Health Canada has proposed new targeted provisions and regulatory amendments to the Food and Drug Regulations (FDR) and Medical Devices Regulations (MDR) in an effort to harmonize regulations and modernize health product practices. Stakeholders can provide feedback until April 26, 2023 on the proposed changes, which are not yet law.
What you need to know
The proposed changes expand health product safety and reduce certain regulatory barriers. They include:
- earlier market access for drugs eligible for a rolling review;
- modernized requirements for biologic drugs;
- amending requirements for certain drugs that claim a manufacturer's standard;
- expanded use of terms and conditions on approvals;
- expanded use of risk management plans; and
- disaggregated data to evaluate drug safety in diverse populations.
The push for changes
The reduction of "regulatory irritants and roadblocks to innovation" is intended to streamline health product regulation in Canada to facilitate access to promising therapies while aligning with international standards. The evolution in health products and personalized therapies has challenged current regulatory frameworks. Operational pressures from COVID-19 also highlighted the need for increased regulatory agility and continue to influence and inform Health Canada's modernization efforts.
Market access for drugs eligible for a rolling review
Proposed "rolling reviews" will permit a manufacturer to file certain new drug submissions (NDS) and supplementary new drug submissions (SNDS) with Health Canada where only partial information on the safety and effectiveness of a drug is available, provided the missing information is submitted within a reasonable amount of time thereafter. With this process, Health Canada would begin reviewing the submission earlier, however, the decision to authorize the drug would only be made once all the required information has been provided and is found to be acceptable1. Currently, rolling reviews are available in only limited circumstances (e.g., annual updates of seasonal influenza vaccines or designated COVID-19 drugs).
Rolling review options for NDS and supplementary SNDS
Under the proposal, manufacturers of drugs for human and veterinary use seeking a notice of compliance (NOC) will be subject to modified requirements for the submission of information at the time of filing the NDS and SNDS, as long as the drug is needed to address emerging infectious diseases and/or the drug is recommended for the treatment, prevention, mitigation or diagnosis of serious diseases or conditions where 1) the recommended purpose does not fall within the recommended purpose of any other drug with an active drug identification number (DIN) or 2) the new drug is significantly more effective, or possesses a significantly lower risk, compared to every other drug with an active DIN for the same recommended purpose2.
There will still be certain minimum information requirements that must be met when the submission is initially filed in order to enable Health Canada to begin to assess the safety and effectiveness of the drug. Information respecting the formulation, medicinal ingredient, use and dosage-form of the drug will also be required at the time of filing.
Under the rolling review process, the information that would be accepted after initial filing includes information respecting the tests and evidence to establish the safety and effectiveness of the new drug, information respecting the investigators to whom the new drug has been sold, evidence that test batches of the new drug were manufactured in a way that is representative of market production, the withdrawal period of the new drug in food-producing animals, a risk management plan and any summaries and sectional reports for any studies that have yet to be completed3.
A final decision will only be made once all outstanding information has been submitted and examined, however, the rolling review process is expected to benefit applicants in respect of time-to-market access, since Health Canada will be able to begin (and ultimately complete) the review process sooner.
Modernized requirements for biologic drugs
Health Canada has commented that the current provisions related to biologic drug products are overly prescriptive, product-specific and outdated4. These are proposed to be replaced with broader, more flexible regulations that reflect current practices, including changes to the requirements for labelling and quality control.
Health Canada is proposing to remove the product-specific provisions for biologic drugs in the FDR5 and replace them with more general requirements. For example, the following changes are proposed with respect to the regulation of biologic drugs:
- removing certain personnel, storage and transportation requirement provisions and relying, instead, on the existing Good Manufacturing Practices of the FDR;
- replacing outdated individual standards for purity and potency prescribed in the FDR for biologics with specifications provided by the manufacturer during review of the drug submission;
- amending the lot release program to better support a risk-based, tiered approach and formalize into regulation the current discretionary practice of providing yearly biologic product reports; and
- amending labelling requirements for biologics to align with current practices, for example, requiring a statement indicating the approved storage conditions, indicating whether the drug is derived directly from a human source or an animal source (including species of origin) and additional information when necessary to prevent injury to health of the consumer/patient (multi-dose, pediatric use, age group, warning, etc.)6.
The pace of innovation in biologic drugs has outrun the product-specific regulations of the FDR, many of which were first introduced in the 1950s and 1960s7. The proposal to modernize the regulation of biologics is intended to reduce the burden for industry and accommodate new products and therapies.
Amending requirements for certain drugs that claim a manufacturer's standard
Drug standards presently include criteria and test methods that help to assure the quality of a drug. These are set out in a pharmacopoeia listed under Schedule B of the FDR or developed by the manufacturer of the drug. Currently, when a manufacturer's own standard is used, the drug must meet the highest degree of purity and the least variation in potency for that drug of any of the listed pharmacopoeias8. Health Canada is aware that this requirement has occasionally resulted in drug products being unavailable for the Canadian market and proposes to relax these requirements for new drugs (other than radiopharmaceutical drugs)9. Drugs that are not new drugs would continue to be subject to the current requirements.
Expanded use of terms and conditions on approvals
A terms and conditions (T&C) obligation may be imposed by Health Canada on the holder of a therapeutic product authorization to conduct or restrict an activity with respect to the product. Currently, T&Cs can be imposed on opioid drugs and designated COVID-19 drugs. The proposed amendments would allow Health Canada to better manage risk by imposing T&Cs on any drug or medical device licence10.
Expanded use of risk management plans
Risk management plans (RMPs) describe risks related to a drug and the pharmacovigilance measures that a manufacturer intends to put in place to manage these risks. The proposed amendments would formalize requirements for RMPs to be filed with an application for a drug identification number, a new drug submission or an abbreviated new drug submission for a human drug if Health Canada takes the position that there is significant uncertainty regarding the risks associated with the drug or where the regulator believes the drug poses a serious risk of injury to human health that warrants measures beyond changes to the label11.
Disaggregated data to evaluate drug safety in diverse populations
The amendments also propose a requirement for Health Canada to receive disaggregated data about clinical trial participants to support the evaluation of submissions for new drugs or supplements to new drug submissions. The collection of disaggregated data as proposed would enable Health Canada to assess drug safety and effectiveness within diverse subpopulations (e.g., women, racial minorities, children and the elderly) and identify whether the drugs pose an increased risk for such subpopulations as compared to other subpopulations12.
What's next?
Manufacturers and other stakeholders have an opportunity to provide feedback by April 26, 2023 on the regulator's proposed amendments by providing comments on the draft regulations and on the several supplementary guidance documents that have been published by Health Canada.
Footnotes
1. Regulatory Impact Analysis Statement, Regulations Amending Certain Regulations Made Under the Food and Drugs Act (Agile Licensing), (17 December 2022) C Gaz I, vol 156, no 51, online: https://canadagazette.gc.ca/rp-pr/p1/2022/2022-12-17/html/reg1-eng.html.
2. Ibid.
3. Ibid.
4. Ibid.
5. Spanning between C.04.050 and C.04.683 of the FDR.
6. Ibid.
7. Ibid.
8. Ibid.
9. Ibid.
10. Ibid. For Class II, III and IV medical devices.
11. Ibid.
12. Ibid.
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