A Year In Review for R2D2
R2D2. No, it’s not another space-age movie. The acronym stands for Regulatory Review of Drugs and Devices and it is a Health Canada initiative to improve the efficiency of our regulatory system and to provide more timely access to therapeutic products “that are aligned with healthcare system needs.” With so much focus last year on the Patented Medicines Regulations and the Patented Medicine Prices Review Board (PMPRB) Guidelines, as well as all the media attention given to national pharmacare, some of the proposed or implemented modifications to our regulatory system may have been overlooked.
Overall, there are 14 projects under the R2D2 initiative that can be bucketed into the following categories: 
- Expanded collaboration with health partners
- More timely access to drugs and devices
- Enhanced use of real-world evidence
- Modern and flexible operations
1. Expanded collaboration with health partners: The aligned review process between Health Canada and the Canadian Agency For Drugs And Technologies In Health (CADTH) was implemented to reduce the time interval from approval to HTA recommendation. As of November 2019, 47% of all eligible submissions (26/55) opted into the aligned review and informationsharing process. Another joint effort between Health Canada and CADTH is the parallel scientific advice process. Sponsors may seek a joint face-to-face meeting with Health Canada and CADTH, years before filing for approval, to obtain advice regarding a drug’s clinical development plan. (INESSS may attend as an observer only).
Internationally, Health Canada is collaborating with other national regulatory authorities to streamline the process of joint reviews and gain efficiencies for submissions for drugs for human use. Health Canada is involved in several consortiums including the Australia-Canada-Singapore-Switzerland (ACSS) and the FDA/Canada/Australia consortium which have both approved drugs in all relevant jurisdictions.
2. More timely access to drugs and devices: To improve access to generic drugs, the federal government has proposed expanding the criteria required to show generic equivalence to a Canadian Reference Product (CRP). The proposed Regulations Amending the Food and Drug Regulations (Improving Access to Generics) would change what constitutes an “identical medicinal ingredient” to include different physiochemical forms of the drug (i.e. salt formulation) in comparison to the CRP, making these drugs eligible for filing through the ANDS pathway. Health Canada has also proposed in these regulations that a manufacturer could file an ANDS in a situation where the CRP is a biologic, as referred to in Schedule D, even if the “follow-on” drug is chemically synthesized and thus not referred to in Schedule D (i.e. a “generic” version of the biologic).
Proposed changes to the Special Access Program are expected to bring greater efficiencies with less administrative burden. The proposed amendment is expected to simplify the process for the prescribing physician, allow drugs to be shipped directly to community pharmacies (of particular importance in rural communities), and allow for pre-positioning of a drug so that it can be physically present in Canada prior to a specific request.
3. Enhanced use of real-world evidence: In the spring of 2019, Health Canada announced it was inviting submissions based on RWE for drugs/ diseases where clinical trials are unethical (emergency situations), unfeasible (rare disease) or where certain populations are excluded from evidence-based clinical trials.
Real-world evidence will also be of value to Health Canada’s post market authorization of drugs and devices. Strengthening post-market surveillance of medical devices was a key focus of the feds over the last year. Health Canada created the new Medical Devices Directorate to review medical devices within a life-cycle approach (before and after reaching market authorization). In June 2019, Health Canada published a guidance document on mandatory reporting of serious adverse drug reactions and medical device incidents by hospitals whereby these institutions must report in writing, within 30 days of the incident.
4. Modern and flexible operations: Fees for regulatory services were affected by changes made to the federal agency’s Appropriate Cost Recovery Framework in 2019. Health Canada published its Final Report: Fees for Drugs and Medical Devices as a means to better recover its costs associated with regulatory activities for human drugs, veterinary drugs and medical devices. The revised fees, to be implemented April 1, 2020, will be phased in over four to seven years and adjusted annually based on the CPI. Among other specific revisions, Health Canada will allow a fee mitigation for small business and apply a 25% rebate for missing performance standards.
In line with Vanessa’s Law, regulations surrounding the disclosure of information with respect to clinical trials were published in Canada Gazette II, March 2019. This proactive public release of clinical information in drug submissions and medical device applications was to be phased in by submission type over four years starting in 2019. Clinical information that was not used by the manufacturer in the drug submission; as well as chemistry, manufacturing and other non-clinical information; will be protected from public release.
Listed above are several of the projects either proposedor already underway as part of Health Canada’s R2D2 Initiative. There are some projects that may lead to more timely approvals and access for innovative medicines, including drugs for rare disease, while others may affect go/no-go decisions on whether to file a drug submission. Introduced in 2017, the Regulatory Review of Drugs and Devices is expected to continue with its initiatives throughout 2021. Over the course of this coming year, we will no doubt see several of the proposed guidelines and regulations move towards completion and implementation. Visit Pangaea's Insights for updates on this and other industry trends over 2020.
Originally published in the Canadian Pharmaceutical Marketing Volume 33, #1, 2020.
For further information, please contact Marla Weingarten, Director, The Pangaea Group.