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Vol. 137, No. 13 — June 18, 2003 Registration FOOD AND DRUGS ACT Natural Health Products RegulationsP.C. 2003-847 5 June, 2003 Her Excellency the Governor General in Council, on the recommendation of the Minister of Health, pursuant to subsection 30(1) (see footnote a) of the Food and Drugs Act, hereby makes the annexed Natural Health Products Regulations. TABLE OF CONTENTS (This table is not part of the Regulations.) NATURAL HEALTH PRODUCTS REGULATIONS
PART 1 — PRODUCT LICENCES
PART 2 — SITE LICENCES
PART 3 — GOOD MANUFACTURING PRACTICES
PART 4 — CLINICAL TRIALS INVOLVING HUMAN SUBJECTS
PART 5 — GENERAL
PART 6 — AMENDMENTS, TRANSITIONAL PROVISIONS AND COMING INTO FORCE
SCHEDULE 1 — INCLUDED NATURAL HEALTH PRODUCT SUBSTANCES SCHEDULE 2 — EXCLUDED NATURAL HEALTH PRODUCT SUBSTANCES (* * * * *) NATURAL HEALTH PRODUCTS REGULATIONS INTERPRETATION 1. (1) The following definitions apply in these Regulations. "Act" means the Food and Drugs Act. (Loi) "adverse reaction" means a noxious and unintended response to a natural health product that occurs at any dose used or tested for the diagnosis, treatment or prevention of a disease or for modifying an organic function. (réaction indésirable) "brand name" means a name in English or French, whether or not it includes the name of a manufacturer, corporation, partnership or individual
(b) under which a natural health product is sold or advertised. (marque nominative) "case report" means a detailed record of all relevant data associated with the use of a natural health product in a subject. (fiche d'observation) "Compendium" means the Compendium of Monographs published by the Department of Health and as amended from time to time. (Compendium) "distributor" means a person who sells a natural health product to another person for the purpose of further sale by that other person. (distributeur) "expiry date" means the earlier of
(b) the date, expressed at minimum as a year and month, after which the manufacturer recommends that the natural health product should not be used. (date limite d'utilisation) "immediate container" means the container that is in direct contact with a natural health product. (contenant immédiat) "importer" means a person who imports a natural health product into Canada for the purpose of sale. (importateur) "inner label" means the label on or affixed to an immediate container of a natural health product. (étiquette intérieure) "lot number" means any combination of letters, figures, or both, by which a natural health product can be traced in manufacture and identified in distribution. (numéro de lot) "manufacturer" means a person who fabricates or processes a natural health product for the purpose of sale, but does not include a pharmacist or other health care practitioner who, at the request of a patient, compounds a natural health product for the purpose of sale to that patient. (fabricant) "natural health product" means a substance set out in Schedule 1 or a combination of substances in which all the medicinal ingredients are substances set out in Schedule 1, a homeopathic medicine or a traditional medicine, that is manufactured, sold or represented for use in
(b) restoring or correcting organic functions in humans; or (c) modifying organic functions in humans, such as modifying those functions in a manner that maintains or promotes health. However, a natural health product does not include a substance set out in Schedule 2, any combination of substances that includes a substance set out in Schedule 2 or a homeopathic medicine or a traditional medicine that is or includes a substance set out in Schedule 2. (produit de santé naturel) "outer label" means the label on or affixed to the outside of a package of a natural health product. (étiquette extérieure) "principal display panel" has the same meaning as in the Consumer Packaging and Labelling Regulations. (espace principal) "probiotic" means a monoculture or mixed-culture of live micro-organisms that benefit the microbiota indigenous to humans. (probiotique) "proper name" means, in respect of an ingredient of a natural health product, one of the following:
(b) if the ingredient is a plant or a plant material, an alga, a bacterium, a fungus, a non-human animal material or a probiotic, the Latin nomenclature of its genus and, if any, its specific epithet; and (c) if the ingredient is other than one described in paragraphs (a) or (b), the chemical name of the ingredient. (nom propre) "recommended conditions of use" means, in respect of a natural health product,
(b) its dosage form; (c) its recommended route of administration; (d) its recommended dose; (e) its recommended duration of use, if any; and (f) its risk information, including any cautions, warnings, contra-indications or known adverse reactions associated with its use. (conditions d'utilisation recommandées) "security package" means a package having a security feature that provides reasonable assurance to consumers that the package has not been opened prior to purchase. (emballage de sécurité) "serious adverse reaction" means a noxious and unintended response to a natural health product that occurs at any dose and that requires in-patient hospitalization or a prolongation of existing hospitalization, that causes congenital malformation, that results in persistent or significant disability or incapacity, that is life threatening or that results in death. (réaction indésirable grave) "serious unexpected adverse reaction" means a serious adverse reaction that is not identified in nature, severity or frequency in the risk information set out on the label of the natural health product. (réaction indésirable grave et imprévu) "specifications" means a description of a natural health product that contains the information described in subsection 44(2). (spécifications) (2) Subject to subsection (3), the words and expressions used in the provisions of the Food and Drug Regulations that are incorporated by reference by these Regulations shall have the meanings assigned to them by these Regulations, but if no meanings are assigned, they shall have any meaning assigned to them by the Food and Drug Regulations. (3) The word "manufacturer" in the provisions of the Food and Drug Regulations that are incorporated by reference by these Regulations shall have the meaning assigned to it by the Food and Drug Regulations. APPLICATION 2. (1) These Regulations apply to
(b) the manufacture, packaging, labelling and importation for sale of natural health products; (c) the distribution of natural health products; and (d) the storage of natural health products for the purposes of any of the activities referred to in paragraphs (b) and (c). (2) For the purposes of these Regulations, a substance or combination of substances or a traditional medicine is not considered to be a natural health product if its sale, under the Food and Drug Regulations, is required to be pursuant to a prescription when it is sold other than in accordance with section C.01.043 of those Regulations. 3. Except where otherwise indicated in these Regulations, the provisions of the Food and Drug Regulations do not apply to natural health products. PART 1 PRODUCT LICENCES Prohibition 4. (1) Subject to subsections (2) and (3), no person shall sell a natural health product unless a product licence is issued in respect of the natural health product. (2) No product licence holder, manufacturer, importer or distributor of a natural health product for which a product licence is issued shall sell the natural health product during any period that the sale of that natural health product is directed to be stopped under section 17. (3) No person shall sell a natural health product for which a product licence is issued
(b) after cancellation of the licence under paragraph 20(b). Licence Application 5. An application for a product licence shall be submitted to the Minister and shall contain the following information and documents:
(b) if the address submitted under paragraph (a) is not a Canadian address, the name, address and telephone number, and if applicable, the facsimile number and electronic mail address of the applicant's representative in Canada to whom notices may be sent; (c) for each medicinal ingredient of the natural health product,
(ii) its quantity per dosage unit, (iii) its potency, if a representation relating to its potency is to be shown on any label of the natural health product, (iv) a description of its source material, and (v) a statement indicating whether it is synthetically manufactured; (e) each brand name under which the natural health product is proposed to be sold; (f) the recommended conditions of use for the natural health product; (g) information that supports the safety and efficacy of the natural health product when it is used in accordance with the recommended conditions of use; (h) the text of each label that is proposed to be used in conjunction with the natural health product; (i) a copy of the specifications to which the natural health product will comply; and (j) one of the following attestations, namely,
(ii) if the natural health product is not imported, an attestation by the applicant that the natural health product will be manufactured, packaged, labelled, distributed and stored in accordance with requirements set out in Part 3. Sixty-Day Disposition 6. (1) Subject to subsection (2), the Minister shall dispose of an application submitted under section 5 within 60 days after the day on which it is submitted if, in support of the application, the only information submitted by the applicant under paragraph 5(g) is that which is
(b) in the case of an application respecting a natural health product that has more than one medicinal ingredient, contained in a monograph for that combination of medicinal ingredients in the Compendium. (2) If the Minister requests that additional information or samples be submitted under section 15, the 60-day period referred to in subsection (1) does not include the number of days beginning on the day on which the request is made and ending on the day on which the additional information or samples are received. (3) For the purposes of this section, the Minister disposes of an application on the earlier of the day on which
(b) the applicant is sent a notice under subsection 9(1). Issuance and Amendment 7. The Minister shall issue or amend a product licence if
(b) the applicant submits to the Minister all additional information or samples requested under section 15; (c) the applicant does not make a false or misleading statement in the application; and (d) the issuance or amendment of the licence, as the case may be, is not likely to result in injury to the health of a purchaser or consumer. Product Number 8. (1) The Minister shall assign a product number to each natural health product in respect of which a product licence is issued. (2) In the case of a natural health product that is a drug for which a drug identification number is assigned in accordance with subsection C.01.014.2(1) of the Food and Drug Regulations, the product number required under subsection (1) shall be the drug identification number. Refusal to Issue or Amend 9. (1) If the Minister refuses to issue or amend a product licence, the Minister shall send the applicant a notice that sets out the reason for the refusal. (2) Within 30 days after the day on which the notice is sent, the applicant may make a request that the Minister reconsider the application. (3) If the applicant makes a request in accordance with subsection (2), the Minister shall
(b) reconsider the application after giving the applicant that opportunity. 10. (1) After reconsidering the application, the Minister shall issue or amend the product licence if the requirements of section 7 are met. (2) If the Minister again refuses to issue or amend the product licence, the Minister shall send the applicant a final notice that sets out the reason for the refusal. Amendment 11. (1) If the licensee makes any of the following changes in respect of the natural health product, the licensee shall not sell any lot or batch of the natural health product affected by the change unless the product licence is amended accordingly:
(b) a change to its recommended duration of use; (c) the deletion or modification of risk information shown on any of its labels, including the deletion or modification of a caution, warning, contra-indication or known adverse reaction associated with its use; (d) a change of its recommended use or purpose; (e) a change of the source material of any of its medicinal ingredients; (f) changing any of its medicinal ingredients to or from being synthetically manufactured; (g) a change to the potency of any of its medicinal ingredients; (h) a change affecting its safety or efficacy that does not arise as a result of
(ii) the addition or substitution of a medicinal ingredient, (iii) a change to its dosage form, or (iv) a change to its recommended route of administration; or
(ii) the modification of a test method set out in the specifications in a manner that widens the purity tolerances of the natural health product or the quantity, identity or potency tolerances of any of its medicinal ingredients, or (iii) the modification of a test method set out in the specifications in a manner that renders it less precise, accurate, specific or sensitive. (2) An application to amend a product licence shall be submitted to the Minister and shall contain the following information and documents:
(b) a statement identifying each change described in subsection (1) that has been made; (c) information demonstrating that the natural health product is safe and efficacious after the change; (d) the text of each label to be used in conjunction with the natural health product after the change, if the change is any of those described in paragraphs (1)(a) to (h); and (e) a copy of the revised specifications, if the change is any of those described in paragraph (1)(g) or (i). Notification 12. (1) If the licensee makes any of the changes described in subsection (2) in respect of the natural health product, the licensee shall, within 60 days after the day on which the change is made,
(b) provide the Minister with the text of each label used in conjunction with the natural health product since the change, if the change is any of those described in paragraphs (2)(d) to (f). (2) For the purposes of subsection (1), changes in respect of a natural health product are
(b) a change to any of the information provided under section 22; (c) the addition or substitution of a non-medicinal ingredient, the addition or substitution of which does not affect its safety or efficacy; (d) its sale under a brand name other than one submitted under paragraph 5(e); (e) a change of the common or proper name of any of its medicinal ingredients; and (f) the addition of risk information to any of its labels, including the addition of a caution, warning, contra-indication or known adverse reaction associated with its use. Fundamental Change 13. For greater certainty, if the licensee makes any of the following fundamental changes in respect of the natural health product, the licensee may not sell the natural health product affected by the change unless a product licence is issued in accordance with section 7 for the natural health product as changed:
(b) the addition or substitution of a medicinal ingredient; (c) a change to its dosage form; or (d) a change to its recommended route of administration. Licence Contents 14. (1) A product licence shall set out the following information:
(b) the product number of the natural health product; (c) the dosage form that is authorized for the natural health product; (d) the recommended route of administration that is authorized for the natural health product; (e) the recommended dose that is authorized for the natural health product; (f) the recommended duration of use, if any, that is authorized for the natural health product; (g) in respect of each medicinal ingredient of the natural health product
(ii) its authorized potency, if any, and (iii) its authorized source material; (i) the date on which the licence was issued. (2) Within 60 days after the day on which the product licence is issued, the licensee shall notify the Minister of any information set out on the licence that the licensee knows to be incorrect. Additional Information or Samples 15. If the information and documents submitted in respect of a product licence application under section 5 or an application for amendment under subsection 11(2) are insufficient to enable the Minister to determine whether the product licence should be issued or amended, as the case may be, the Minister may request that the applicant provide such additional information or samples of the natural health product as are necessary to make the determination. Safety Information 16. If the Minister has reasonable grounds to believe that a natural health product may no longer be safe when used under the recommended conditions of use, the Minister may request that the licensee provide the Minister, within 15 days after the day on which the request is received, with information and documents demonstrating that the natural health product is safe when used under the recommended conditions of use. Direction to Stop Sale 17. (1) The Minister may direct the licensee, manufacturer, importer and distributor to stop their sale of a natural health product if
(b) the information and documents provided by the licensee in accordance with section 16 do not demonstrate that the natural health product is safe when used under the recommended conditions of use; (c) in the case of a natural health product that is imported, the Minister has reasonable grounds to believe that the natural health product is not manufactured, packaged, labelled, imported, distributed or stored in accordance with the requirements set out in Part 3 or in accordance with requirements that are equivalent to those set out in Part 3; (d) in the case of a natural health product that is not imported, the Minister has reasonable grounds to believe that the natural health product is not manufactured, packaged, labelled, distributed or stored in accordance with the requirements set out in Part 3; or (e) the Minister has reasonable grounds to believe that the natural health product is not packaged or labelled in accordance with the requirements set out in Part 5. (2) The Minister shall lift a direction to stop the sale of a natural health product if the licensee provides the Minister with information and documents demonstrating that
(b) in the case of a direction to stop sale arising under paragraph (1)(c), the natural health product is manufactured, packaged, labelled, imported, distributed and stored in accordance with the requirements set out in Part 3 or in accordance with requirements that are equivalent to those set out in Part 3; (c) in the case of a direction to stop sale arising under paragraph (1)(d), the natural health product is manufactured, packaged, labelled, distributed and stored in accordance with the requirements set out in Part 3; (d) in the case of a direction to stop sale arising under paragraph (1)(e), the natural health product is packaged and labelled in accordance with the requirements of Part 5; or (e) the situation giving rise to the direction to stop the sale of the natural health product did not exist. Suspension and Cancellation 18. (1) Subject to subsection (2), the Minister may suspend a product licence if the Minister has reasonable grounds to believe that
(b) the licensee has made a false or misleading statement in the application submitted under section 5 or the application for amendment under subsection 11(2). (2) Subject to section 19, the Minister shall not suspend a product licence unless
(b) the licensee has not, within 90 days after the day on which the notice referred to in paragraph (a) is received, provided the Minister with information or documents demonstrating that the licence should not be suspended on the grounds that
(ii) the situation giving rise to the intended suspension has been corrected. 19. The Minister shall suspend a product licence before giving the licensee an opportunity to be heard if, as a result of any circumstance, the Minister has reasonable grounds to believe that it is necessary to do so to prevent injury to the health of a purchaser or consumer. 20. If the Minister suspends a product licence under section 18 or 19, the Minister shall send the licensee a notice that sets out the reason for the suspension and the day on which the suspension is effective, and the Minister shall
(b) cancel the licence if, within 90 days after the day on which the suspension is effective, the licensee has not provided the Minister with the information or documents referred to in paragraph (a). 21. If the Minister cancels a licence under paragraph 20(b), the Minister shall send the licensee a notice that sets out the reason for the cancellation and the day on which the cancellation is effective. Site Information 22. (1) Subject to subsection (2), the licensee shall provide the Minister with the following information prior to commencing the sale of the natural health product:
(ii) if the person conducts the activity in Canada, the number assigned to the site licence issued in respect of that activity; (c) the address of each building in which the natural health product is manufactured, packaged or labelled; (d) the address of each building in which the natural health product is stored for the purposes of importation or distribution; and (e) if the natural health product is imported, evidence demonstrating that the natural health product will be manufactured, packaged, labelled, imported, distributed and stored in accordance with the requirements set out in Part 3 or in accordance with requirements that are equivalent to those set out in Part 3. (2) If the natural health product is one in respect of which a drug identification number is assigned in accordance with subsection C.01.014.2(1) of the Food and Drug Regulations and at the time the product licence is issued in respect of the natural health product it is already being sold, the licensee shall provide the information referred to in subsection (1) within 30 days after the day on which the product licence is issued. Records 23. (1) Every licensee who sells a natural health product shall maintain the following records:
(b) records containing sufficient information to enable the recall of every lot or batch of the natural health product that has been made available for sale. (2) The records shall be maintained by the licensee for a period of one year following the expiry date of the natural health product to which that record relates. Reaction Reporting 24. (1) A licensee shall provide the Minister with
(b) a case report for each serious unexpected adverse reaction to the natural health product that occurs inside or outside Canada, within 15 days after the day on which the licensee becomes aware of the reaction. (2) A licensee who sells a natural health product shall annually prepare and maintain a summary report that contains a concise and critical analysis of
(b) all reactions for which a case report is required to be provided under subsection (1), that have occurred
(ii) at a dose used or tested for the diagnosis, treatment or prevention of a disease or for modifying organic functions in humans. (3) If after reviewing a case report provided under subsection (1) or after reviewing any other safety data relating to the natural health product, the Minister has reasonable grounds to believe that the natural health product may no longer be safe when used under the recommended conditions of use, the Minister may request that, within 30 days after the day on which the request is received, the licensee
(b) prepare and provide to the Minister an interim summary report containing a concise and critical analysis of
(ii) all reactions for which a case report is required to be provided under subsection (1), that have occurred
(B) at a dose used or tested for the diagnosis, treatment or prevention of a disease or for modifying organic functions in humans. Recall Reporting 25. Every licensee who commences a recall of a natural health product shall provide the Minister with the information referred to in section 62 within three days after the day on which the recall is commenced. PART 2 SITE LICENCES Application 26. This Part does not apply to any activity that is conducted in respect of a natural health product solely for the purposes of a clinical trial as defined in section 63. Prohibition 27. (1) Subject to subsection (2), no person shall manufacture, package, label or import a natural health product for sale unless
(b) the person conducts the activity in accordance with the requirements set out in Part 3. (2) No person who holds a site licence shall manufacture, package, label or import a natural health product for sale
(b) after cancellation of the licence under paragraph 41(b). Licence Application 28. An application for a site licence shall be submitted to the Minister and shall contain the following information and documents:
(b) a statement specifying which one or more of the activities of manufacturing, packaging, labelling or importing the applicant is proposing to conduct; (c) if the applicant is proposing to manufacture, package or label a natural health product, the address of each building in which each activity is proposed to be conducted; (d) if the applicant is proposing to import a natural health product, the address of each building in which that natural health product is proposed to be stored; (e) for each activity specified under paragraph (b), a statement indicating whether or not the applicant is proposing to conduct the activity in respect of a natural health product in sterile dosage form; and (f) in respect of the buildings, equipment, practices and procedures used to conduct each activity specified under paragraph (b), a report from a quality assurance person demonstrating that they comply with the requirements set out in Part 3. Issuance and Amendment 29. (1) The Minister shall issue or amend a site licence if
(b) the applicant provides the Minister with all additional information requested under section 37; and (c) the applicant does not make a false or misleading statement in the application. (2) If the Minister issues a site licence, the Minister shall assign that licence a site licence number. Refusal to Issue or Amend 30. (1) If the Minister refuses to issue or amend a site licence, the Minister shall send the applicant a notice that sets out the reason for the refusal. (2) Within 30 days after the day on which the notice is sent, the applicant may make a request that the Minister reconsider the application. (3) If the applicant makes a request in accordance with subsection (2), the Minister shall
(b) reconsider the application after giving the applicant that opportunity. 31. (1) After reconsidering the application, the Minister shall issue or amend the site licence if the requirements of subsection 29(1) are met. (2) If the Minister again refuses to issue or amend the site licence, the Minister shall send the applicant a final notice that sets out the reason for the refusal. Amendment 32. (1) A licensee shall not conduct any of the following activities unless the site licence is amended accordingly:
(b) if the licensee is authorized to manufacture, package or label a natural health product, conduct that activity in a building that is not one in which the conduct of that activity is authorized; (c) if the licensee is authorized to import a natural health product, store a natural health product in a building that is not one in which the storage is authorized; or (d) if the licensee is authorized to conduct an activity, but not already authorized to conduct it in respect of a natural health product in sterile dosage form, conduct the activity in respect of a natural health product in that form. (2) An application to amend a site licence shall be submitted to the Minister and shall contain the following information and documents:
(b) a statement that specifies each activity referred to in subsection (1) that the licensee is proposing to conduct; and (c) a report from a quality assurance person demonstrating that the buildings, equipment, practices and procedures used in respect of each activity conducted by the licensee will remain in compliance with the requirements set out in Part 3. Notification 33. If the licensee makes any of the following changes, the licensee shall notify the Minister of the change within 60 days after the day on which the change is made:
(b) a change that substantially alters any building, equipment, practice or procedure in respect of which a report from a quality assurance person was submitted under paragraph 28(f). Licence Contents 34. A site licence shall set out the following information:
(b) the site licence number; (c) each activity that the licensee is authorized to conduct and a statement indicating whether the activity is authorized to be conducted in respect of a natural health product in sterile dosage form; (d) if the licensee is authorized to manufacture, package or label a natural health product, the address of each building in which the licensee is authorized to conduct that activity; and (e) if the licensee is authorized to import a natural health product, the address of each building in which the licensee is authorized to store that natural health product. Expiry 35. (1) A site licence expires on the first anniversary of the day on which it was issued unless it is renewed in accordance with section 36. (2) A site licence that is renewed in accordance with section 36 expires on the day on which the renewal period ends unless the licence is further renewed in accordance with section 36. Renewal 36. (1) The Minister shall renew a site licence if
(b) the licensee provides the Minister with all additional information requested under section 37; and (c) the renewal of the licence is not likely to result in injury to the health of a purchaser or consumer. (2) If the Minister renews a site licence, the Minister shall renew it for a period of
(b) two years, if on the next anniversary of the day on which the licence was issued, the licensee will have held the licence for a period of at least three years but less than nine years; or (c) three years, if on the next anniversary of the day on which the licence was issued, the licensee will have held the licence for a period of nine years or more. (3) A site licence renewal becomes effective on the day after the anniversary of the day on which the licence was issued. Additional Information 37. If the information and documents submitted in respect of an application under section 28, an application for amendment under subsection 32(2) or a request for renewal under section 36 are insufficient to enable the Minister to determine whether the licence should be issued, amended or renewed, as the case may be, the Minister may request that the applicant provide the Minister with such additional information as is necessary to make the determination. Relinquishment of Authorization 38. (1) A licensee may, by amendment of the site licence, relinquish any part of the authorization given to the licensee under this Part. (2) An application to amend the site licence for the purposes of subsection (1) shall be submitted to the Minister and shall contain the following information and documents:
(b) an attestation, signed and dated by a quality assurance person, stating that after the relinquishment, the buildings, equipment, practices and procedures used in respect of each activity conducted by the licensee will remain in compliance with the requirements set out in Part 3. (3) The Minister shall amend the site licence as requested by the licensee in paragraph (2)(a) if the licensee provides the Minister with an application that is in accordance with subsection (2). Suspension and Cancellation 39. (1) Subject to subsection (2), the Minister may suspend a site licence if the Minister has reasonable grounds to believe that
(b) the licensee has made a false or misleading statement in the application submitted under section 28 or the application for amendment under subsection 32(2). (2) Subject to section 40, the Minister shall not suspend a site licence unless
(b) the licensee has not, within 90 days after the day on which the notice referred to in paragraph (a) is received, provided the Minister with information or documents demonstrating that the licence should not be suspended on the grounds that
(ii) the situation giving rise to the intended suspension has been corrected. 40. The Minister shall suspend a site licence before giving the licensee an opportunity to be heard if, as a result of any circumstance, the Minister has reasonable grounds to believe that it is necessary to do so to prevent injury to the health of a purchaser or consumer. 41. If the Minister suspends a site licence under section 39 or 40, the Minister shall send the licensee a notice that sets out the reason for suspension and the day on which the suspension is effective, and the Minister shall
(b) cancel the licence if, within 90 days after the day on which the suspension is effective, the licensee has not provided the Minister with the information or documents referred to in paragraph (a). 42. If the Minister cancels a licence under paragraph 41(b), the Minister shall send the licensee a notice that sets out the reason for the cancellation and the day on which the cancellation is effective. PART 3 GOOD MANUFACTURING PRACTICES Prohibition 43. (1) Subject to subsection (2), no person shall sell a natural health product unless it is manufactured, packaged, labelled, imported, distributed or stored, as the case may be, in accordance with this Part. (2) A person may sell a natural health product that is manufactured, packaged, labelled, imported, distributed or stored, as the case may be, in accordance with requirements that are equivalent to those set out in this Part if the natural health product is imported. Specifications 44. (1) Every natural health product available for sale shall comply with the specifications submitted in respect of that natural health product under paragraph 5(i) and with every change to those specifications made by the product licence holder. (2) The specifications shall contain the following information:
(b) for each medicinal ingredient of the natural health product, detailed information respecting its quantity per dosage unit and its identity, including statements indicating its quantity and identity tolerances; (c) if a representation relating to the potency of a medicinal ingredient is to be shown on a label of the natural health product, detailed information respecting the potency of the medicinal ingredient, including statements indicating its potency tolerances; and (d) a description of the methods used for testing or examining the natural health product. (3) The specifications and every change to those specifications shall be approved by a quality assurance person. Premises 45. (1) Every natural health product shall be manufactured, packaged, labelled and stored in premises that are designed, constructed and maintained in a manner that permits the activity to be conducted under sanitary conditions, and in particular that
(b) permits the effective cleaning of all surfaces in the premises; (c) permits the natural health product to be stored or processed appropriately; (d) prevents the contamination of the natural health product; and (e) prevents the addition of an extraneous substance to the natural health product. (2) Every natural health product shall be stored under conditions that will maintain the quality and safety of the natural health product. Equipment 46. Every natural health product shall be manufactured, packaged, labelled and stored using equipment that is designed, constructed, maintained, operated and arranged in a manner that
(b) permits it to function in accordance with its intended use; (c) prevents it from contaminating the natural health product; and (d) prevents it from adding an extraneous substance to the natural health product. Personnel 47. Every natural health product shall be manufactured, packaged, labelled and stored by personnel who are qualified by education, training or experience to perform their respective tasks. Sanitation Program 48. Every natural health product shall be manufactured, packaged, labelled and stored in accordance with a sanitation program that sets out
(b) procedures for effectively cleaning the equipment used in the activity; (c) procedures for handling any substance used in the activity; and (d) all requirements, in respect of the health, the hygienic behaviour and the clothing of the personnel who are involved in the activity, that are necessary to ensure that the activity is conducted in sanitary conditions. Operations 49. Every natural health product shall be manufactured, packaged, labelled and stored in accordance with standard operating procedures that are designed to ensure that the activity is conducted in accordance with the requirements of this Part. 50. Every manufacturer, packager, labeller, importer and distributor shall establish and maintain a system of control that permits the rapid and complete recall of every lot or batch of the natural health product that has been made available for sale. Quality Assurance 51. (1) Every manufacturer, packager, labeller, importer and distributor shall
(ii) has the training, experience and technical knowledge relating to the activity conducted and the requirements of this Part; and (2) Every natural health product shall be manufactured, packaged and labelled using only material that, prior to its use in the activity, has been approved for that use by a quality assurance person. (3) Every natural health product shall be manufactured, packaged, labelled and stored using methods and procedures that, prior to their implementation, have been approved by a quality assurance person. (4) Every lot or batch of a natural health product shall be approved by a quality assurance person before it is made available for sale. (5) Every natural health product that is sold and subsequently returned to its manufacturer, packager, labeller, importer or distributor, as the case may be, shall be approved by a quality assurance person before that natural health product may be made available for resale. Stability 52. Every manufacturer and every importer shall determine the period of time that, after being packaged for sale, the natural health product will continue to comply with its specifications when
(b) if it does not have recommended storage conditions, it is stored at room temperature. Records Manufacturers 53. Every manufacturer who sells a natural health product shall maintain the following records at the site at which the natural health product is manufactured:
(b) a list of all ingredients contained in each lot or batch of the natural health product; (c) records of any testing conducted in respect of a lot or batch of raw material used in the manufacture of the natural health product; (d) records of any testing conducted in respect of a lot or batch of the natural health product; (e) a copy of the specifications for each natural health product that is being manufactured at the site; (f) records demonstrating that each lot or batch of the natural health product was manufactured in accordance with the requirements of this Part; (g) a record of each determination made by the manufacturer in accordance with section 52 and the information that supports that determination; (h) records containing sufficient information to enable the recall of every lot or batch of the natural health product that has been made available for sale; (i) a list of all natural health products that are being manufactured at the site; and (j) a copy of the sanitation program in use at the site. Packagers 54. Every packager who sells a natural health product shall maintain the following records at the site at which the natural health product is packaged:
(b) records demonstrating that each lot or batch of the natural health product was packaged in accordance with the requirements of this Part; (c) records containing sufficient information to enable the recall of every lot or batch of the natural health product that has been made available for sale; (d) a list of all natural health products that are being packaged at the site; and (e) a copy of the sanitation program in use at the site. Labellers 55. Every labeller who sells a natural health product shall maintain the following records at the site at which the natural health product is labelled:
(b) records containing sufficient information to enable the recall of every lot or batch of the natural health product that has been made available for sale; (c) a list of all natural health products that are being labelled at the site; and (d) a copy of the sanitation program in use at the site. Importers 56. Every importer who sells a natural health product shall maintain the following records:
(b) a list of all ingredients contained in each lot or batch of the natural health product; (c) records of any testing conducted in respect of a lot or batch of the natural health product; (d) a copy of the specifications for the natural health product; (e) a record of each determination made by the importer in accordance with section 52 and the information that supports that determination; (f) records containing sufficient information to enable the recall of every lot or batch of the natural health product that has been made available for sale; and (g) a copy of the sanitation program in use by the importer. Distributors 57. Every distributor shall maintain the following records at the site at which the natural health product is stored:
(b) a list of all natural health products that are being stored at the site; and (c) a copy of the sanitation program in use at the site. Record Maintenance 58. Every person required under this Part to maintain a record that relates to a lot or batch of a natural health product shall maintain that record for a period of one year following the expiry date of the natural health product to which that record relates. Sterile Natural Health Products 59. Every natural health product that is intended to be sterile shall be manufactured and packaged
(b) under the supervision of a person trained in microbiology; and (c) using a method scientifically proven to ensure its sterility. Ophthalmic Use 60. (1) Section C.01.064 of the Food and Drug Regulations applies in respect of natural health products except that it shall be read without reference to the words "or parenteral". (2) Section C.01.065 of the Food and Drug Regulations applies in respect of natural health products except that it shall be read without reference to
(b) the words "or to its common name if there is no proper name". Lot or Batch Samples 61. (1) Subject to subsection (3), if the Minister has reasonable grounds to believe that a lot or batch of a natural health product made available for sale may result in injury to the health of a purchaser or consumer, the Minister may require the manufacturer, importer or distributor to provide a sample of that lot or batch. (2) The sample shall be of sufficient quantity to enable a determination of whether the lot or batch of the natural health product complies with the specifications for that natural health product. (3) The Minister shall not require a sample of a lot or batch referred to in subsection (1) to be provided if more than one year has elapsed since the expiry date of that natural health product. Recall Reporting 62. Every manufacturer, importer or distributor who commences a recall of a natural health product shall provide the Minister with the following information in respect of that natural health product within three days after the day on which the recall is commenced:
(b) each brand name under which it is sold; (c) its product number; (d) the number of each lot or batch recalled; (e) the name and address of each manufacturer, importer and distributor of the natural health product; (f) the reasons for commencing the recall; (g) the quantity manufactured or imported into Canada; (h) the quantity that was distributed in Canada; (i) the quantity remaining in the possession of each manufacturer, importer and distributor of the natural health product; and (j) a description of any other action that the manufacturer, importer or distributor, as the case may be, is taking in respect of the recall. PART 4 CLINICAL TRIALS INVOLVING HUMAN SUBJECTS Interpretation 63. The following definitions apply in this Part. "adverse event" means any adverse occurrence in the health of a clinical trial subject who is administered a natural health product, that may or may not be caused by the administration of the natural health product, and includes an adverse reaction, a serious adverse reaction and a serious unexpected adverse reaction. (incident thérapeutique) "clinical trial" means an investigation in respect of a natural health product that involves human subjects and that is intended to discover or verify its clinical, pharmacological or pharmacodynamic effects, to identify any adverse events that are related to its use, to study its absorption, distribution, metabolism and excretion, or to ascertain its safety or efficacy. (essai clinique) "good clinical practices" means generally accepted clinical practices that are designed to ensure the protection of the rights, safety and well-being of clinical trial subjects and other persons, and the good clinical practices referred to in section 74. (bonnes pratiques cliniques) "import" means to import a natural health product into Canada for the purpose of sale in a clinical trial. (importer) "investigator's brochure" means a document containing the preclinical and clinical information in respect of the natural health product that is described in paragraph 66(e). (brochure du chercheur) "protocol" means a document that describes the objectives, design, methodology, statistical considerations and organization of a clinical trial. (protocole) "qualified investigator" means the person responsible to the sponsor for the conduct of the clinical trial at a clinical trial site, who is entitled to provide health care under the laws of the province where the clinical trial site is located and who is
(b) in any other case, a physician and a member in good standing of a professional medical association. (chercheur qualifié) "research ethics board" means a body that is not affiliated with the sponsor, and
(b) that has at least five members, that has a majority of members who are Canadian citizens or permanent residents under the Immigration Act, that is composed of both men and women and that includes at least
(ii) one member knowledgeable in complementary or alternative health care, (iii) one member knowledgeable in ethics, (iv) one member knowledgeable in Canadian laws relevant to the research to be approved, (v) one member whose primary experience and expertise are in a non-scientific discipline, and (vi) one member who is from the community or is a representative of an organization interested in the areas of research to be approved and who is not affiliated with the sponsor or the site where the clinical trial is to be conducted. (comité d'éthique de la recherche) "sponsor" means an individual, corporate body, institution or organization that conducts a clinical trial. (promoteur) Application 64. (1) Subject to subsection (2), this Part applies to the sale or importation of natural health products to be used for the purposes of clinical trials involving human subjects. (2) Except for paragraph 65(1)(a), subsection 65(2), section 68, paragraphs 74(a) to (i), subsections 75(1) and 76(1) and (2), paragraphs 76(3)(a) to (d) and (f) to (h), subsection 76(4) and sections 77 and 80 to 83, this Part does not apply to the sale or importation of a natural health product for the purposes of a clinical trial authorized under section 68. Prohibition 65. (1) Despite section 4 and subject to subsection (2), no person shall sell or import a natural health product for the purposes of a clinical trial unless
(b) the person complies with this Part and section C.01.064 of the Food and Drug Regulations; and (c) if the natural health product is to be imported, the person has a representative in Canada who is responsible for the sale of the natural health product. (2) No person shall sell a natural health product for the purposes of a clinical trial
(b) after cancellation of the authorization under paragraph 82(b). Application for Authorization 66. An application by a sponsor for authorization to sell or import a natural health product for the purposes of a clinical trial shall be submitted to the Minister and shall contain the following information and documents:
(b) a copy of the statement, as it will be set out in each informed consent form, that states the risks and anticipated benefits arising to the health of clinical trial subjects as a result of their participation in the clinical trial; (c) a clinical trial attestation, signed and dated by the sponsor, containing
(ii) the brand name or the code for the natural health product, (iii) for each medicinal ingredient of the natural health product
(B) the quantity of the ingredient per dosage unit of the natural health product, (v) the dosage form of the natural health product, (vi) the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of the sponsor, (vii) if the natural health product is to be imported, the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of the sponsor's representative in Canada who is responsible for the sale of the natural health product, (viii) the address of each clinical trial site,
(ix) for each clinical trial site, the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of the qualified investigator,
(B) that all information contained in, or referenced by, the application is complete and accurate and is not false or misleading; (e) an investigator's brochure that contains the following information, namely,
(ii) the chemistry and manufacturing information of each synthetically manufactured medicinal ingredient of the natural health product, (iii) the pharmacological properties of the natural health product, including its metabolites in all animal species tested, if any, (iv) the pharmacokinetics of the natural health product and the natural health product metabolism, including the biological transformation of the natural health product in all animal species tested, if any, (v) the toxicological effects in any animal species tested under a single dose study, a repeated dose study or a special study in respect of the natural health product, if any, (vi) the results of carcinogenicity studies in any animal species tested in respect of the natural health product, if any, (vii) the results of clinical pharmacokinetic studies of the natural health product, if any, (viii) the information regarding natural health product safety, pharmacodynamics, efficacy and dose responses of the natural health product that were obtained from previous clinical trials in humans, if any, (ix) the known contra-indications for and the precautions to be taken in respect of the natural health product, and (x) the recommended treatment in the event of an overdose of the natural health product, if any; and Authorization 67. (1) The Minister shall authorize a sponsor to sell or import a natural health product for the purposes of a clinical trial if
(b) the sponsor provides the Minister with all additional information or samples requested under section 73; and (c) the Minister has reasonable grounds to believe, based on an assessment of the application, an assessment of any samples or information provided under section 73 or a review of any other information that
(ii) the clinical trial is not contrary to the best interests of the clinical trial subjects, and (iii) the objectives of the clinical trial will be achieved. (2) The Minister shall authorize the sponsor to sell or import a natural health product for the purposes of a clinical trial by sending the sponsor a notice of the authorization. 68. A sponsor is authorized to sell or import a natural health product for the purposes of a clinical trial if the clinical trial is in respect of a recommended use or purpose for which that natural health product is issued a product licence. Commencement Notice 69. The sponsor shall notify the Minister of the date on which the sale or importation of a natural health product for the purposes of a clinical trial will commence at a clinical trial site at least 15 days before the day on which that sale or importation commences. Notification 70. If the sale or importation of a natural health product for the purposes of a clinical trial is authorized under this Part, the sponsor may make one or more of the following changes if the sponsor provides the Minister with notification of the change within 15 days after the day on which the change is made:
(b) a change to the protocol that does not alter the risk to the health of a clinical trial subject, other than a change for which an amendment is required by section 71. Amendment 71. (1) Subject to subsection (2), if the sale or importation of a natural health product for the purposes of a clinical trial is authorized under this Part, the sponsor may not make any of the following amendments unless the authorization is amended accordingly:
(b) an amendment to the protocol that affects the evaluation of the clinical efficacy of the natural health product; (c) an amendment to the protocol that alters the risk to the health of a clinical trial subject; (d) an amendment to the protocol that affects the safety evaluation of the natural health product; (e) an amendment to the protocol that extends the duration of the clinical trial; and (f) an amendment to the information referred to in subparagraph 66(e)(ii) that may affect the safety or quality of that natural health product. (2) If the sponsor is required to immediately make one or more of the amendments referred to in subsection (1) because the clinical trial or the use of the natural health product for the purposes of the clinical trial endangers the health of a clinical trial subject or other person, the sponsor may immediately make the amendment and shall provide the Minister with the information referred to in subsection (3) within 15 days after the day on which the amendment is made. (3) An application by the sponsor to amend the authorization for the sale or importation of a natural health product under this Part shall be submitted to the Minister and, in addition to a reference to the application submitted under section 66, shall contain the following information and documents:
(ii) for each clinical trial site, the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of the research ethics board that approved the amended statement;
(ii) a copy of the protocol submitted under paragraph 66(a), (iii) the rationale for the amendment, (iv) for each clinical trial site, the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of the research ethics board that approved the amended protocol, and (v) the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of any research ethics board that has previously refused to approve any amendment to the protocol, its reasons for doing so and the date on which the refusal was given; (d) if the application is in respect of an amendment referred to in paragraph (1)(f), a copy of the amended chemistry and manufacturing information that indicates the amendment, and the rationale for that amendment. (4) The Minister shall amend the authorization to sell or import a natural health product for the purposes of a clinical trial if
(b) the sponsor provides the Minister with all additional information or samples requested under section 73; and (c) the Minister has reasonable grounds to believe, based on an assessment of the application for amendment, an assessment of any samples or information submitted under section 73 or a review of any other information that
(ii) the clinical trial is not contrary to the best interests of the clinical trial subjects. (5) The Minister shall amend the authorization to sell or import a natural health product for the purposes of a clinical trial by sending the sponsor a notice of the amendment. 72. If the authorization to sell or import a natural health product for the purposes of the clinical trial is amended in accordance with subsection 71(5), the sponsor shall
(ii) maintain records concerning the information referred to in subparagraph 66(c)(ix), if any of that information has changed since it was submitted, and the information referred to in paragraph 66(f); and Additional Information and Samples 73. If the information and documents submitted in respect of an application under section 66 or an application for amendment under subsection 71(3) are insufficient to enable the Minister to determine whether the sale or importation of the natural health product should be authorized or whether the authorization should be amended, as the case may be, the Minister may request that the sponsor provide the Minister with samples of the natural health product or additional information relevant to the natural health product or the clinical trial that are necessary to make the determination. Sponsor's Obligations Good Clinical Practices 74. Every sponsor shall ensure that a clinical trial is conducted in accordance with good clinical practices and, without limiting the generality of the foregoing, shall ensure that
(b) the clinical trial is conducted, and the natural health product is used, in accordance with the protocol and this Part; (c) systems and procedures that assure the quality of every aspect of the clinical trial are implemented; (d) for each clinical trial site, the approval of a research ethics board is obtained before the clinical trial begins at the site; (e) at each clinical trial site, there is no more than one qualified investigator; (f) at each clinical trial site, medical care and medical decisions, in respect of the clinical trial, are under the supervision of the qualified investigator; (g) each individual involved in the conduct of the clinical trial is qualified by education, training and experience to perform his or her respective tasks; (h) written informed consent, given in accordance with the applicable laws governing consent, is obtained from every person before that person participates in the clinical trial but only after that person has been informed of
(ii) all other aspects of the clinical trial that are necessary for that person to make the decision to participate in the clinical trial; (j) the natural health product is manufactured and stored in accordance with the requirements set out in Part 3 except for section 61. Labelling 75. (1) The sponsor shall ensure that the natural health product bears a label that sets out the following information in both official languages:
(b) the brand name or code of the natural health product; (c) the expiry date of the natural health product; (d) the recommended storage conditions for the natural health product, if any; (e) the lot number of the natural health product; (f) the name and address of the manufacturer; (g) the name and address of the sponsor; and (h) the protocol code or identification. (2) Sections 86 to 94 do not apply to a natural health product used for the purposes of a clinical trial. Records 76. (1) The sponsor shall record, handle and store all information in respect of a clinical trial in a way that allows its complete and accurate reporting as well as its interpretation and verification. (2) The sponsor shall maintain complete and accurate records to establish that the clinical trial is conducted in accordance with good clinical practices and these Regulations. (3) The sponsor shall maintain complete and accurate records in respect of the use of a natural health product in a clinical trial, including
(b) records respecting each change made to the investigator's brochure, including the rationale for each change and documentation that supports each change; (c) records respecting all adverse events in respect of the natural health product that have occurred inside or outside Canada, including information that specifies the dosage form and the use and purpose of the natural health product at the time of the adverse event; (d) records respecting the enrolment of clinical trial subjects, including information sufficient to enable all clinical trial subjects to be identified and contacted in the event that the sale of the natural health product may endanger the health of the clinical trial subjects or other persons; (e) records respecting the shipment, receipt, disposition, return and destruction of the natural health product; (f) for each clinical trial site, an undertaking from the qualified investigator that is signed and dated by the qualified investigator prior to the commencement of his or her responsibilities in respect of the clinical trial, that states that
(ii) the qualified investigator will immediately, on discontinuance of the clinical trial by the sponsor, in its entirety or at a clinical trial site, notify both the clinical trial subjects and the research ethics board of the discontinuance, provide them with the reasons for the discontinuance and advise them in writing of any potential risks to the health of clinical trial subjects or other persons; (h) for each clinical trial site, an attestation, signed and dated by the research ethics board for that clinical trial site, stating that it has reviewed and approved the protocol and informed consent form and that the board carries out its functions in a manner consistent with good clinical practices. (4) The sponsor shall maintain all records referred to in this Part for a period of 25 years. Submission of Information and Samples 77. (1) The Minister shall require a sponsor to provide, within two days after the day on which the request is received, information concerning the natural health product or the clinical trial, or samples of the natural health product, if the Minister has reasonable grounds to believe that
(b) the clinical trial is contrary to the best interests of a clinical trial subject; (c) a qualified investigator is not respecting the undertaking referred to in paragraph 76(3)(f); or (d) information submitted or provided in respect of the natural health product or the clinical trial is false or misleading. (2) The Minister may require the sponsor to provide, within seven days after the day on which the request is received, any information or records referred to in section 76, or samples of the natural health product, in order to assess the safety of the natural health product or the health of clinical trial subjects or other persons. Reaction Reporting 78. (1) During the course of a clinical trial, the sponsor shall notify the Minister of any serious adverse reaction and any serious unexpected adverse reaction to the natural health product that has occurred inside Canada as follows:
(b) if it is fatal or life threatening, within seven days after the day on which the sponsor becomes aware of the information. (2) The sponsor shall, within eight days after the day on which the Minister is notified under paragraph (1)(b), provide the Minister with a complete report in respect of that information that includes an assessment of the importance and implication of any findings made. Discontinuance of a Clinical Trial 79. (1) If the sponsor discontinues a clinical trial in its entirety or at a clinical trial site, the sponsor shall
(b) provide the Minister with the reason for the discontinuance and its impact on the proposed or ongoing clinical trials in respect of the natural health product conducted in Canada by the sponsor; (c) as soon as possible, notify all qualified investigators of the discontinuance and of the reasons for the discontinuance, and advise them in writing of any potential risks to the health of clinical trial subjects or other persons; and (d) in respect of each discontinued clinical trial site, stop the sale or importation of the natural health product as of the day of the discontinuance and take all reasonable measures to ensure the recovery of all unused quantities of the natural health product that have been sold. (2) If the sponsor discontinues a clinical trial in its entirety or at a clinical trial site, the sponsor may resume selling or importing the natural health product for the purposes of the clinical trial in its entirety or at the clinical trial site if, in respect of each clinical trial site where the sale or importation is to be resumed, the sponsor submits to the Minister the information referred to in subparagraphs 66(c)(ix) to (xi) and paragraphs 66(d) and (f). Suspension and Cancellation 80. (1) Subject to subsection (2), the Minister may suspend the authorization to sell or import a natural health product for the purposes of a clinical trial, in its entirety or at a clinical trial site, if the Minister has reasonable grounds to believe that
(b) any information submitted or provided in respect of the natural health product or clinical trial is false or misleading; (c) the sponsor has failed to comply with good clinical practices; or (d) the sponsor has failed to
(ii) notify the Minister or provide a report under section 78. (2) Subject to section 81, the Minister shall not suspend the authorization unless
(b) the sponsor has not, within 30 days after the day on which the notice referred to in paragraph (a) is received, provided the Minister with information or documents demonstrating that the authorization should not be suspended on the grounds that
(ii) the situation giving rise to the intended suspension has been corrected. 81. The Minister shall suspend the authorization to sell or import a natural health product for the purposes of a clinical trial, in its entirety or at a clinical trial site, before giving the sponsor an opportunity to be heard if, as a result of any circumstance, the Minister has reasonable grounds to believe that it is necessary to do so to prevent injury to the health of a clinical trial subject or other person. 82. If the Minister suspends the authorization under section 80 or 81, the Minister shall send the sponsor a notice that sets out the reason for the suspension, the day on which the suspension is effective and indicating whether the authorization is suspended in its entirety or at a clinical trial site, and the Minister shall
(b) cancel the authorization in its entirety or at a clinical trial site, as the case may be, if within 30 days after the day on which the suspension is effective the sponsor has not provided the Minister with the information or documents referred to in paragraph (a). 83. If the Minister cancels the authorization under paragraph 82(b), the Minister shall send the sponsor a notice that sets out the reason for the cancellation, the day on which the cancellation is effective and indicating whether the authorization is cancelled in its entirety or at a clinical trial site. PART 5 GENERAL Electronic Signatures 84. Any signature that is required by these Regulations to be shown on a record or document may be an electronic reproduction of the required signature. Electronic Records 85. Any record that is required to be maintained by these Regulations may be maintained in any electronic format from which a printed copy of the record can be produced. Labelling and Packaging General 86. (1) No person shall sell a natural health product unless it is labelled and packaged in accordance with these Regulations. (2) Despite subsection (1), a person may sell a natural health product that is not labelled and packaged in accordance with these Regulations if the sale is to a manufacturer or distributor. 87. (1) Subject to subsection (2), when required by these Regulations to be shown on a label, the following information respecting a natural health product shall be in both English and French:
(b) the common name and proper name of each medicinal ingredient and each non-medicinal ingredient that it contains; (c) a description of the source material of a medicinal ingredient; and (d) its storage conditions. (2) The common name or proper name of a medicinal ingredient or non-medicinal ingredient shall be shown in any other language if the name does not have an English or French equivalent. 88. The statements, information and declarations required by these Regulations to be shown on a label of a natural health product shall be
(b) readily discernible to the purchaser or consumer of the natural health product under the customary conditions of purchase and use. 89. If a natural health product has only one label, that label shall show all the statements, information and declarations required by these Regulations to be shown on both the inner and outer labels. 90. Every lot number required by these Regulations to be shown on a label of a natural health product shall be preceded by one of the following designations:
(b) "Lot No."; (c) "Lot"; or (d) "(L)". 91. Every product number required by these Regulations to be shown on a label of a natural health product shall
(b) in any other case, be preceded by the designation "NPN". 92. No reference, direct or indirect, to the Act, the Food and Drug Regulations or to these Regulations shall be made on any label of or in any advertisement for a natural health product unless the reference is specifically required by law. 93. (1) Subject to section 3 of the Act and section 94, the inner and outer labels shall show the following information in respect of a natural health product:
(ii) its product number, (iii) its dosage form, (iv) if it is sterile, the words "sterile" and "stérile", and (v) the net amount in the immediate container in terms of weight, measure or number; and
(ii) if it is imported, the name and address of the importer, (iii) the common name of each medicinal ingredient that it contains, (iv) the proper name of each medicinal ingredient it contains, but only if the proper name is not the chemical name, (v) a list by proper name, or by common name if the proper name is the chemical name, that sets out the quantity of each medicinal ingredient per dosage unit and, if any, the authorized potency of that medicinal ingredient, (vi) its recommended use or purpose, (vii) its recommended route of administration, (viii) its recommended dose, (ix) its recommended duration of use, if any, (x) its risk information including any cautions, warnings, contra-indications or known adverse reactions associated with its use, (xi) its recommended storage conditions, if any, (xii) its lot number, (xiii) its expiry date, and (xiv) a description of the source material of each medicinal ingredient that it contains. (2) In addition to the requirements set out in subsection (1), the outer label shall show
(b) if the natural health product contains mercury or any of its salts or derivatives as a non-medicinal ingredient, a statement that sets out the quantity of mercury contained in the natural health product. Small Package Labelling 94. (1) Subject to section 3 of the Act, the natural health product shall be labelled as follows if the immediate container is not large enough to accommodate an inner label that complies with the requirements of section 93:
(ii) a qualitative list by proper name, or by common name if the proper name is the chemical name, that in descending order of quantity per dosage unit, sets out all medicinal ingredients that it contains, (iii) its recommended dose, (iv) its recommended duration of use, if any, (v) its lot number, (vi) its expiry date, (vii) its product number, (viii) if it is sterile, the words "sterile" and "stérile", (ix) the net amount in the immediate container in terms of weight, measure or number, (x) its recommended use or purpose, and (xi) if it does not have an outer label, a statement that refers the purchaser or consumer to the leaflet that is required in accordance with subsection (2); and (2) If the natural health product does not have an outer label, the statements, information and declarations required to be shown on the outer label under section 93 shall be shown in a leaflet that is affixed or attached to the immediate container. Security Packaging 95. (1) Subject to subsection (2), no person shall sell or import a natural health product that is packaged unless the natural health product is contained in a security package. (2) Subsection (1) does not apply to lozenges. (3) Subject to subsection (4), a statement or illustration that draws attention to the security feature of the security package referred to in subsection (1) shall be shown
(b) if the security feature is a part of the outer package, on the outer label. (4) Subsection (3) does not apply if the security feature of a security package is self-evident and is an integral part of the immediate container. Pressurized Containers 96. Sections A.01.061 to A.01.063 of the Food and Drug Regulations apply in respect of natural health products. Cautionary Statements and Child Resistant Packages 97. Subsections C.01.001(2) to (4) and C.01.028(1), paragraphs C.01.028(2)(b) and (c), section C.01.029, subsection C.01.031(1), paragraphs C.01.031.2(1)(a) and (c) to (g), subsection C.01.031.2(2), and paragraphs C.01.031.2(3)(a) and (c) of the Food and Drug Regulations apply in respect of natural health products. Medicinal Ingredient Representations 98. Section C.01.012 of the Food and Drug Regulations applies in respect of natural health products. Inspectors 99. Sections A.01.022 to A.01.026 of the Food and Drug Regulations apply in respect of natural health products. Imported Natural Health Products 100. In addition to these Regulations, sections A.01.040 to A.01.044 of the Food and Drug Regulations apply in respect of natural health products. Export Certificates 101. Section A.01.045 of the Food and Drug Regulations and Appendix III to those Regulations apply in respect of natural health products. Sampling of Articles 102. Sections A.01.050 and A.01.051 of the Food and Drug Regulations apply in respect of natural health products. Tablet Disintegration Times 103. Subsection C.01.015(1) and paragraphs C.01.015(2)(d) to (f) of the Food and Drug Regulations apply in respect of natural health products. PART 6 AMENDMENTS, TRANSITIONAL PROVISIONS AND COMING INTO FORCE Amendments Food and Drug Regulations 104. Section C.01.030 of the Food and Drug Regulations (see footnote 1) is repealed. 105. Division 4 of Part D of the Regulations is repealed. 106. Sections D.05.001 to D.05.007 of the Regulations are repealed. 107. Section D.05.010 of the Regulations is repealed. Transitional Provisions 108. (1) Subject to section 110, a person may, without complying with these Regulations, sell a drug to which these Regulations apply that is assigned a drug identification number in accordance with section C.01.014.2(1) of the Food and Drug Regulations, until the earlier of
(b) December 31, 2009. (2) A person who sells a drug under subsection (1) shall conduct that sale in accordance with the requirements of the Food and Drug Regulations. 109. An application for a product licence that is made in respect of a drug referred to in subsection 108(1) on or before December 31, 2009 is not required to contain the information referred to in paragraph 5(g). 110. A sale or importation of a drug to which these Regulations apply that, before January 1, 2004, is authorized for the purposes of a clinical trial under Division 5 of Part C of the Food and Drug Regulations shall continue to be regulated under that Division. 111. Until December 31, 2009, a person may sell a lot or batch of a drug referred to in section 108 that is not labelled or packaged in accordance with the requirements of Part 5 if the lot or batch is packaged in accordance with the requirements of the Food and Drug Regulations. 112. If during the period beginning on January 1, 2004 and ending on December 31, 2005, the information referred to in section 22 is not available to the licensee prior to commencing the sale of the natural health product or within 30 days after the day on which the license is issued in respect of the natural health product, as the case may be, the licensee shall provide the information to the Minister immediately after it is available to the licensee. 113. (1) A person who, before January 1, 2004, manufactures, packages, labels or imports for sale a drug to which these Regulations apply may continue to conduct the activity in respect of that drug without complying with the requirements of Parts 2 and 3, until the earlier of
(b) December 31, 2005. (2) A person who conducts an activity under subsection (1) shall conduct that activity in accordance with the requirements of the Food and Drug Regulations. 114. (1) A person who, before January 1, 2004, distributes a drug to which these Regulations apply may continue to conduct the activity in respect of that drug without complying with the requirements of Part 3 until December 31, 2005. (2) A person who conducts an activity under subsection (1) shall conduct that activity in accordance with the requirements of Division 2 of Part C of the Food and Drug Regulations. 115. A person may sell a lot or batch of a drug referred to in section 108 that is not manufactured, packaged, labelled, imported, distributed or stored, as the case may be, in accordance with the requirements of Part 3 if
(b) any manufacturing, packaging, labelling, importation, distribution or storage of the lot or batch that is not conducted in accordance with the requirements of Part 3 is conducted in accordance with the requirements of Division 2 of Part C of the Food and Drug Regulations. Coming into Force 116. (1) Except for section 6, these Regulations come into force on January 1, 2004. (2) Section 6 comes into force on July 1, 2004. SCHEDULE 1 INCLUDED NATURAL HEALTH PRODUCT SUBSTANCES
SCHEDULE 2 EXCLUDED NATURAL HEALTH PRODUCT SUBSTANCES
REGULATORY IMPACT ANALYSIS STATEMENT (This statement is not part of the Regulation.) Description Recent surveys have shown that more than one-half of Canadian consumers regularly take vitamins and minerals, herbal products, homeopathic medicines and the like, products that have come to be known as natural health products (NHPs). The purpose of this amendment is to adopt the Natural Health Products Regulations (NHP Regulations) under the authority of the Food and Drugs Act. The Regulations contain requirements for the manufacture, packaging, labelling, storage, importation, distribution and sale of NHPs. These Regulations are intended to provide Canadians with ready access to natural health products that are safe, effective, and of high quality, while respecting freedom of choice and philosophical and cultural diversity. The NHP Regulations will be administered by the Natural Health Products Directorate (NHPD), Health Products and Food Branch, Health Canada. This amendment repeals all provisions in Divisions 4 and 5 of Part D of the Food and Drug Regulations, except D.05.008 and D.05.009 (relating to drugs containing fluorine). Divisions 4 and 5 of Part D relate to the labelling of vitamins and minerals and the health claims that may be associated with them. The repeal of the provisions brings the treatment of vitamins and minerals into line with that of other products that fall within the NHP definition. As well, this amendment repeals section C.01.030 of the Food and Drug Regulations which relates to the labelling of a product containing elemental iron and the label statement "for therapeutic use only". This amendment also incorporates, as part of these Regulations, certain provisions which are important risk management tools. Other provisions, such as those that are incorporated from Part A, are imperative to the proper administration (including compliance and enforcement activities) of the present Regulations. Therefore, the following provisions are incorporated by reference from Part A and Part C of the Food and Drug Regulations.
A.01.022 to and including A.01.026, A.01.040 to and including A.01.044, A.01.045, A.01.050, A.01.051 (general administration of the regulatory regime)
This amendment was pre-published in the Canada Gazette, Part I (CGI) on December 22, 2001. Based on comments received, on subsequent discussions with stakeholder groups, and on the Business Impact Test (BIT), a number of adjustments to the proposed Regulations were made. These changes are detailed in the sections which follow. Other minor modifications to the Regulations were also made to ensure consistency and clarity of the text. Based on recommendations from the House of Commons Standing Committee on Health ("Standing Committee"), set out in its 1998 report entitled: A New Vision: Report of the Standing Committee on Health, the main components of the Regulations are definitions, product licensing, adverse reaction reporting, site licensing, good manufacturing practices, clinical trials, and labelling and packaging. These Regulations place requirements on persons who sell NHPs, namely manufacturers, distributors, importers, packagers and labellers. The NHPD considers that growers, who handle and/or treat a product in order to preserve the integrity of the raw material, are not considered manufacturers. Health care practitioners (for example, pharmacists, Traditional Chinese Medicine (TCM) practitioners, herbalists, naturopathic doctors, etc.) who compound products at the request of a patient are not included within the manufacturer definition. The NHP Regulations are not aimed at regulating the practice of complementary and alternative health care practitioners or the practice of traditional Aboriginal medicine. The NHPD intends to adopt a guidance document regarding the distinction between manufacture and sale of NHPs and compounding and distribution of compounded products by complementary and alternative health care practitioners and Aboriginal healers. Phase-In Policy Transitional provisions, which also form a part of the Regulations, have been developed in consultation with stakeholders to provide for staged implementation, thereby providing time for training, education, and public awareness to assist stakeholders in coming into compliance. In developing the transitional provisions, the views heard during consultations were kept in mind, particularly those from the BIT that was conducted from December 6, 2002 to January 22, 2003 (see section on BIT for more information). When the proposed NHP Regulations were pre-published in CGI on December 22, 2001, a two year transition period was originally proposed from the date of publication in the Canada Gazette, Part II (CGII). However, following results from the BIT and comments received that a longer transitional period for product licensing would be appropriate to allow industry a longer time to adjust to the new scheme, the transition period is staggered in the following manner: January 1, 2004: Coming into force of all provisions except section 6 related to the 60-day disposition clause. The transition period for product licences (for products that have a Drug Identification Number — DIN) and labelling has been extended from two years to six years. Thus, all products that fit under the NHP definition must obtain their product licences by December 31, 2009. The transition period for good manufacturing practices (GMPs) and site licensing remains two years as proposed in CGI. July 1, 2004: Coming into force of section 6, the 60-day disposition clause of product licensing. Details on the transitional provisions are found within the product licensing, adverse reaction reporting, site licensing, good manufacturing practices, and labelling and packaging sections (see "Phase In"). Definition of a Natural Health Product NHPs are drugs at the level of the Food and Drugs Act. The NHP definition has two components to it, a function component and a substance component. The function component relates to the intent of the NHP definition, which is to capture those substances which are manufactured, sold or represented for use in:
(ii) restoring or correcting organic functions in humans; or (iii) modifying organic functions in humans, such as modifying those functions in a manner that maintains or promotes health. At CGI, it was proposed that the third (iii) component read "maintaining or promoting health or otherwise modifying organic functions in humans". However, comments were received that it should be reworded to more clearly indicate that "maintain or promote health" is inextricably tied to "modifying an organic function". This better reflects the understanding that many NHPs, through their effects on organic functions, can contribute to good health. Consistent with the Standing Committee's recommendations, the NHP definition allows for a full range of health claims, including structure-function, risk-reduction, and therapeutic or treatment claims. The substance component relates to the fact that the NHP definition is medicinal ingredient driven. There is an inclusion list (see Schedule 1), outlining the medicinal ingredients that can be contained within NHPs, and an exclusion list (see Schedule 2), indicating those substances that are not NHPs. The definition includes homeopathic medicines and traditional medicines, as well as the items on the inclusion list. Homeopathic products are commonly referred to in other regulatory schemes in various ways: homeopathic medicines, homeopathic drugs, and homeopathic preparations. The NHPD has received comments from practitioners of homeopathy, and manufacturers and distributors of homeopathic products that the NHP Regulations should refer to "homeopathic medicines" (instead of preparations as originally proposed in CGI) because this term better reflects the nature of the products used in homeopathy. Thus, all references to "homeopathic preparations" in the NHP Regulations have been replaced by "homeopathic medicines"to reflect their unique nature. The NHPD has received comments from practitioners of homeopathy and manufacturers and distributors of homeopathic products that the NHP Regulations should apply to homeopathic medicines prepared from or containing Schedule D listed substances, for example, Lachesis mutus. (Schedule D is a schedule to the Food and Drugs Act.) The view expressed was that the Regulations should allow access to these types of homeopathic medicines. Also, certain NHPs, including probiotics, digestive enzymes, etc., are prepared from micro-organisms. The NHPD is of the view that these substances should be regulated by the Regulations and not excluded (see explanation under the Exclusion list section). In addition, the definition of "homeopathic medicines" will be elaborated in a guidance document and may make reference to various pharmacopoeias. The guidance document will be posted on the NHPD Website http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn. During an extensive consultation period, the NHPD received a number of other comments regarding the proposed definition of natural health products as pre-published in CGI. For a full list of comments received, see the section on Comments and Responses at the end of this document. Inclusion list: Specifically, the schedule of express inclusions indicates that medicinal ingredients of NHPs include:
(a) a plant or plant material, an alga, a bacterium, a fungus, or non-human animal material;
It is important to note that synthetic duplicates of NHPs are included, as mentioned in (f) above. Inclusion of "an extract or isolate of a plant or plant material, an alga, a bacterium, a fungus, or non-human animal material, the primary molecular structure of which is the same as that which it had prior to its extraction or isolation", is intended to capture NHPs of natural origin and which maintain their original structure. However, the NHPD recognizes that new drug substances may also be derived from nature. In these cases, the substances are often altered chemically after being extracted from the natural source. For this reason, the NHP definition specifies that the substances must be unaltered from what is found in the natural source to be considered an NHP. Comments were received that the term "microflora" included in the definition of probiotic is an antiquated term and should be replaced by the currently used term "microbiota" and that the definition of probiotic should include tyndalized micro-organisms. The NHPD is of the view that the more widely acceptable definition is that probiotics include live micro-organisms, however, the definition has been modified since CGI and refers now to microbiota, instead of microflora. A recommendation has been made by the NHPD's Expert Advisory Committee that the dietary reference intakes (DRIs) naming be the terms used in the Regulations. Recognizing that the DRIs are (or will become) standard internationally, the NHPD wishes that the proper name of vitamins be the name included in the DRIs. As such, the proper names of the vitamins are listed in Schedule 1. In addition, comments were received that the names of substances in the publications (pharmacopoeias, formularies) included in Schedule B to the Food and Drugs Act, referenced in the definitions of common and proper name, are not standard names. Also, the comment was made that the names for NHPs in these publications are inconsistent. It was suggested that no reference to these publications should be made in the common and proper name definitions. Therefore, all references to Schedule B in the definition of proper name and common name within the NHP Regulations have been removed. In addition, comments were received that the proper name should more properly refer to the genus and specific epithet and not the genus and species which in some cases can be one and the same. Some have also commented that the proper name of homeopathic medicines is the Latin name of the substance and not the chemical name. Thus, the revised definition of "proper name" now reads: "means, in respect of ingredient contained in a natural health product, one of the following names: (a) if the ingredient is a vitamin, the name set out for that vitamin in item 3 of Schedule 1; (b) if the ingredient is a plant or a plant material, an alga, a bacterium, a fungus, a non-human animal material or a probiotic, the Latin nomenclature of its genus and specific epithet; and (c) if the ingredient is other than one described in paragraphs (a) or (b), the chemical name of the ingredient. Recognizing that the NHP definition excludes substances that require a prescription (see details below) and that Vitamin K is currently listed on Schedule F to the Food and Drug Regulations without any qualifiers, the NHPD has removed Vitamin K from Schedule 1 until the qualifier for Vitamin K has been determined. The NHPD is examining whether regulatory amendments for the vitamins, minerals and amino acid, which are currently listed in Schedule F, are needed. Exclusion list: The schedule of express exclusions is intended to ensure that a product, which might otherwise fall within the NHP definition is, in fact, excluded. Schedule 2 indicates the following do not fall under the scope of the NHP Regulations: an antibiotic or its synthetic duplicate, a substance that is administered by puncturing the dermis, a substance regulated under the Tobacco Act, a substance set out in any of Schedules I to V of the Controlled Drugs and Substances Act, or a substance described in Schedule C (radiopharmaceuticals) to the Food and Drugs Act. In addition, a substance set out in Schedule D (biologics) to the Act is excluded, except for the following:
(b) any substance set out on Schedule D when it is prepared in accordance with the practices of homeopathic pharmacy. The NHPD will further define in guidance documents what is considered to be a NHP in order to further clarify when a NHP or substance that falls under Schedule D will be regulated under the NHP Regulations. At CGI, the exclusion list referred to "a substance intended to be administered by injection". The word injection could include insertion into cavities and canals of the body generally, which would mean that, for example, suppositories would be excluded from the NHP definition. It is not NHPD's intent to exclude products like vaginal or rectal suppositories but rather to exclude only true injectables that are administered by puncturing the dermis. This has therefore been replaced by "a substance that is administered by puncturing the dermis". At CGI, Schedule 2 of the proposed NHP Regulations did not make specific reference to the Controlled Drugs and Substances Act (CDSA). Earlier draft versions of the NHP Regulations did exclude CDSA substances. The NHPD received comments that the Regulations should more clearly exclude substances regulated under the CDSA. It is the intent of the NHPD to clarify the scope of a NHP as it pertains to the CDSA. For products that are best regulated under other regulatory schemes, they should remain under those schemes. The NHPD is of the view that the NHP definition is most accurately defined by expressly stating Schedules I to V of the CDSA in Schedule 2 (exclusion list) of the NHP Regulations. Substances that are set out in Schedule VI ("precursors") that otherwise fall within the NHP definition are regulated under the NHP Regulations. It should be noted that the CDSA still applies to a substance that is an NHP and a precursor or other substance listed on Schedule VI. Comments were received that the NHP Regulations should not include Schedule F drugs or Schedule F as a risk management tool. The concern is that, in general, only medical doctors can prescribe listed products. In CGI, it was proposed that products that met the NHP definition and were shown to have a wide margin of safety would now be regulated by the new NHP Regulations. Comments were also received that the "margin of safety" criterion is not clear and will be very difficult to apply. As well, some are concerned that its inclusion may in fact mean that many products would not be considered NHPs simply because of the lack of specific, documented data on their use. The margin of safety criterion is only one factor of the Schedule F factors that are considered to determine whether a substance should be placed on Schedule F (a substance can be placed on this Schedule if it meets other factors or the totality of the factors). Schedule F factors are an administrative list of factors currently used to determine whether a substance/drug should be placed on Schedule F (see www.hc-sc.gc.ca/hpb-dgps/therapeut/zfiles/en-glish/policy/issued/listschf_e.html). The NHPD's intention in including the margin of safety criterion in the proposed Regulations at CGI was to allow the Regulations to apply to those substances that can be safely used for self-care, i.e., products that can be selected and used by consumers without requiring practitioner intervention. While the criterion will continue to be applied as part of the standards of evidence framework, the Regulations now state that: "For the purposes of these Regulations, a substance or combination of substances or a traditional medicine is not considered to be a natural health product if it is a substance the sale of which under the Food and Drug Regulations is required to be pursuant to a prescription when it is sold other than in accordance with section C.01.043 of those Regulations". This clearly distinguishes prescription drugs from NHPs. While this addition makes no specific mention of homeopathic medicines, it is the NHPD's intent that, by leaving the mention absent, a homeopathic medicine could contain or be made from a Schedule F substance and remain regulated as an NHP under the Regulations. This clarifies the original policy intent of the NHP Regulations to regulate substances that are safe for over-the-counter use. It was not the intent of the Regulations to take substances off Schedule F or to regulate substances that require a prescription or have a narrow margin of safety. Earlier draft versions of the NHP definition referred to a list of herbs. The intent was that this list would distinguish between herbs sold as foods and ones sold for their medicinal properties. Those herbs, which for health or safety reasons should be captured independent of the form in which they are sold, would be listed on this short list of herbs. The NHPD considers that certain herbs, whether sold in a dosage form such as a capsule, or in loose or bulk form, fall within the NHP definition based on safety concerns. Similarly, the Food Directorate considers that such herbs are not appropriate to be sold as foods, having no recognized food purpose. An administrative list setting out these herbs will be prepared by both Directorates and will be made available on the NHPD Website, at http://www.hc-sc.gc.ca/hpfb-dgpsa/ nhpd-dpsn. Although "dosage form" is not an express part of the definition, the NHPD recognizes that NHPs are usually sold in capsule, pill, tablet, liquid or bulk form. As well, certain other forms, such as gum or bars, have come to be considered acceptable dosage forms. The NHP definition does not include conventional foods. Further, the definition is not intended to capture a product in a food medium which might otherwise fall within the definition (because it contains vitamins or minerals, for example) if that food is primarily consumed to provide nourishment, nutrition or hydration, or to satisfy hunger, thirst or a desire for taste, texture or flavour. The NHPD is undertaking internal discussions to further clarify the approach to categorizing NHPs. This approach will be elaborated in a guidance document which will be available on the NHPD Website. In addition, the NHP definition does not include cosmetics. The distinction between a cosmetic and a drug is currently addressed by Departmental guidance documents. The NHPD will also address this issue, with input from the Cosmetics Bureau, in the aforementioned guidance document. The following sections summarize the main components of the regulatory regime that will apply to natural health products. Main Components of Natural Health Products Regulations The main components of the Natural Health Products Regulations are: definitions, product licensing, adverse reaction reporting, site licensing, good manufacturing practices, clinical trials involving human subjects, and labelling/packaging. Transitional provisions ("Phase In") are included below under each main component. Modifications that have been made to these various components based on comments received following pre-publication in CGI, consultations and the BIT are reflected below. It is important to note that the NHP Regulations have also been modified since pre-publication in CGI in order to permit the complete filing and submission of electronic documents under all provisions. Product Licensing (Part 1 of the Regulations) The intent of product licensing is to assess and manage the benefits and risks associated with the use of NHPs. Each NHP sold in Canada will go through a pre-market review process before it is authorized for sale by the Minister of Health. Application An application for a product licence must include specific information about the NHP, for example, the quantity of the medicinal ingredients it contains, the specification it complies with, the recommended use or purpose for which the NHP is intended to be sold, and the supporting safety and efficacy data. The NHPD is developing a standards of evidence framework and guidance documents (which will be available on the NHPD Website http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn) intended to indicate the type of information that will be necessary to support various health claims for NHPs. A product licence applicant is required to attest that the product is manufactured, packaged, labelled, distributed and imported in accordance with good manufacturing practices (GMPs, further explained below). At CGI, product licence applicants were required to submit the name and site licence information for the manufacturer, packager, labeller and distributor. However, the NHPD received stakeholder feedback that this information was not always available at the product licence application stage. The NHPD is of the opinion that it is important to maintain the link between the product licence and site licence in order to ensure that quality products are manufactured in accordance with good manufacturing practices (i.e., in licenced facilities). Recognizing this information may not be available at the product licence stage, the NHPD will allow both Canadian and foreign site information to be submitted after the licence is issued but before sale of the product commences. The Regulations have been amended since pre-publication in CGI to require that this information be provided before sale commences. For products that are imported for sale, the applicant is required to submit evidence of compliance with the GMPs set out in these Regulations or equivalent GMPs (through an internal report from their quality assurance person). The NHPD will also work to develop Memoranda of Understanding (MOUs) with foreign site inspection authorities, and Mutual Recognition Agreements (MRAs) with foreign regulatory agencies to establish equivalency of GMPs. At CGI, the strength and potency of medicinal ingredients were requested. The NHPD received comments from stakeholders that strength and potency are often used interchangeably and that these terms were unclear. To clarify, the term "strength" has been replaced throughout the Regulations with "quantity of medicinal ingredient" and "potency", where applicable. Respondents to the BIT also expressed reservations about the product licence application process and the increased administrative time and cost this would entail. The NHPD has streamlined this process as much as possible. The Industry Working Group has given feedback on the proposed application form. An electronic system is being developed for easy and fast submission of applications. Monographs will be available for fast tracking of certain applications through the 60-day disposition clause stream. In the case of NHPs that are currently marketed with a Drug Identification Number (DIN), the NHPD recognizes that they have already undergone the appropriate premarket review processes. Therefore, during the transition period for product licences, the NHPD expects applicants for these products to submit an abbreviated product licence application and to attest to the safety and efficacy data during the transition period. In addition, recognizing that certain non-medicinal ingredients in the NHP may change as the product is being developed for market, and that these changes may not generally affect the safety and efficacy review of the product, the NHP Regulations allow for "proposed" non-medicinal ingredients (NMIs) to be provided in the application. In administering these Regulations, the NHPD will allow for an attestation only of the proposed NMIs as long as they are set out in the list of acceptable NMIs in the appendix of the product licence guidance document (see NHPD Website). If the NMI is not set out in the list, it must be submitted for review. The NHP Regulations also call for the inclusion of both the proper and common names of an NHP at the application stage. Sections pertaining to standards and grades including C.01.009, C.01.011(1), C.01.011(4) were initially incorporated from Part C of the Food and Drug Regulations at the time of pre-publishing in CGI. The NHPD is now of the view that standards and grades, such as those outlined in the United States Pharmacopeia, are not required at the time of submission of the product licence application. Instead, applicants may refer to the NHPD product licence guidance document which will reference the applicable standards, grades and procedures. 60-day Disposition Clause and Compendium of Monographs A 60-day disposition clause has also been included in the Regulations, recognizing that the NHPD should be able to review certain NHP licence applications within 60 days. The NHPD is developing performance standards for the assessment and authorization for sale of all NHP applications. These standards will be outlined in the product licence guidance document that will be posted on the NHPD's Website. The 60-day disposition clause, sometimes referred to as a performance standard, applies to an application which references a monograph in the Compendium of Monographs developed by the NHPD. Medicinal ingredients are the focus of the monographs, and are developed based on public literature. The Compendium of Monographs will ease the administrative burden on industry and ensure more efficient processing of product licence applications. Development of single-medicinal ingredient monographs is ongoing. The monographs provide support for the safety and the claim of the NHP, and therefore additional safety and efficacy data are not required in the application for a product licence. The Compendium will be available in both English and French, in hard copy and on the Website. Amendments will be made to the Compendium as required from time to time. New medicinal ingredient monographs will be added to the Compendium as the NHPD determines that the available body of evidence related to their safety and efficacy supports their inclusion. The NHPD is also developing a combination product policy that will be included in the Compendium. Notifications, Amendments and New Product Licences The product licensing scheme provides that certain changes made after the product has been authorized for sale, for example the addition of a caution, warning, contra-indication or known adverse reaction associated with the use of that NHP requires that the NHPD be notified within 60 days of the change. Other changes, for example, a change to the recommended dose, duration of use, potency of any of the medicinal ingredients, or quantity per dosage unit of the NHP requires that the product licence be amended. Since changes to whether a product is "synthetically manufactured" can have an effect on safety and efficacy, this type of change also requires an amendment to the product licence. A new product licence is required for any changes to the quantity or addition or substitution of an NHP's medicinal ingredients, dosage form, or route of administration. The NHPD does not require that a new label text be submitted in the case of an addition or substitution of a non-medicinal ingredient (NMI), if that NMI is included on the list of acceptable NMIs in the appendix of the product licence guidance document (see NHPD Website). However, a revised label is required for an amendment to the product licence regarding a change in potency of any medicinal ingredient of the NHP and for a change in synthetic manufacturing. Stop Sale and Suspension and Cancellation A stop sale provision and a suspension and cancellation provision have been included in the product licensing scheme. The stop sale provision is, in essence, a request to stop shipping. It is designed to allow licensees time to provide the Minister with additional information, if requested to do so, and in light of new information not available at the time the product licence was issued. This provision may also be used to require certain corrective changes (for example, the addition of risk information to a product's label) without having to invoke the product licence suspension and cancellation provisions. The suspension and cancellation provisions provide that the product could not be sold, even at the retail level. Any of these provisions will only be invoked when appropriate to the circumstances. The suspension and cancellation provisions allow the product licence holder to demonstrate to the Minister that the intended action, for example, the suspension of a product licence, is not warranted. In consideration that certain infractions should not always lead to a suspension or cancellation of a licence (for example, minor technical infractions, or infractions which are easily correctable), the suspension provision has been changed from "shall" at CGI to "may". At the same time, to safeguard the health and safety of consumers, the suspension and cancellation provisions allow for an immediate suspension of a product licence when it is necessary to prevent injury. Still, the licence holder is provided with a time period (90 days) to show that the licence should be reinstated. Comments were received from industry following pre-publication in CGI asking that the Minister ensures transparency in the product licence review and issuance process. The product licensing scheme now includes a provision requiring that the Minister provide a reason for the refusal (of initial issuance or amendment) and allow the applicant an opportunity to be heard. The NHPD is developing a guidance document for an appeals process, a necessary companion to these provisions. The document will be available on the NHPD Website. Product Licensing Phase In Following publication of these Regulations in CGII, the product licence provisions, except section 6 related to the 60-day disposition clause, will come into force on January 1, 2004 with a six year transition period (for products with a DIN ending December 31, 2009. The 60-day disposition clause will come into force on July 1, 2004. The current DIN provisions of the Food and Drug Regulations continue to apply for products that are already on the market with an assigned DIN until the products receive an NHP licence. Once the product licence provisions come into force, all new products that fit the NHP definition must comply with the NHP Regulations and undergo a full application process. In the case of products that already have DINs, they will be able to submit an abbreviated application which will include an attestation to safety and efficacy during the transition period. The sale of all natural health products must comply with the Regulations by January 1, 2010. Adverse Reaction Reporting An adverse reaction reporting system sets out the requirements for the monitoring and reporting of adverse reactions associated with the use of health products. This type of reporting system is an important part of a product review system based on risk assessment and the corresponding management of risks. Under the NHP Regulations, product licence holders are responsible for providing Health Canada with information regarding adverse reactions to their products. There are several definitions relevant to this component of the Regulations, including: adverse reaction, serious adverse reaction, and serious unexpected adverse reaction. While all serious and serious unexpected adverse reactions to any dose of an NHP must be reported within 15 days of becoming aware of them ("case report"), the report to be prepared annually need include only those adverse reactions occurring at the labelled dose ("summary report"). It should be noted that, although annual reports are to be compiled, they are to be submitted to the Minister only if requested. Adverse Reaction Reporting Phase In Adverse reaction reporting requirements come into effect for each product once that product receives a product licence. Products with a DIN, that have not received a natural health product licence and until the NHP Regulations come into effect, shall continue to conduct adverse reaction reporting in accordance with the requirements of the Food and Drug Regulations. During the transitional time frame that the NHP Regulations are being phased in, the NHPD will work with industry to assist them in understanding and implementing the reporting system. Site Licensing (Part 2 of the Regulations) A site licensing system assists Health Canada in ensuring that quality NHPs are sold to the public, and that quick and effective product recalls can be undertaken when necessary. A site refers to any building or location in which an NHP is imported, manufactured, packaged, or labelled prior to sale. The site licence lays out the activities permitted at the site for which it is issued. A site licence is required for importers, manufacturers, packagers and labellers of NHPs. At CGI, it was proposed that distributors would also be required to hold site licences. However, comments were received from industry through the BIT that the distributors should not be required to hold a site licence given that their activities are usually limited to the handling of a finished, packaged product and do not involve manufacturing, packaging or labelling. Based on a risk assessment, the activities of distributors were felt to be more in line with retailers and to be of extremely low risk of product interaction and adulteration. Accordingly, it was decided that, while GMPs and record requirements need to be followed, the site licensing provisions do not apply to distributors. This should save distributors the time and money that would have been needed for the application and administration of a site licence. In addition, the definition of "distributor" has also been changed. The NHPD's intent in defining distributors at CGI was to distinguish between a wholesaler (who would not usually include their name on the product label) and a distributor whose name is usually included on the product label. The NHPD understood this distinction to be important to industry respecting the proposed site licensing requirements. However, both types of distributors would have been subject to GMP requirements. Given the change to site licensing requirements, wholesalers are now included within the definition of distributor by deleting the words "bearing a label showing that person's name and address" from the definition. The product licence holder continues to have responsibility in ensuring that GMPs are followed throughout all stages of the manufacturing and distribution processes. GMPs are one of the main prerequisites that must be met before a site licence is issued. At CGI, it was originally proposed that applicants would be required to submit either a report from a Health Canada inspector or a third party audit report to demonstrate compliance with GMPs. Based on stakeholder concerns expressed in the BIT regarding costs and timeframes associated with this process, the NHPD re-examined this requirement. It was decided that site licence applicants can submit a report by the internal quality assurance (QA) person (as required under the GMP provisions), covering all areas of GMPs and giving sufficient detail for the NHPD to assess compliance, as evidence of GMPs. A template outlining the requirements for the QA report will be included in the site licence application as part of the site licence guidance document. This guidance document will be available on the NHPD Website. The QA person must also submit their résumé, including their training, experience and technical knowledge, relating to the activity conducted and the GMP requirements. This should save companies time and expense, while adjusting to the new requirements of the Regulations and while continuing to ensure that products are manufactured, packaged and labelled, both domestically and abroad, in accordance with GMPs to ensure safety and quality. When the NHPD conducts a review of the NHP Regulations in four years, it will re-examine this provision, with the intent to determine if it is necessary to increase the requirements to the use of third party auditors or Health Canada inspectors. The site licensing scheme provides that certain changes made after the site licence has been issued requires that Health Canada be notified within 60 days of the change. Other changes require that the site licence be amended before the change is made. The changes requiring an amendment include adding an activity or a building to the site licence, or conducting a licensed activity in respect of a sterile dosage form. A suspension and cancellation provision has been included in the site licensing scheme, which operates in the same way as with product licences. However, in order to reflect the actual holding and operation of the site licence applicant, and in order to allow continued compliant activities or use of buildings when there is non-compliance of a single activity or building, the Regulations also now include a provision to allow for site licence applicants to request an amendment to their site licence. The application from a site licence holder to "relinquish authorization" must include the following:
name and address of the site licence holder;
In addition, as with product licences, a provision has been added since CGI to ensure transparency in the site licensing review and issuance process. Site Licensing Phase In The site licence provisions will come into force on January 1, 2004 with a two year transition period ending December 31, 2005. The Food and Drug Regulations continues to apply until manufacturers, importers, packagers and labellers obtain an NHP site licence. Those that already have an Establishment Licence (under the Food and Drug Regulations) will be able to apply through an abbreviated application form for an NHP site licence during the transition period and demonstrate they are in compliance with the GMPs under the NHP Regulations. Good Manufacturing Practices (GMPs) (Part 3 of the Regulations) GMPs are measures which ensure an effective overall approach to product quality control and risk management. They do so by setting appropriate standards and practices regarding product specifications, manufacture, storage, handling and distribution. The GMPs apply to manufacturers, packagers, labellers, importers and distributors, and indicate that no person shall sell an NHP unless it has been manufactured, packaged, labelled and stored in accordance with the GMPs. The provisions cover: specifications (product), premises, equipment, personnel, sanitation program, operations, quality assurance, stability, records, sterile products, lot or batch samples, and recall reporting. Given the variety of products included in the definition of NHPs and the uniqueness of this industry, the GMPs are designed to be appropriate to the various types of NHPs. The GMPs were drafted to be outcome-based rather than procedure-based. The Regulations specify the requirements, without dictating how these requirements must be met. The GMPs guidance document, which suggests different ways in which manufacturers, packagers/labellers, importers and distributors of these products can meet the GMP requirements, will be available on the NHPD Website. In consideration of the nature of activities of manufacturers, importers, packagers, distributors, labellers, and product licence holders, the NHPD has adjusted the record keeping requirements that were proposed in CGI based on their specific activities, while ensuring that an effective recall mechanism is possible in a timely manner. Packagers, distributors and labellers are now required to maintain on site a distribution list of products. Product licence holders are now required to have access, within a reasonable time frame, to a list of all ingredients contained in each lot or batch that have been made available for sale as well as records containing sufficient information to enable recall of every lot or batch of a NHP that has been made available for sale. Since changes have been made to the labelling provisions (i.e., that the common name must be labelled when the proper name is a chemical name), the recall reporting section has also been modified since CGI, whereby it now calls for both the proper name and common name of each medicinal ingredient that product contains. In order to ensure adequate GMP record keeping requirements, a provision has been added since CGI that the site licence holder is required to maintain at the site the sanitation program (i.e., a record of procedures versus performance) set out as a record. Good Manufacturing Practices Phase In GMP requirements come into effect on the earlier of the following: (i) the date a site licence is issued, or (ii) the end of the transition period for site licensing, December 31, 2005. It should be noted that the current GMP requirements in Division 2 of the Food and Drug Regulations continue to apply to NHPs in the interim period. A compliance and enforcement guidance document will be available on the NHPD Website. Clinical Trials Involving Human Subjects (Part 4 of the Regulations) The Standing Committee envisaged a system where a range of health claims could be supported by various standards of evidence ranging from traditional references, expert committee reports, and observational studies to randomized controlled clinical trials. As part of this range of evidence, the conduct of clinical trials was determined to be an integral component. The clinical trials component of the Regulations provide investigators with clear and transparent requirements for conducting human clinical trials with NHPs. They provide the NHP industry with a means to test new products without a long history of traditional use, including products that have not yet received market authorization, where no other data is available, and/or for obtaining evidence to support new claims, if they wish. A few modifications were made to this section based on comments received following pre-publication in CGI and in order to ensure consistency with other modifications made to the NHP Regulations. This includes a requirement that both the proper and common names of an NHP be provided in the clinical trial application. Also, recognizing that the proposed start date of the clinical trials are often adjusted (even after obtaining approval from the REB), the Minister must be notified of the actual start date before the clinical trial begins. In addition, while at times the clinical trials will be carried out in the office of the practitioners or in health care facilities, these sites are not required to hold a site licence. In order to ensure consistency with the Food and Drug Regulations, the section on authorization includes an additional criterion that the objectives of the clinical trial will be achieved. This criterion was first suggested in the September 21, 2001 version of the proposed Framework for NHPs that was posted on the NHPD Website. This component of the Regulations has been developed to recognize the generally accepted principles of good clinical practice. A brief summary of the elements contained in the clinical trials portion of the Regulations follows. The Clinical Trial provisions of the NHP Regulations will come into force on January 1, 2004. At CGI, "clinical trial investigators" could be any health care practitioner regulated by the laws of the province where the clinical trial site would be located, and whose role within the clinical trial was within their scope of practice. Comments were received that it is not appropriate to allow the definition of clinical trial investigator to include persons other than medical doctors. The concern was expressed that while it may be acceptable for such persons to act as principal investigators, it is not appropriate for them to be the "qualified investigator" (as this term is used in the newly adopted Division 5 of the Food and Drug Regulations). Comments were made that, at an international level, it is increasingly clear that clinical trials involving human subjects are to be conducted by qualified investigators, i.e., medical doctors. Therefore, this has been changed to be consistent with Division 5 of the Food and Drug Regulations in that a "qualified investigator" is limited to licensed medical doctors or, in the case of dental drugs, licensed dentists in order to provide the necessary medical care to the trial subjects. The NHPD strongly encourages that clinical trials be conducted with input of relevant practitioners. The NHPD recognizes the necessity of having an individual knowledgeable in complementary or alternative health care on the REB that will approve a trial protocol. For this reason, there is a requirement for one member of the REB to be knowledgeable in complementary or alternative health care. Given this change in the definition of "qualified investigator", a related change has been made to the section of good clinical practices (GCP) concerning medical care and medical decisions. Good Clinical Practices (GCP) Clinical trials with NHPs must be conducted in accordance with generally accepted principles of GCP. The Regulations outline specific GCP that must be met. However, in general terms, GCP must provide that the clinical trial:
is scientifically sound and clearly described in a protocol that has received research ethics board approval;
Labelling NHPs used in clinical trials must be labelled in accordance with specified labelling requirements. The requirements include the following:
a statement indicating that the NHP is an investigational NHP to be used only by a clinical trial investigator;
Adverse Reaction Reporting The sponsor must report to Health Canada on an expedited basis any serious or serious unexpected adverse reactions based on the reporting schedule contained within the Regulations hereunder. The Regulations also provide the Minister with the authority to request additional information from the sponsor if there is concern respecting the safety of the clinical trial NHP and to take action if required. Records The sponsor must keep all records related to the conduct of a clinical trial in a format that facilitates verification for the purpose of an inspection. The records must be maintained for a period of 25 years. The sponsor must submit requested records within 48 hours if safety concerns arise. Additionally, the Minister can request the submission of information within seven days to facilitate an inspection of a site. This will enable Health Canada to investigate health and safety concerns and to respond in a timely fashion. Amendments Sponsors must submit an application for an amendment prior to introducing the following changes. Applications must be filed for:
changes to the protocol that affect patient selection, monitoring and dismissal, clinical efficacy and safety requirements;
Notification Sponsors must notify Health Canada of the following changes, within 15 calendar days of the date of the change:
changes to the chemistry and manufacturing information of a synthetically produced NHP ingredient that do not affect the quality or safety of the NHP; and
Inspection System Health Canada will inspect clinical trial sites and trial sponsors to ensure that the generally accepted principles of GCP are met. The objectives of the inspection will be to ensure that participants in clinical trials are not subjected to undue risks, to validate the quality of the data generated or to investigate complaints. The Minister will use the information collected as a result of these inspections to ensure compliance with the regulatory framework and will take enforcement action, when deemed necessary, and consistent with current Health Products and Food Branch Inspectorate (HPFBI) targets. Labelling and Packaging (Part 5 of the Regulations) Labelling requirements are measures which ensure that certain information appears on the labels of health products sold to the public. Under these Regulations, NHP labels assist consumers in selecting products that meet their particular needs and expectations, and in understanding the merits and limitations of the products they choose, as all labels list complete conditions of use (including the recommended use or purpose, sometimes referred to as the health claim), as well as any cautions, warnings, contra-indications or known adverse reactions associated with the NHP. Several changes have been made to the labelling requirements since CGI based on comments received during the consultation period. The product number designation "NHP - PSN" as proposed at CGI was shortened to "NPN" referring to "Natural Product Number" or "Numéro de produit naturel", reflecting both the French and English acronym of the product number that will be issued with the product licence. In the case of homeopathic medicines, the prefix will be "DIN-HM" (please see the comments / response section at the end of this document for further details). These letter series indicate to consumers that Health Canada has authorized the product for sale and is an indication to compliance and enforcement officers of regulatory status. Many have commented throughout the consultations that labels should be as complete as possible to permit informed choice by consumers. It has been suggested that all NHPs should clearly set out their list of non-medicinal ingredients after the term "non-medicinal ingredients" as it may be difficult to differentiate between medicinal and non-medicinal ingredients unless expressly stated. Thus, the label now requires that "non-medicinal ingredients" be listed on the label, preceded by the term "non-medicinal ingredients". This is to ensure clear labelling of all ingredients. In addition, the common name of the medicinal ingredient must appear on any panel. A quantitative list by proper name of each medicinal ingredient per dosage unit setting out the quantity must also appear on any panel, unless the proper name is a chemical name. In addition to the quantity, if a representation relating to the potency of the ingredient is made in the product licence application and has been authorized, the potency must then be declared on the label (e.g., standardized herbal product). When the proper name is a chemical name, a list by common name is required. A revised label is also required for an amendment to the product licence application regarding a change in potency of any medicinal ingredients of an NHP. In addition, the section in CGI related to the declaration of mercury has been clarified. Under the NHP Regulations, the required labelling information includes all of the following:
the brand name;
Comments were made that products should be labelled with complete product safety information in both English and French. Many NHPs sold in Canada already provide this label information in English and French. The NHPD is of the view that it is important that products be consistently labelled in this manner. It should be noted that the Regulations make an exception for the proper and common names of ingredients where these names do not have English or French equivalents. For example, the name of an ingredient of a homeopathic medicine is the Latin name of the ingredient or substance as set out in pharmacopeias. As well, the naming convention for plants, plant materials, algae, bacteria, fungi, probiotics or non-human animal materials is the Latin name of its genus and specific epithet, if any, for example, Echinacea angustifolia. Thus, for all labels, certain information, namely the names of the medicinal and non-medicinal ingredients, the recommended conditions of use, the storage instructions, if any, and the source of the medicinal ingredient of the NHP must be in both English and French (any other language may also be used in addition). Comments were received regarding the need to address the tension between section 3 and Schedule A of the Food and Drugs Act and the requirements under the proposed Regulations to include the use or purpose on the label of an NHP. Therefore, the labelling provisions have been clarified. Where section 3 would prohibit the inclusion on the label of the use or purpose, the product will not be subject to the label requirement in that regard (see sections 93 and 94 of the Regulations). Small Packages Recognizing that many NHPs are usually sold in small containers and that label space is limited, the Regulations include a provision for small package labelling. The provision provides that, despite the limited amount of space on the label, consumers are still able to make informed choices with respect to NHPs. Certain information is required to appear on the inner label of the small package, namely:
the brand name;
Further, where information for the consumer is provided in a leaflet, the leaflet should be attached to the package, and the package should refer the consumer to the leaflet. Labelling and Packaging Phase In While the NHPD recommends that new labels that meet the requirements under the NHP Regulations be used once a product licence is issued, old label stock (i.e., labels that comply with the Food and Drug Regulations) can be used throughout the transition period for NHPs currently on the market. Products are required to be labelled and packaged in accordance with the NHP Regulations by the end of the transition period for product licences (December 31, 2009). New products are required to meet all labelling and packaging requirements as soon as their product licence is obtained. Alternatives A number of options were explored by a variety of formally structured committees who have studied the treatment of natural health products in Canada, including the Advisory Panel on Natural Health Products, the House of Commons Standing Committee on Health and the Transition Team. They recognized that, internationally, these products are managed in varying manners ranging from treatment of these products as drugs, foods, dietary supplements, or with minimal regulation, either on a pre-market assessment or post-market notification basis. To introduce concepts such as voluntary standards would be a move towards deregulation of these products. This is not in line with consumer demands for higher safety assurances, more complete and accurate labelling, and consistency of product. In similar Health Canada initiatives, such as nutritional labelling, efforts to introduce voluntary standards have met with limited success. The fact that nutritional information was hard to find, hard to use and inconsistent, and that there was a patchwork of information, provided the impetus to move towards mandatory nutritional labelling. A parallel can easily be drawn to the treatment of natural health products. Given that regulation, albeit inconsistent, is currently in place for these products, deregulation or voluntary standards were not considered feasible options. They were considered unlikely to address consumer demands for safe, high quality products, whose labels include complete information to allow informed choices. Another alternative to the present Regulations is consideration of the system adopted in the United States. Currently, that system is a post-market system permitting only limited health claims that are not assessed by the regulatory authority and allows marketing without proof of safety. However, in March 2003, the United States Food and Drug Administration (FDA) announced proposed changes to labelling and manufacturing standards. It should be noted that internationally, natural health products are regulated on the basis of safety and quality and to varying degrees, efficacy. Countries such as Australia and those of the European Union consider these products to be drugs. The United States exists as an anomaly, having classified many natural health products as "dietary supplements". Through consultations with consumers and deliberations of the Standing Committee, is was clear that product users wanted assurances of safety, quality and efficacy, with evidence to support the health claims, through a system of pre-market product review. The Standing Committee studied this matter for over a year, and provided Health Canada with strong direction in their final report. Its recommendations, which were accepted in its entirety by the Government, focussed on a separate regulatory regime and authority for NHPs, based on the unique nature of these health products. The Standing Committee envisaged changes to the Food and Drugs Act, and indicated these changes to the Act should not unnecessarily delay the implementation of its recommendations. At the same time that the Transition Team was appointed (per recommendation of the Standing Committee), Health Canada established a separate authority within the Department to deal with all matters pertaining to the treatment of natural health products. Now known as the NHPD, this organizational unit reports directly to the Assistant Deputy Minister of the Health Products and Food Branch. There was clear direction from the Transition Team that changes to the Act would delay implementation of the Standing Committee's recommendations, and it was agreed that change at the level of regulation would bring about the desired outcome. A regulatory amendment was required to provide for a framework specific to NHPs. Great consideration was given to the type of regulation, and Canadians were consulted widely on the matter. The options considered were the creation of a separate set of regulations specific to NHPs which would be situated under the Food and Drugs Act, or the creation of a separate division for NHPs in the Food and Drug Regulations. It was decided the most effective regulatory mechanism was to create a new set of Regulations specific to NHPs which would be situated under the Food and Drugs Act. Benefits and Costs In terms of the scope of this industry, Canadian sales are estimated at about $4.3 billion and to number around 40,000 to 50,000 products. Vitamins represent over 50% of retail sales, and involve over 18% of Canadian companies involved in the NHP industry. Herbs and botanicals represent another 30% of sales. The NHPD undertook a benefit-cost analysis of the proposed NHP Regulations. This project was carried out prior to CGI using the first draft of the proposed regulatory framework, "Seeking Your Input on a Proposed Regulatory Framework". The findings from the benefit-cost analysis were used to develop subsequent working drafts of the regulatory framework, as well as these Regulations. In addition, through targeted consultations with stakeholder groups (including consumers) and consultation feedback, significant information was gained by the Directorate with respect to benefits and costs from the industry and product user perspectives. A BIT was also conducted from December 6, 2002 to January 22, 2003. Information packages were mailed to 2,300 stakeholders and 1,000 subscribers to the NHPD listserve were also advised of the Test, which was posted on the NHPD Website. A summary of the BIT findings is included in the following subsection. In terms of anticipated benefits, the NHP Regulations will provide Canadians with ready access to NHPs that are safe, effective, and of high quality, while respecting philosophical and cultural diversity. The consumer will benefit from having more information available to make informed decisions, and by having regulatory approvals that increase their confidence in the safety and efficacy of NHPs, possibly resulting in an increase in consumer self-medication, and a possible decrease in medical problems and associated costs. Practitioners will benefit from the added confidence in the safety and efficacy of NHPs, and will be better able to make product recommendations to their patients due to the increased information on product labels. Consumer confidence will also be enhanced by government review of products in a pre-market system, which assures them that what is on the label is what is in the bottle, and that health claims are supported by appropriate standards of evidence. Since NHPs will no longer be sold as either foods or drugs, a clear set of Regulations specific to NHPs will decrease confusion in the industry as to the appropriate regulatory environment for NHPs. Industry may benefit from a potential increase in a long-term, stable demand for NHPs, and will be better able to compete domestically and internationally through knowledge that Canadian NHPs meet regulatory requirements. Generally, Canadian manufacturers and distributors of NHPs want to put more, rather than less, information on labels, as long as the information is deemed reasonable by the industry. Adverse reaction reporting was an area that many stakeholders believed could yield substantial benefits to the industry in terms of increased consumer confidence in NHPs without adding appreciably to costs, if it were implemented cost-effectively. As with any new regulatory regime, a short-term cost increase is anticipated. In support, however, consumers have indicated a willingness to pay more to get more. Similarly, industry expects the increase in consumer confidence that should result from these Regulations to translate into increased long term demand and decreased cost to consumers. Manufacturers recognized that those NHP manufacturers who also manufacture drugs (and, therefore, hold valid establishment licences), would not incur significant costs for any additional NHP specific requirements. Based on size, manufacturers of NHPs would probably incur some to substantial costs. There were no reports of labelling as a major cost concern if the Regulations were phased in slowly to allow for existing label inventories to be used up and to allow sufficient lead time for the ordering of new labels. Concerns were, however, expressed regarding labels for small packages and for many traditional medicines that are imported from abroad. With respect to meeting good manufacturing practices requirements, for those companies who also make drugs and are therefore already GMP compliant, additional costs to meet the natural health products GMPs would be minimal, if any. Some predict savings. To assist those who require extra effort to come into compliance with GMPs, the NHPD will undertake to provide awareness, education and training sessions, generic standard operation procedures as well as a transitional time period. Concerns were also raised that meeting these Regulations may create additional paper burden, therefore the NHP Regulations ensure for the full e-submission of applications, record-keeping and communication with the NHPD. There are increased costs to Health Canada as the NHP Regulations will not be cost recovered at the time the Regulations come into force. Therefore, costs associated with administration, product licensing, site licensing, inspections, and compliance and enforcement are borne by Health Canada. Costs have also been incurred to develop guidelines and policies to support these Regulations. Business Impact Test (BIT) As part of the extensive consultations undertaken on the proposed Regulations, a BIT was undertaken. One hundred and one (101) usable responses were received, which is considered by Consulting and Audit Canada as a strong response. Responses were received from all provinces, all segments of the industry and types of business operations. For example, 59% of respondents were involved in distributing NHPs; 57% in manufacturing and formulating; almost 50% in packaging/labelling; just over 30% in exporting or importing; just over 20% in consulting; 20% in testing; and almost 20% were involved in other activities. Additionally, more than 55% of respondents worked with traditional herbal medicines, 50% were involved with vitamins and minerals, almost 50% worked with botanicals, approximately 20% each with isolates, homeopathics and sports nutrition. Over 30% of respondents also dealt with other products. More than 55% of respondents identified themselves as small or micro firms, with 19 employees or less, and almost 75% of respondents had less than 50 employees. The NHP industry is dominated by small and cottage businesses, and these results are seen as generally reflective of the sector as a whole. Almost all BIT respondents were involved in a variety of activities. The majority of respondents supported the intent of the Regulations and recognized the importance of safety and quality control in the industry. Just over 70% of respondents were fully or mostly meeting the requirements of the Regulations at the time of the survey and 56% felt that they would either not need changes in major operating practices or changes in only a few areas to fully comply with the regulatory requirements. Perception and concerns about the proposed Regulations varied based on business size, but not activity. The smaller the firm the greater the concern expressed regarding anticipated costs of complying with the proposed Regulations. Changes to facilities, standard operating procedures, staffing requirements and training are identified as major areas of challenge. Fifty-five per cent (55%) of micro firms and 58% of small firms anticipate major increases in costs of facilities and software costs. Forty-five per cent (45%) of micro firm respondents and 55% of small firms also anticipate major or minor cost increases in equipment costs. Forty-five per cent (45%) of micro and 75% of small firm respondents projected major or minor increases in the cost of hiring new employees. Fifty per cent (50%) of micro firms and 75% of small firm respondents in this category project minor or major increases in training and retraining of employees. Micro, small and medium sized firms all identified product licensing requirements as potential areas of increased administrative burden and projected a possible decrease in the number of products available for sale. While more than 50% of medium firm respondents expect the Regulations to have a positive or no impact on consumer acceptance of products, an equal number felt there would be a negative or prohibitive affect on availability and variety of products available for sale on the Canadian market. Large firms, for the most part, do not anticipate extra costs in complying with the Regulations, in some cases they project costs savings; Thirty (30) — 56% — of large firm respondents actually anticipate no impact or a minor decrease in the costs of business inputs. Large firms are primarily concerned about the implications for export products and foreign trade. The NHPD has analysed these concerns and made regulatory and administrative changes (as described above), where possible and where safety and quality are not affected, to address the concerns articulated through the BIT. The decision was taken to initiate consultations on cost recovery after the Regulations have been gazetted. This will allow the NHPD to work with industry to devise a cost recovery scheme appropriate for this sector, particularly in the case of smaller companies. This ensures that costs that may be incurred with external charging are not inappropriately added to those of meeting the GMPs. The transition period has been extended from two years to six years in the case of product licensing (for products that have a DIN) to allow companies currently in the market time to gradually adjust their business practices and spread any associated costs over an extended period of time. In order to facilitate these changes in operating procedures, the NHPD is developing generic standard operating procedures (SOPs) that will be available for download from the NHPD Website. The Directorate will also be conducting joint industry and Inspectorate training programs on the new GMP requirements. Materials from these sessions will also be available on the NHPD Website for easy reference. The NHPD will be working with regulatory authorities in foreign jurisdictions on applying current drug mutual recognition agreements (MRAs) and MOUs, where possible, and begin negotiating new agreements once the Regulations come into force. Many respondents specifically referred to products imported from China and this will be a priority country for the Directorate. In summary, from an overall perspective, it is expected that there will be significant benefit to consumers from the new regulatory framework. Many studies have indicated that there are societal net benefits from informed and effective self-care, including maintenance of good health. By allowing more information on labels regarding health claims associated with NHPs, and by establishing a regulatory framework that increases consumer confidence in NHPs, the new regulatory regime may lower the cost of maintaining one's health or increase the healthiness of consumers. Complete labelling also provides the consumer with full disclosure of NMIs and any warnings or contra-indications, thereby increasing consumers' knowledge and awareness regarding sensitivities, allergens, and interactions. As a direct result, negative reactions to certain substances could be reduced, and the corresponding need for medical attention decreased. As well, as indicated earlier, the consumer benefits from having more information available to make informed decisions, and regulatory approvals that increase their confidence in the safety and efficacy of NHPs. Increased consumer confidence will lead to stability or an increase in sales of these products from an industry perspective. Industry has indicated that while it recognizes there will be incremental costs associated with regulation specific to NHPs, it also values increased consumer confidence in these products, and overall benefits to consumers regarding informed choice. Health Canada has considered the benefits and costs associated with the introduction of these Regulations from the perspective of all stakeholders including industry and consumers, and concluded that the benefits outweigh the costs of adopting this regulatory framework. Consultation The NHPD has undertaken a very comprehensive approach to consultation in the development of these Regulations. Consisting of four phases, the NHPD used a series of tools to gain the widest input from a variety of stakeholders groups, including consultation sessions across the country, workbooks, slide presentations, questionnaires, surveys, effective use of the Website, mailings, general and targeted consultations, etc. Stakeholders have commented that the development of the framework has been consistent and responsive to stakeholder concerns, and the elaboration of the Regulations has been undertaken as a joint effort. In terms of the first phase of the consultation approach, from June to September 2000, the NHPD conducted open consultation meetings with interested Canadians across the country on the proposed regulatory framework for NHPs. Advertisements were placed in local newspapers, and sessions were open to anyone interested in attending. Over 2,100 participants in 11 cities (Ottawa, Kingston, Halifax, Fredericton, Montréal, Québec, Vancouver, Calgary, Regina, Winnipeg and Toronto) took part in the consultation meetings. In addition, over 7,000 hard copies of the consultations workbook were distributed. Another 14,000 copies were downloaded from the NHPD Website, and many individuals submitted their input through this site. Others mailed their completed feedback sheets from the workbook to us, or sent their comments separately from the workbook. The NHPD also met with stakeholder groups, both in Ottawa and across the country, through teleconference and in-person meetings. All feedback from the consultation sessions, including consumer, stakeholder and professional association feedback, was analysed and modifications were made to the proposal based on the feedback. In response to this phase of consultations, the NHPD received: 38 written submissions from industry representatives, 29 from industry associations, 4 from consumer associations, 8 from professional associations, 2 from academics, and 180 from consumers. A second version of the proposed regulatory framework was drafted and released at the end of March 2001 in the second phase of the consultations. Key stakeholders, as well as other companies, associations and individuals in the NHPD database, were notified of the release of the document. Phase II of the consultation process was held between March and May 2001. There were 2,500 copies of the Phase II documents distributed to associations, stakeholders and individuals in the NHPD database. Feedback was accepted on the proposal, and targeted stakeholder consultation sessions were held at the request of the stakeholder. At the end of the consultation period, all feedback, including consumer, stakeholder and professional association feedback, was analyzed and modifications were made to the proposal based on the feedback. Further, on September 28, 2001 a working draft of the proposed regulatory framework was shared with stakeholders through its posting on the NHPD's Website. Updates on outstanding issues were also communicated via the Website. The NHPD received written submissions on the Phase II consultation document from industry representatives (23), industry associations (24), consumer associations (5), professional associations (8), provincial governments (5), academics (6), and consumers (32). In addition, comments were received from NHP practitioners and individuals interested in the area of NHPs. Approximately 20 interventions were received from individual consumers through the NHPD's Website. In addition, the NHPD held two 2-day workshops (March 2001 and October 2001), in which various stakeholders and experts were brought together to assist in the development of the GMP and SOE guidance documents, respectively. Approximately 50 people were involved in the GMP workshop, including industry, academics, researchers, consumers and others. Approximately 40 participants took part in the SOE workshop, representing industry, academia, researchers, consumers, practitioners and others. The proposed NHP Regulations were pre-published in the CGI, on December 22, 2001. Subsequently, there was a 90-day comment period (Phase III) in which the public could submit their comments on the proposed Regulations to the NHPD. However, the consultations extended well beyond the formal 90-day period. The NHPD has undertaken an extensive approach to acquiring comments in response to CGI. Approximately, 632 comments were received, and taken into consideration for modifying the proposed NHP Regulations. These comments represent a variety of stakeholders groups, consumers, professional associations, industry associations, academics, health professionals, government representatives and NHPD's EAC. A summary of these comments follows later in this section. In a fourth phase, the NHPD also conducted several comprehensive consultations in over eight cities across Canada following pre-publication in CGI. The consultations focussed on the following areas for natural health products: Good Manufacturing Practices (GMPs): Consultations were held in six cities: Halifax, June 11, 2002 (15 participants); Winnipeg, June 13, 2002 (20 participants); Edmonton, June 19, 2002 (80 participants); Vancouver, June 21, 2002 (100 participants); Toronto, June 24, 2002 (90 participants); and Montreal, July 8, 2002 (80 participants). Standards of Evidence (SOE): Open consultations were held in five cities. There was a wide range of participants which included representatives from industry, practitioners, academics and consumers as follows: Halifax, November 7, 2002 (41 participants); Saskatoon, November 12, 2002 (38 participants); Toronto, November 18, 2002 (238 participants); Vancouver, November 25, 2002 (164 participants); and Montreal, November 28, 2002 (181 participants). In addition to these open consultations, the NHPD held two focussed invitational roundtables with members of the Canadian and international research community. Input was also sought from the Directorate's health promotion working group. Aboriginal: Consultations were conducted through a number of initiatives, including two roundtable discussions, attendance at an Elder's conference in British Columbia in July 2002 and interviews with leading experts across the country. Nearly 40 Aboriginal people from across the country were contacted and invited to participate in the interviews to comment on the NHP Regulations. All initiatives took place between April and November 2002 and included a good cross-representation of the Aboriginal community. Both roundtables (April 4, 2002, 14 participants; October 19, 2002, 13 participants) included representatives from a number of national Aboriginal organizations and experts in traditional medicine. Bulk Herbs: This consultation, held in Toronto on March 25, 2002 included 15 participants. Homeopathic Medicines Consultations were held in Ottawa on May 15-16, 2002 and included 40 participants. As clarifications and amendments were made to the regulatory framework to address comments received, these changes were conveyed to industry and consumers through various ways, including specific industry-NHPD meetings and general public sessions. These revisions, as reflected above, do not denote significant change in the overall impact of the NHP Regulations but rather serve to clarify their intent. As appropriate, comments will be further clarified and provided in appropriate guidance documents, individual response letters and summary reports. Definitions Comments:
(a) that "homeopathic medicines" should be included in the NHP definition instead of "homeopathic preparations";
Response:
(a) After consultation with homeopathic medicine practitioners, manufacturers, consumers, academics and regulators, all references to "homeopathic preparations" has been replaced by "homeopathic medicines". The definition will be elaborated in a guidance document.
Product Licence Comments:
(a) that the product licence application be amended to provide "proposed" non-medicinal ingredients;
Response:
(a) This recommendation was accepted and the product licence application section has been amended to include a list of "proposed" non-medicinal ingredients.
Site Licence / Good Manufacturing Practices / Labelling and Packaging Comments:
(a) that GMPs not be complex and drug like;
Response:
(a) The NHPD drafted the GMPs to be outcome-based rather than procedure-based, in that they specify the requirements without dictating how these requirements must be met. The NHPD undertook consultations on GMPs on the following: herbals and botanicals, homeopathic medicines, traditional herbal medicines, and vitamins and minerals. The NHPD is developing a GMP guidance document that suggests ways in which manufacturers, packagers, labellers, importers and distributors can meet the GMP requirements.
Adverse Reaction Reporting Comments:
(a) that adverse reaction reporting (ARR) be amended to include "presumed" adverse reaction reporting;
Response:
(a) The NHPD recognizes that adverse reactions do not always mean a direct cause to a particular product. Other factors may cause the adverse reaction and will require further validation. The NHPD is drafting a guidance document to clarify that adverse reactions that are reported may not be due to the NHP that was taken, as other factors may be involved.
Clinical Trials Comments:
(a) that a site licence not be required for clinical trial sites;
Response:
(a) This recommendation was accepted.
Implementation Comments:
(a) that NHPD backlog or workload for product licences not disadvantage the industry;
Response: (a) The transition period for the NHP Regulations will be staggered in the following manner: January 1, 2004: Coming into force of all provisions except section 6 related to the 60-day disposition clause. The transition period for site licensing remains two years (as proposed in CGI), however, the transition period for product licences (for products that have a DIN) has been extended to six years. Thus, all products that fit under the NHP definition will have to obtain their product licences by December 31, 2009. July 1, 2004: Coming into force of section 6, the 60-day disposition clause of product licensing. In addition, industry will have an opportunity to provide feedback on the NHPD's performance. The NHPD will set internal performance targets, examine performance data and make adjustments where necessary.
(b) The NHPD conducted a BIT to measure the impact of the regulations on Canadian businesses. Changes were made to the proposed NHP Regulations and guidance documents to address concerns expressed in the BIT and to ensure efficient and equal treatment. In addition, the transition provisions have been extended. A mitigation strategy for small businesses is also being considered.
Compliance and Enforcement Comment: (a) that there be an appeal process. Response: (a) The Regulations were changed to include appeal timelines. The NHPD is developing an appropriate dispute resolution mechanism. Performance Measures The NHPD will assess the effectiveness of the present regulatory framework after some experience has been gained under the new framework. The NHPD will conduct a full review of the NHP Regulations over the first four years to make modifications where appropriate. This will include reviewing the effectiveness of the approach to site licensing. The NHPD will consider whether or not using a QA audit report has been sufficient or if the requirements for site licensing should be increased from an internal QA audit report to a third party audit report or Health Canada inspection report. Education and Outreach The NHPD will initiate a public awareness campaign in Fall 2003, to inform both stakeholders and consumers of the Regulations, and what they will mean. In particular, the Directorate will work with industry to educate them about the new requirements under the NHP Regulations. The NHPD acknowledges the importance of accessible and understandable information for Canadians to make informed decisions about their health. As such, it will continue to consult with stakeholders — industry, consumers, health practitioners, researchers and academics — to determine their information needs, and how best to address them. Compliance and Enforcement A phased-in approach is important to permit industry and government time to adapt to the new requirements as well as provide the opportunity for the development of education and compliance tools. Education will be an integral component of this initiative. The NHPD will develop educational tools for inspection staff and industry. During the transition period, the NHPD will hold GMP training sessions for inspectors and industry and look at effective ways to communicate with the stakeholders on the new requirements. The NHPD will work with the Heath Products and Food Branch Directorate (HPFBI) to ensure compliance and enforcement is carried out. The Inspectorate will deliver inspection, investigation, and related laboratory analysis programs for the NHPD. In addition, the Inspectorate will undertake investigations with regards to product violations and customs surveillance. The Inspectorate laboratory services will provide analysis in support of inspection, investigation and surveillance. The NHPD is anticipating undertaking random sampling of NHPs to check for compliance and may seek support from HPFBI. The NHPD will provide technical support and input to HPFBI on compliance and enforcement activities. The NHPD will provide assistance by responding to industry and consumer enquiries related to the new Regulations, product and site licensing, and various guidance documents, whereas the HPFBI will respond to enquiries related to compliance and enforcement activities. During the transitional phase, all manufacturers, packagers, labellers and importers of natural health products are encouraged to apply for their products and site licences. Non-compliance with the NHP Regulations could result in several actions, depending on whether the non-compliant party is the product licence holder, manufacturer, importer, labeller, or packager. Enforcement activities could include a direction to stop sale and/or recall for a specific product, the suspension or cancellation of a product licence, the suspension or cancellation of a site licence or criminal prosecution. The NHPD will develop an interim phase-in policy relating to compliance and enforcement. Further details and updates on the NHPD's approach will be posted on the Web site at http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn. Contacts
Telephone: (613) 952-2558 Kiran Hanspal, Director, Policy Development and Regulatory Affairs, Telephone: (613) 946-1610 Peter Chan, Director, Bureau of Product Review and Assessment, Telephone: (613) 941-3073 Heather Throop, Director, Promotion, Liaison and Development, Telephone: (613) 946-1787 Marie-Josée Lafleur, Policy Analyst, Policy Development and Regulatory Affairs, Telephone: (613) 954-3244
Health Products and Food Branch Health Canada Address locator: 3302A 2936 Baseline Rd., Tower A Ottawa, Ontario K2H 1B3 S.C. 1999, c. 33, s. 347 C.R.C., c. 870 |
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