Draft guidance on notifying Health Canada of foreign actions

On this page

• Purpose
• Background
• Scope and application
• Interpretation
• How to report
• Contact us
• Note about guidance documents in general

Purpose

This guidance document:

• outlines the requirements for notifying Health Canada of foreign regulatory actions, as set out in sections C.01.050 (2)(a), (b) and (c) and C.01.050 (3) of the Food and Drug Regulations
• helps market authorization holders (MAH) comply with the requirements

Many drugs may be marketed years in advance or in higher volume in other countries. For this reason, important safety signals are often detected earlier in a foreign jurisdiction.

The foreign notification provisions make it possible for us to know early on about regulatory actions taken in foreign jurisdictions.

With this knowledge, we can:

• better identify and assess risks to people in Canada throughout the life cycle of drug products and
• take appropriate action to mitigate those risks when warranted

We may seek further information about a regulatory action if necessary, including from MAHs.

Background

The regulation to notify us of foreign regulatory actions aims to put into operation certain safety provisions of the Protecting Canadians from Unsafe Drugs Act (also known as Vanessa's Law). This act received Royal Assent on November 6, 2014.

The regulations to which this guidance applies were published in the Canada Gazette, Part II on May 2, 2018.

The World Health Organization (WHO) describes pharmacovigilance as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug related problem. This activity takes place over the life of a drug, before, during and after marketing.

MAHs are responsible for the safety of their products throughout their life cycle and must comply with all Canadian legislative and regulatory requirements.

The management of safety signals is part of routine pharmacovigilance and is essential to ensuring that manufacturers and regulatory authorities have the most up-to-date information on a drug.

For MAHs, good pharmacovigilance practices involve:

• monitoring, detecting and managing safety signals
• analyzing or assessing signals that may indicate significant changes in a drug's benefits and risks (its risk-benefit profile)
• taking any follow-up actions that may be needed, based on the outcome of the assessment
• notifying us as required by regulation, for example, of actions that involve a label change or a recall in Canada
• preparing summary reports of periodic (for example, annual) analysis of safety information and reporting significant changes to us
• updating risk management plans (RMP) as needed

For information on implementation including personnel, training and other good vigilance practices, consult:

• Good vigilance practices (GVP) guidelines (GUI-0102)

For information on preparing summary reports, consult

• Guidance on preparing and submitting summary reports for marketed drugs and natural health products

For information on updating an RMP, consult:

• Submitting risk management plans guidance document

For information on reporting recalls in Canada, consult:

• Guidance: Drug, natural health product and biocide recall guide (GUI-0039) - Canada.ca

Scope and application

The requirement to notify us of foreign regulatory actions applies to 3 classes of drugs to which a Drug Identification Number (DIN) (C.01.014.2 (1)) or a Notice Of Compliance (NOC) (C.08.004 or C.08.004.01) has been assigned, throughout their life cycle:

1. prescription drugs
2. drugs that are required to be sold under a prescription by Part G of the Food and Drug Regulations, the Benzodiazepines and Other Targeted Substances Regulations or the Narcotic Control Regulations
3. drugs that are permitted to be sold without a prescription but that are to be administered only under the supervision of a practitioner

The MAH is responsible for the notification of foreign actions under section C.01.050 of the Food and Drug Regulations for as long as they hold the market authorization of the drug.

The requirement applies to both human and veterinary drugs when a foreign action is taken in respect of a serious risk of injury to human health.

The requirement does not apply to drugs still under review for market authorization.

Visit the regulations for more information:

• Benzodiazepines and Other Targeted Substances Regulations
• Narcotic Control Regulations
• Food and Drug Regulations

Interpretation

This section gives detailed guidance of the requirement to notify us.

Foreign actions that require notification

MAHs must notify us within 72 hours after they receive or become aware of information that concerns the safety of a drug authorized in Canada that:

• presents a serious risk of injury to human health and
• is associated with certain specific actions taken in any of the specified foreign jurisdictions

If an action in respect of a serious risk of injury to human health arises from foreign good manufacturing practices (GMP) issue and affects a Canadian product, it is considered relevant.

For issues relating to toxicity or safety signals, actions related to similar ingredients or molecules to your product authorized in Canada must be reported.

An action that affects a reference product (Canadian or foreign) with the same active ingredient or biosimilar as the Canadian product is considered relevant.

The regulatory requirements in subsections C.01.050(2)(a), (b) and (c) only apply to foreign actions that have taken place, not foreign actions that are being considered.

Examples of types of information that relate to a serious risk in a specified foreign jurisdiction and are notifiable (with section of the regulations noted):

• A manufacturing issue that poses a serious risk of injury to human health and is communicated by the foreign regulatory authority or a manufacturer (C.01.050(2)(a)).
• Serious risks related to a new contraindication or warning and is communicated by the foreign regulatory authority or a manufacturer (C.01.050(2)(a)).
• Changes to a drug's labelling that are communicated to or requested by the foreign regulatory authority (C.01.050(2)(b)).
  • Examples include new dosages, indications, directions for use, warning statements, contraindications, interactions, changes to mitigate incorrect use.
• Recalls that have taken place within the jurisdiction of any foreign regulatory authority (C.01.050(2)(c)).
• Reassessments of market authorizations that resulted in new or additional risk mitigation measures for a drug or enhanced vigilance requirements (C.01.050(2)(c)).
  • Examples include changes to RMPs or risk evaluation and mitigation strategies.
• Suspending or revoking manufacturing authorizations (C.01.050(2)(c)).
  • For example, site licences.
• Suspending or revoking market authorizations (C.01.050(2)(c)).
  • For example, permission to sell.
• The foreign action speaks to a class effect and the drug being sold in Canada contains an ingredient in that class.

An issue may give rise to more than one notification as different actions are taken in response to it. For example, a serious risk of injury may lead to both a label change and a recall. In this case, the label change and the recall are each notifiable.

While it is normal for MAHs to discuss serious risks with regulatory authorities, such discussions do not always result in actions taken to mitigate them. A request for data from a regulatory authority does not need to be reported to us. We interpret C.01.050(2)(a) to include only communications taken to mitigate risks or identify them publicly. Examples include

• letters to health professionals or patient groups
• public warnings or advisories
• completed signal reviews or related information (such as a summary or key information) posted on regulatory web sites

We will:

• review the information provided by the MAH and
• work with them to ensure that follow-up actions to mitigate these risks are implemented in Canada, as needed

Where the MAH becomes aware of multiple jurisdictions taking the same action, they must only notify us of the earliest action. Once an MAH has notified us of an action taken in 1 country, they do not need to notify us of similar actions taken in other countries that:

• address the same issue and
• involve the same safety information

One notification is sufficient.

If different actions are taken in 2 different jurisdictions for the same issue, 2 separate notifications are required, each with their own submission sequence. Examples of actions that are different and must each be reported include:

• A warning is added to a label in 1 jurisdiction and a public advisory is issued in another jurisdiction instead to address the same issue.
• A recall is issued to the wholesale level in 1 jurisdiction and to the retail level in another jurisdiction.
• A warning is added to a label in 1 jurisdiction and another jurisdiction issues a recall on the same issue.

What is "serious risk"

Under the regulations, an MAH must notify us about certain actions taken by foreign regulatory authorities concerning a serious risk of injury to human health.

To determine whether a therapeutic product presents a serious risk of injury to human health, consult:

• Annex A to Guide to authorities under the Protecting Canadians from Unsafe Drugs Act (Vanessa's Law)

A qualified person for the MAH must determine if the risk meets this threshold. The qualified person should have, or should consult with someone who has, sufficient medical knowledge and appropriate training or experience.

For information on personnel and training, consult:

• Good pharmacovigilance practices (GVP) guidelines (GUI-0102)

MAHs should contact us if they are not sure if the seriousness of a risk meets the threshold for sharing information.

Quality-related issues requiring notification

Examples of quality-related issues that require notification:

• Equivalent to a Type I recall in Canada, a prescription drug is recalled in another jurisdiction because using or being exposed to it may cause serious adverse health consequences or death.
• Another regulatory authority issues a safety notice about a prescription drug because a violation of GMP could cause a serious adverse health problem.
• The regulatory authority in another country suspends a manufacturer's licence for a non-prescription drug that's administered under healthcare professional supervision because a critical deficiency in good manufacturing practice poses a serious risk of injury to human health.

Safety-related issues requiring notification

Examples of safety-related issues requiring notification:

• Another country's regulatory authority issues a public warning about a prescription drug after learning about a serious new safety issue when users take the drug along with certain foods.
• In another jurisdiction, the label of a generic medication has been changed to include warnings about serious health effects in children under the age of 12.
• Another country's regulatory authority revokes a licence of a prescription drug when a rare but serious adverse reaction is discovered after many years on the market.
• A public safety communication is issued about serious human health risks from accidental self-injection of a drug during administration to an animal.
• The warnings section of the label of a veterinary topical product is updated to mitigate serious human health risks when it's administered to animals.
• Another country's regulatory authority suspends a drug's marketing authorization pending a safety assessment of its risk profile due to its frequent off-label use.

Foreign regulatory authorities covered under the requirements

The regulatory requirement only applies to those countries that appear in the three-part list of foreign regulatory authorities. This list is incorporated by reference in the Food and Drug Regulations.

However, you may notify us of actions taken in a country not listed to address serious risk. This information is valuable to us for safety monitoring purposes.

Information that should be included

To comply with the regulations, MAHs should provide the:

• name and contact information of the holder of the Canadian market authorization and the Canadian importer, if different
• brand name(s) and DIN(s) of their relevant Canadian drug(s)
• brand name of the foreign drug
• name of the authorization holder in the foreign jurisdiction
• lot number(s) and expiration date(s) of the relevant Canadian drug(s), if applicable and known
• foreign regulatory authority or foreign jurisdiction involved in the action
• information or event that triggered the action
  • for example, a report from the foreign regulator
• detailed information on the action taken by the foreign regulatory authority or by the MAH in the foreign jurisdiction
  • for example, include information on whether the action was communicated, and if so, how (we may ask for copies of these documents later)
• foreign site where the issue took place (if different from the manufacturing site)
• reasons (or information about those reasons) for the action
  • for example, product quality, GMP versus product safety, adverse reaction, unsafe use

MAHs should also:

• perform relevant signal management activities
• describe how the issue that resulted in foreign action is relevant to the safety of the drug authorized in Canada
• list the actions they took in Canada following the serious safety issue
• describe in detail follow-up actions they intend to take, and when, in Canada, such as:
  • submit a supplement to a new drug submission (SNDS) to update the Canadian product monograph
  • submit an updated RMP
  • issue a risk communication
  • withdraw the drug from the market
  • recall relevant lots of the drug from the market and submit a recall notification
• provide a rationale for the follow-up actions you have taken or intend to take in Canada
• provide a rationale if they decide not to take further action in Canada

MAHs who do not make a decision about follow-up actions in Canada before the 72-hour deadline:

• must still report the foreign action before the deadline
• should indicate in their report that they have not yet decided on which follow-up actions to take in Canada
• should send an update promptly, once they make a decision to take a follow-up action in Canada
• should report follow-up actions in Canada and their results, as appropriate, without delay

We will follow up if we need more information.

How to report

To report foreign actions involving:

• safety signals or toxicity
• adverse reactions
• unsafe use

from human pharmaceutical or biologic drugs or veterinary pharmaceutical drugs, use this PDF form. For information on how to submit the form via the Electronic Submissions Gateway (ESG) and how to report follow-up actions or information, consult

• Management of post-market vigilance submissions guidance document

To report foreign actions involving:

• GMP or manufacturing issues
• product specific quality issue
• a product recall

from either human or veterinary drugs, use this online form.

Language of notification reports

Notification reports must be in either English or French.

Other documents such as recall notices and risk communications relating to the issue are not required by regulation. If we request them, they may be provided in their existing language.

Monitoring foreign regulatory actions

Environmental scanning is a fundamental element of safety monitoring.

MAHs are expected to collect safety information in ways that promote compliance with this regulation. This could include communicating regularly and often with their affiliates operating in the specified foreign jurisdictions. Communication could involve:

• ensuring the local affiliates make their global head office aware of the types of issues and products referred to in the regulation
• determining the relevance of the actions to products sold in Canada

MAHs that are not affiliated with foreign companies are expected to:

• monitor safety issues and adverse events by conducting pharmacovigilance activities
• monitor information sources from listed authorities for relevant activities (for example, communication of risks, changes to labelling, recalls)
• screen for information that helps when assessing the seriousness of the risk to human health and
• determine relevance to prescription or non-prescription drugs that they sell in Canada and are administered under the supervision of a practitioner

Environmental scanning for relevant safety information is part of routine vigilance. It should be conducted regularly and documented. The timing, frequency and nature of scanning depend on such factors as the product's risk profile, known or specific emerging issues and the scheduling of the summary report.

Identified and potential safety issues, as well as knowledge gaps (for example, toxicity in vulnerable groups, interactions with other products, emergent use patterns) may require more active monitoring.

Training records for qualified people should be documented and the training process described in a way that would enable internal and regulatory auditing.

The documented process should also include an assessment of whether the risk to human health meets the threshold for notifying us.

Authorization holders of generic or biosimilar products may be required to file submissions in Canada to update their labelling if there are labelling changes to their reference product.

Learn more:

• Guidance on preparing and submitting summary reports for marketed drugs and natural health products
• Notifying safety labelling changes to the product monographs of pharmaceutical drugs
• Good pharmacovigilance practices guidelines (GUI-0102)

Monitoring and assessing compliance

Documentation for receiving, assessing and reporting foreign regulatory actions is critical to show MAHs are complying with the regulations.

Documentation could include, for example:

• relevant quality documents, such as standard operating procedures or contractual agreements
• operational records that show information received and assessed, decisions and actions taken

An automatic confirmation will be issued once the information has been submitted, which the MAH may maintain.

• For notifications submitted using the PDF form, an automatic confirmation will be generated by the system.
• For notifications submitted through the online form, an automatic confirmation will be sent by email.

We may:

• assess the ability to monitor and assess foreign regulatory actions during an inspection
• verify compliance with these regulations by reviewing incoming reports against information we gather through other means, such as:
  • agreements with foreign regulatory authorities
  • our own environmental scans

For more information, consult:

• Good pharmacovigilance practices (GVP) guidelines (GUI-0102)

Information reports and public accessibility

Information submitted to us is subject to the Privacy Act.

These reports supplement existing regulatory monitoring. As such, they will be handled and shared according to the provisions in place for the results of safety reviews and establishment licensing decisions. These include:

• regulatory transparency and openness
• safety reviews
• powers to require and disclose information

Contact us

Reports should be submitted using the appropriate PDF or online forms.

Contact us if there are issues relating to this guidance as follows:

• Safety signals or toxicity, adverse reactions or unsafe use of human pharmaceuticals (non-biologic): mpb.rpm-gpr.bppc@hc-sc.gc.ca
• Safety signals or toxicity, adverse reactions or unsafe use of human biologics: bbrs.rpm-gpr.bbra@hc-sc.gc.ca
• Safety signals or toxicity, adverse reactions or unsafe use of veterinary drugs: pv-vet@hc-sc.gc.ca
• GMP and manufacturing issues: foreign.site-etranger@hc-sc.ca.ca
• Product specific quality issue and recalls: hpce-cpsal@hc-sc.gc.ca

For inquiries about this guidance document, include the phrase "Guidance on notifying Health Canada of foreign actions" in the subject line. Submit your request by email: mhpdpolicy-politiquesdpsc@hc-sc.gc.ca.

Note about guidance documents in general

Guidance documents provide assistance to industry and health care professionals on how to comply with governing statutes and regulations. They also provide guidance to Health Canada staff on how mandates and objectives should be met fairly, consistently and effectively.

Guidance documents are administrative, not legal, instruments. This means that flexibility can be applied. However, to be acceptable, alternate approaches to the principles and practices described in this document may be acceptable provided they are supported by adequate justification. They should be discussed in advance with the relevant program area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.

As always, Health Canada reserves the right to request information or material, or define conditions not specifically described in this document, to help us adequately assess the safety, efficacy or quality of a therapeutic product. We are committed to ensuring that such requests are justifiable and that decisions are clearly documented.

This document should be read along with the relevant sections of other applicable guidance documents.