process, which requires considerable resources from Canada's Drug Agency to screen the new information, initiate further discussions with clinical experts, and undertake additional revisions to review reports.
• It is important that drug reviews contain the relevant information. However, Canada's Drug Agency is typically not provided with advance notice that new clinical studies or analyses are being submitted during the review phase, which significantly impacts review efforts and could delay discussion at the expert committees.
• Canada's Drug Agency has also noted that in many cases where regulatory applications are withdrawn from Health Canada, sponsors have not informed Canada's Drug Agency in a timely manner, which results in work resources that could be assigned to new submissions.

The procedural revisions documented in the following are required to ensure that the Canada's Drug Agency reimbursement review process is as efficient as possible and that Canada's Drug Agency can continue to manage the growing number of submissions. Canada's Drug Agency will continue to examine options regarding the inclusion of new information throughout the review and reconsideration phases, including discussions with stakeholders.

1. New Information Will Not Be Accepted After Draft Reports Are Distributed

To help address some of the previously noted concerns, effective immediately, the Procedures for Canada's Drug Agency Reimbursement Reviews have been revised to state that no new information can be filed after the draft review reports have been sent for sponsor review and comment. This includes, but is not limited to:

• new economic models
• new economic evaluations
• new clinical studies (i.e., those not included in the initial application package)
• new data cutoffs or other analyses for studies included in the Canada's Drug Agency review reports
• new indirect treatment comparisons.

Canada's Drug Agency is encountering an increasing number of situations where sponsors have filed new information (including new economic models) after receiving the draft Canada's Drug Agency review reports for sponsor comments. This is not the intent of the sponsor comment period, which is based on the information that has already been provided by the sponsor. The provision of new data can impact review timelines, including the target expert committee meeting, and may result in delays in issuing the reimbursement recommendation. As such, if a sponsor wants to file new information after receiving the draft Canada's Drug Agency review report, they will be required to formally withdraw and refile their application. This will ensure that all submissions are being treated in a fair and consistent manner, as well as that expert committees are reviewing the most relevant data.

2. Revisions to the Reconsideration Process

2.1 New Information During Reconsideration Phase

Canada's Drug Agency introduced a procedural amendment in September 2021 that would allow a sponsor to file new information as part of the reconsideration process in select circumstances where the new information was not available during the review phase and addresses an important gap in the evidence that was explicitly identified by the expert committee. The volume of new information provided by sponsors exceeds what was expected when this change was introduced. As previously noted, new data requires considerable time and effort to screen for potential inclusion in the reports and undertake revisions to the clinical reports to incorporate the new information. To ensure the overall review process is as efficient as possible, Canada's Drug Agency will only be accepting new information during the reconsideration process for files that are accepted for review through the complex review process. This procedural revision is effective for drugs targeting the October 2022 expert committee meetings and beyond for an initial recommendation (i.e., ongoing reconsiderations that have been filed before the October 2022 expert committee meetings will continue through the previous process).

Canada's Drug Agency remains committed to having a robust, fair, and inclusive reconsideration process and will undertake an internal review and evaluate further options regarding the inclusion of new information in the reconsideration phase as required.

2.2 Revised Reconsideration Template

Effective immediately, Canada's Drug Agency has revised the reconsideration request template. The maximum number of pages for the completed template is now 5 pages (not including references). Please refer to reconsideration request template for complete instructions. This procedural revision is effective for any reconsiderations filed for drugs targeting the September 2022 expert committee meetings and beyond (i.e., ongoing reconsiderations that have been filed before the September 2022 expert committee meetings will continue through the previous process).

2.3. Reminder: Reconsideration Templates Versus Stakeholder Feedback Template

Canada's Drug Agency has recently encountered situations where sponsors are filing the stakeholder feedback on draft recommendation template, but requesting revisions to the content of the recommendation that would require a request for reconsideration. These situations can result in delays as Canada's Drug Agency is required to seek clarification from the sponsor regarding whether the intent was to request reconsideration (i.e., whether the incorrect form was filed). Sponsors are reminded that comments in the stakeholder feedback on draft recommendation template are limited to requests for editorial revisions to the recommendation. To ensure fairness within all reviews, requests from sponsors to alter the content of the reimbursement conditions cannot be considered by Canada's Drug Agency unless filed using the reconsideration request template.

3. Revised Application Templates

Canada's Drug Agency is introducing revised application templates to address important limitations with the existing application and review the process with respect to new information. As previously noted, Canada's Drug Agency is typically not provided with advance notice regarding the submission of new clinical studies or analyses during the review phase (i.e., after the application has been screened and accepted for review). Canada's Drug Agency has historically made every effort to accommodate sponsors in their requests to include new information; however, this can create substantial inefficiencies for Canada's Drug Agency and places further strain on review timelines as a result of revising clinical and economic review reports that are often complete or near complete, re-running economic analyses, and further engaging with clinical specialists (including scheduling additional panel meetings to ensure robust consideration of the new information).

3.1 Table of Studies

Canada's Drug Agency has revised the table of studies template and sponsors will now be required to clearly identify planned analysis dates for the clinical studies included in their application. For any forthcoming analyses (i.e., those not included in the application at the time of acceptance for review by Canada's Drug Agency), sponsors will be required to provide the following information:

• whether or not they are intending for the analyses to be submitted and reviewed by Canada's Drug Agency
• the anticipated date the information will be submitted to Canada's Drug Agency (if applicable).

Please refer to the instructions in the revised template of table of studies template for complete details.

3.2 Application Overview

Canada's Drug Agency has revised the application overview template and sponsors will now be required to clearly identify the following information at the time of filing the application:

• if they are planning to file new studies or new analyses during the review phase
• the anticipated date the information will be submitted to Canada's Drug Agency (if applicable).

Please see the revised application overview template for complete details.

Sponsors with currently active files will be contacted by Canada's Drug Agency to determine if they are planning to file new information during the review.

4. Notifying Canada's Drug Agency Regarding Regulatory Status Updates

The Procedures for Canada's Drug Agency Reimbursement Reviews have been revised to state that sponsors must notify Canada's Drug Agency within 1 business day of any of the following events:

• the sponsor has withdrawn from the Health Canada review process
• Health Canada has issued a Notice of Deficiency and the sponsor has not or will not consent to the information-sharing process
• Health Canada has issued a Notice of Deficiency — Withdrawal or Notice of Non-Compliance.

Canada's Drug Agency has previously requested that sponsors provide notification of these events as soon as possible; however, there have recently been situations where sponsors are not informing Canada's Drug Agency in a timely manner. When Canada's Drug Agency continues to work on files that must be withdrawn from the process, resources are impacted and work may be diverted from incoming submissions. Canada's Drug Agency appreciates that sponsors may need to manage communications regarding withdrawn files; as a result, when requested, delayed posting of the withdrawn status on the Canada's Drug Agency website can be accommodated.

5. Canada's Drug Agency and Canadian Blood Services Interim Plasma Protein and Related Product Review Process

Canada's Drug Agency and Canadian Blood Services are announcing revisions to the naming and eligibility criteria of the Interim Plasma Protein and Related Product (PPRP) Review Process. There are no other changes to the interim process and all reviews continue to be completed in accordance with the Procedures for Canada's Drug Agency Reimbursement Reviews.