Good pharmacovigilance practices (GVP) guidelines (GUI-0102): Glossary

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• Acronyms
• Terms

Acronyms

ADR:

adverse drug reaction

AE:

adverse event

ASR:

annual summary report

DIN:

Drug Identification Number

ICH:

International Council for Harmonisation

ICSR:

individual case safety report

IRSR:

issue-related summary report

GVP:

good pharmacovigilance practices

MAH:

market authorization holder

NOC:

notice of compliance

ODCS:

organized data collection system

PSP:

patient support program

QHCP:

qualified healthcare professional

RMP:

risk management plan

T&C:

terms and conditions

UFIE:

unusual failure in efficacy

Terms

These definitions explain how terms are used in this document. If there is a conflict with a definition in the Food and Drugs Act (act) or Food and Drug Regulations (regulations), the definition in the act or regulations prevails.

Adverse drug reaction (ADR):

A noxious and unintended response to a drug, which occurs at doses normally used or tested for the diagnosis, treatment or prevention of a disease or the modification of an organic function.

(C.01.001(1) of the regulations)

The phrase “response to a drug” means that a causal relationship between a drug and an adverse event is at least a reasonable possibility. A reaction, in contrast to an event, is characterised by the fact that a causal relationship between the drug and the occurrence is suspected.

For regulatory reporting purposes, if an event is spontaneously reported, even if the relationship is unknown or unstated, it meets the definition of an adverse drug reaction.

(adopted from ICH E2D (R1) (PDF))

Adverse event (AE):

An adverse event is any untoward medical occurrence in a patient exposed to a health product and which does not necessarily have a causal relationship with the health product. An AE can therefore be any unfavourable and unintended sign, for example, an abnormal laboratory finding, symptom, or disease temporally associated with the use of a health product, whether or not considered causally related to this health product.

(adopted from ICH E2D (R1) (PDF))

Annual summary report (ASR):

A comprehensive assessment of all known safety information for a marketed drug. It provides an update on the worldwide safety profile at defined intervals throughout the post-authorization life cycle of the drug or product.

Audit:

An assessment of compliance or applicable requirements that the manufacturer or MAH conducts on itself or its third-party vendors or affiliates.

Case report:

A detailed record of all relevant data associated with the use of a drug in a subject.

(C.01.001(1) of the regulations)

Causality assessment: 

The evaluation of the likelihood that a drug was the causative agent of an observed ADR in a specific individual. Causality assessment is usually made according to established algorithms. 

Closed signal:

A signal for which an evaluation was completed during the reporting interval.

(ICH E2C (R2) (PDF))

Cross-licensed product:

It is a drug product (for which a licensee is seeking market authorization) where all aspects of the submission or application are identical to that of the licensor in terms of all clinical data, chemistry and manufacturing data, product formulation, strength, route of administration, dosage form, authorized indication(s) and condition(s) of use as well as all product labels. For a cross-licensed product to be eligible for administrative processing the licensor's product must have received authorization from us; its DIN must not have a cancelled status at the time of the licensee's submission or application filing.

Refer to Guidance document: Administrative processing of submissions and applications involving human or disinfectant drugs for more information.

Data lock point:

The end date of a reporting interval as covered by the respective ASR. Also the cut-off date for data to be included in the ASR.

Day zero (Day 0):

The start date of the regulatory time clock for reporting ADRs or UFIE. This is the date when any personnel of the manufacturer or the third party acting on their behalf has all the information satisfying the minimum criteria of an Individual Case Safety Report (ICSR).

For follow-ups, day 0 is the day on which the manufacturer receives new clinically or medically significant/relevant information from a previously submitted case.

Digital platform:

A digital platform is the software and technology used to enable transmission of information between users. Digital platforms include but are not limited to social media, web sites, internet forums, chat rooms, mobile health technologies, and software applications (apps).

(adopted from ICH E2D (R1) (PDF))

Drug:

Any substance or mixture of substances manufactured, sold or represented for use in:

• the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state, or its symptoms, in human beings or animals,
• restoring, correcting or modifying organic functions in human beings or animals, or
• disinfection in premises in which food is manufactured, prepared or kept;

(Section 2 of the act)

Drug Identification Number (DIN):

A computer-generated 8 digit number assigned by us to a drug upon market authorization under subsection C.01.014.2 (1) of the regulations. It uniquely identifies each drug under the regulations, sold in a dosage form in Canada, and is located on the package label of prescription and non-prescription drugs that have been evaluated and authorized for sale in Canada.

A DIN uniquely identifies the following characteristics:

• Product Name
• Manufacturer Name
• Active Ingredient(s)
• Strength of Active Ingredient(s)
• Dosage Form
• Route(s) of Administration
• Species (for veterinary drugs only)

Identified risk:

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

Individual case safety report (ICSR):

A description of an ADR in a single patient at a specific point of time. A valid ICSR must include these minimum criteria:

• at least 1 ADR
• an identifiable patient
• at least 1 suspect product
• at least 1 identifiable reporter

(adopted from ICH E2D (R1) (PDF))

Important medical events (IMEs)

Events that may not be immediately life-threatening or result in death or hospitalization, but might, in the clinician’s judgement:

• jeopardize the patient or
• require intervention to prevent a serious outcome (refer to the outcomes in the serious ADR definition)

Examples of IMEs include:

• intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization
• development of dependency or substance use disorder

(adopted from ICH E2D (R1) (PDF))

Inspection:

An assessment of compliance against any of the applicable requirements of the act and its regulations by a designated inspector of a regulatory authority.

Issue-related summary reports (IRSR):

It is prepared upon our request and contains a concise, critical analysis of a specific safety or effectiveness issue, concerning a marketed drug, based on an analysis of adverse reaction reports.

Label:

label includes any legend, word or mark attached to, included in, belonging to or accompanying any food, drug, cosmetic, device or package; 

(section 2 of the act)

Label includes:

• Labels affixed to the container or packaging of the drug
• Any separate package inserts
• Prescribing Information
• Fact sheets
• Consumer information/patient medication information (i.e., patient leaflets)
• Patient diaries
• Product Monograph, or
• Other material containing information specific to the drug

Package labels generated by the manufacturer may be included in the packaging or supplied to the consumer at the time of dispensing.

Manufacturer:

A person, including an association or partnership, who under their own name, or under a trade-, design or wordmark, tradename or other name, word or mark controlled by them, sells a food or drug.

(A.01.010 of the regulations)

Where the market authorization holder (MAH) is the entity that sells a drug under a name it controls, the MAH would be considered the manufacturer. For this reason, MAHs are subject to good pharmacovigilance practices (GVP) inspections as they sell a drug under their own name, or a trade-, design or wordmark, tradename or other name, word or mark that they control. However, other scenarios may apply and each scenario will need to be assessed on a case-by-case basis. 

Market authorization holder (MAH):

For the purpose of this guidance document, the entity that holds the notice of compliance (NOC) or the drug identification number (DIN) is the MAH.

Market research program:

Market research programs are Organized Data Collection System (ODCS) which are used for planned collection of healthcare professional and/or consumer insights by a manufacturer/MAH, or third party acting on their behalf, on drugs and/or a disease area, for the purpose of marketing and business development.

(adopted from ICH E2D (R1) (PDF))

New drug:

A drug:

1. that contains or consists of a substance, whether as an active or inactive ingredient, carrier, coating, excipient, menstruum or other component, that has not been sold as a drug in Canada for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that substance for use as a drug;
2. that is a combination of 2 or more drugs, with or without other ingredients, and has not been sold in that combination or in the proportion in which those drugs are combined in that drug, for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that combination and proportion for use as a drug; or
3. with respect to which the manufacturer prescribes, recommends, proposes or claims a use as a drug, or a condition of use as a drug, including dosage, route of administration or duration of action and that has not been sold for that use or condition of use in Canada, for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that use or condition of use of that drug.

(C.08.001 of the regulations)

In general, if a notice of compliance was issued for a drug, it is considered to be a "new drug", regardless of how long it has been on the market.

Non-interventional studies:

A type of study conducted by the manufacturer or MAH (or on behalf of the manufacturer of MAH) in which participants receive an approved product during routine medical practice and are not assigned to a specific intervention or treatment. For the setup and conduct of non-interventional studies, MAHs should have a protocol in place as discussed under organized data collection system (ODCS).

(adopted from ICH E2D (R1) (PDF))

Non-interventional studies with primary data collection:

A type of study where the data used are generated prospectively specifically to address the study objectives by collecting data directly from participants, caregivers, healthcare professionals or other persons involved in the participant’s care.

Primary data may be collected from, for example:

• case report forms
• laboratory measurements
• electronic patient reported outcomes
• mobile health technologies

(adopted from ICH E2D (R1) (PDF))

Non-interventional studies with secondary use of data:

The design of such studies is characterized by the utilization of data previously collected for other purposes.

Examples of existing data sources that can be used in non-interventional studies:

• historical clinical studies 
• publicly available databases on death/poisoning
• AEs, ADRs, disease and drug registries 
• claims data and  
• medical and administrative records from routine medical practice. 

(adopted from ICH E2D (R1) (PDF))

Notice of compliance (NOC):

A notification, issued pursuant to paragraph C.08.004 (1) (a), indicating that a manufacturer has complied with sections C.08.002, C.08.002.1 or C.08.003 and C.08.005.1 of the regulations. NOCs are issued to a manufacturer following the satisfactory review of a submission.

Organized data collection system (ODCS):

An activity that gathers data relevant to the manufacturer or MAH’s product or medical disease area, in a planned manner, thereby enabling review to be performed.

We require manufacturers or MAHs to have a protocol for certain types of ODCS, such as clinical trials and non-interventional studies. In this context, a protocol means a document that describes the objectives, design, methodology, statistical considerations and organization of a clinical trial or study. The term “protocol” encompasses successive versions of the protocol and protocol modifications.  

For ODCS activities that are not conducted according to a protocol, such as a sentiment analysis or a patient support program, the manufacturer or MAH should have documentation in place describing at least the: 

1. Objectives of the ODCS activity 
2. Source(s) of the data 
3. Dataset that manufacturer or MAHs will collect or receive and review in order to meet the objectives of the activity detailed under item 1, including the lookback period and/or duration of the data collection
4. Method used to review the dataset to meet the objective of the activity 
5. Process for collection and management of any ADRs or other observations that may be identified. 

Examples of ODCS include: 

• clinical trials 
• non-interventional studies such as, pharmacoepidemiologic, drug utilisation studies, registries 
• patient support programs
• market research programs 
• manufacturer or MAH activity using a patient forum on a digital platform to assess patient perceptions of the safety of disease treatments 
• product-specific sentiment analysis the manufacturer or MAH conducts using posts on social media networking sites 
• an activity where the manufacturer or MAH monitors and analyzes user communications on a social media site, often referred to as social listening or digital listening

(adopted from ICH E2D(R1) (PDF))

Ongoing signal:

A signal that remains under evaluation at the data lock point.

(ICH E2C (R2) (PDF))

Patient support program (PSP):

An organized data collection system initiated by the manufacturer or MAH:

• in which patients enroll for the purpose of supporting their use of the manufacturer or MAH’s drug, or the management of their medical condition, and
• which include a mechanism for two-way communication between the manufacturer or MAH (or third party acting on their behalf) and patients or healthcare professionals.

Examples of PSPs include adherence support, disease management, certain reimbursement programs, and educational program.

PSPs:

• solicit medical information about the patient’s use of a drug and/or
• will foreseeably receive medical information about the patient’s use of a drug, for example, when a program involves HCP interaction with a patient to administer medication or provide medical advice.

Note:

• manufacturer or MAH-initiated programs that do not meet the criteria above (for example, delivery of a product to a patient’s home, provision of vouchers or coupons) are not considered PSPs, as long as the manufacturer or MAH does not request medical information about the patient’s use of a drug.
• PSPs exclude:
  • clinical trials
  • non-interventional studies, such as post-authorization safety studies which have a scientific intent or are testing a hypothesis
  • all forms of compassionate use, and
  • named patient supply
• Similar terms may also be used such as patient assistance program.

(adopted from ICH E2D(R1) (PDF))

Pharmacovigilance:

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

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

Examples include:

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

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

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

Examples include safety studies or registries.

Phase IV (post-market or post-authorization) clinical trials/studies:

It includes those trials that involve the use of:

• a new drug that has been issued a NOC under subsection C.08.004(1) of the regulations, if the clinical trial is in respect of a purpose or condition of use for which the NOC was issued; or
• a drug, other than a new drug, that has been assigned a drug identification number (DIN) under subsection C.01.014.2(1) of the regulations, if the clinical trial is in respect of a use or purpose for which the DIN was assigned.

Phase IV clinical trials are performed after the drug has been authorized by us for the market, and within the parameters of the authorized NOC or DIN application.

Potential risk:

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

Product monograph:

A factual, scientific document on a drug product that describes the properties, claims, indications, and conditions of use for the drug. It also contains information that may be required for optimal, safe, and effective use of the drug but should not contain promotional material.

Qualified healthcare professional (QHCP):

A medically-qualified person such as a physician, dentist, pharmacist, nurse, coroner, or an individual with appropriate healthcare education and therapeutic expertise.

Qualitative signal detection:

Case-by-case manual screening of each individual case report of a suspected adverse drug reaction submitted to a spontaneous reporting system that must be performed by an assessor. The assessor uses his/her human intellect to evaluate the likelihood that the adverse event was caused by the suspect drug.

(CIOMS Cumulative Pharmacovigilance Glossary: Version 1.0 (PDF))

Quantitative signal detection:

Computational or statistical methods used to identify drug-event pairs (or higher-order combinations of drugs and events) that occur with disproportionately high frequency in large spontaneous report databases.

(CIOMS Cumulative Pharmacovigilance Glossary: Version 1.0 (PDF))

Risk management plan (RMP):

A document that describes:

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

Risk minimization measures (or “activities”):

Interventions that:

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

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

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

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

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

Examples include controlled access or distribution programs or educational programs.

Sell:

Sell includes

• (a) 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
• (b) lease, offer for lease, expose for lease or have in possession for lease; 

(section 2 of the act)

Serious adverse drug reaction:

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

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

(C.01.001 (1) of the regulations)

Notes:

• Important medical events are also considered serious
• Life-threatening refers to a reaction in which the patient was at risk of death at the time of the reaction; it does not refer to a reaction which hypothetically might have caused death if it were more severe.  

(adopted from ICH E2D(R1) (PDF))

Serious unexpected adverse drug reaction:

A serious adverse drug reaction that is not identified in nature, severity or frequency in the risk information set out on the label of the drug.

(C.01.001 (1) of the regulations)

Signal:

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).

(adopted from CIOMS Cumulative Pharmacovigilance Glossary: Version 1.0 (PDF))

Signal detection:

The act of looking for and/or identifying signals using event data from any source.

(CIOMS Cumulative Pharmacovigilance Glossary: Version 1.0 (PDF))

Signal evaluation:

A multi-faceted approach:

• to collect the evidence to evaluate whether there is a causal link between the event and the administration of the drug,
• to determine whether the signal represents a potential or identified risk and, if this is the case, to characterize the qualitative and quantitative profile of the risk, and,
• if a risk has been characterized, to communicate the risk and to propose measures aimed at preventing its occurrence or minimizing its consequences.

(adopted from CIOMS Practical Aspects of Signal Detection in Pharmacovigilance (PDF))

Signal management:

A set of activities such as signal detection and evaluation to determine whether a signal represents a risk which may warrant further assessment, communication, or other risk minimization actions in accordance with the medical importance of the issue.

(adopted from CIOMS Cumulative Pharmacovigilance Glossary: Version 1.0 (PDF))

Significant change:

Refer to the Guidance on preparing and submitting summary reports for marketed drugs and natural health products.

Solicited reports:

Reports derived from an ODCS. Manufacturers or MAHs should conduct a causality assessment for solicited ICSRs.

(adopted from ICH E2D (R1) (PDF))

Spontaneous reports:

Reports not derived from an ODCS. They are communicated by a healthcare professional or consumer to a manufacturer or MAH, regulatory authority or other organization (for example, Regional Pharmacovigilance Center). Manufacturers or MAHs should assume implied causality for spontaneous ICSRs.

There are certain AEs/ADRs that, although not direct communications to the manufacturer or MAH, if required to be reported as ICSRs, should be managed as spontaneous reports.  

Note: Also known as unsolicited reports.

(adopted from ICH E2D (R1) (PDF))

True copy:

An exact verified copy of an original record.

Unusual failure in efficacy (UFIE):

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

Unexpected ADR: 

When its nature, severity, specificity or frequency of an ADR is either not identified, or is not consistent with the terms or description used in the Canadian product labelling.

(adopted from ICH E2D (R1) (PDF))