Policy statement: Use of pharmacometrics in drug submissions and clinical trial applications

Pharmacometric approaches play an increasing role in developing drug submissions and clinical trial applications (CTAs). Find out what sponsors should consider when preparing drug submissions and CTAs that use pharmacometric approaches.

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Pharmacometrics is the science of using quantitative analysis and modelling and simulation (M&S) approaches to inform and enhance drug development and regulatory review. Pharmacometrics also encompasses quantitative system pharmacology and model-informed drug development (MIDD) approaches.

Common applications of pharmacometric analyses for regulatory drug submissions include using modeling and simulation to:

Pharmacometric analyses can improve:

Using pharmacometrics provides efficient and cost-effective approaches to support and optimize drug safety and effectiveness. While sponsors have used pharmacometric approaches during the drug discovery and development process for some time, pharmacometrics is an emerging science. Regulators are working to find the best way to evaluate pharmacometric approaches for drug evaluation and regulatory decision-making.

Purpose and scope

The intent of this statement is to inform sponsors of the principles they should consider when filing drug submissions and CTAs that use pharmacometric approaches.

This document applies to sponsors intending to use pharmacometric approaches within a drug submission or CTA for a pharmaceutical or biologic drug intended for human use.

We may continue to update this policy statement in response to new scientific knowledge, best practices and gained experience.

Policy objectives and statements

We recognize that the application of pharmacometrics can be an important part of drug discovery and development processes. Our goal is to clarify what evidence based on pharmacometric approaches is acceptable in the regulatory review of drug submissions and CTAs.

When developing and evaluating drug submissions and CTAs that use pharmacometric approaches, 4 principles should be considered:

  1. A fundamental objective of human drug development is to understand the benefits and risks of a drug for an intended use and patient population. There is also a need to minimize health risks and optimize therapeutic outcomes for patients and clinical trial subjects. These objectives should guide the use of pharmacometric approaches during drug discovery and development.
  2. We accept pharmacometric approaches in drug development and submissions for marketing authorization. During the review process, we will evaluate whether sponsors have integrated pharmacometric analyses appropriately and in the most suitable context. In reviewing drug submissions that use pharmacometric analyses, we will consider:
    • the quality of the data and analyses
    • the strengths and limitations associated with their use
    • the feasibility of alternative conventional approaches, for example, randomized controlled trials
  3. These considerations will guide the extent to which the results of pharmacometric analyses may inform our regulatory decision on a drug submission.
  4. When using pharmacometric methods to support a drug submission or CTA, sponsors should conduct benefit-risk assessments to the same regulatory standards as for submissions supported by conventional clinical trial data. We will perform a thorough evaluation of the drug submission or CTA before making a decision.

Considerations for sponsors

Sponsors should consider these factors when filing drug submissions or CTAs that use pharmacometric approaches:

  1. To facilitate the review of submissions at Health Canada that rely heavily on novel pharmacometric approaches or methods, sponsors are encouraged to seek advice from the relevant Directorate.
  2. The sponsor should provide a scientific rationale that clearly describes and justifies the purpose and extent of the pharmacometric approaches in their submission. This rationale should make clear linkages to relevant parts of the drug submission or CTA, such as:
    • label claims
    • suggested study design
    • product quality evaluation
  3. Drug submissions and CTAs that use pharmacometric analyses must meet the requirements of the Food and Drug Regulations. We require full Canadian data packages in accordance with the regulations and related Health Canada guidance documents. The sponsor's comprehensive benefit-risk assessments should describe the limitations of the pharmacometric analysis. This includes any potential impacts the analysis may have on the reliability of related claims and conclusions.
  4. The sponsor should provide the pharmacometric study reports at the time of filing the full data package. These reports should include sufficient details about the:
    • objectives
    • methodology
    • software platform and versions
    • model development and evaluation
    • applications and limitations of the pharmacometric approaches used
    • pharmacometric analyses including the:
      • dataset(s)
      • sources of data
      • programming codes

Health Canada will hold confidential business information filed in drug submissions or CTAs in the strictest confidence. Canadian Data Packages will be subject to the requirements of the Public Release of Clinical Information: Guidance Document. However, the pharmacometric data will remain confidential.

Contact us

Drug-submission process of pharmaceutical drugs

Regulatory Project Management Division
Office of Planning, Performance and Review Services
Therapeutic Products Directorate (TPD)
Health Products and Food Branch
Health Canada
Finance Building, Address Locator: 0202D
101 Tunney's Pasture Driveway
Tunney's Pasture
Ottawa, Ontario K1A 0K9
Email: hc.rpmd-dgpr.sc@canada.ca

Scientific and technical questions about pharmacometric data in any pharmaceutical drug submissions

Office of Science
Bureau of Policy, Science, and International Programs
Therapeutic Products Directorate (TPD)
Health Products and Food Branch
Health Canada
1600 Scott St., Address Locator: 3102C
Ottawa, Ontario K1A 0K9
Email: hc.tpd.biostats.enquiries-dpt.biostats.renseignements.sc@canada.ca

Use of pharmacometric data in any CTA for pharmaceutical drugs

Office of Clinical Trials
Therapeutic Products Directorate (TPD)
Health Products and Food Branch
Health Canada
Address Locator: 3105A
Ottawa, Ontario K1A 0K9
E-mail: hc.oct.enquiries-requetes.bec.sc@canada.ca

Use of pharmacometric data in any drug submission or CTA for biologic drugs or radiopharmaceuticals

Office of Regulatory Affairs
Biologic and Radiopharmaceutical Drugs Directorate (BRDD)
Health Products and Food Branch
Health Canada
Building 6, Address Locator: 0601B
100 Eglantine Driveway
Tunney's Pasture
Ottawa, Ontario K1A 0K9
Email: hc.bgtd.ora.sc@canada.ca

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