Natural Health Products
In Canada, Natural Health Products (NHPs) are subject to the Food and Drugs Act and Regulations. Products that fall within these Regulations include Herbal Remedies, Homeopathic Medicines, Vitamins, Minerals, Traditional Medicines, Probiotics, Amino Acids, and essential Fatty Acids.
NHPs require a product license before they can be sold in Canada. Obtaining a license will require submitting detailed information on the product to Health Canada (HC), including Medicinal Ingredients Quantity, Potency, and Recommended Use. Once a product has been assessed for Safety and Efficacy and granted Market Authorization, the product label will bear an eight-digit product license number preceded by the distinct letters NPN, or in the case of a homeopathic medicine, by the letters DIN-HM.
Classes of Applications
Health Canada has developed and published a Compendium of Monographs that allows applicants to support the safety, efficacy, and quality of Natural Health Products as part of their application.
There are three classes of applications, which are differentiated by their use of monographs. The classes are described as follow:
Class I applications:
Must comply with all of the parameters of an individual Health Canada monograph (exactly as worded in the monograph).
Class II applications:
Are general and traditional applications supported entirely by a combination of 2 or more monographs as well as the following scenarios:
1. Applications supported entirely by an individual monograph or a combination of monographs with a deviation to one or more monograph statements; which maintains the intent of the monograph(s) statements.
2. Products supported entirely by a combination of Health Canada monographs with the addition of common fruits or vegetables listed in the Canadian Nutrient File.
Class III applications:
Are comprised of General, Traditional and Homeopathic applications requiring Full Assessment and include, but are not limited to, the following scenarios:
1. Products with a novel preparation and/or dosage delivery system presenting unique safety and/or efficacy profiles;
2. Products with ingredient combination issues (including those covered by a monograph) that may require safety assessment. These combinations include applications such as stimulant laxatives combined with diuretics, and weight management ingredients/claims in combination with diuretics. These combinations are reviewed on a case by case basis.
3. Applications partially referencing monograph information but going beyond the parameters established in the relevant monograph(s). For example, a dosage form or route of administration not indicated on the monograph(s) that requires further assessment.
4. Homeopathic applications with specific claims.
PROCESSING
All applications (new submissions, amendments and notifications) submitted to NNHPD will be screened for administrative requirements. If the administrative requirements are met, notifications are processed and new applications or amendments (for all classes) proceed to regulatory screening. Following regulatory screening, Class I and II applications and amendments will be issued a regulatory decision. Class III applications and amendments that have successfully completed the regulatory process will proceed to assessment.
ASSESSMENT
Upon successful completion of the screening process, Class III applications and amendments will be assessed for the safety and efficacy requirements.
A Notice of Refusal will be issued at the assessment stage if the applicant failed to meet the requirements of the NHPR due to failure to submit the requested information in response to deficiencies within a timeline or when the applicant answers are incomplete (deficient response).
Service Standards
The following table outlines the service standards for each application type.
TABLE (1) - Service Standards According To Application type
| APPLICATION TYPE | TYPE OF NOTICE ISSUED | ASSESSMENT | REGULATORY DECISION ISSUED | SERVICE STANDARDS | |
| CLASS I | Compendial Class I Amendment | Notice of Refusal – no Acknowledgement notice applies for this class | Not Applicable | Product Licence or Notice of Refusal | 60 Calendar Days |
| CLASS II | General Traditional Class II Amendment | Application Acknowledgement or Notice of Refusal | Not Applicable | Product Licence or Notice of Refusal | 90 Calendar Days |
| CLASS III | General Traditional Homeopathic Traditional Homeopathic Class III Amendment | 180 Calendar Days | Product Licence or Notice of Refusal | 210 Calendar Days | |
TABLE (2) - Applications Requirements
| REQUIREMENTS | CLASS I | CLASS II & CLASS III | ||
| COMPENDIAL | (GENERAL) NON-TRADITIONAL | TRADITIONAL | HOMEOPATHIC | |
| Licence Application form | Required | Required | Required | Required |
| Label text | Required | Required | Required | Required |
| Summary Report (Evidence, Safety and/or Quality) | Not applicable | Recommended | Recommended | Recommended |
| Evidence | Not applicable | Required | Required | Required |
| Animal Tissue Form (if applicable) | Required | Required | Required | Required |
| Finished Product Specifications | Not applicable | Required | Required | Required |
SUMMARY REPORT
Safety and Efficacy Evidence
Non-Traditional applications are considered to be the most difficult applications for both applicants and the regulatory bodies (NHPD & USFDA). This is because these applications require (from the applicant) various supporting materials on the ingredient’s safety and efficacy and because it requires from the regulating authority thorough assessments to ensure that the evidence provided is appropriate for the product.
Summary reports are recommended to assist in the assessment process and reduce the time of completion, particularly for more complex submissions (e.g., for multi ingredients where some of these ingredients are not listed in HC lists of monographs). In general, the summary report should capture how each piece of information submitted addresses some or all aspects of the recommended conditions of use for the product. These summary reports serve to reflect the totality of available information relevant to the NHP and provide context that speaks to what may otherwise appear as gaps/uncertainties in the information concerning the safety, efficacy, and/or quality of the product.
Risk Categories
A risk-based assessment approach is used to categorize evidence recommendations into three levels of risk: low, medium, and high. These levels are proportionate to the standard of evidence necessary to support safety and efficacy of a product.
1. Efficacy Evidence for the High-Risk Category
Products that make claims for the treatment, prevention or cure of serious health conditions should meet the evidence criteria for the high-risk category.
2. Efficacy Evidence for the Medium Risk Category
Natural Health Products (NHPs) making claims for major health conditions and diseases should meet the evidence criteria of the medium risk category. Should usually be assessed compared to current standard therapy.
3. Efficacy Evidence Requirements for the Low Risk Category
This category includes most vitamins, minerals, essential nutrients, and other nutrients recommended for use by healthy adults. These types of ingredients are often associated with the Natural Health Products Directorate (NHPD) pre-cleared information.
Table(3) outlines the minimum safety and efficacy evidence for the three risk categories.
Acceptable Minimum Safety And Efficacy Evidence By Risk Category
| EVIDENCE TYPE | CONSIDERATIONS |
|---|---|
| NHPD published monographs | N/A |
| Phase III or phase IV clinical trials (randomized, controlled, well-designed) | For treatment, cure, and prevention claims or for health support claims when they imply treatment, cure, prevention, and risk reduction claims if the study is not multi-center, at least two studies are required. |
| Meta-analysis (controlled and well-designed) | Conclusions should be based primarily on phase III trials, not phase II trials; primary evidence may be requested. |
| Prospective observational studies or combinations of one prospective study and one retrospective study | Two pieces of evidence of equivalent ranking or higher are required to support efficacy |
| Evidence of a positive decision from another regulatory agency | Documentation in the form of an authorization letter or positive decision must be submitted that includes details on what was approved. |
| EVIDENCE TYPE | CONSIDERATIONS |
|---|---|
| All acceptable minimum evidence requirements for the high-risk category | N/A |
| Systematic review other than meta-analysis | Conclusions should be based primarily on phase III trials, not phase II trials; primary evidence may be requested. |
| Published, peer-reviewed, detailed narrative reviews which cite detailed primary evidence | Detail should include: defining characteristics of the ingredient; primary endpoints/outcomes with statistical and clinical significance; the studied sub-populations age, gender, and health state; the dosing regimen and dosage form; the route of administration; the directions of use; any restrictions to study entry of participants based on interactions/risk; any identified adverse reactions |
| Phase II clinical trials | Two pieces of evidence of equivalent ranking or higher are required to support efficacy. When the evidence provided to support the claim is methodologically weak, it should be supplemented to demonstrate consistency in results and plausibility. |
| Epidemiological studies | Evidence only meets minimum requirements for prevention and risk reduction claims. Two pieces of evidence of equivalent ranking or higher are required to support efficacy. |
| Published compilations referring to traditional use | Evidence can be used to support safety only |
| EVIDENCE TYPE | CONSIDERATIONS |
|---|---|
| All acceptable minimum evidence requirements for the high and medium risk categories | N/A |
| Phase II clinical trials | One piece of evidence of equivalent ranking or higher is required to support efficacy. |
| Epidemiological studies | Evidence only meets minimum requirements for prevention and risk reduction claims. |
| Pilot and open label studies | Two pieces of evidence of equivalent ranking are required to support efficacy. The two different studies may be of equivalent or higher ranking. |
| Reputable textbooks | Textbook should reflect human in vivo data if the ingredient is an essential nutrient. |
| Demonstration of food use | Evidence can be used to support safety only. |
Recommendations on Efficacy Evidence
1. Efficacy evidence should support the association of the medicinal ingredient(s) with the health claim(s);
2. And demonstrate that therapeutic efficacy of the product will be supported by at least one medicinal ingredient or the combination of more than one.
3. The evidence should support the claim with respect to the specific target population intended and the specific directions of use.
4. Ensure that the same evidence may be sufficient to support both safety and efficacy.
5. The minimum type of evidence from a higher risk category may be used to support a claim in a lower category as long as it is appropriate for the condition.
6. The evidence package should include a complete critical summary reflecting the totality of evidence.
7. Evidence should be presented in the form of a systematic review outlining the validity and causality elements for each reference by providing a critical analysis of the study design types, and the quality and quantity of each evidence type that supports and disproves the claim.
8. Evidence provided should demonstrate statistically significant outcomes, clinically meaningful differences, relevance to the target population, and overall consistency of the results across all studies of acceptable quality.
9. The Efficacy Evidence for the Medium Risk Category can be submitted as individual references, Evidence should ideally demonstrate:
a. A well described study population;
b. A record of the flow of subjects through the trial;
c. Power analysis to determine proper number of subjects;
d. Random allocation;
e. Blinded assessment of outcome;
f. Intention to treat analysis;
10. Additional evidence to support interactions and a complete summary reflecting the totality of evidence should be provided in addition to evidence recommendations listed in Table 1
