Switching a medicinal ingredient from prescription to non-prescription status draft guidance document: Assessing PDL principles and factors

On this page

• Appendix B: Completing the PDL principles and factors assessment
• Appendix C: Consumer use studies
• Appendix D: Market experience data
• Appendix E: Template for the PDL principles and factors assessment

Appendix B: Completing the PDL principles and factors assessment

All applicants should complete a "PDL Principles and Factors Assessment" (see template in Appendix E). The applicant should provide summaries of evidence and rationales demonstrating that none of the PDL principles and factors applies to the medicinal ingredient under the proposed conditions of use. In other words, the applicant demonstrates that the product does not require practitioner oversight and is therefore appropriate for self-care.

Below, under the headings for each of the PDL principles and factors, Health Canada outlines points for the applicant to consider when developing the evidence and rationale for each of the principles and factors.

In addition, for a complete understanding of the PDL principles and factors, Health Canada advises the applicant to read the guidance document “Determining Prescription Status for Human and Veterinary Drugs”.

Note that the term “condition” in the text that follows refers to diseases, conditions, disorders, abnormal physical states or their symptoms.

In this part of the template, the applicant should include additional information associated with this principle that the applicant has not explicitly detailed under Factors 1.1 to 1.8 below. In the case where there is no additional information to that detailed under Factors 1.1 to 1.8, the applicant should indicate that all the information relative to this principle is included in Factors 1.1 to 1.8 below.

This factor relates to concerns associated with misdiagnosis. Products intended for the non-prescription setting should be for conditions that are amenable to self-diagnosis.

For this factor, the applicant should include the following:

• a description of how the condition is diagnosed
• an assessment of the ease with which the consumer would be able to self-diagnose
• an assessment of the risks associated with a misdiagnosis
• possible risk mitigation measures that would decrease the seriousness of the potential health consequences if the condition is misdiagnosed

Description of diagnosis

The applicant should outline how the condition in question is typically diagnosed and in so doing, reference a reputable medical text or clinical practice guidelines.

Ease of consumer self-diagnosis

In terms of the assessment of the ease with which the consumer would be able to self-diagnose, the applicant needs to demonstrate that the consumer can accurately determine the nature of the condition on the basis of well-recognized symptomatology as well as the severity and duration of symptoms.

If the symptoms in question are common to a number of conditions, the applicant needs to demonstrate that the consumer can differentiate between these conditions. The applicant may need to provide consumer use studies to help demonstrate that the consumer has the ability to self-diagnose the condition correctly. For more information on consumer use studies, refer to Appendix C.

The applicant should indicate whether laboratory tests or other procedures involving a practitioner are required for diagnosis. If this is required for diagnosis, generally, the product would maintain its prescription status.

If effective use of the product requires additional measures, such as a monitoring device, the applicant needs to demonstrate that these measures or devices do not require practitioner involvement. For more information on medical devices, refer to section 19.3.

Risks associated with misdiagnosis

The applicant’s assessment of the risks associated with a misdiagnosis of symptoms should address the following:

• the impact of a delay in using the appropriate treatment
• the impact of the use of sub-optimal treatment
• the long-term effects of an inappropriately selected treatment (i.e., the risk of long-term exposure to the product with no health benefit to the consumer)

If the applicant’s assessment identifies risks, the applicant needs to demonstrate that the measures put in place, such as labelling, mitigate these risks.

In rare cases, Health Canada may authorize a product for self-care use where an initial diagnosis is required by a practitioner to ensure that the consumer is completely familiar with the symptomatology (e.g., vaginal antifungals). In these cases, the applicant should demonstrate that the consumer is able to conduct subsequent diagnoses. The applicant also needs to address the risks of a consumer choosing not to see a practitioner for the initial diagnosis and the resulting consequences of product use.

This factor relates to the potential risk that use of a product could hide a serious condition. Specifically, a consumer may treat his or her own symptoms with a product and obtain relief of those symptoms. However, in obtaining relief, the consumer may be less likely to consult a practitioner, potentially resulting in a more serious condition not being addressed in a timely manner. Products for self-care should not mask other serious conditions.

To address this factor, the applicant should include the following:

• information on the product’s mechanism of action as this will help identify potential conditions which might be masked
• an assessment of whether the pharmacological effects of the product have the potential to mask underlying condition(s) requiring medical attention

If a potential risk of masking other conditions exists, the applicant should also include an assessment of the consequences resulting from each of the following situations:

• a significant worsening of the underlying condition
• a delay in diagnosis and proper treatment of the serious condition
• any other situation that could prevent a more successful therapy for the underlying condition

The applicant should provide an assessment of whether the product labelling, or other measures, could mitigate the identified consequences of masking other conditions.

Note that if the risk of masking other conditions pertains to a serious condition, generally, the prescription status is maintained.

This factor relates to whether the indication is suitable for the non-prescription context and the consumer’s ability to self-treat and self-monitor. Generally, conditions suitable for self-care are self-limiting, that is, they will resolve on their own. Many conditions are not suitable for self-care. Thus, in summary, the use of the product, as well as the condition itself, cannot require practitioner supervision if the product is to obtain a non-prescription status as an NHP or NPD.

The applicant should include an assessment of how the use of the product is amenable to self-treatment and self-monitoring. In this assessment, the applicant needs to demonstrate that the consumer can correctly do all of the following without practitioner assistance:

• identify that he or she belongs to the intended target population for the product on the basis of the age range and the risk statements (precautions, warnings, contraindications) included in the product labelling;
• make an appropriate product selection;
• understand what potential side effects may emerge and how to manage them;
• determine whether or not the treatment is being effective;
• identify what foods or medication to avoid while taking the product;
• perform any additional measures (e.g., use of an ancillary medical device);
• understand and follow the dosage regimen proposed for the product; and
• identify situations where treatment should be discontinued and/or medical advice sought.

Consumer use studies may be necessary to substantiate an applicant’s position that the involvement of a practitioner is unnecessary. For more information on consumer use studies, refer to Appendix C. Note that if effective use of the product requires additional measures, such as a monitoring device, the applicant needs to demonstrate that these measures do not require practitioner supervision. For more on medical devices, refer to 19.3.

The applicant should provide a rationale for why the condition and product do not require practitioner expertise for treatment and monitoring activities. The rationale should address the reasons why practitioner expertise is not needed for any of the following:

• the selection of the correct product for the individual;
• the management of adverse reactions;
• decisions on dose adjustments and discontinuation;
• the development of risk mitigation strategies for the individual;
• any testing required prior, during or following the use of the product; and
• adjustments of the treatment and monitoring relative to comorbidities.

Products for use in self-care should not require practitioner involvement to tailor the use of the product to an individual’s unique circumstances or to explain product information. Consumers should be able to easily understand the product information and use the product. Therefore, the applicant should demonstrate that the product’s use does not involve any of the following:

• dose titration
• complex dosage regimens
• doses tailored to the individual’s specific circumstances
• complex instructions

Some examples of the above situations that would lead to the prescription status being maintained include the following:

• where the dose needs to be determined based on co-morbidities and/or test results
• where the product elicits tolerance requiring increasing doses to maintain efficacy
• where the product requires adjustments of the dose for the individual by a practitioner
• where the product elicits clinically significant withdrawal or discontinuation symptoms that require tapering or symptom monitoring upon product removal
• where there are complex risk statements

With respect to the degree of complexity of directions for use, risk statements, etc., results from consumer use studies can assist the applicant in demonstrating the consumer’s ability to understand the instructions without practitioner assistance. For more information on consumer use studies, refer to Appendix C.

Products with non-prescription status should be easy for consumers to self-administer. To demonstrate this, the applicant should provide the following:

• a description of why practitioner expertise is not needed to administer or oversee the administration of the product
• an assessment of the consequences of the product being administered improperly
• a discussion of any risk mitigation measures the applicant has put in place

Note that Health Canada considers most injectable products unsuitable for self-care use.

The margin of safety is the difference between the optimal effective dose and the dose at which undesirable or unmanageable side effects begin to appear. For products that have a narrow therapeutic index, the individual must receive precisely the right dose to prevent serious consequences. In contrast, products for use in self-care ideally have a wide margin of safety to ensure minimal risk to health if the consumer uses the product incorrectly.

Safety profile

The applicant’s evidence and rationale for this factor should include a summary of the product’s safety profile. The summary should reflect the following:

• the content of the most recent Health Canada approved Product Monograph or Prescribing Information for the prescription drug, if that exists;
• the safety data from all in vitro, pre-clinical and clinical studies;
• the market experience data (refer to Appendix D);
• the published literature;
• the safety assessments from other major regulatory jurisdictions as well as any available safety information from the World Health Organization or other national or international health organizations; and
• for products that contain known psychoactive substances, information on the dose at which unintended and intended psychotropic drug effects occur.
  • These psychotropic drug effects can include, but are not limited to, alterations in perception, cognition, levels of arousal and mood.

The applicant needs to demonstrate that there is an adequate margin between the product’s therapeutic dose(s) and the doses at which clinically significant adverse reactions occur. Adverse reactions can be clinically significant because of their seriousness, severity or frequency. They can also be clinically significant if there are no suitable preventative measures.

Assessment of the consequences of inaccurate dosing and risk mitigation measures

The applicant should show that the impact of minor dose deviations would not result in significant harm. To this end, the applicant needs to:

• address the likelihood and the severity of the risks associated with inaccurate dosing; and
• summarize any related market experience data that is available.

Note that in terms of inaccurate dosing, the applicant should address overdosing as it pertains to the product’s margin of safety and under-dosing as it pertains to a lack of efficacy. The applicant also needs to demonstrate how the directions for use could help mitigate these risks.

Additionally, the applicant should identify whether the product has a narrow margin of safety in particular sub-populations, such as pregnant and nursing women, children and the elderly. The applicant should also identify any risk mitigation measures that the applicant has made with respect to these sub-populations and the effectiveness of those measures.

In some cases, an NHP and prescription drug, or an NPD and prescription drug, will co-exist on the market after a successful switch. If this is the anticipated outcome of the switch, the applicant should address how the risks of consumer taking both products at the same time are being mitigated.

This factor relates to the potential harm arising from serious adverse reactions or interactions with commonly used medications (prescription drugs, NPDs and NHPs) or foods. To be suitable for self-care use, the product should not be associated with potential or known serious adverse reactions or serious drug-drug or drug-food interactions in the target population.

The applicant should include an assessment of the serious adverse reactions and potential serious interactions of the product with food or other drugs, at the proposed dose and regimen, with reference to the following:

• the safety results for all relevant clinical trials;
• drug-drug and drug-food interaction studies;
• available market experience data (refer to Appendix D); and
• any other available safety data.

Other available safety data includes information from in vitro studies; Absorption, Distribution, Metabolism and Excretion (ADME) studies; mechanism of action studies; toxicological studies and other relevant pharmacokinetic and pharmacodynamics studies.

If applicable, the applicant is expected to describe any risk mitigation measures, including labelling, that may address the risk of serious adverse reactions or potential serious interactions. The applicant can use data from consumer use studies to help demonstrate that these measures are effective in altering consumer behaviour so that serious adverse reactions and potential serious interactions are avoided. For more information on consumer use studies, refer to Appendix C.

The applicant also needs to identify any special considerations for vulnerable sub-populations, such as pregnant and nursing women, children and the elderly.

Products for use in self-care should not have the potential to cause dependence and/or addiction^{Footnote 3}.

Some products have the potential to induce psychoactive effects. These effects can be the primary/desired effect of the product (e.g., sedatives) or unintended/undesired secondary effects. These effects include symptoms such as dizziness, anxiety, cognitive impairment or irritability; but also symptoms that can be experienced as reinforcing, such as euphoria, changes in consciousness, perception and/or mood. Psychoactive ingredients that cause these types of reinforcing effects are of particular concern as they may carry a heightened risk for dependence and/or addiction (refer also to Factor 3.2).

Some products have the potential to induce symptoms related to discontinuing or reducing the dose, including withdrawal and rebound effects. These types of adverse reactions can result in a consumer having significant difficulty with stopping use of the product. For example, patients who no longer require the use of a product may continue to use it because an attempt to discontinue it had resulted in worsening symptoms. Practitioner oversight in this situation may be necessary to determine if the symptoms are solely rebound in nature or if the underlying condition still exists. In addition, some products may require dose tapering or secondary medications to manage the withdrawal symptoms and thus require practitioner oversight (refer to Factor 1.4). Importantly, discontinuation symptoms are not confined solely to psychoactive ingredients.

The applicant should demonstrate that the use of the product does not cause the following:

• clinically significant psychoactivity requiring practitioner oversight
• symptoms upon discontinuation or rapid dose reduction that require practitioner oversight

The applicant may demonstrate this by providing data from clinical trials that include adverse event profiles and outcomes from specific validated scales or questionnaires, as well as post-market data or literature.

Note that Health Canada expects the product to have clinically significant effects when its indication is based on a psychoactive effect (e.g., sedatives); nonetheless, the applicant still needs to provide evidence to characterize these effects and demonstrate that these effects are manageable in a non-prescription context without practitioner involvement.

In some cases, secondary psychoactive effects may be sufficient to necessitate maintaining prescription status. However, in other cases the effects may be effectively mitigated (for example, through labelling) such that practitioner involvement is not required. For instance, slight drowsiness may be addressed through label warnings for a product used to treat the symptoms of allergies and may not necessitate practitioner intervention. The applicant should include information on any mitigation measures the applicant has instituted relative to secondary psychoactive effects and the effectiveness of these measures.

This principle relates to the possibility that some uncertainties may remain about the product, such as:

• a lack of market experience (e.g., new product, new use, small target population and/or a lack of adequate post-market data);
• a lack of full characterization of its pharmacological effects; and/or
• unknown consequences of its long-term use.

Note that where uncertainties exist, the product would generally maintain its prescription status.

In contrast, products for self-care use should have a long history of use under the proposed conditions of use and be well characterized. Ideally, a product is well characterized if in addition to its safety and efficacy, the pharmacodynamics, the pharmacokinetics and the toxicological profile of the product are known and well documented.

The applicant needs to provide any information relevant to this principle not mentioned under Factor 2.1 (described below). The applicant should demonstrate that the proposed NHP or NPD has limited uncertainties that do not warrant practitioner oversight. The applicant needs to summarize where uncertainties and gaps in the information exist, including analysis on the following:

• uncertainties and gaps in the data regarding the toxicology and safety of the product
• uncertainties and gaps in the body of evidence supporting the product’s safety and efficacy relative to its proposed use in the non-prescription context and under the proposed conditions of use

The applicant needs to substantiate that there is only a minimal level of uncertainty and minimal gaps in the evidence. Furthermore, the applicant should explain the reason(s) any remaining uncertainties and/or gaps would not result in a need for practitioner oversight.

Products for which there is limited market experience typically maintain their prescription status. Market experience may be limited with respect to years of sales or in terms of volume of sales (population exposure).

The applicant should address all the elements outlined in Appendix D of this guidance document when demonstrating that there is adequate market experience supporting the safety of the product.

To be granted non-prescription status, products should not pose a danger to the health and safety of individuals, animals or the public at large. If the applicant has identified ways to mitigate potential dangers, the applicant should demonstrate that the mitigation measures are effective.

If the applicant has additional information relevant to this principle that is not covered in the sections on Factors 3.1 and 3.2 (detailed below), the applicant should include it in this part of the template. If the applicant does not have additional information, the applicant should indicate in this section of the template that all the information relative to this principle is included under Factors 3.1 and 3.2.

To be suitable for self-care use, the widespread or improper use of a product should not have the potential to cause public health issues.

Examples of public health issues are the development of drug resistance in strains of microorganisms (bacteria, viruses, or fungi) and parasites emerging as opportunistic pathogens. A product whose use in the non-prescription setting could contribute to the development of drug resistance will generally maintain its prescription status.

For this factor, the applicant should include an assessment of whether there is potential for harm to public health and if applicable, any risk mitigation measures.

A product for use in the non-prescription setting should not have the potential to lead to abuse^{Footnote 4Footnote 5} and/or diversion. Products that have the potential to lead to abuse typically have reinforcing or rewarding properties (refer to Factor 1.8). These properties can be associated with alterations in perception, cognition, mood and/or levels of arousal and, therefore, could lead to harmful patterns of use. The potential for diversion of these products also exists, both between individuals, as well as from veterinary use to human use. Generally in these cases the medicinal ingredient will be regulated as a controlled substance under the Controlled Drugs and Substances Act and its regulations.

In order for the product to be switched to non-prescription status, the applicant should demonstrate that it has a low likelihood for abuse^{Footnote 6}. This may necessitate that the applicant provides some or all of the following:

• an examination of whether the structure of the medicinal ingredient in question is similar to other known substances associated with abuse
• receptor binding studies to determine the affinity of the medicinal ingredient and its metabolites to cellular targets known to be common to drugs associated with abuse
• functional assays to determine the nature of neurotransmitter activity
• non-clinical and clinical studies designed to assess whether the ingredient or its metabolites contain reinforcing or rewarding properties and whether there is an increased likelihood that the product will be used for these reinforcing properties
• an assessment of whether the product elicits withdrawal symptoms upon discontinuation
• dose-response studies to characterize the psychoactivity as well as the total content of the medicinal ingredient available in each dose/container/package
• a review of available information^{Footnote 7} to determine if abuse or diversion has been reported with the ingredient
• a summary of market experience listing adverse events associated with abuse

The applicant should be clear on what effects are observed under normal conditions of use (the conditions for which the switch is being sought) versus those seen under other conditions of use, such as at higher doses. The applicant should also address whether the product could be tampered with in order to accentuate the reinforcing psychoactive properties.

For a product to be granted non-prescription status, the applicant needs to demonstrate that these types of concerns do not exist or can be successfully mitigated without practitioner involvement. In all situations, the applicant should address whether there are any special concerns for particular sub-populations, such as those with a history of problematic drug use.

Appendix C: Consumer use studies

Consumer use studies help provide evidence that consumers can use the proposed product safely and effectively without practitioner oversight.

There are four main types of consumer use studies:

1. label comprehension studies
2. self-selection studies
3. actual use studies
4. human factors studies

Health Canada expects the applicant to provide all or some combination of the above-noted consumer use studies in switch submissions. The applicant is encouraged to discuss the need for consumer use studies with Health Canada before filing their submissions.

Ideally, consumer use studies should be conducted using study subjects who are representative of Canadian demographics.

In terms of language, in some cases, consumer use studies can be conducted solely in English or French if the text of the other language on the product label is an accurate translation of the tested label. In other cases, such as for all label comprehension studies, Health Canada may request that studies be conducted in both official languages. Health Canada will give consideration to consumer use studies conducted in French- or English- speaking foreign countries on a case-by-case basis, if equivalent studies are not available for the Canadian population.

The applicant may choose to follow methodologies for consumer use studies suggested by other regulatory agencies^{Footnote 8} and can discuss their choice of methodologies at a pre-submission meeting.

C.1 Label comprehension studies

Central to justifying a switch is the demonstration that the labelling effectively supports the consumer using the proposed product without practitioner involvement. Label components can include the outer and inner product labels; and package inserts. A label comprehension study assesses the consumer’s understanding of the major communication elements that relate to the safe and effective use of the product.

This may include assessing the consumer’s understanding of the following:

• what the product is indicated for;
• the dose and interval;
• when to stop using the product; and
• any potential contraindications, warnings and interactions with other medication.

The labels used in the label comprehension studies should be as close as possible to the final proposed label to be included in the switch submission. Label comprehension studies should include a heterogeneous group of subjects, representative of the target population, that vary in age, sex, underlying medical conditions, concomitant medications and level of literacy. Studies should include individuals who have a low level of literacy as assessed by a validated instrument such as the Rapid Estimate of Adult Literacy in Medicine (REALM) test, the Test of Functional Health Literacy in Adults (TOFHLA) or the Short Test of Functional Health Literacy in Adults in French (Fren-STOFHLA). Proper study design and an appropriately constructed questionnaire are critical for an accurate interpretation of the study results. Note that online questionnaires are not acceptable evidence, due to the increased risk of bias.

The applicant needs to include a comprehensive statistical analysis plan in the study protocol being provided to Health Canada. The applicant should also provide an analysis of both quantitative and qualitative data to support and interpret study findings. Additionally, the applicant should organize the results by age cohorts and literacy levels. Generally, a success rate of 80% is expected for the major communication elements relating to safety and efficacy. These label elements include, but are not limited to, the following:

• indication;
• treatment duration;
• route of administration;
• dose and dosing interval;
• non-medicinal ingredient(s);
• medicinal ingredient(s) and strength(s);
• circumstances requiring the consumer to stop treatment and seek medical advice; and
• risk information including precautions, warnings, contraindications and interactions with other medication or food.

C.2 Self-selection studies

Label comprehension studies do not necessarily predict correct self-selection or the actual way the consumer will use the proposed product. Therefore, self-selection studies are conducted to test whether consumers can apply the label information to their personal medical situations and make correct decisions to use or not use the product.

In self-selection studies, researchers answer the following key questions:

• Can consumers identify the purpose of the product?
• Based on their health conditions, can they demonstrate good judgment about whether the product is right for them?

Self-selection studies therefore assess the ability of consumers to determine whether a product is appropriate for them based on their personal health history and the recommended use(s) of the product, dosing, precautions, warnings and contraindications specified on the proposed product label.

Self-selection studies involve the use of well-planned recruitment and sampling strategies; a well-developed and pre-tested questionnaire; and specifically trained interviewers to ask the questions. Exclusion criteria should be minimal and limited to the inability to speak, read or understand either official language. Additionally, open-ended questions should be asked to assess the reasons subjects make incorrect self-selection decisions.  Responses to these questions will guide labelling modifications that may be required to improve self-selection.

As is the case with any study, the applicant should include a comprehensive statistical analysis plan in the protocol for the self-selection study that is being submitting to Health Canada. Additionally, the applicant should provide an analysis of both quantitative and qualitative data to support and interpret study findings.

C.3 Actual use studies

Actual use studies incorporate elements from self-selection and label comprehension studies. These studies are intended to simulate the way consumers will use the proposed products in a “real life” setting.

Observation of study participants in the actual use studies can assist in anticipating what the implications would be of removing a practitioner’s involvement in the diagnosis of the condition, the selection of the product and the monitoring of its use. The design and interpretation of the results of actual use studies are complex. These studies provide information about the following:

• consumer compliance and adherence with the product labelling
• safety issues that arise during actual product use

The applicant should consult the Office of Clinical Trials in the TPD to determine if a Clinical Trial Application is required for their actual use studies.

C.4 Human factors studies

When the switch requested pertains to a prescription drug with a medical device or prescription drug-device combination product, human factors studies may be necessary in order to provide evidence of the safety and efficacy of the medical device with the proposed product for the intended use(s) by consumers and in the intended use environments.

Human factors studies:

• assess the ability of the user to understand the packaging and labeling information;
• assess the ability of the user to safely and effectively use the product with the device;
• validate the performance of the device;
• provide information on device design; and
• assess the adequacy of the device-user interface in order to eliminate or mitigate potential user related hazards.

Appendix D: Market experience data

In the context of this guidance document, market experience is knowledge gained about an authorized product once it is being sold. Market experience provides additional information on the safety and effectiveness of a product in a much larger and diverse population than that of a clinical trial.

D.1 Information to be provided

The applicant needs to provide post-market experience information from Canada and other jurisdictions as part of submission for a switch, if available. This information should ideally be related to the proposed NHP or NPD under the same conditions of use, and when that is not available, the information should be presented relative to products with the same medicinal ingredient and similar conditions of use.

Health Canada expects the applicant to provide the following information from Canada and other jurisdictions, if available:

• a summary of adverse reaction data including, if applicable, information from the applicant’s own safety databases (e.g., a summary of Canadian Adverse Reaction Reports);
• a summary of the safety signals discussed in Periodic Safety Update Reports (PSURs) and Periodic Benefit-Risk Evaluation Reports (PBRERs);
• a summary of the findings from the applicant’s comprehensive review of scientific literature containing safety information;
  • The applicant should include the comprehensive review, the reference articles and the search methodology in the submission package.
• a summary of safety information from any available clinical trials involving the product;
• information on accidental overdose and/or intentional or unintentional misuse;
• a summary of all serious and non-serious medication incidents including near misses, reports of concern (potential errors) and complaints; and
• a summary of any foreign regulatory actions taken with respect to the product’s safety, including a summary of available risk communications and/or recalls.

The applicant should analyze the data above to determine whether safety signals differ when the status of the product is prescription vs non-prescription, if applicable.

With respect to adverse reaction information, Health Canada reminds the applicant to do the following:

• The applicant should consult the World Health Organization’s Vigibase for information on adverse reactions as well as reporting signals from other international databases and include their findings in their analysis.
• When highlighting adverse reactions reported in clinical trials that have occurred since product authorization, the applicant should also address the comparability of the product tested in the clinical trials to that of the proposed NHP or NPD.
• The applicant should take into account the regulatory requirements and procedures by which adverse reactions are collected in the foreign country to contextualize the data. For example, the applicant should outline whether in the foreign country adverse reaction reporting is voluntary or mandatory and under which circumstances (e.g., only mandatory in hospital settings).

D.2 Additional contextual information for key regulatory jurisdictions to be provided

Health Canada expects the applicant to contextualize the market experience information obtained from other key regulatory jurisdictions (e.g., European Union - European Medicines Agency (EMA), United States – Food and Drug Administration (US FDA)). This contextual information will be helpful in Health Canada’s evaluation of the market data provided. To this end, the following details about the product and its regulation in these jurisdictions are necessary:

• foreign product information
• regulatory status
• level of health professional involvement and consumer access
• foreign labelling and other risk mitigation measures
• level of product exposure

The subsections below include further guidance on the difference types of contextual information.

Foreign product information

The applicant should describe the degree of similarity between the foreign product(s) and the proposed NHP or NPD to be marketed in Canada. This includes addressing recommended single and maximum daily dose; duration of use; route of administration; dosage form; and indications in the foreign jurisdiction(s).

Regulatory status

Health Canada expects the applicant to provide information on the regulatory status of the product in key regulatory jurisdictions. That is, the applicant should indicate whether these jurisdictions have classified their product as a prescription drug, non-prescription product, behind-the-counter product, a food supplement, etc.

Level of health professional involvement and consumer access

If there are key regulatory jurisdictions in which the product is not a prescription drug (i.e., has non-prescription status), the applicant should outline the restrictions from all levels of government that pertain to the product’s oversight and access. Specifically, the applicant should indicate the level of health professional involvement in the selection and sale of the product. For example, in some key jurisdictions, the product may be non-prescription but can only be obtained through consultation with a pharmacist or naturopath. The applicant should also indicate how accessible the product is for purchase. For example, in some key regulatory jurisdictions, the product may be freely available for purchase in all retail locations, while in others, its sale may be restricted only to pharmacies or hospital pharmacies.

Labelling and other risk mitigation measures

The applicant should highlight the differences between their proposed labelling and the approved foreign product labelling if the product is non-prescription in any of the key regulatory jurisdictions.

The applicant should also present information about any specific risk mitigation measures in place for the product’s use in any other countries and any significant safety-related changes highlighted in PBRER reports.

Level of product exposure

The applicant should indicate, when applicable, the length of time the product has been marketed and estimate the product exposure in the key regulatory jurisdictions.

Appendix E: Template for the PDL principles and factors assessment

To apply for a switch, complete the PDL Principles and Factors Assessment using the headers of all the principles and the factors as shown below in the template. Include the assessment in Module 1.0.7 of the SNDS or NDS.

When completing the template, ensure the following:

• Each section contains the summary of evidence and the rationale to show that the indicated principle or factor does not apply to the proposed NHP or NPD.
• Each section includes a reference to the location of the full data in your submission package, where applicable.
• No section is left blank or only contains “N/A”; otherwise, Health Canada may issue a Screening Rejection Letter or Screening Deficiency Notice.

Table 2: Template