Submitting risk management plans guidance document: Definitions

The definitions and terminology consider documents prepared by Health Canada and other regulators, such as the European Medicines Agency (EMA).

Brand name:

With reference to a drug, the name, whether or not including the name of any manufacturer, corporation, partnership or individual, in English or French:

• that is assigned to the drug by its manufacturer
• under which the drug is sold or advertised and
• that is used to distinguish the drug

Existing risk management plan:

The most recent risk management plan that is provided to the Minister by a manufacturer and found to be acceptable.

Identified risks:

Untoward occurrences or undesirable clinical outcomes for which there is sufficient scientific evidence to show they are caused by the drug.

“Important identified risks” are identified risks that are likely to impact the benefit-risk balance of the drug or have implications for public health. Important identified risks included in the RMP usually require measures to prevent, reduce or further characterize them.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH):

A joint regulatory-industry initiative for the international harmonization of regulatory requirements for drugs. The parties in ICH represent the regulatory bodies and research-based industry in 3 regions: North America, Europe and Japan. Most new medicines are developed in these regions.

ICH E2E:

An ICH guidance that helps plan pharmacovigilance activities, especially in preparation for the early post-marketing period of a new drug. It focuses primarily on specific aspects of a safety specification and pharmacovigilance plan that sponsors/MAHs may submit when they apply for market authorization.

Label:

Includes any legend, word or mark attached to, included in, belonging to or accompanying any drug.

Medication error:

Any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care provider, patient or consumer. These may be related to professional practice, drug products, procedures and systems. They may also include errors in relation to:

• prescribing
• communicating orders
• product labelling, packaging and nomenclature
• compounding
• dispensing
• distribution
• administration
• education
• monitoring
• use

Missing information:

Information on the safety of the drug that may:

• have a likely impact on its benefit-risk balance or
• have implications for public health
• be missing and needs to be collected and further characterized
• include gaps in knowledge about its safety
  • for example, gaps in particular patient populations or for certain anticipated uses

New active substance (NAS):

A new drug (pharmaceutical or biologic) that:

• contains a medicinal ingredient not previously approved in a drug in Canada
• is not a variation of a previously approved medicinal ingredient

Note: “Approved” means for human or veterinary use.

Periodic Benefit-Risk Evaluation Report (PBRER):

A pharmacovigilance document that provides a comprehensive, concise and critical analysis of new or emerging information on the risks of the drug and its benefit in approved indications. Health Canada uses the PBRER to appraise the drug's overall benefit-risk profile.

As per the updated ICH E2C(R2) guidance, Periodic Safety Update Reports (PSURs) for marketed drugs are used to evaluate safety, benefits and risks, as well as all relevant available information accessible to sponsors/MAHs.

Periodic Safety Update Report (PSUR):

Sponsors/MAHs use the PSUR to summarize interval safety data and conduct a systematic overall safety evaluation on a regular basis. As well as covering ongoing safety issues, the PSUR includes updates on:

• emerging or urgent safety issues
• major signal detection and evaluation

Pharmacovigilance:

The science and activities for detecting, assessing, understanding and preventing adverse events or any other drug-related problems.

“Routine pharmacovigilance measures” (or “activities”) are activities or methods that are sufficient for post-approval safety monitoring of drugs where there are no special concerns.

Examples include:

• monitoring the safety profile of the drug through signal detection activities
• preparing reports, such as PSURs, for regulatory authorities

“Additional pharmacovigilance measures” (or “activities”) are activities or methods that are used to address products with special safety concerns that cannot be sufficiently addressed by routine measures. These special safety concerns include the need for additional data to:

• better characterize risks or
• evaluate the effectiveness of additional risk minimization measures

Examples include safety studies or registries.

Potential risk:

Unexpected occurrences or undesirable clinical outcomes where scientific evidence indicates the possibility of a causal relationship with the drug and  there is not enough evidence to conclude the relationship is causal.

“Important potential risks” are potential risks that if further characterized and confirmed would impact the risk-benefit balance of the drug or have implications for public health. Such risks included in the RMP would usually require further evaluation as part of the pharmacovigilance plan.

Reference RMP:

A sponsor/MAH’s company core RMP or EU-RMP that contains the essential elements of a risk management plan, which may be supplemented with a Canadian-specific addendum. This should not be confused with an RMP for a reference product used in a biosimilar or generic submission or application.

Risk management plan (RMP):

A document that describes:

• a set of pharmacovigilance measures and interventions to identify and characterize risks associated with the drug and to prevent or reduce those risks and address uncertainties and
• the assessment of the effectiveness of those interventions

Risk minimization measures (or “activities”):

Interventions that:

• prevent or reduce the occurrence of adverse reactions associated with the exposure to a drug or
• reduce their severity or impact on the patient should adverse reactions occur

“Routine risk minimization measures” (or “activities”) are those that apply to all drugs.

Examples include information on risks minimization in the Canadian Product Monograph, patient medication information and limitations on package size.

“Additional risk minimization measures” (or “activities”) are beyond routine risk minimization measures and are needed to:

• prevent or reduce the probability of an undesirable outcome or
• reduce its severity should it occur

Examples include controlled access or distribution programs or educational programs.

Risk minimization tools (RMTs):

Documents or materials used in the implementation of the additional risk minimization measures. Examples include:

• educational materials (such as health care professional guides or checklists, patient guides, patient cards)
• communications tools used in direct health care professional communications
• tools, documents and materials used in a pregnancy prevention program or a controlled access or distribution program

Safety specification:

A detailed description of important identified risks, important potential risks and missing information relating to the safety of a drug. The safety specification should address:

• the populations potentially at risk (where the drug is likely to be used) and
• outstanding safety questions that warrant further investigation to refine understanding of the benefit-risk profile during the post-authorization period

Serious adverse drug reaction:

A noxious and unintended response to a drug that occurs at any dose and:

• requires in-patient hospitalization or prolongation of existing hospitalization
• causes congenital malformation
• results in persistent or significant disability or incapacity
• is life-threatening or
• results in death