Health Products and Food Branch Inspectorate - Annex to the Natural Health Products (NHPs) Compliance and Enforcement Policy for Exempt NHPs under the Natural Health Products (Unprocessed Product Licence Applications) Regulations (UPLAR) (POL-0093)

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.

Letter

Our Mandate:
To promote good nutrition and informed use of drugs, food, medical devices and natural health products, and to maximize the safety and efficacy of drugs, food, natural health products, medical devices, biologics and related biotechnology products in the Canadian marketplace and health system.

Supersedes: New document

Date issued:
August 27, 2010

Date of implementation:
August 27, 2010

Disclaimer:

This document does not constitute part of the Food and Drugs Act (Act) or its associated Regulations and in the event of any inconsistency or conflict between that Act or Regulations and this document, the Act or the Regulations take precedence. This document is an administrative document that is intended to facilitate compliance by the regulated party with the Act, the Regulations and the applicable administrative policies. This document is not intended to provide legal advice regarding the interpretation of the Act or Regulations. If a regulated party has questions about their legal obligations or responsibilities under the Act or Regulations, they should seek the advice of legal counsel.

Table of Contents

• 1.0 Purpose
• 2.0 Background
• 3.0 Scope
• 4.0 Definitions
• 5.0 Identification of an Exempt NHP
• 6.0 Requirements under the NHP-UPLAR
  • 6.1 Requirement to Report Recalls
  • 6.2 Reporting of site information related to a product
  • 6.3 Labelling of the Exemption Number on an Exempt Product
• 7.0 Compliance and Enforcement Approach under the NHP-UPLAR
  • 7.1 Sale and/or Importation of Exempt NHPs.
  • 7.2 Exempt NHPs for which the PLA has been withdrawn or refused
  • 7.3 Marketed NHPs differing from the PLA for which the EN has been granted
  • 7.4 Exempt NHP meets the specified risk criteria
  • 7.5 Exempt NHP being advertised, labelled or sold in a false or misleading manner
  • 7.6 Exempt NHP not labeled with the EN
• 8.0 Risk Management Tools
• 9.0  Repeal
• 10.0 Reference Material
• Appendix A: Ingredients Prohibited or considered Adulterants under the FDR
• Appendix B: Ingredients subject to a stop sale and recall if found in NHPs

1.0 Purpose

The purpose of this annex to the Natural Health Product Compliance and Enforcement Policy (POL-0044) (NHP C&E Policy) is to provide clarification on the compliance and enforcement approach for products that are exempt under the Natural Health Products Unprocessed Product Licence Applications Regulations (NHP-UPLAR).

This annex is to be used in conjunction with the NHP C&E Policy (POL-0044) and the Compliance and Enforcement (POL-0001)

All provisions of the Natural Health Products Regulations (NHPR) apply to exempt NHPs except where otherwise indicated in the NHP-UPLAR. These exceptions are described in this annex.

2.0 Background

The NHP-UPLAR came into force on August 4, 2010. These Regulations allow for natural health products (NHPs) to obtain an exemption from the prohibition, outlined in section 4(1) of the NHPR, against the sale of an NHP without a product licence.

Before an NHP can be exempted, a certain process must be followed: the Natural Health Products Directorate (NHPD will send applicants a letter requesting their consent to the posting on the Health Canada website of their name, the Exemption Number (EN) and the brand name(s) of the NHP. In addition, the applicants must provide a statement of confirmation that the product does not meet any one of the specified risk criteria as outlined in section 2(3) of the NHP-UPLAR. An NHP which meets any one of these criteria is not eligible for an exemption. If this information is received by NHPD within 60 days of the letter, the exemption number (EN), as well as the applicant name and brand name(s) will be posted in the Exempted Products Database on the Health Canada website at which point, the product is considered to be an exempt NHP. The website will be updated daily and will include the status of the exempt NHP. Consumers will be able to determine if the exemption granted with respect to a particular product is still valid or is no longer valid either because the applicant has withdrawn the application or because Health Canada has assessed and disposed of the application (i.e., granted a product licence or refused to licence the product).

For further information, please refer to the “Exempted Products” link on the NHPD website.

3.0

This annex to the NHP C&E Policy applies only to those NHPs exempted under the NHP-UPLAR. This annex does not apply to NHPs for use in clinical trials in human subjects which remain governed by the requirements of Part 4 of the NHPR.

4.0 Definitions

These definitions have been created for the purpose of this Annex. They do not constitute any part of the FDA, the NHPR and/or the NHP-UPLAR. 

EN Holder:

the person who is deemed to have been issued a product licence as per section 3(1) of the NHP-UPLAR.

Exemption Number (EN):

a number assigned to a specific NHP, and its associated brand name(s), under the NHP-UPLAR.

Exempt NHP:

an NHP that has been assigned an EN which is posted on the Health Canada website and which has not been suspended or otherwise rendered invalid is exempt from the prohibition section 4(1) of the NHPR (sale of an NHP without a product licence).

Marketed NHP:

the NHP that is available for sale.

Product Licence Application (PLA):

the application submitted to the NHPD under section 5 of the NHPR to obtain a product licence.

Specified Risk Criteria:

criteria outlined in section 2(3) of the NHP-UPLAR. Specifically, if the NHP:

• is a sterile ophthalmic preparation or;
• contains an ingredient prohibited under the Food and Drug Regulations (FDR) sections C.01.036, C.01.036.1, C.01.038 (a), (b), (d), (e), C.01.040, or C.01.040.1, as summarized in Appendix A to this Annex or;
• contains an ingredient that is the subject of a recall or stop sale based upon a serious risk to health attributed to that ingredient, as summarized in Appendix B to this Annex; or;
• contains a claim relating to the treatment or cure, prevention of any of the diseases, disorders or abnormal physical states referred to in Schedule A to the Food and Drugs Act (FDA) or;
• is recommended for use in children under 12 years old or;
• is recommended for use during pregnancy or breast feeding

5.0 Identification of an Exempt NHP

As required in the NHP-UPLAR, the brand name(s), EN holder name and EN number of all exempt NHPs will be posted in the Exempted Products Database on the Health Canada website. In addition, exempt NHPs may be identified by the appearance of the prefix “EN” followed by a six digit number on the marketed product label. However, it is possible that not all exempt NHPs being marketed will have the EN on the product label, as it may take some time for new product labels to reach the retail level. Therefore, the Exempted Products Database should be consulted in cases of uncertainty.  The website will indicate whether the exemption is valid, invalid or whether the product has been licensed.

When a suspected non-compliance with the FDA, NHPR or NHP-UPLAR is brought to the attention of the Inspectorate, the Inspectorate will first verify the licensing and/or exemption status of the product.   The EN holder may be asked to provide Health Canada with the EN for the product(s) in question in the event of a suspected non-compliance. The marketed product may be verified against the PLA information submitted to the NHPD for which the EN was granted.

6.0 Requirements under the NHP-UPLAR

The FDA and the NHPR apply to exempt NHPs, except where otherwise indicated in the NHP-UPLAR. Under the NHP-UPLAR, EN holders are considered to be the product licence holders under the NHPR.  As such, exempt NHPs must meet most of the requirements in the NHPR including but not limited to:

• Site Licensing Requirements (Part 2 of the NHPR)
• Good Manufacturing Practices (Part 3 of the NHPR)
• Record Maintenance (Section 23 of the NHPR)
• Adverse Reaction Reporting Requirements (Section 24 of the NHPR)
• Labelling and Packaging Requirements (Part 5 of the NHPR)

Below are some additional points of clarification with respect to requirements under the NHP-UPLAR for exempt NHPs.

6.1 Requirement to Report Recalls

As per section 6 of the NHP-UPLAR, any recall initiated for an exempt NHP must be reported to the Inspectorate within 3 days after the day on which the recall is commenced along with the necessary recall information, including the EN.  This is consistent with section 62 of the NHPR, with the exception of having to provide the NPN for the product (paragraph 62(c) of the NHPR). Further information can be found in the Inspectorate’s  Recall Policy (POL-0016).

6.2 Reporting of site information related to a product

Section 5 of the NHP-UPLAR requires that site information related to an exempt NHP, as required by section 22(1) of the NHPR, be provided to the NHPD prior to commencing sale of an exempt NHP. It is important that EN holders have all the information referenced in section 22 of the NHPR readily available to provide to Health Canada upon request.

6.3 Labelling of the Exemption Number on an Exempt Product

As per section 7 of the NHP-UPLAR, the product’s exemption number (EN) must be shown on the label in accordance with sections 88 and 93 and, if applicable, with sections 89 (single label requirements) and 94 (small package labelling requirements) of the NHPR within a reasonable period of time (e.g., the sooner of the next label run or 12 months from the time the NHP becomes exempt).   This section has been incorporated in place of subparagraphs 93(1)(a)(ii); and 94(1)(a)(vii) of the NHPR which refer to the product licence (NPN) number.

7.0 Compliance and Enforcement Approach under the NHP-UPLAR

The compliance and enforcement approach outlined in the NHP C&E Policy applies to exempt NHPs in that the risk to health, as well as a number of additional factors (such as the likelihood of compliance by the regulated party), are taken into consideration in determining the compliance and enforcement approach and risk management tools employed. 

This section clarifies certain details respecting exempt NHPs and the compliance and enforcement approach.

7.1 Sale and/or Importation of Exempt NHPs

The primary exemption to the NHPR for an exempt NHP is section 4(1) of the NHPR, the prohibition against sale without a product licence. NHPs which have been exempted from the application of section 4(1) can be legally sold in Canada. As such, section 6.1.1 of the NHP C&E Policy (the sale and/or importation of an unlicensed NHP) does not apply to exempt NHPs.

7.2 Exempt NHPs for which the PLA has been withdrawn or refused

Exempt NHPs for which the PLA has been withdrawn by the applicant or refused pursuant to section 9 of the NHPR are no longer considered to be exempt.  Further sale of these products would be considered to be in violation of section 4 of the NHPR and may pose a risk to health. Should a PLA for an exempt NHP be refused pursuant to section 9 of the NHPR, the responsible party should immediately stop sale and recall any products available for sale. Recall information must be submitted to the Inspectorate as referenced in section 6.1 of this annex. Compliance and enforcement actions may be taken in accordance with the NHP C&E Policy.

7.3 Marketed NHPs differing from the PLA for which the EN has been granted

An EN is granted based on the information provided by the applicant to the NHPD in the PLA. If an exempt NHP is being sold, it is required to be consistent with the information for which the EN has been granted.

Should the EN holder wish to make changes to the exempt NHP, only those considered to be notifications as outlined in section 12 of the NHPR are acceptable for exempt NHPs. These include changes which do not impact the safety, efficacy and/or quality of the product and include:

• the company information as required by section 5(a) or (b) of the NHPR
• the site information as required by section 22 of the NHPR
• the addition or substitution of a non-medicinal ingredient that does not affect the safety or efficacy of the product
• the brand name of the product
• the common or proper name of any of the medicinal ingredients
• the addition of risk information

If any of the above changes are made to an exempt NHP, EN holders should consult the Post-Licensing Guidance Document for information on how to submit a notification to NHPD.  Rather than referencing the NPN or DIN-HM, the EN holder would reference the EN. The exemption database would be updated accordingly. It is also possible for applicants to contact their NHPD submission coordinator associated with the PLA with any questions of clarification surrounding these types of changes. This notification should take place as soon as possible, but is required within 60 days of making the change to a marketed exempt NHP.

Changes initiated by the applicant and considered to be amendments as per section 11 of the NHPR are not acceptable for exempt NHPs. These include but are not limited to: changes to the recommended dose, duration or recommended use or purpose, deletion or modification of risk information, a change to the source material or potency of any medicinal ingredient, certain changes to product specifications, among others.  These changes may have an impact on the safety, efficacy or quality profile of the NHP and may significantly impact the assessment of information for which the EN has been granted. Further information can be found in the Post Licensing Guidance Document A product may be subject to compliance and enforcement actions if the product being marketed differs from the PLA for which the EN was granted in relation to any of the changes considered to be amendments.

It is important to note that during the course of the PLA review by the NHPD following assignment of an EN, NHPD may request changes to the PLA as part of the licensing process. In some instances, NHPD may request changes that have an impact on the safety, efficacy or quality of the NHP.  In these cases, if a risk to health is identified with the original exempt NHP and the NHP is being marketed, certain risk management actions may need to be taken (such as a product recall and relabeling) to bring the product into compliance and to be consistent with the new PLA information. These actions are based on the level of risk associated with the marketed product and in accordance with the NHP C&E Policy.

7.4 Exempt NHP meets the specified risk criteria

In order to obtain an exemption, applicants are required to provide a statement that the NHP does not meet any one of the specified risk criteria set out in subparagraphs 2(3)(a)(i) to (v) nor, to the best of the person’s knowledge, in paragraph 2(3)(b) of the NHP-UPLAR.  NHPs that meet any of the specified risk criteria are not eligible for an exemption as they require a higher level of oversight which is provided by a complete safety, efficacy and quality assessment required for product licensing. If it is determined that an exempt NHP meets any one of the specified risk criteria, the exempt NHP may be subject to compliance and enforcement actions in accordance with the NHP C&E Policy for that of a higher risk non-compliance. In addition, the EN for that product may be suspended pursuant to section 4(b) of the NHP-UPLAR (see also section 8.0 of this annex).

7.4.1 Sterile ophthalmic products

Sterile ophthalmic products are sensitive to quality requirements and as such, a non-compliant sterile ophthalmic product that has not undergone a full quality assessment through product licensing may pose a risk to health.

7.4.2 Products containing an ingredient referred to in the Food and Drug Regulations (FDR) sections C.01.036, C.01.036.1, C.01.038, C.01.040, or C.01.040.1 and/or contains an ingredient that has been subject to a stop sale or recall as it is likely to pose a risk to health.

Under the FDR, Ingredients found in Appendix A are prohibited to be sold if they are in drug products. In addition, there are several ingredients which have been identified by Health Canada as being likely to pose a risk to health if they are found in an NHP and have been subject to a stop sale or recall of marketed NHPs.  These ingredients are found in Appendix B. Appendix B is not an exhaustive list of ingredients. As scientific information changes, new ingredients may be identified and added to Appendix B.

7.4.3 Products that contain a claim relating to the treatment, prevention or cure of any of the diseases, disorders or abnormal physical states referred to in Schedule A to the FDA.

As per section 3 of the FDA, an NHP cannot be labelled or advertised to the general public for the prevention, treatment or cure of diseases listed in Schedule A of the FDA. Diseases listed in Schedule A, such as cancer and diabetes, all require the intervention of a medical practitioner. The use of a product through self-medication may result in harm to the consumer. Although regulatory amendments were made to the NHPRon June 1, 2008 to allow NHPs (and non-prescription drugs) to make preventative claims for diseases listed in Schedule A, unapproved preventative claims for Schedule A diseases are still considered to pose a higher risk, and require a full assessment which is provided for through the licensing process.  For this reason, NHPs which are exempt under the NHP-UPLAR cannot make preventative claims for Schedule A diseases (see section 3(a)(iii) of these Regulations). The complete list of schedule A diseases (http://laws.justice.gc.ca/eng/F-27/page-3.html#anchorsc:1) can be found in the FDA.

7.4.4 Products recommended for use in children under 12 years old or during pregnancy or breastfeeding

Vulnerable sub-populations may be more susceptible to adverse health effects and as such, an NHP marketed towards a vulnerable sub-population that has not been fully assessed for safety, efficacy or quality for that sub-population may pose a higher risk to health.

7.5 Exempt NHP being advertised, labelled or sold in a false or misleading manner

The position for exempt NHPs is consistent with that outlined in section 6.2.2 of the NHP C&E Policy. As per section 9 of the FDA, the labelling, sale or advertising of any therapeutic product must be done in a manner that is not false, misleading or likely to create an erroneous impression regarding its character, value, quantity, composition, merit or safety.  A product that is being labelled, sold or advertised in a manner consistent with that product’s PLA, absent other factors, would not generally be false or misleading or likely to create an erroneous impression with respect to its character, value, quantity, composition, merit or safety.  Any products or advertising materials brought to the attention of Health Canada will be evaluated and may be subject to compliance and enforcement actions on the basis of section 9 of the FDA. A product may be subject to compliance and enforcement actions if the product being marketed differs from the PLA for which the EN was granted in relation to any of the changes considered to be amendments.

7.6 Exempt NHP not labeled with the EN

Labelling of the EN on the product label must be done within a reasonable period of time. Health Canada interprets this to mean the lesser of the next label run or 12 months from the date of issuance of the EN. Compliance with this part is of benefit to the regulated party as well as to consumers to help identify products that have obtained an EN. Non-compliance with this section of the NHP-UPLAR is considered a lower priority for compliance and enforcement actions by the Inspectorate.

8.0 Risk Management Tools

The risk management tools available outlined in POL-0001 as well as the NHP C&E Policy apply to exempt NHPs. Most of the tools specified in the NHPR available for licensed NHPs under the NHPR also apply to exempt NHPs. These tools include:

• a request for additional safety information under section 16 or 24 of the NHPR,
• a direction to stop sale under section 17 of the NHPR, and;
• a suspension or cancellation of a product licence under section 19 of the NHPR.

The intent to suspend a product licence under section 18(1) of the NHPR has been excluded for exempt NHPs. This section has been replaced with section 4 of the NHP-UPLAR, in which an EN may be suspended if Health Canada has reasonable grounds to believe that the person to whom the licence is deemed to have been issued has contravened the NHP-UPLAR, or if the exempt NHP meets any one of the specified risk criteria set out in subparagraphs 2(3)(a)(i) to (v) or is described in paragraph 2(3)(b) of the NHP-UPLAR.  In this case, section 18(2) of the NHPR continues to apply in that an applicant would be given 90 days from the date of notice to provide information demonstrating the situation did not exist or has been corrected.  If this information is not provided or is insufficient, the exemption may be suspended. If an EN is suspended, the product may no longer legally be sold, as per section 4(3) of the NHPR. Compliance and enforcement actions may be taken in accordance with the NHP C&E Policy. Further information can be found in the NHP Post Licensing Guidance Document.

9.0 Repeal

This annex to the NHP C&E Policy will remain in effect for 30 months and will be removed upon the repeal of the NHP-UPLAR.

10.0 Reference Material

For information regarding the compliance and enforcement approach for NHPs:

• The Natural Health Products Compliance and Enforcement Policy (POL-0044)
  *Additional reference materials may be found in this policy

• Compliance and Enforcement (POL-0001)

For information regarding the NHP-UPLAR:

• For further information, please refer to the “Exempted Products” link on the NHPD website.

For information regarding making post-licensing changes:

• Post Licensing Guidance Document

Appendix A:

Ingredients Prohibited or considered Adulterants under the FDR

Ingredient		FDR
1	Arsenic and its salts and derivatives	C.01.040
2	Chloroform	C.01.040
3	Echimidine and its salts	C.01.038
4	Mercury and its salts and derivativesTable 1 footnote	C.01.036
5	Methapyrilene and its salts	C.01.038
6	Methyl salicylate (for internal use in humans)	C.01.040.1
7	Nitrous oxide	C.01.036.1
8	Oxyphenisatin	C.01.036
9	Oxyphenisatin acetate	C.01.036
10	Phenacetin in combination with any salt or derivative of salicylic acid	C.01.036
11	Phenisatin	C.01.036
12	Any of the following plant species or extracts or tinctures thereof:(i) Symphytum asperum,(ii) Symphytum x uplandicum, or(iii) any other plant species containing echimidine	C.01.038
13	Strychnine and its salts, extracts or tinctures of(i) Strychnos nux vomica(ii) Strychnos Ignatii, or(iii) a Strychnos species containing strychnine, other than those species mentioned in (i) and (ii)	C.01.038

Appendix B: Ingredients subject to a stop sale and recall if found in NHPs

Products containing an ingredient on this list may be considered to pose a serious risk to health. NHPs containing these ingredients have been subject to a stop sale and/or recall in the past due to the concerns with the ingredients.

Proper Name	Common Names	Source Material	Exceptions	Rationale
Aphanizomenon flos-aquae	Aphanizomenon flos-aquae, Blue green algae	Whole cell	None	High probability that products containing Aphanizomenon flos-aquae could be contaminated with the hepatotoxins microcystin-LR and -LA.  There are known severe side effects (including hepatotoxicity and death) associated with the ingestion of microcystins.
Collodial Silver	Collodial Silver		Collodial Silver is acceptable in homeopathic medicines at potencies of 3X or higher. Topical colloidal silver is acceptable.	Evidence indicates that risks to health likely outweigh possible benefits. The amount of silver provided by an oral daily dose of silver may exceed the Tolerable Daily Intake (or oral reference dose) for silver from all sources for any subpopulation.
D-Amygdalin Laetrile	D-Amygdalin Laetrile	Prunus armeniaca  (Seed)	None	Likelihood of serious adverse health consequences from cyanide released by ingestion of amygdalin.
Ephedra sinica Stapf (Ephedraceae)	Cao ma-huang Chinese ephedra Chinese joint-fir Ephedra Ma-huang	Whole plant Branchlet and/or branch, stem	Ephedrine hydrocholoride is acceptable in homeopathic medicines at potencies of 12 CH or higher.	Adverse effects associated with ephedra/ephedrine can include dizziness, headache, decreased appetite, anxiety, restlessness or nervousness, gastrointestinal distress, irregular or fast heartbeat, insomnia, flushing, sweating, hypertension, stroke, seizures, psychosis and death.
l-Ephedrine	l-Ephedrine	l-Ephedrine l-Ephedrine hydrochloride l-Ephedrine sulfate
Laree tridentate Larrea divaricata	Chaparral Creosote-bush Paloondo	Leaf	Larrea divaricata is acceptable in homeopathic medicines at potencies of 1X or higher. Topical chaparral is acceptable.	Potential for liver and kidney problems.
Lumbrokinase	Earthworm fibrinolytic enzymes (EFE)		None	Fibrinolytic enzymes should only be used under the supervision of a health care practitioner.  They may interact with other prescription or non-prescription fibrinolytic or blood-thinning drugs.
Nattokinase	Nattokinase
Piper methysticum	Kava Kava-kava Kava pepper Kawa pepper Yanggona	Piper methysticum (Whole plant)	Piper methysticum is acceptable in homeopathic medicines at potencies of 1X or higher.	Adverse events including liver toxicity can occur when kava is administered.
Synephrine AND Caffeine	Synephrine AND Caffeine	Citrus aurantium (Fruit peel) AND Camellia sinensis (Leaf) Coffea arabica (Seed) Cola acuminata (Seed) Ilex paraguariensis (Leaf) Paullinia cupana (Seed)	None	Potential for cardiovascular toxicity.