Good pharmacovigilance practices (GVP) guidelines (GUI-0102): The regulations

On this page

• Terms and conditions
• Prohibition
• Serious adverse drug reaction (ADR) reporting
• Annual summary report (ADR) and case reports
• Issue-related summary report (IRSR)
• Maintenance of records
• Foreign action related to serious risk of injury to human health
• Unusual failure in efficacy
• Label update

For each section below, the exact text from the regulations are provided first. This is followed by the rationale (why the rule is important) and our interpretation (what you should do to be compliant), where needed.

To sell a drug, the manufacturer or MAH must comply with the regulations and apply Good Pharmacovigilance Practices (GVP) as described in this guidance. As a manufacturer or MAH, you must ensure that your products are safe and effective throughout their lifecycle.

The act defines “sell” as:

• offer for sale, expose for sale or have in possession for sale, or distribute to one or more persons, whether or not the distribution is made for consideration, and
• lease, offer for lease, expose for lease or have in possession for lease

Note: The responsibility to comply with C.01.014.21 of the regulations starts as soon as a term and condition is imposed on your Drug Identification Number (DIN).

Note: The responsibility to comply with C.01.050 of the regulations starts once you receive a DIN (subsection C.01.014.2(1)) or a Notice of Compliance (NOC) (section C.08.004 or C.08.004.01).

Terms and conditions

C.01.014.21 of the regulations

Note: As part of the amendment of certain regulations (Agile Licensing) under the act, there are legislative changes that will allow for the future application of terms and conditions to all DINs. Refer to Regulations Amending Certain Regulations Made Under the Food and Drugs Act (Agile Licensing): SOR/2024-238 for the coming into force date and other information.

Rationale

Terms and conditions (T&Cs) are a regulatory tool that can be applied for additional oversight on the safety, efficacy, and quality of an authorized drug throughout its life cycle. The main objective of imposing T&Cs is to ensure that a drug retains the favourable benefit-risk profile demonstrated at the time of market authorization.

Interpretation

This section should be read along with the following guidance documents. You are expected to fulfill all the requirements outlined within:

• Submission of targeted risk management plans and follow-up commitments for prescription opioid-containing products – Guidance for industry
• Guidance on the Food and Drug Regulations for public health emergency drugs
• Submitting risk management plans guidance document

A new T&C may be imposed on a drug identification number (DIN) or the existing T&Cs on a DIN may be amended at any time. As the MAH/manufacturer, you must comply with them.  

T&Cs vary depending on the product and can include pharmacovigilance and risk minimization activities/measures.

You should have a system and process in place to execute the activities/measures outlined in the T&Cs in a timely manner or within the specified timelines. All elements of a pharmacovigilance system should be applied. You should also monitor the progress on these activities and resolve any challenges to ensure proper execution of the T&Cs.

Prohibition

C.01.016 of the regulations

Serious adverse drug reaction (ADR) reporting

C.01.017 of the regulations

Rationale

As the manufacturer, you must collect, evaluate, and submit adverse drug reactions (ADRs) in a timely manner. This allows you to monitor the safety and effectiveness of drugs being sold and submit ADR information to us accordingly.

Interpretation

This section should be read along with the following guidance document. You are expected to fulfill all the requirements outlined within:

• Reporting adverse reactions to marketed health products – Guidance document for industry

Overall considerations

Domestic serious ADRs and foreign serious unexpected ADRs are subject to expedited reporting. You should have approved written procedures and instructions for receiving, handling, documenting, processing, evaluating, and submitting ADR. All elements of a pharmacovigilance system should be applied. Documented information on domestic and foreign ADRs should be accurate, complete, and consistent. You must submit this information to us within 15 calendar days of receiving a report, if the Individual Case Safety Report (ICSR) qualifies for expedited reporting.

Receiving, handling, documenting, and processing ADR data

Overview

An Adverse Event (AE)/ADR may be received from internal departments or external third parties delegated to act on your behalf. These include, for example:

• entities that conduct patient support programs (PSP)
• entities that conduct post-marketing activities such as studies or literature search
• international entities under the same ownership or corporate structure or entities on the product label
• the entity that handles customer service or marketing activities that are owned, controlled, or operated by you

You should ensure your systems and procedures:

• define the terms used in pharmacovigilance activities
  • for example, ADRs and serious ADRs
• enable the receipt and handling of incoming correspondences that represent potential domestic and foreign ADRs
• transfer any AEs/ADRs received to the pharmacovigilance department, including programs or studies managed by third parties or other departments
  • consider the need to set up contractual agreements, as applicable
• identify the responsible personnel or contact person who receives incoming correspondences from the contact point identified on the product label, advertising material, or digital platform
• assign an unique identifier to each incoming case
• define day zero (day 0) as the day when all 4 minimum criteria of the ICSR are available to you or the party delegated to conduct pharmacovigilance activities on your behalf
• define the process to validate and invalidate ICSRs
  • The record of invalidated cases should be maintained for inspection/audit purposes
• define timelines and workflow for triaging safety information to the pharmacovigilance department for processing
• define the process for after-hours operations
  • for example, timeline for handling incoming voice messages and incoming text messages via digital platforms
• clarify who is responsible and the process for translating AE/ADR correspondence into English or French, when necessary

To ensure completeness of ADR information, you should exercise due diligence in seeking and recording key data elements. You should:

• obtain consent to follow-up when necessary, document any follow-up attempts, and information obtained from follow-up
• query the reporter to obtain the most complete information possible, while ensuring to avoid inferences and imputations 
• include the verbatim term used by the reporter, or an accurate translation if provided in a language other than English or French
• provide an unbiased and unfiltered report of information received

Note: Please refer to the Environmental scanning section for guidance on conducting literature searches. While reviewing the scientific literature, you may become aware of ICSRs qualifying for expedited reporting under C.01.017 of the regulations.

Note: Compulsory licence holders of Canada’s Access Medicines Regime (CAMR) are subject to the requirements for reporting foreign ADRs on drugs sold under CAMR.

Coding

You are encouraged to use the Medical Dictionary for Regulatory Activities (MedDRA) for coding. To promote accurate and consistent term selection when different options are possible, you should use recommendations detailed in the MedDRA® Term Selection: Points to consider document.

Your approved procedures and instructions should ensure that:

• AE/ADR terms are coded consistently  
  • any inconsistencies should be justified and documented by the Qualified Healthcare Professional (QHCP)
• the coding reflects up-to-date MedDRA terminology, conventions and exceptions
  • MedDRA: Support documentation
• a risk-based strategy is identified that requires the QHCP to verify the coding selection of complex or less-intuitive AEs/ADRs
• the MedDRA version update process is outlined and that any impact analysis and risk-based review will be conducted

Duplicates

Your approved procedures and instructions should describe:

• the strategy or algorithm in place to find ICSRs that are potential duplicates
• the verification process when potential duplicates in your pharmacovigilance database are identified
• how to manage duplicates in the database once validated
• effectiveness evaluations on the strategies or algorithms used and necessary steps to address any inadequacies

If you identify duplicates within your database after the reports have been submitted to us, you should nullify the duplicate via submission to Canada Vigilance and ensure that a master case is retained in your system and in Canada Vigilance. If the duplicate contained additional information, then the duplicate may need to be merged with the master case before you nullify it.

The above-mentioned principles are important for proper ADR evaluations, ADR submissions, Annual Summary Report (ASR) preparation and Issue-Related Summary Report (IRSR) preparation.

Following up with the reporter or patient

You should have approved procedures and instructions for following up with the reporter or patient. For example, you should:

• seek the reporter’s or patient’s consent to follow-up, where necessary
• reference the initial report in your follow-up submission to the Canada Vigilance Program
  • update corresponding data fields
  • identify new information and date of receiving follow-up information
  • ensure that the date of receipt on follow-up information does not precede the latest date of previous report versions
• tailor follow-up methods to collect any missing information that allows meaningful case evaluation:
  • 4 minimum criteria of the ICSR
  • key data elements
  • verify duplicate information and resolve any information that conflicts with the original information that was collected
• document all follow-up efforts to show diligence and optimization to collect missing information
  • document decisions and justifications to either not follow-up or to discontinue follow-up efforts
• involve QHCPs with the appropriate level of pharmacovigilance training and therapeutic expertise in the collection of information and direct follow-up of reported cases, when possible
• document information received from follow-up systematically
• prioritize the different types of case reports for follow-up considering the seriousness and expectedness, as well as case reports of special interest
  • Note: Although some of these cases may not be subject to expedited reporting, you should still pursue follow-up on these reports.
• have a risk-appropriate strategy based on QHCP’s judgment, to determine the amount of follow-up as appropriate
• conduct follow-up on other observations without an AE/ADR such as overdose, abuse, misuse, medication error, occupational exposure, pregnancy exposure (maternal or paternal) or lactation exposure to ensure that information is as complete as possible regarding the suspected product and the context of occurrence
  • in the case of pregnancy or lactation exposure, collect information on the outcome of the pregnancy, health of the newborn, and, where appropriate, development of the child. Note: this follow-up is not expected for cases of exposure during pregnancy for products specifically indicated for use during pregnancy, if not associated with an AE/ADR.

Note: When additional clinically or medically significant/relevant information is received from an ICSR previously submitted to the Canada Vigilance Program, the regulatory reporting time clock of this follow-up information begins again. You must report it within 15 calendar days of receipt.

You should submit follow-up on clinically or medically significant/relevant information, for example:

• new or changed suspected adverse reaction(s)
• additional or changed suspect product(s)
• a change in the causality assessment
• any new or updated information about the case that affects its medical interpretation

You should seek the clinical or medical judgment of a QHCP on significant/relevant new information that requires expedited reporting.

The above-mentioned principles are important for proper ADR evaluations, ADR submissions, ASR preparation and IRSR preparation.

Evaluating ADR reports

You should have approved procedures and instructions for evaluating AE/ADR reports you received and retrieved. For your AE/ADR report, you should:

• assess seriousness consistently for a given ADR
  • consider how serious ADRs are defined in the regulations and based on the ICH official definition of seriousness
  • consider medically important events consistently when assessing “seriousness”
• determine the expectedness for both domestic and foreign AE/ADR reports from the current product monograph, labelling standards, information approved for market authorization, or product label
• verify if an AE/ADR report is solicited or spontaneous
  • If solicited, you must assess causality before submitting a report to us. In addition, you must respect the opinion or causality assessment of the reporter, that is, not downgrade the report even if you disagree with the reporter.
  • If spontaneous, ADR reports have implied causality. As such, your causality assessment will not affect whether the report should be submitted to us.
• record the opinions or assessment of both the reporter and you if there is disagreement about the seriousness or causal relationship between the suspected product and the reported AE/ADR
• evaluate and document the assessment if follow-up information changes the seriousness, expectedness and/or causality assessment
• evaluate if follow-up yields clinically or medically significant/relevant information that prompts the need to submit a report to us
• justify the evaluation of an AE/ADR and document the QHCP’s medical assessment

Submitting ICSRs to us

You should have approved procedures and instructions for submitting an ICSR. For example, you should:

• require that domestic serious ADRs and foreign serious unexpected ADRs be submitted to us within 15 calendar days of receiving or becoming aware of the adverse drug reaction (refer to the day 0 definition in the Glossary)
• complete all the processes (triage, transfer of safety information, processing, documentation, evaluation) in time to meet the 15-calendar day timeline of submission after receiving or becoming aware of the ADR
• verify that your reporting rules meet the Canadian reporting requirements if you use an electronic pharmacovigilance system
• submit clinically or medically significant/relevant follow-up information related to a previously submitted ADR report to us within 15 calendar days of receiving such follow-up information
• submit nullifications on ICSRs previously reported to the Canada Vigilance database only if further information confirms that the case is a duplicate or the case was found to be erroneous
  • Furthermore:
    • The record of nullification and associated documents should be maintained.
    • Documented procedure and process should be in place describing when ADR reports may be nullified.
    • A nullified case is one that should no longer be considered for scientific evaluation.

Note: ICSRs from post-authorization safety studies based on secondary use of data are not subject to expedited reporting. However, they should be considered as part of environmental scanning when preparing ASRs.

Annual summary report (ASR) and case reports

C.01.018 of the regulations

Rationale

The annual summary report (ASR) is a tool which summarizes interval safety data and allows the manufacturer to conduct an overall safety evaluation. The ASR can be used to identify safety signals or changes to what is known about the risks and benefits of the drug.

Interpretation

This section should be read with the following guidance documents. You are expected to fulfill all the requirements within:

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

Preparing ASRs

The ASR should provide a concise and critical analysis of interval safety data. The preparation of an ASR is an ongoing activity throughout the reporting period linked to signal management processes and monitoring activities. Continuous and periodic signal management processes and monitoring activities, such as environmental scanning, are important for the preparation of an ASR. As the manufacturer, you should conduct regular, systematic analyses of safety data to identify new or emerging information on a drug’s benefits and risks.

A significant change in what is known about the risks and benefits of a drug can occur at any time during the preparation of the ASR, depending on the available evidence. The ASR does not need to be complete for you to conclude that there has been a significant change. If there is a significant change in what is known about a drug’s risks and benefits, you must notify us without delay.

Refer to the Guidance on preparing and submitting summary reports for marketed drugs and natural health products for the definition of significant change and to obtain information on what to include in the notification to us.

You should have a system including approved procedures and instructions. All elements of a pharmacovigilance system should be applied. Your system should enable you to:

• prepare, review, and approve ASRs in a timely manner
  • involve the qualified healthcare professional (QHCP), where appropriate
  • include all the sections and information expected by ICH E2C (R2) periodic benefit-risk evaluation report (PBRER), ICH E2C (R1) periodic safety update report (PSUR), or non-standardized format and as explained in Guidance on preparing and submitting summary reports for marketed drugs and natural health products
  • apply consistent processes when preparing and/or presenting the data required in the ASRs such that each annual assessment illustrates trends from 1 year to another
    • justify, document, and indicate the impact when the process has changed
  • conduct signal management and environmental scanning in order for the ASR to include the outcome of these activities
• assess and notify us without delay if you conclude that there has been a significant change
• submit ASR and case reports if requested or necessary

Signal management

As part of ASR preparation, continuous and periodic signal management processes are needed.

A signal is information that:

• arises from 1 or multiple sources
  • including observations and experiments
• suggests a new potentially causal association, or a new aspect of a known association, between an intervention and an event or set of related events (adverse or beneficial).

As part of preparing the ASR, you should have a written procedure for your signal management practices.

Overall considerations

You should ensure that:

• your system allows a consistent approach in the signal management process, such as the detection and evaluation of signals
  • document and justify the search terms being used such as the MedDRA term, the level of MedDRA hierarchy, and the MedDRA version
  • justify changes, if any, made to the search strategy
  • demonstrate the data retrieved using the previous and new search terms are comparable (note any differences and document impact analysis)
• the pharmacovigilance department meets regularly with a periodicity based on risk to review and discuss safety signals
• you involve QHCPs with the relevant area of expertise in the signal management process
• you track the status of each safety signal, including at minimum:
  • trigger or origin
  • its assessment or justification,
  • follow-up actions such as necessary updates to the product label or risk management plan (RMP) for Canada and its proposed timelines,
  • any significant change in what is known about the risks and benefits of the drug 
• you perform signal management in a timely manner
• if it applies to a cross-licensed product, you have a contractual agreement in place between the licensor and licensee describing 2-way responsibilities for the exchange and assessment of safety information
• you keep case reports and any information related to the signal management process for 25 years from when they are created as per C.01.020 of the regulations

Signal detection

You should:

• conduct signal detection on an ongoing basis
  • the timing, frequency, and nature of monitoring activities depend on several factors, such as:
    • volume of ADRs received
    • known or specific emerging issues
    • the drug’s risk and uncertainty profile
    • scheduled timing or preparation of the ASR
  • justify and document the decision that the agreed upon periodicity to conduct signal detection is sufficient
• ensure that the types of report being accounted for in the ASR of a product are consistently used across all reporting intervals
• identify and document search criteria used and results in signal detection
• describe the qualitative and quantitative methods used to detect signals
  • use them consistently across different reporting intervals and justify changes where applicable
  • document medical assessment and statistical considerations to identify an appropriate threshold

Signal evaluation

You should:

• determine an appropriate risk-based strategy when analyzing available information in a timely manner, which could involve, for example:
  • causality analysis
  • utilization and exposure analysis
  • medical analysis
  • scientific analysis
  • assessment of previous actions taken
  • review of Canadian and international perspectives and considerations
  • assessment of actions from other regulatory agencies
• date, sign, and document any justifications and decisions on signals such as those that are closed or ongoing (time stamps attributable to a user or other methods of authenticated activity logging may also be used)
• establish and document the timeline to resolve any ongoing signals, supported by risk-relevant information
• communicate the outcome of signal evaluation to all relevant stakeholders

Environmental scanning

To conduct a critical analysis of the ADRs and serious ADRs to the drug, continuous monitoring activities such as environmental scanning is needed. Environmental scanning should include literature searches, Canadian regulatory authority database searches, and foreign regulatory authority database searches. Please also refer to the Foreign action section for specific classes of products subject to C.01.050 of the regulations.

Consolidated efforts on environmental scanning among different MAHs may be acceptable if:

• contractual agreement is available between the parties to clarify that the MAHs involved are ultimately responsible to ensure that their respective product comply with the regulatory requirements
• there is a well-defined process agreed upon between the MAHs and third parties involved
• the MAH has adequate oversight to ensure these activities on its own products are conducted according to the agreed upon process
• environmental scanning results are made available to the MAH responsible for the respective ASR preparation

Noted: MAHs do not have to submit the ADR if they have documented evidence that the contractual partner has already submitted the same ADR to Canada Vigilance.

Conduct a literature search for ADRs and safety concerns at least once every two weeks or provide a rationale to justify a reasonable risk-based search frequency. A similar process should be put in place to systematically retrieve ADRs and safety concerns from other sources of environmental scanning.

You should:

• establish a process to identify and document ADRs, indicate:
  • the search frequency
  • the search strategy such as terms, limits, and sources
  • how to determine if the literature is within scope of the drug in question
• identify Canadian and international literature sources relevant to the drug you sell, such as:
  • large reference databases
  • scientific journals that are not indexed in worldwide databases
  • specialized publications
• keep the list of Canadian and international literature sources updated, adding relevant new journals as necessary
• identify and document a risk-based strategy on the appropriate product search terms used (including the medical justification), such as:
  • indexed terms
  • active ingredient
    • consider the same combination of active ingredients even if the formulation, dosage form, strength, route of administration or indication vary
  • variations in spelling or names of the active ingredient if it is not indexed, such as:
    • chemical or brand names, active metabolites or names previously used in clinical trials
  • medically relevant variants or compounds of the active ingredient that would be considered the same drug
  • product brand name or alternate product names of the same drug sold by other manufacturers or MAHs locally and globally
  • class of drug
• have a process for monitoring automated literature retrievals, to ensure they continue to function effectively and generate the intended results
• consider post-authorization safety studies with primary data collection or secondary use of data
  • note: Individual Case Safety Report (ICSR) submission is not required for studies based on secondary use of data. However, the analysis derived from it should be considered and included in ASRs.
• account for safety findings such as interactions, overdose, drug abuse, misuse, off-label use, pregnancy or lactation exposure, experience in vulnerable sub-population, long-term exposure effects
• always document the literature reference and verify if any duplication exists within your pharmacovigilance database
• retrieve the complete article that may be relevant for ICSR submission or summary report   
• document the medical reason for using search terms related to risks
  • accounting for terms such as “risks under active surveillance” that regulatory authorities may have requested
• ensure that there are no gaps on the date ranges used for the searches
• keep records of literature searches, including records of:
  • search strategies
  • sources or databases searched
  • search results for a given date range, even when the search did not yield any results
  • important decisions made during the literature search

Actions taken based on your analysis for safety reasons

Your ASR should address and assess the need for actions taken for safety reasons. This can include changes to the product label or the introduction of/update to the RMP for Canada and summarize changes as appropriate.

If no follow-up actions are necessary, you should document your justification. 

You should continuously evaluate whether any revision of the product label is needed when new safety information arises. This ensures ASRs are prepared based on the latest information on the label. Refer to the Label update section for more information.

The proposal to update label or introduce or update the RMP should be included in the ASR. Your system and processes should allow implementation of these proposals. In the event where the RMP or element(s) of the RMP is a T&C applied on your DIN, refer to the Terms and conditions section for more information.

Note: If there is a significant change on what is known about the risks and benefits of the drug, you must notify us without delay. Refer to Guidance on preparing and submitting summary reports for marketed drugs and natural health products on notifications to us.

Issue-related summary report (IRSR)

C.01.019 of the regulations

Rationale

The issue-related summary report (IRSR) is a practical tool that summarizes a specific issue regarding a drug, at the request of the Minister, for the purposes of assessing its safety and effectiveness.

Interpretation

This section should be read with the following guidance documents. You are expected to fulfill all the requirements outlined within:

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

As the manufacturer, you should have a system including approved procedures and instructions to prepare, review, approve and submit an IRSR. All elements of a pharmacovigilance system should be applied.

You should:

• provide the IRSR within the timeframe specified by the Minister
• ensure the pharmacovigilance department has mechanisms in place, within its own department or in collaboration with relevant departments, so that IRSR requests are received, triaged to the appropriate department, prepared and reviewed by responsible personnel, and submitted to us by the specified timeline
• follow the search strategy specified in the IRSR request to retrieve cases
  • document discussions with us if the search strategy was revised to retrieve a more comprehensive set of safety data
  • document the rationale of the search strategy (such as the particular MedDRA level and search terms being included) if not already specified by the IRSR request
• verify that all the relevant data are provided as per the IRSR request
• justify and document if aspects of the requested safety issue have been excluded
• ensure the data used in the IRSR analysis are complete and accurate
• maintain and make available upon request the IRSR and all data used to compile the report
• involve the Qualified Healthcare Professional (QHCP) to write, review and/or approve the IRSR
• follow record retention principles as per section C.01.020 of the regulations to safeguard the integrity of the historical data

Maintenance of records

C.01.020 of the regulations

Rationale

Good documentation is an essential part of the pharmacovigilance system and promotes compliance with Good Pharmacovigilance Practices (GVP) requirements regarding record maintenance and retention. A good data governance system helps you, as the manufacturer, establish, control, monitor and record all activities that directly and indirectly impact the safety of drugs.

Interpretation

Overview

Documentation may be paper-based and/or in electronic form. The various types of documents and different forms of documentation used should be fully defined through written procedures of the pharmacovigilance system. 

As the manufacturer, you are responsible for maintaining and retaining records related to sections C.01.017-C.01.019 of the regulations for 25 years, regardless of the form of documentation (paper records or electronic records). This responsibility applies to you even when a pharmacovigilance activity is delegated to a third-party vendor. To fulfill this responsibility, you should have oversight on record keeping practices by third-party vendors.

You should have approved and up-to-date procedures and instructions for record maintenance and retention. Record retention involves:

• keeping applicable records for at least 25 years after they were created, including at minimum:
  • all records, including source documents, follow-up, evaluations, submissions, of adverse drug reactions (ADRs)/case reports/unusual failure in efficacy (UFIE)
  • Annual summary reports (ASRs), the data used, and related communications with us
  • Issue-related summary reports (IRSRs), the data used, and related communications with us
• accessing records within a reasonable timeframe during the retention period
• providing documentation requested by us in 1 of the official languages
• outlining the procedure used to maintain ADR records, including the filing system or electronic database used to retrieve these records
• ensuring the data is secured by physical or electronic means against willful or accidental damage or loss
  • refer to the Data integrity, Business continuity plan and Validation of automated computerized systems sections for principles related to records maintenance and retention
• data back up at regular and predefined intervals to protect against potential data loss due to system issues or data corruption or unexpected events
• applying good documentation principles to demonstrate that the QHCP was involved in key pharmacovigilance activities

Data integrity

You are responsible for establishing a data governance system that ensures the integrity of the retained data. You should:

• ensure that documentation is reliable, complete, consistent and accurate
• ensure controls are in place to prevent and detect data integrity issues throughout the product’s lifecycle, for example:
  • have procedures that outline management’s expectations for how data should be acquired, modified, reviewed and stored
  • when applicable, having validated computer systems
• apply the general principles of good documentation practices to all records, including those that are modified
• having the ability to trace records to their source through:
  • physical or electronic initials and signatures
  • secure user identification
  • time and date stamps
  • change history and audit trails that capture relevant information, such as the assessment or any change on seriousness, expectedness, causality and other entries such as date of receipt
• having legible records, with no parts of the data obscured or removed. If archived, they must be retrievable in a timely way. Any changes to records must also be documented and traceable
• ensuring that data are recorded, documented or saved when they’re generated, with reliable evidence that this was done
• granting access to view, create, modify, and store data to authorized personnel only, to protect personal information, as well as ensure confidentiality and accuracy
• ensuring that records are kept in their original format as an original record or as a true copy which has undergone a qualified conversion process that maintains data integrity
• ensure that records are generated and maintained under the oversight of a pharmacovigilance system that ensures their accuracy
  • cloud computing servers are to be treated as a delegated service, with risks identified and addressed, and responsibilities clearly outlined in a contractual agreement

Additional considerations for electronic records

If you use an electronic system to create, modify or store records required under section C.01.020 of the regulations, you should validate the system for its intended use.

You should:

• control all access and user rights in electronic systems to prevent system users from compromising data integrity
• keep an up-to-date list of individuals who are authorized to access the system with defined user rights that support their roles and responsibilities
• control electronic records in a way that ensures the records:
  • can only be created and modified by authorized personnel
  • are protected against intentional or accidental deletion
  • are named and organized so they can be traced easily
  • are tracked through an audit trail, which should include:
    • changes made to the record
    • who made the change
    • the time and date the record was changed
    • the reason the record was changed, if applicable
  • are available for review during an inspection/audit and can be easily retrieved in a suitable format
  • include all necessary metadata

When signatures are required, an electronic signature is an acceptable alternative to a handwritten signature. Ensure appropriate controls are in place for electronic signatures, including:

• valid electronic signature systems to show that the systems are suitably secure and reliable
  • document this validation
• a procedure for creating electronic signatures, with controls in place to ensure each one is unique
• a time and date stamp (for audit trail requirements)

Inform users that electronic signatures are considered an equivalent to handwritten signatures. Keep records to show that users are aware of their responsibilities when using electronic signatures.

Foreign action related to serious risk of injury to human health

C.01.050 of the regulations

Note: For the purpose of this guidance document, only foreign actions related to the safety of the drug will be reviewed during a Good Pharmacovigilance Practices (GVP) inspection.

Rationale

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 a foreign jurisdiction.

Interpretation

This section should be read with the following guidance document. You are expected to fulfill all the requirements outlined within:

• Notifying Health Canada of foreign actions – Guidance Document for Industry

As the MAH who holds a Drug Identification Number (DIN) and Notice Of Compliance (NOC), you must provide us with information on foreign actions that have taken place within 72 hours after you receive or become aware of the information, whichever occurs first.

As the responsibility to report foreign actions remains with the MAH, you must define roles and responsibilities with any global counterparts, affiliates, and any third-party vendors through procedures and contractual agreements. Contractual agreement that allows timely information exchange without delay is needed when you delegate part of the responsibility of identifying foreign action to an affiliate or third-party. The MAH should notify HC within 72 hours of becoming aware of a foreign action that has taken place. 

Your procedures and/or contractual agreements should enable your organization to regularly receive or become aware of foreign actions and provide this information to us in a timely manner, when applicable. The procedure and/or contractual agreements should include information on, for example:

• roles and responsibilities to receive or become aware of foreign actions, recommend actions to be taken in Canada, and notify us
• how you receive and become aware of foreign actions
• how a serious risk of injury to human health is defined and document your medical assessment
• how to determine relevance to the safety of the drug you sell and document your medical assessment
• maintaining records that notifications have been submitted to us

Although you may rely on communications with foreign affiliates as a way to receive and become aware of foreign actions, you should also consider the need to scan information sources from listed authorities:

• consider how often and when you scan an agency’s website based on factors such as:
  • agency’s publishing history
  • the product’s risk profile
  • known or specific emerging issues
  • scheduling of any summary report
• document and apply scanning strategies that identify foreign actions on products that are within scope
• document and date scan results
• have a manual scanning process, with established timelines if foreign regulatory authorities do not have an automated alert system
• have a process for receiving automated alert systems, to ensure they continue to function effectively and generate the intended results

Unusual failure in efficacy

C.08.007 (1)(h) and C.08.008 (c) of the regulations

Rationale

As a manufacturer, you must collect, evaluate, maintain, and submit records on Unusual Failure in Efficacy (UFIE). This allows you to monitor the safety and effectiveness of drugs being sold and submit UFIE information to us accordingly.

Interpretation

This section should be read along with the following guidance document. You are expected to fulfill all the requirements outlined within:

• Reporting adverse reactions to marketed health products – Guidance document for industry

Please refer to the Reporting adverse reactions to marketed health products – Guidance document for industry for the definition of UFIE.

As a manufacturer, you should have systems and procedures to report UFIEs to us within 15 calendar days of receiving such information on new drugs marketed in Canada. All elements of a pharmacovigilance system should be applied.

You should:

• follow the principles discussed in section C.01.017 when receiving, handling, documenting, processing, following up, evaluating and submitting UFIE reports
• refer to section C.01.020 regarding record maintenance and retention for unusual failure in efficacy reports as they are subject to annual summary reports (ASRs) and issue-related summary reports (IRSRs)
• have a Qualified Healthcare Professional (QHCP) evaluate and document if the case qualifies for expedited 15 calendar days reporting

Label update

C.08.003 of the regulations

Note: For the purpose of this guidance document, only changes or processes related to the safety or efficacy of the drug will be reviewed during a Good Pharmacovigilance Practices (GVP) inspection. It is your responsibility to ensure compliance with other applicable regulatory requirements set out within the act and regulations for your products.

Rationale

For a new drug that has been issued a notice of compliance, you, the manufacturer has the responsibility to file a supplemental submission if current information is significantly different from information that supported your authorization.

Interpretation

This section should be read along with the following guidance documents. You are expected to fulfill all the requirements outlined within:

• Guidance Document: Product Monograph
• Guidance Document: Post-Notice of Compliance (NOC) Changes: Safety and Efficacy Document (for pharmaceutical, biologic and radiopharmaceutical drugs for human use only)
• Guidance document: Administrative processing of submissions and applications involving human or disinfectant drugs

It is your responsibility to update product labels to be consistent with current scientific information and medical treatment.

If an update to the product label is warranted, you should have a system and procedures in place to allow timely label update. All elements of a pharmacovigilance system should be applied. You should:

• establish a tracking system to monitor product safety updates that are pending, submitted, approved and implemented
• outline a risk-based process with your regulatory affairs department to ensure that product safety updates are communicated with us or submitted in a timely manner