Guidance for industry on safety monitoring and reporting requirements for marketed biocides: Safety monitoring

On this page

• Overview
• Effective and timely detection of issues
• Information to compile
• Review of safety information and incidents
• Significant safety issues
• Notifying Health Canada of significant safety issues
• Requests for information

Overview

Safety monitoring, outlined under section 40 of the Biocides Regulations (regulations), refers to the requirement for you to:

• monitor the safety of your marketed biocide in a manner that reliably allows you to detect significant safety issues that emerge as a result of real-world use
• notify us, without delay, of any significant safety issues that have been detected

Effective and timely detection of issues

The regulations specify that you must compile and review information that you become aware of involving your biocide in a manner that ensures the effective and timely detection of significant safety issues. This means that you must have systems and procedures in place to ensure that this can be done.

Systems and procedures

Safety monitoring includes an expectation that you have systems and procedures in place to compile and review the information collected. The design of the systems and procedures, their form, execution and maintenance are at your discretion. However, you must ensure that your systems and procedures are adequate so you can consistently meet your obligations under the regulations.

You should:

• ensure that your systems and procedures are implemented as designed
• review procedures from time to time to ensure they remain current and reflect the current practices (such as your internal practices, industry standards)
• have independent internal or external personnel audit the systems and procedures to ensure they are followed and are effective
• improve the collection and review of information when and if the systems and procedures fail to detect significant safety issues associated with the biocide

Documentation

You should document your safety monitoring activities and your systems and procedures. Such documentation should be maintained in a manner that is sufficient to demonstrate compliance with regulatory requirements.

Documentation of safety monitoring systems and procedures can include as applicable:

• written procedures
• contractual agreements
• a description of the system and how it operates
• training standards or programs and their records

You should keep documentation in a format that can be provided to us, upon request. However, the form and manner of the documentation is at your discretion.

Qualified individual in charge

You are responsible for:

• safety monitoring
• ensuring that individuals undertaking safety monitoring activities are duly trained to conduct these activities as described in your systems and procedures

Safety monitoring activities should be conducted under the supervision of a qualified individual. The person should be qualified through a combination of relevant factors such as:

• education, such as a recognized university degree in a relevant field of study
• training relevant to their assigned responsibilities or
• practical experience related to their assigned responsibilities

This individual should also have knowledge of all applicable sections of the regulations related to safety monitoring and serious incident reporting requirements. They should also understand the key activities that are performed as part of your safety monitoring systems and procedures.

The qualified individual in charge should be responsible for:

• creating and maintaining the safety monitoring systems and procedures
• ensuring that safety monitoring activities are in accordance with those systems and procedures
• training and supervising additional qualified individuals undertaking safety monitoring activities, if applicable

Information to compile

You must:

• compile information to detect significant safety issues associated with your biocide
• document the information compiled
• document the source of the information

What to compile

You must compile, review and document safety information relating to incidents, both domestic and foreign, relevant to your biocide, including:

• notable incidents
• serious incidents, including those that are unexpected

For foreign incidents, you should monitor information concerning your own foreign equivalent products that are also marketed in Canada with the same combination of active ingredients, regardless of variations in the:

• physical form
• conditions of use
• method of application
• formulation, including variations in formulants

You must also compile, review and document relevant information about actions that have been taken outside of Canada to address significant safety issues.

Find more information on the review of safety information and incidents in the following sub-sections.

Notable incidents

The regulations define notable incidents to include both:

• a response to a biocide that adversely affects human health or
• failures in effectiveness that could have resulted in serious harm to a person

Health Canada interprets a response that adversely affects human health to be very wide in scope. It can include any minor response that a person may experience associated with the use of the biocide, such as:

• burns
• rashes
• coughing
• feeling faint
• burning eyes
• difficulty breathing

You must compile and document all notable incidents that you become aware of as part of your safety monitoring activities.

Serious incidents and serious unexpected incidents

Serious incidents and serious unexpected incidents are defined in the regulations.

A serious incident includes a response to a biocide, or a failure in the effectiveness of a biocide, that results in one of the following:

• in-patient hospitalization or prolonged hospitalization
• chronic or significant disability or incapacity
• congenital malformation
• a life-threatening event
• death

A serious unexpected incident includes serious incidents that have not been identified in nature, severity or frequency in the risk information set out on the Canadian label of the biocide.

You must compile, review and document all serious (expected and unexpected) domestic incidents and serious unexpected foreign incidents that you become aware of as part of your safety monitoring activities. You must also report any serious incident that occurs in Canada and any serious unexpected incident that occurs outside Canada under the serious incident reporting requirements.

User error, misuse, accidental exposure and occupational exposure

A serious or notable incident is not limited in scope to incidents that occur in accordance with the directions of use. You must compile both notable and serious incidents resulting from user error and misuse of a biocide, and accidental exposure and occupational exposure to a biocide, where the response to a biocide adversely affects human health.

User error and misuse include instances where:

• multiple products were mixed
• safety statements on the label were not followed
• directions for use on the label were not read, properly understood or purposely not followed
• the product was used improperly, unforeseeably or not as intended despite the presence of proper use instructions or warnings

Accidental exposure includes instances where there is an unintentional and unexpected outcome resulting from the use of the biocide. Examples of accidental exposure include:

• spills
• splashes
• inhalation

Occupational exposure includes the chronic, acute or accidental exposure to a biocide product during the normal course of one's occupation and results in serious risk to human health.

Failure in effectiveness

A failure in effectiveness has occurred when the expected performance of the biocide has substantially failed. In other words, the anticipated effect of the biocide on the targeted microorganism:

• did not occur or
• did not meet the threshold established to obtain the labelled claim per the market authorization

Failure in effectiveness is included in the definitions of both notable incidents and serious incidents:

• A failure in effectiveness is a serious incident when serious harm to a person occurred as a result of the failure.
• A failure in effectiveness is a notable incident when serious harm to a person could have occurred or could occur if the failure were to recur.

You are responsible for validating the information received and its relationship to the reported outcome of the failure in effectiveness. If you cannot confirm the validity of the information immediately, you should collect information, where possible, to determine if there has been a:

• substantial failure
• plausible causal link between the substantial failure and the illness or disease:
  • contracted for a serious incident or
  • that could have been contracted for a notable incident

If you do not suspect the information is linked to the harm, it may not be reasonable to conclude that a failure in effectiveness has occurred. However, you should retain this information for potential review should similar information become available in the future.

For example, to validate the information received, you may consider:

• evidence of effectiveness of a suspected lot or batch
• the performance of the biocide, such as through laboratory testing under approved conditions of use or through chemical analysis
• whether other similar reports have been received for the product, relative to the amount of product sold
• the seriousness of the harm or potential harm
• how the product was used

Foreign regulatory measures

You must compile and review information on measures taken in foreign jurisdictions to mitigate a significant safety issue for all your biocide products authorized for sale in Canada that are sold in foreign jurisdictions. These can be measures taken by foreign regulatory authorities or measures taken by manufacturers, importers or authorization holders in the foreign jurisdiction for the purpose of mitigating a serious injury to human health.

Note: For products authorized under the Use of Foreign Decisions pathway, paragraph 27(1)(e) of the Biocides Regulations requires that you notify us without delay if the foreign biocide has been recalled or the authorization to sell the foreign biocide has been suspended or revoked. Paragraph 27(1)(f) requires that you provide us with a description and, if known, the reasons for a change required by a foreign regulatory authority with respect to the foreign biocide.

How to compile

You may receive information directly or become aware of relevant safety information or incidents from a variety of sources. For example:

• consumer complaints
• studies conducted by you or the manufacturer
• health professional communications, Health Canada-issued public advisories or public communications
• problems reported directly to you, such as from hospitals, health care professionals or poison control centres

However, to ensure the effective and timely detection of significant safety issues regarding the safety of your biocide, you should scan additional sources for further information on the safety of your biocide. Reliable sources may include:

• local and international media reports, including social media
• actions or measures taken by other market authorization holders (MAHs) or manufacturers regarding similar products or products with the same active ingredients
• scientific or medical literature, including studies conducted by groups or persons not associated with you
• reports or communications from specific groups, such as poison control centres or patient support or disease management groups
• regulatory authority sources, such as measures taken by foreign regulators, expedited reporting databases of foreign jurisdictions and Health Canada's Canada Vigilance Database

Note: When searching the Canada Vigilance Database, you must search for all reported adverse events, including voluntary reports and reports submitted by hospitals. Serious adverse drug reaction reports from hospitals are considered serious incidents.

If you suspect that information for a product could be related to your biocide, but the information does not specify the product source, brand or trade name of the biocide, you should assume it was your own product. You should document that the specific brand was not identified.

You may also become aware of other safety information relating to the use of your biocide or its failure in effectiveness, such as:

• results of tests and studies conducted using laboratory animals
• trends in information on serious harms to animals that could result in serious unexpected harm or signal potential harm to humans

You should review and document all safety information compiled as part of your safety monitoring activities.

Scanning of safety information and incidents

You should conduct scanning activities to detect significant safety issues in a timely manner. Your qualified individual should use their professional judgment to determine the appropriate timing, frequency, scope and method of any scanning activities based on factors such as:

• the safety profile of your product
• any known or specific emergent issues

Sources of information that may provide a higher potential for identifying relevant safety information or incidents for your biocide should be scanned more frequently. These include:

• poison control centres
• the Canada Vigilance Database
• information published by foreign regulatory authorities and other international and intergovernmental agencies

The sources and types of information sought should reflect the approved conditions of use of the biocide, which include:

• its intended uses or purposes
• the settings in which it is intended to be used
• its risk information
• the directions for use
• the directions for storage

For example, when monitoring for failure in effectiveness, you should prioritize higher-risk settings such as hospital or long-term care settings or commercial food premises for which your biocide has been approved. In these settings there may be an increased risk in the spread of microorganisms or a substantial failure of the biocide that could lead to serious harm.

Your rationale for the timing, frequency, scope and method of the scanning activities should be based on a logical link with the risks and uncertainties of your product and should consider:

• frequency of environmental scanning and whether any new safety information has been identified
• the length of time the frequency for scanning has been in place without new safety information
• the sources consulted (such as databases, websites) and the search parameters
• how you propose to identify any significant safety issue if one arises

Review of safety information and incidents

The systems and procedures that you have in place must include provisions for reviewing compiled information. Such a review would be used to identify, in a timely manner, significant safety issues that you may not already know.

The review of safety information and incidents should occur after or concurrently with the compilation of information. This is to ensure that all the safety information and incidents related to significant safety issues are considered together.

Your qualified individual should use their professional judgment to determine the appropriate timing, frequency and method for reviewing compiled safety information to adequately detect significant safety issues in a timely manner.

Your rationale for the timing, frequency and method of the safety review should be based on a logical link with the risks and uncertainties of your product and should consider:

• your product's safety profile
• known or specific emergent issues
• shifts in consumer use patterns
• timing and frequency of previous review activities
• timing and frequency of scanning activities for safety information and incidents
• new safety information identified in previous reviews
• indication for a need to increase frequency of review of safety information based on results of previous reviews
• whether follow-up reviews are required based on previous findings

Significant safety issues

A significant safety issue is one that you have detected through your safety monitoring activities. The significant safety issue can be detected as a result of a single piece of information that has come to your attention. It could also be an accumulation of information, from various sources, that when examined together, result in the detection of the significant safety issue.

How to determine a significant safety issue

A significant safety issue is more than just a possible issue. You must evaluate the safety issue detected and examine how it relates to the risks and benefits of your biocide.

Issues related to the failed effectiveness of the biocide are considered significant safety issues when serious harm to a person or serious injury to human health has occurred or could occur as a result.

The significance of the safety issue relates to whether the safety issue detected reveals new information that could have bearing on the terms of the market authorization, and therefore may warrant further consideration.

You should validate the safety issue detected. Your qualified individual should:

• review the safety issue that's been detected using objective evidence
• apply their professional judgment to review, evaluate and validate the information to determine if a significant safety issue exists

You should document your review activities, including your findings and any decisions made regarding the significance and validation of potential safety issues.

Trends and accumulation of information

You may detect a significant safety issue related to your biocide following a review of trends noted in a range of safety information. Or, you may decide there is a significant safety issue after evaluating an accumulation of information.

During your review, you may also detect a series of similar incidents. On their own, these do not constitute a safety issue, but together they suggest there may be a significant safety issue.

Safety information that inherently represents a significant safety issue

In the course of your safety monitoring activities, you may become aware of information that itself represents a significant safety issue. In these instances, a significant safety issue can be determined based on 1 piece of information or 1 incident.

For the purposes of your safety monitoring, you should consider the following types of safety issues to be significant:

• foreign regulatory measures in response to a safety signal or issue
• notable incidents of validated failure in effectiveness

Foreign regulatory actions in response to a safety signal or issue

You should consider regulatory measures by foreign regulatory authorities, manufacturers, importers or market authorization holders to mitigate a serious injury to human health as significant. Examples include:

• recalls
• public risk communications
• reassessments of an authorization
• suspensions or revocations of an authorization
• labelling changes that have been communicated to or requested by a relevant foreign regulatory authority

These regulatory measures are only significant and notifiable if they:

• relate to a safety issue associated with a biocide authorized for sale in Canada and
• are taken to mitigate a serious risk of injury to human health

For information on determining whether a product presents a serious risk of injury to human health, refer to:

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

Notable incidents of validated failure in effectiveness

Some notable incidents of failure in effectiveness that originate from a credible source (where the data has been validated) can be significant safety issues. Such incidents include situations where a substantial failure in the performance of the biocide against a microorganism has occurred.

Credible sources may include studies or reports from:

• hospitals
• commercial settings
• regulatory authorities
• peer-reviewed scientific journals
• results of testing in laboratory or university settings

For example, results from a study by a credible source that examined the performance of the biocide concluded:

• there was a substantial failure in respect of the claims made or
• the possible development of antimicrobial resistance would be a significant safety issue

Examples of a significant safety issue

The following are examples of potential notifiable significant safety issues that could be detected by safety monitoring under section 40 of the Biocides Regulations (regulations):

• You have received several reports from consumers who have developed a rash after using your biocide product. After reviewing the compiled information, you determine that the number of reports received is much higher than what could have been anticipated. Together, this large number of reports of rashes could indicate a significant safety issue.
• A foreign regulatory authority reassesses the authorization for an equivalent biocide to the one you are marketing in Canada after a finding that the biocide poses a potential new or increased risk of injury to human health.
• A foreign manufacturer or regulatory authority issues a risk communication to the public stating that persons with certain pre-existing health issues shouldn't use biocides containing a certain active ingredient. There may be an increased risk of injury to health associated with its use in that population.
• A series of swab tests for listeria at a food processing plant indicates that your biocide, with an approved claim against listeria, did not perform as intended against the bacteria despite its use according to the label directions. There were no cases recorded of employees or consumers of the food product(s) contracting listeria. However, serious injury to human health could have occurred if an employee or consumer had contracted the bacteria.
• A study by a foreign regulatory authority on the effectiveness of biocides concludes that the active ingredient of your biocide performed below expectations. It was only effective against a specific claim 73% of the time.
• While reviewing the compiled information, you notice a new trend in reports from consumers feeling faint or fainting and having difficulty breathing after mixing your biocide with a specific type of cleaning product.
• Your biocide is for commercial use. Several reports of miscarriages have been reported over a number of years following daily use through occupational exposure of your biocide product in a commercial setting.

Examples of serious incidents reportable under section 39 of the regulations can be found under serious incident reporting.

Notifying Health Canada of significant safety issues

When you identify a significant safety issue, you must notify us, without delay. This means that you should notify us immediately after you have validated that the safety issue is significant.

You should include in your notification (using the non-eCTD format):

• your contact information
• your biocide's identification number
• the brand name of your product in Canada
• the brand name of the foreign product, if applicable
• a detailed description of the safety issue
• why it is considered significant
• information on the steps you took, or plan to take, in response to the safety issue, if applicable

If you have questions about how or when to notify us of a significant safety issue, please contact the Regulatory Project Management Office at the Marketed Health Products Directorate (MHPD).

Regulatory Project Management Office
Bureau of Strategic Engagement and Integrated Management Services
Health Canada
Address Locator 0702L
200 Tunney's Pasture Driveway
Ottawa ON K1A 0K9
Email: bbrs.rpm-gpr.bbra@hc-sc.gc.ca

Requests for information

We may request that you provide information compiled relevant to the risks and benefits of your biocide. The information you compile could include documentation of:

• notable incidents, serious incidents, serious unexpected incidents and other safety information that you gathered as part of your safety monitoring activities
• measures that have been taken outside of Canada to address significant safety issues
• your review activities, including your findings
• your safety monitoring systems and procedures

We may ask for this information at any time, if we become aware of new information concerning the risks and benefits associated with your biocide.

You must provide the information to us within the timeframe outlined in our request letter. Our letter will specify a reasonable timeframe in which you must submit the information. This timeframe is typically a 30-day period. However, the timeframe we specify may be longer as needed or shorter than 30 days if the information is needed quickly for us to determine if your biocide poses a serious and imminent risk of injury to human health.

All information provided to us must be in either English or French.