Handbook for health care professionals on biosimilar biologic drugs: Monitoring safety and effectiveness

On this page

• The risk management plan
• Updating labelling information
• Identifying biosimilars in prescribing, dispensing and ADR reporting
• Health care professionals and pharmacovigilance

The risk management plan

Health Canada monitors the safety of all drugs on the market, including biosimilars, by:

• conducting market surveillance
• monitoring adverse reaction reports
• investigating complaints and reports of problems
• monitoring actions taken by other regulators, such as the:
  • Food and Drug Administration (FDA)
  • European Medicines Agency (EMA)

Each manufacturer must comply with requirements to enhance drug safety, including:

• setting up a system to monitor reported adverse reactions
• periodically reassessing whether the drug's benefits outweigh its risks
• notifying Health Canada about new safety information
• reporting new information received about serious adverse reactions to Health Canada
• submitting a risk management plan (RMP) as part of the application for authorization
• requesting authorization and providing clinical data to support any major changes to the:
  • dosage regimen
  • manufacturing process
  • recommended uses of the drug
  • labelling for use in special populations (for example, pregnancy)
  • safety or efficacy profile

As part of the authorization process, Health Canada asks manufacturers to submit and maintain an RMP for all biologic drugs, including biosimilars. RMPs outline activities that drug manufacturers must carry out to monitor and detect potential safety signals following market authorization.

The RMP should:

• consider all identified and potential risks associated with the use of the reference biologic drug
• provide details on how these risks will be addressed in a post-market setting

The RMP of a biosimilar generally includes monitoring and risk minimization activities that are similar to those in place for its reference biologic drug. Health Canada works with manufacturers to ensure they develop a suitable RMP before we authorize the biosimilar. The surveillance criteria for the biosimilar should:

• be described in accordance with requirements for any new biologic drug
• include detailed information on how the immunogenicity potential of the biosimilar will be monitored once it is in clinical use

A biosimilar's RMP should include:

• specific (routine or additional) pharmacovigilance and risk minimization activities similar to those in place for its reference biologic drug
  • activities that are not relevant for the biosimilar should include a justification
• a discussion about methods to distinguish adverse event reports for the biosimilar from those for other licensed products, including the reference biologic drug

The RMP should be maintained and implemented throughout the lifecycle of the product.

Adverse drug reaction (ADR) reporting is required following authorization under section C.01.016 of the Food and Drug Regulations. The manufacturer must conduct a concise, critical analysis of ADRs and serious ADRs every year or as requested by Health Canada.

Manufacturers must also prepare and submit periodic safety update reports (PSUR) or benefit-risk evaluation reports from time to time. These reports must be consistent with the appropriate guidelines for marketed products issued by the International Council on Harmonization of Technical Requirements for Pharmaceuticals for Human Use.

We can compel drug manufacturers to do additional tests and studies at any time if there are significant uncertainties relating to the benefits or harms associated with a drug.

Updating labelling information

All manufacturers must:

• monitor the post-market safety profile of their own product
• make safety updates to the biosimilar product monograph (PM) as appropriate

This ensures that the PM stays up to date and supports effective and safe conditions of use. At the time of authorization, the safety information in the PM for a biosimilar is based on information in the reference biologic drug's PM. However, once authorized, a biosimilar is considered a standalone product.

A biosimilar and its reference biologic drug are not identical and are manufactured by independent processes. As such, newly identified safety issues that affect the reference biologic drug may or may not affect the biosimilar, and vice versa. Therefore, manufacturers should also:

• monitor the Canadian reference biologic drug's PM
• assess any updates
• reflect any updates in the PM for the biosimilar

Health Canada may ask manufacturers of both the reference biologic drug and the biosimilar to update their PMs if there is a new safety issue related to that drug type or class.

Health Canada requests that all biosimilar manufacturers, as appropriate, assess the need to update their PMs when:

• a safety update is made to the Canadian PM of:
  • a reference biologic drug
  • another biosimilar to the same reference biologic drug or
  • any other drug with shared medicinal ingredients
• there is a chance of a drug class effect

Identifying biosimilars in prescribing, dispensing and ADR reporting

All biologic drugs authorized by Health Canada will have a:

• unique brand name
• unique drug identification number (DIN)
• non-proprietary (common/proper) name of the medicinal ingredient

To help ensure effective post-market monitoring and surveillance, the specific biosimilar product should be clearly identified when:

• prescribing
• dispensing
• reporting an ADR

This is particularly important as numerous biosimilars enter the market and there are more biologic drugs with the same non-proprietary name.

The naming convention for biologic drugs, including biosimilars, consists of a unique brand name (such as Grastofil) and the non-proprietary (common or proper name, such as filgrastim). This non-proprietary name is generally the international non-proprietary name (INN) that the World Health Organization (WHO) assigns to the medicinal ingredient.

Biosimilars share the same non-proprietary name as their reference biologic drug. However, they are distinguished by their unique brand names and other product-specific identifiers, such as the drug identification number (DIN).

To help identify products and avoid product dispensing errors for biologic drugs, including biosimilars, Health Canada recommends that health care professionals use throughout the medication process:

• unique brand names
• non-proprietary names
• other product-specific identifiers, such as the DIN and lot number

Product-specific identifiers should be included in ADR reports to help us trace an adverse reaction to a specific suspect drug product.

Learn more about our:

• Policy statement on the naming of biologic drugs

Health care professionals and pharmacovigilance

Health care professionals play a key role in pharmacovigilance of drugs, including biosimilars. Observing and reporting a patient's response to a drug is key to understanding the drug's safety profile once it moves past the clinical trial stage and into clinical use.

To help in the assessment of association between adverse reaction reports with a particular health product, adverse reaction reports require:

• patient information, including age, sex, co-morbidities
• name of the health product, including brand name and lot number, if available
• description of the adverse reaction, including date of onset and resolution
• date when the health product was started and stopped
• date the adverse reaction started
• other health products taken
• patient's pertinent past therapies and medical conditions
• results of relevant lab tests, imaging or other investigations, if available
• if the person reporting the adverse reaction believes it is due to the drug product
• contact information of the person reporting

Health care professionals should report serious adverse reactions in accordance with the following guides:

• Adverse reaction reporting and health product safety information - Guide for health professionals
• Mandatory reporting of serious adverse drug reactions and medical device incidents by hospitals

Medication incident reports are another important source of information on the safety of a health product.

Medication incidents should be reported to the Canadian medication incident reporting and prevention system (CMIRPS) under the How do I report tab.

Health Canada uses the information gathered through CMIRPS as part of our ongoing activities to monitor and improve the safety of medications and other health products in Canada. We analyze medication incident reports to reduce and prevent the occurrence of medication incidents related to health product names, packages and labels.

By reporting an adverse reaction to Health Canada, health care professionals can help us:

• identify rare or serious adverse reactions that were previously unknown
• contribute to international data on the benefits and risks of health products
• make changes to product safety information or remove an unsafe product from the Canadian market
• develop and disseminate new and better information to enhance people's knowledge about the safety of health products

Health care professionals can help improve pharmacovigilance for biosimilars by ensuring that key pieces of information are tracked in the prescribing and dispensing of biosimilar drugs and provided in all ADR reports. In particular, they should:

• record the medicine's brand name and non-proprietary name at all levels, from prescribing to dispensing (including any switches from 1 biologic drug to another) and patient administration
• record the lot number whenever possible
• report the brand name and lot number in case of a suspected adverse drug reaction

In some cases, health care professionals may have to work closely with patients to collect and record pharmacovigilance information.