New regulations have been enacted by Health Canada to satisfy its objective of making clinical information in drug submissions and medical device applications (collectively, the submissions) publicly available for non-commercial purposes following a final regulatory decision. Health Canada's approach to disclosure of clinical information is now in line with that of the European Medicines Agency and the U.S. Food and Drug Administration, both of which have increased clinical data transparency over the past decade.
What you need to know
- Health Canada will this year be proactively publishing clinical information in new drug submissions, following a final regulatory decision. Proactive publication will be phased in by submission type over four years.
- Beginning in 2021, Health Canada intends to proactively publish clinical information in new medical device applications and amendment applications for Class III and Class IV medical devices, following a final regulatory decision. Proactive publication will be phased in by application type over four years.
- Clinical information that will remain confidential business information (CBI) following a final regulatory decision, and therefore will not be proactively disclosed, includes (i) all clinical information that was not used by the manufacturer in the submissions to support the proposed conditions of use, and (ii) clinical information that describes tests, methods or assays used exclusively by the manufacturer.
- Clinical information in submissions that received a final regulatory decision before March 4 may be made available by request to Health Canada.
- Individual patient records will not be publicly released with other clinical information.
- Manufacturers should be mindful of the timeframes set forth by Health Canada for receipt and finalization of redacted clinical trial reports, to mitigate the risk of Health Canada releasing clinical trial information without the manufacturer's input.
Following the December 9, 2017 publication of the proposed amendments to the Food and Drugs Regulations and the Medical Devices Regulations, Health Canada published a guidance document on the public release of clinical information on March 12, 2019, and launched the Clinical Information Portal, a database containing the published clinical information, on March 13. The final regulations were promulgated in Canada Gazette, Part II, on March 20, (Regulations), but came into force on March 4. The final Regulations did not differ from the proposed amendments published on December 9, 2017.
What clinical information will be made public?
Following a final regulatory decision, information in respect of a clinical trial or investigational testing will no longer be considered CBI in the following circumstances, and therefore will be proactively disclosed by Health Canada:
- clinical summaries;
- reports and supporting data of clinical trials submitted in support of a drug submission upon the issuance of a notice of compliance, notice of non-compliance withdrawal, or notice of deficiency-withdrawal; and
- reports and supporting data of clinical trials or investigational testing in humans submitted in support of any Class III or Class IV medical device application upon the issuance of a medical device license, medical device license amendment, or a refusal letter.
Clinical case report forms and individual patient records will not be publicly released with other clinical information. Adverse events and other significant participant-level results are reported in the main body of the clinical study report and will be published in an anonymized format.
What information will continue to be treated as confidential?
The following clinical information will not cease to be CBI following a final regulatory decision, and therefore will not be proactively released:
- information not used by the manufacturer in a drug submission to support the proposed conditions of use and purpose for the drug;
- information not used by the manufacturer in a medical device application to support the conditions, purposes and uses for which the device is manufactured, sold or represented; and
- information that describes tests, methods or assays that are used exclusively by the manufacturer.
For example, chemistry and manufacturing information for drugs, manufacturing and design features for medical devices, non-clinical (preclinical testing) information, and sales information will remain CBI following Health Canada's final regulatory decision and therefore may be redacted prior to disclosure of any documents.
How will the proactive disclosure of clinical information be implemented?
Proactive release of clinical information for submissions that received a final regulatory decision on or after March 4 will be implemented in four phases by year. Health Canada will aim to publish the clinical information for in the following sequence.
- Stage/Year 1: New active substances (NDS-NAS), representing submissions for drugs that are not variations of previously approved medicinal ingredients in Canada (i.e., innovative drugs); supplemental new drug submissions containing confirmatory trials (SNDS-c) following the issuance of a notice of compliance with conditions as agreed to in the letter of undertaking; and submissions to switch an authorize medicinal ingredient to non-prescription status.
- Stage/Year 2: All new drug submissions (both NDS-NAS and those not categorized as new active substances).
- Stage/Year 3: All SNDS, and in-scope clinical information within Class IV medical device applications; and
- Stage/Year 4: All abbreviated new drug submissions (ANDS), and from Class III medical device applications.
What about clinical information from past submissions?
Clinical information from submissions that received a final regulatory decision prior to March 4 may be requested through Health Canada's Clinical Information Portal by submitting an electronic request form identifying the product name, the name of the manufacturer, the related indication, the information requested, the reason for the request and the requester's contact information. Information in submissions that received a final decision after March 4, but was not yet subject to proactive publication is also available on request made through the Clinical Information Portal. List of requests will be updated on the Clinical Information Portal website.
What is the procedure for publication of clinical information?
The publication of clinical information under the Public Release of Clinical Information initiative will proceed through five distinct phases:
- Initiation: The timelines for
publication of clinical information vary depending on the type of
final regulatory decision.
- For positive regulatory decisions, issuance of the decision initiates the process. Health Canada will send an email notification to the manufacturer identifying the documents that will be publicly released.
- For a negative regulatory decision in respect of a drug submission, Health Canada will initiate the process 31 calendar days after the date of the notice of the decision, unless a Letter of Intent for Reconsideration has been received from the manufacturer. Health Canada will send an email notification to the manufacturer identifying the documents that will be publicly released.
- For a negative regulatory decision in respect of a medical device application where the manufacturer submits a Letter of Intent to Appeal, Health Canada will initiate the process upon issuance of a decision of the appeal process.1 Health Canada will send an email notification to the manufacturer identifying the documents that will be publicly released.2
- Submission: Manufacturers must submit an annotated version of all clinical information in scope of publication with any and all proposed redactions highlighted and a detailed justification for the redaction on the proposed redaction control sheet within 60 calendar days of the email notification (if applicable, manufacturers may also submit final redacted documents of a drug submission that were previously accepted by the European Medicines Agency).
- Review: Health Canada will review the manufacturer's justifications for each proposed redaction within the annotated documents, assessed against the exceptions permitted under the Regulations;3
- Finalization: Following Health Canada's review, manufacturers must submit a final version of the documents in accordance with Health Canada instructions.
- Publication: Final documents will be made publicly available 120 calendar days following the initiation of the process for non-commercial purposes through the Clinical Information Portal.
Prior to the initiation of the publication of clinical information process, a sponsor may elect to attend a one-on-one Process Initiation Meeting (PIM) via teleconference, which allows a sponsor to consult with Health Canada on the clinical documents in consideration for release. A PIM may be requested 120 calendar days prior to the final regulatory decision, and up to 20 calendar days following the final regulatory decision.
Despite Health Canada's commitment in its guidance document to notifying manufacturers, it should be noted that Health Canada has the authority to disclose clinical information once it has ceased to be CBI under the Regulations without notification or consent.4
Health Canada's approach to disclosure of clinical information is very closely aligned with the European Medicines Agency's policy on publication of clinical data for drug products (EMA Policy 0070), and drug manufacturers can leverage the EMA Policy 0070 to provide Health Canada with redacted documents that have been previously accepted by the EMA.
Based on information provided on the EMA website, there is currently no clinical information disclosure requirement for medical device applications in Europe. However, this will change once new regulations come into full application, anticipated to occur on May 26, 2020 for medical devices and May 26, 2022 for in vitro diagnostics.
Unlike the electronic common technical document submission format of International Conference on Harmonisation required for drug submissions, Canadian medical device applications currently vary in structure, requiring Health Canada to assess the sections eligible for public release on a case-by-case basis. Health Canada has signaled its intention to adopt an internationally harmonized format for medical device applications, and the delayed implementation of proactive publication for medical device applications in Year 3 should address this current lack of international alignment. Presumably, once Health Canada adopts a harmonized format for applications, manufacturers will be able to leverage redacted documents prepared for the EU, similar to the current approach for drug information.
Based on the information on the U.S. FDA website, in the United States, a clinical data summary pilot program has been implemented for clinical information related to drug approvals only.
- Clinical information published on the Clinical Information Portal is available for non-commercial purposes only which, without limiting the foregoing, expressly excludes the use of the information to support a marketing authorization application anywhere in the world or the selling or trading of the information to another person.
- There is no apparent restriction on the use of clinical information obtained from the Clinical Information Portal for the purposes of litigation. Depending on the circumstances, this information could conceivably be used as the basis for a civil claim against a marketing authorization holder, or a third-party challenge to Health Canada's decision granting a marketing authorization.
- It is likely the public release of clinical information will reduce the number of access to information requests received by Health Canada. Unredacted CBI may continue to be requested from Health Canada if eligible under section 21.1(3)(c) of the Food and Drugs Act, or potentially through a request under the Access to Information Act.
- Despite Health Canada guidance that manufacturers will be consulted and provided with an opportunity to propose redactions to clinical information, the Regulations do not place a positive obligation on Health Canada to notify manufacturers of the publication of clinical information. Manufacturers should keep in mind that a PIM teleconference may be requested 120 days prior to, and 20 days following, the final regulatory decision. We strongly recommend manufacturers remain engaged throughout the publication of clinical information process to ensure that all CBI is redacted prior to publication.
Clinical information found in drug submissions following a final regulatory decision will be made available throughout 2019 on the Clinical Information Portal. The Clinical Information Portal currently contains the clinical information for one new drug submission, and one Class II medical device application. There are also three medical device applications for currently licensed medical devices, for which clinical information release is currently in progress.
1 If the manufacturer does not submit a Letter of Intent to Appeal within 10 calendar days after the date of the notice of the decision, Health Canada will initiate the publication of clinical information process.
2 For a first-level appeal of a medical device application, Health Canada will initiate publication 21 days after receipt of the manufacturer's Letter of Intent to Appeal to the Bureau Director if the manufacturer does not submit the necessary information supporting the appeal. For a second-level appeal, Health Canada will initiate publication upon notification to the manufacturer of the Directorate's decision on the appeal.
3 Food and Drugs Regulations, C.08.009.2(2) and Medical Devices Regulations section 43.12(2).
4 Food and Drugs Regulations, C.08.009.3 and Medical Devices Regulations section 43.13.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.