Reference: http://www.hc-sc.gc.ca/english/media/releases/2001/2001_136e.htm
http://canada.gc.ca/gazette/part1/ascII/g1-13551_e.txt
Canada Gazette, Part I
Volume 135, Number 51
OTTAWA, SATURDAY, DECEMBER 22, 2001
[51-1-o]
Natural Health Products Regulations
Statutory Authority
Food and Drugs Act
Sponsoring Department
Department of Health
REGULATORY IMPACT ANALYSIS STATEMENT
Description
Recent surveys have shown that more than one-half of Canadian consumers regularly take vitamins and minerals, herbal products, homeopathic preparations, and the like, products that have come to be known as natural health products.
In Canada, the regulatory treatment of these products has been at issue for years. They have been inconsistently regulated as food or drugs. As a result, significant confusion exists in the marketplace as consumers are faced with a substance labeled as a food (without health claims or full product use information) sitting next to the same substance labeled as a drug (with health claims and adequate directions for use). Another consequence of the inconsistent regulatory treatment has been that consumers have asked for assurances of quality, recognizing that processes are needed to ensure that what is on the label is in the bottle.
The regulatory regime for drugs (under the Food and Drug Regulations) is viewed as too rigorous for these products, given the long history of safe use that most of these products have enjoyed. At the same time, regulation as food is not appropriate either. Generally, a food can not carry a health claim on its label and is not subject to a pre-market approval system. Yet, the industry and consumers have strongly advocated that these products provide health benefits and should be labelled as such. It was felt that an appropriate approach would allow people access to products, while providing truthful information on their health benefits.
In response to these concerns, this complex issue was first referred to an advisory panel to Health Canada, and subsequently to the House of Commons Standing Committee on Health (Standing Committee) for resolution. The Standing Committee finalized their deliberations in November 1998. Consistent with their recommendations to create a separate regulatory authority to manage the treatment of natural health products (NHPs) in Canada, the purpose of this proposed amendment is to adopt the Natural Health Products Regulations (the Regulations) under the authority of the Food and Drugs Act (the Act). The Regulations contain requirements for the manufacture, packaging, labelling, storage, importation, distribution and sale of natural health products. 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.
This amendment also proposes the repeal of 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 will bring the treatment of vitamins and minerals into line with that of other products that fall within the NHP definition. As well, the repeal of section C.01.030 of the Food and Drug Regulations is proposed. This section relates to the labelling of a product containing elemental iron and the label statement "for therapeutic use only."
After having carefully reviewed the existing Food and Drug Regulations, the Natural Health Products Directorate (NHPD) proposes to incorporate as part of these Regulations certain provisions which are important risk management tools. Other provisions, such as those that will be incorporated from Part A, are imperative to the proper administration (including compliance and enforcement activities) of the present Regulations. Therefore the following provisions will be 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 adminis-tration of the regulatory regime)
- A.01.061 to and including A.01.063 (pressurized containers)
- C.01.001(2), C.01.001(3), C.01.001(4) (definitions)
- C.01.009, C.01.011(1), C.01.011(4) (standards)
- C.01.012 (release of medicinal ingredients)
- C.01.015(1), C.01.015(2)(d) to and including (f) (disintegration of tablets)
- C.01.028(1), C.01.028(2)(b) and (c), C.01.029, C.01.031(1), C.01.031.2(1)(a) and (c) to and including (g), C.01.031.2(2), C.01.031.2(3)(a) and (c), C.01.037 (cautionary statements and child resistant packaging)
- C.01.041 to and including C.01.046, C.01.048, C.01.049 (Schedule F)
- C.01.064 and C.01.065 (ophthalmic use)
Currently, NHPs in Canada are regulated as either a food or a drug under the Food and Drugs Act. NHPs would be considered a subset of drugs under the Act. The new Regulations would apply to products falling within the definition of an NHP.
Based on recommendations from the Standing Committee (set out in its report entitled A New Vision), 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 would 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. Heath care practitioners (for example, pharmacists, Aboriginal healers, 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, and therefore, the Regulations do not apply to products compounded by these people. The Regulations are not aimed at regulating the activities of retailers of NHPs. They will not apply to a product which may otherwise fall within the definition if that product has a narrow margin of safety between its recommended dose and its toxic dose, as determined by observing the lowest observed dose producing toxicity in humans, the highest observed dose with no toxicity in humans, historical use in humans, clinical experience and adverse reaction reports and/or animal toxicology data.
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, especially those from the benefit cost analysis that was undertaken (see section on Benefits and Costs for more information.) In general, the transitional provisions provide that within two years of publication in the Canada Gazette, Part II, all NHPs must be properly licensed, must be packaged and labelled in accordance with the applicable requirements, must have been manufactured, packaged, labelled and stored at a licensed site under good manufacturing practices, and must have their adverse reactions reported to Health Canada in accordance with the requirements. 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").
History
In May 1997, Health Canada responded to the concerns of Canadian consumers and practitioners regarding the regulation and accessibility of herbal remedies by establishing an Advisory Panel on Natural Health Products, which provided the Department with direction and advice.
Also in 1997, in response to growing concerns, the Minister of Health asked the House of Commons Standing Committee on Health to conduct a full review of how NHPs were regulated in Canada, and how the Government could better provide Canadians with the safety, quality and freedom of choice that they were seeking. The Standing Committee consulted extensively with over 150 associations and coalitions representing many Canadians, including health care providers, industry, consumer groups and practitioners. In November 1998, the Standing Committee published its report entitled A New Vision, which contained a list of 53 recommendations on NHPs, a central component of which was the establishment of a new regulatory authority dedicated to the regulation of natural health products.
On March 26, 1999, the Government accepted all 53 recommendations made by the Standing Committee and announced the creation of the Office of Natural Health Products (now the Natural Health Products Directorate). One of the 53 recommendations was for the Minister to appoint a Transition Team responsible for ensuring that the new framework was established quickly. The Transition Team presented their report, entitled A Fresh Start: Final Report of the ONHP Transition Team, to the Minister of Health on March 31, 2000.
Throughout the work of the Advisory Panel, the Standing Committee, and the Transition Team, an important part of the deliberations has been the definition of what constitutes a natural health product. This matter has also been consulted on widely with the stakeholder communities and debated by the NHPD Expert Advisory Committee.
As a result, the following has received acceptance as the most accurate depiction of health products that should be classified as NHPs.
Proposed Definition of a Natural Health Product
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:
(i) the diagnosis, treatment, mitigation or prevention of a disease, disorder, or abnormal physical state or its symptoms in humans;
(ii) restoring or correcting organic functions in humans; or
(iii) maintaining or promoting health or otherwise modifying organic functions in humans.
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, outlining the medicinal ingredients that can be contained within NHPs, and an exclusion list, indicating those substances that are not NHPs. The definition includes homeopathic preparations and traditional medicines, as well as the items on the inclusion list.
Inclusion list
Specifically, the schedule of express inclusions indicates that medicinal ingredients of NHPs include:
(a) a plant or plant material, alga, fungus or non-human animal material,
(b) an extract or isolate of (a), the primary molecular structure of which is the same as that which it had prior to its extraction or isolation,
(c) a vitamin (a term which is defined in the Regulations) or any of its salts or derivatives,
(d) an amino acid or any of its salts,
(e) an essential fatty acid,
(f) a synthetic duplicate of (b) to (e),
(g) a mineral; and
(h) a probiotic (a term which is defined in the Regulations and is intended to capture such things as acidophilus).
It is important to note that synthetic NHPs are included, as mentioned in (f) above.
Inclusion of "an extract or isolate of a plant or plant material, alga, 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. Still, conjugates or salts of natural compounds would remain within the NHP definition. Furthermore, the exclusion of substances with a "narrow margin of safety" (see application provision of these Regulations) would exclude any new products containing naturally derived substances that, for safety reasons, would be more appropriately regulated under the Food and Drug Regulations.
It should be noted that these Regulations incorporate provisions from the Food and Drug Regulations relating to Schedule F, as Schedule F may be used by the NHPD as a risk management tool.
Exclusion list
With respect to the 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. The schedule indicates that NHPs do not include the following: an antibiotic, a substance intended for injection, a substance regulated under the Tobacco Act, or a substance described in Schedule C (radiopharmaceuticals) or D (biologics) to the Food and Drugs Act.
Earlier draft policy versions of the NHP definition referred to a list of herbs (Table 1). 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 given their known physiologic or pharmacological properties. 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 Web site, at http://www.hc-sc.gc.ca/hpb/onhp.
Although "dosage form" is not an express part of the definition, the NHPD recognizes that NHPs are usually sold in capsule, pill, tablet or liquid 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 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 and labelling/packaging. Transitional provisions (Phase In) are included under each main component.
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 an assessment before it is authorized for sale by the Minister of Health.
Application
An application for a product licence will include specific information about the NHP, for example, the quantity of the medicinal ingredients it contains, the specification it complies with, the 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 intended to indicate the type of information that will be necessary to support various health claims for NHPs. The framework will be available on the NHPD Web site. A product licence applicant will also be required to show that the product will be manufactured, packaged, labelled, distributed and imported in accordance with good manufacturing practices (GMPs, further explained below). In the case of a product manufactured, packaged, labelled and stored in Canada, this information will come from the site licence number of each site (site licensing is further explained below). In the case of a product that will be imported for sale, the applicant will be required to submit other evidence of compliance with the GMPs set out in these Regulations, or equivalent GMPs. The Regulations provide that applicants will be required to submit either a report from a Health Canada inspector, or a compliance audit conducted, signed and dated by a person having technical expertise and training relating to the applicable good manufacturing practice requirements. 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.
Authorization
An authorization for the sale of an NHP (a "product licence") issued by the Minister would indicate the name and address of the licensee, the product licence number of the NHP, dosage form of the NHP, recommended route of administration of the NHP, source material and strength or potency of each medicinal ingredient of the NHP, recommended use or purpose of the NHP, and the date on which the product licence was issued.
Sixty-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 appropriately within 60 days. We will be developing performance standards for the assessment and authorization for sale of all NHP applications. These standards will be outlined in a policy document that will be posted on the NHPD's Web site.
The 60-day disposition clause, sometimes referred to as a performance standard, would apply to an application that 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. Development of monographs is ongoing, and will include both single- and multi-medicinal ingredient monographs. The monograph will provide support for the safety and the claim of the NHP, and therefore additional safety and efficacy data would not be required in the application for a product licence. The Compendium will be made available in both English and French, in hard copy and on the Web site. 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.
Notifications, Amendments and New Product Licences
The product licensing scheme provides that certain changes made to the information provided in the application 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, would require that the NHPD be notified within 60 days of the change. Other changes, for example, a change to the recommended dose or duration of use, would require that the product licence be amended. A new product licence will be required for any changes to an NHP's strength or potency, dosage form, or route of administration.
Stop Sale, 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, designed to allow licensees to provide the Minister with additional information, if requested to do so 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. 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. The NHPD will develop a guidance document for an appeals process, a necessary companion to these provisions.
Product Licensing Phase In
After publication of these Regulations in the Canada Gazette, Part II, an individual would have two years to obtain their product licence. The current Drug Identification Number ("DIN") provisions of the Food and Drug Regulations will continue to apply until products receive an NHP licence.
The NHPD has adopted an approach to the phase-in period. With the publication of these Regulations in the Canada Gazette, Part II, we will request that all individuals marketing NHPs notify that their product is on the market. The notification would include information about their product, including the DIN assigned to it, if applicable. For all products, regardless of whether or not they have a DIN, a compliance and enforcement policy will allow notified products to continue to be sold until they receive a product licence, unless a health and safety concern arises in relation to their sale.
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 approval system based on risk assessment and the corresponding management of risks.
Under the NHP Regulations, product licence holders will be 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 will come into effect for each product once that product receives a product licence. During the two years that the Regulations are being phased in, the NHPD will work with those with notified products, to assist them in understanding and beginning to implement the reporting system even before they have received their licence.
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 in which an NHP is imported, distributed, manufactured, packaged, labelled or stored prior to sale. The site licence will lay out the activities permitted at the site for which it is issued. A site licence will be required for importers, distributors, manufacturers, packagers and labellers of NHPs.
One of the prerequisites that must be met before a site licence is issued is that good manufacturing practices ("GMPs") are employed. The Regulations provide that applicants will be required to submit either a report from a Health Canada inspector, or a compliance audit conducted, signed and dated by a person having technical expertise and training relating to the applicable good manufacturing practice requirements.
The NHPD had considered proceeding first with site licensing for manufacturers, packagers and labellers only, and licensing importers and distributors later in the process. The present Regulations respond to the following concerns: (i) the view of industry that all players in the manufacturing chain should be licensed; (ii) that foreign and Canadian players should be treated in a similar manner; and (iii) that resource requirements (regarding GMP compliance) could be reduced, recognizing that NHPs are generally of lower risk than conventional pharmaceuticals.
The site licensing scheme provides that certain changes made to the information provided in the application after the site has been given a site licence would require that Health Canada be notified within 60 days of the change. Other changes would 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.
Site Licensing Phase In
An individual would have two years from the date of publication in the Canada Gazette, Part II, to obtain a site licence. During these two years, as part of an interim compliance and enforcement policy, a site that is importing, distributing, manufacturing, packaging or labelling NHPs for sale when the Regulations come into force could continue to do so until they receive a site licence, unless a safety concern arises.
The NHPD will ask for the assistance of the industry in preparing for site licensing by requesting that all individuals importing, distributing, manufacturing, packaging or labelling NHPs for sale at the time of publication in the Canada Gazette, Part II, notify the NHPD of their activity, or of their intended activity. The notification would include the address of the individuals or companies involved in the activity, the address of the buildings used or intended to be used for such purposes, the establishment licence number issued under the Food and Drug Regulations, if any, and a brief description of the types of NHPs that will be handled at the sites.
Good Manufacturing Practices (GMPs) [Part 3 of the Regulations]
Good manufacturing practices are measures that ensure an effective overall approach to product quality control and risk management. They do so by setting appropriate standards and practices regarding product design, manufacture, storage, handling and distribution.
The proposed 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 were 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 GMP 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 Web site.
Good Manufacturing Practices Phase In
GMP requirements will come into effect on the earlier of the following: (i) the date a site licence is issued; or (ii) two years after the Regulations come into force. It should be noted that the current GMP requirements in Division 2 of the Food and Drug Regulations will continue to apply to NHPs in the interim period. A compliance and enforcement policy will be developed to address this interim period.
Clinical Trials (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 will provide investigators with clear and transparent requirements for conducting human clinical trials with NHPs. The requirements will ensure the safety of trial participants. They will 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 are available, and/or for obtaining evidence to support new claims, if they wish.
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.
It is important to note that the clinical trial investigator is not limited to a medical doctor or a dentist. Other health professionals regulated by the laws of the province where the clinical trial site is located, and whose role within the clinical trial is within their scope of practice, could be the clinical trial investigator. The term principal investigator is not defined within the Regulations, nor do the Regulations place any requirements on the principal investigator. As is the current practice in this area, academics, health professionals, or researchers could be the principal investigator.
The NHPD recognizes the necessity of having an individual knowledgeable in complementary or alternative health care on the Research Ethics Board (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.
Good Clinical Practices (GCP)
Clinical trials with NHPs must be conducted in accordance with generally accepted principles of good clinical practice. The Regulations outline specific good clinical practices that must be met; however, in general terms, good clinical practices must provide that the clinical trial:
- is scientifically sound and clearly described in a protocol that has received REB approval;
- is carried out by individuals qualified by education, training and experience to perform his or her respective tasks;
- uses an NHP that is manufactured, packaged, labelled and stored in accordance with the applicable good manufacturing practices;
- uses subjects that have freely given their informed consent after having been informed of the risks and anticipated benefits to his or her health arising from participation in the clinical trial;
- provides for medical care of clinical trial participants; and
- meets requirements for record keeping and confidentiality of participants.
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;
- the brand name or code name of the NHP;
- the expiration date of the NHP;
- the recommended storage conditions for the NHP;
- the lot number of the NHP;
- the name and address of the manufacturer;
- the name and address of the sponsor; and
- the protocol code or identification.
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 here-under. 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 discontinuation, clinical efficacy and safety requirements;
- changes to the protocol that result in the extension of the duration of the clinical trial; and
- changes to the chemistry and manufacturing information of a synthetically produced NHP ingredient that may affect safety and quality.
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
- changes to the protocol that do not affect the safety of the trial subjects.
Inspection System
Health Canada will inspect clinical trial sites and trial sponsors to ensure that the generally accepted principles of good clinical practices 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.
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 will 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 will list complete directions for 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.
The required labelling information includes all of the following:
- the brand name;
- the product number (issued with the product licence, preceded by the designation NHP or PSN);
- the dosage form;
- if the NHP is sterile, the notations "sterile" and "stérile";
- if the NHP is one which is available for sale on prescription, the symbol "Pr";
- the net amount of the NHP in terms of weight, measure or number;
- the name and address of the product licence holder;
- if the NHP is imported, the name and address of the importer (and the product licence holder);
- the proper name and, if any, the common name of each medicinal ingredient;
- the strength or potency of the medicinal ingredients (by proper name);
- a qualitative list of all non-medicinal ingredients;
- the recommended use or purpose;
- the recommended route of administration;
- the recommended dose and, if any, the duration of use;
- the risk information relating to the NHP, including any cautions, warnings, contra-indications or known adverse reactions associated with the use of that NHP;
- the recommended storage conditions, if any;
- the lot number;
- the expiration date; and
- a description of the source material from which the medicinal ingredients are derived or obtained (for example, root of plant).
For all labels, certain information, namely the recommended use or purpose of the NHP, the recommended route of administration, the recommended dose and duration of use of the NHP, and the risk information relating to the NHP, including any cautions, warnings, contra-indications or known adverse reactions associated with the use of the NHP must be in both English and French (any other language may also be used in addition).
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;
- a qualitative list by proper name that sets out in descending order of quantity all medicinal ingredients contained in the NHP;
- the recommended dose and duration of use, if any;
- the lot number;
- the expiration date;
- the product number (issued with the product licence, preceded by the designation NHP or PSN);
- if the NHP is sterile, the notations "sterile" and "stérile";
- if the NHP is one which is available for sale on prescription, the symbol "Pr";
- the net amount in terms of weight, measure or number; and
- the recommended use or purpose.
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
After publication in the Canada Gazette, Part II, products would have two years before being required to be labelled in accordance with these Regulations. Products labelled in accordance with the Food and Drug Regulations at the time these Regulations come into force could continue to be sold for a period of two years. When a product is issued a licence under these Regulations, the product must be labelled in accordance with the requirements set out.
For products on the market without DINs when the Regulations come into force, a compliance and enforcement policy will provide that those for which the NHPD received a notification would be permitted to continue to be sold with the existing label and package. These products would be required to meet all labelling and packaging requirements within two years of the Regulations coming into force.
New products would be 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.
It needs to be emphasized that these products are currently regulated in Canada either as foods or drugs under the Food and Drugs Act and the Food and Drug Regulations. To introduce concepts such as voluntary standards would therefore 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 Unites States. 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. 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 exist as an anomaly, having classified many natural health products as "dietary supplements." Through consultations with consumers and deliberations of the Standing Committee, it 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 its final report. Its recommendations, which were accepted in their 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 Natural Health Products Directorate, 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.
Given that these products are currently regulated in Canada as drugs or food, 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. Within these options, elements of voluntary standards were considered and found to be inconsistent with directions provided to Health Canada. 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 to exceed $1.5 billion. As indicated earlier, these products are already regulated as foods or drugs, and are estimated to number around 25 000 to 30 000 products. Vitamins represent over 50 percent of retail sales, and involve over 18 percent of Canadian companies involved in the NHP industry. Herbs and botanicals represent another 30 percent of sales.
The NHPD undertook a benefit-cost analysis of the proposed Natural Health Product Regulations. It is important to note that the project was carried out 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.
Findings
Consumers: Natural Health Products Regulations would 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 would benefit from the added confidence in the safety and efficacy of NHPs, and would 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 approval 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 levels of evidence.
In terms of costs, in a competitive market, costs placed on industry to comply with the Regulations would eventually be passed on to the consumer.
Industry: NHPs will no longer be regulated as either foods or drugs, and 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 resulting increase in a long-term, stable demand for NHPs, and will be generally 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 of the interviewees 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.
In terms of costs, industry would bear most of the costs of the proposed Natural Health Products Regulations. 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. Manufacturers of NHPs only would probably incur some 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 NHP GMPs would be minimal, if any. To assist those who require extra effort to come into compliance with GMPs, the NHPD will undertake to provide awareness, education and training sessions as well as a transitional time period. Concerns were also raised that meeting these Regulations may create additional paper burden, and the NHPD will automate and streamline its processes where possible. In a competitive market, costs placed on industry to comply with the Regulations would eventually be passed on to retailers.
Government: In developing these Regulations, Health Canada would be responsive to Canadians, as it is clear that consumers want NHPs to be regulated in a category separate from foods and drugs. Health Canada would maintain its mandate to protect the health and safety of Canadians, and have a vehicle to do so in an appropriate manner.
There will be increased costs to Health Canada as the Natural Health Products Regulations would 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 would be borne by Health Canada. Costs would also be incurred to develop guidelines and policies to support these Regulations. In response to cost recovery concerns raised by industry and consumers during consultations, the NHPD indicated that the Standing Committee envisioned a system of cost recovery for the program, and that if it were to be introduced as a facet of the NHPD's operations, a separate consultation would take place on this matter.
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-medication and self-preservation 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 will also provide the consumer with full disclosure of non-medicinal ingredients 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 will be decreased. As well, as indicated earlier, the consumer will benefit 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 three 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 Web site, mailings, general and targeted consultations, etc. This consultation approach has been lauded as a best practice within the Branch, due in great part to the effective use of the input received. Stakeholders have commented that the development of the framework has been consistent and responsive to stakeholder concerns, and the building of the Regulations has evolved 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 have been downloaded from the NHPD Web site, 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 analyzed and modifications were made to the proposal based on the feedback. Feedback from these Phase I consultations can be found on the NHPD Web site.
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 then released at the end of March 2001. 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. A summary follows later in this section.
Further, on September 28, 2001, a working draft of the proposed regulatory framework was shared with stakeholders through its posting on the NHPD's Web site. Updates on outstanding issues were also communicated via the Web site.
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 Web site.
Comments made during Phase II of the consultations and the Directorate's responses are summarized as follows:
Claims/Schedule A
Comment:
(a) that Schedule A be amended to permit certain label claims
Response:
The NHPD understands the concern that certain NHPs will be unable to make certain label claims even if there is scientific evidence to justify them, due to the restrictions of section 3 and Schedule A.
The provisions of section 3 of the Food and Drugs Act and Schedule A impact not only on NHPs, but also on other products currently governed by the Food and Drugs Act, including foods, drugs, cosmetics, and medical devices. It has therefore been referred to Health Canada's Legislative Renewal initiative for review and will be the object of public discussions when their second round of consultations is launched.
The NHPD, along with other Directorates within Health Canada, are working to determine how best to address Schedule A in the short and longer term. Among the options being considered are the following: considering symptoms of certain listed diseases or conditions as different from the disease or condition itself so as to permit claims related to those symptoms; defining certain Schedule A diseases and conditions to add clarity as to what is and is not captured; and updating Schedule A to include any diseases or conditions that should be added or to remove those that should be removed. Consideration will be given as to which options can be addressed by policy and which would require regulatory amendment.
Adverse Reaction Reporting
Comments:
(a) that there should be no requirement to conduct an analysis and prepare a report of adverse reactions (i.e. requirement limited to reporting to the NHPD only)
(b) that adverse reaction definition be changed to adverse event
Response:
(a) The NHPD believes that it is appropriate that the product licence holder of the NHP conduct an analysis and prepare a report of adverse reactions. The product licence holder is responsible for determining whether there are patterns of occurrence with respect to adverse reactions.
(b) The NHPD understands that some manufacturers are concerned that the term "adverse reaction" to some may imply a causal link between the NHP and the adverse outcome, when in actual fact a causal link may not have been established. The NHPD has therefore adopted a policy that, where no causal link is made, any reference to the "reaction" will always be accompanied by a statement that no causal link has been made.
Labelling
Comments:
(a) that the terms medicinal and non-medicinal ingredients should be replaced by the terms active and inactive ingredients
(b) that non-medicinal ingredients should be dropped from the product label
(c) that medicinal ingredients could be declared qualitatively (as opposed to quantitatively) on product labels
(d) that brand name, quantity, and product licence number should appear on the main panel of the product label
(e) that lot number and expiration date be permitted to appear on product containers instead of on the inner label
(f) that all labels set out the claims or indications for the product
Response:
(a) The NHPD used a series of focus groups to determine whether consumers better understood, or were more comfortable with, one term over the other, as well as dealing with this issue through targeted consultations. The term medicinal ingredient appears to be well understood not only by the industry but by the consumer.
(b) and (c) Recommendation Number 33 of the Standing Committee stated that NHP labelling provide consumers with all relevant information needed to make informed choices. Consumers have asked for full product information on product labels. The NHPD recognizes that product labels should assist consumers in making informed choices with respect to NHPs. Including a quantitative list of medicinal ingredients and a qualitative list of non-medicinal ingredients on product labels should assist them in selecting products that meet their particular needs and expectations. It should also be noted that we received submissions supporting a quantitative list of medicinal ingredients and a qualitative list of non-medicinal ingredients.
(d) The NHPD has included these recommendations in the Regulations.
(e) The proposed definition of "inner label" would allow this information to be placed on the immediate container. An NHPD guidance document will state that placing the lot number and expiration date on the container is acceptable.
(f) The Standing Committee made five recommendations with respect to efficacy, including Recommendation Number 19: that NHPs be allowed to make health claims, including structure/function claims, risk-reduction claims and treatment claims. As mentioned above, recommendation Number 33 stated that NHP labelling provide consumers with all relevant information needed to make informed choices.
The NHPD recognizes that product labels should assist consumers in making informed choices with respect to NHPs. Including claims on product labels should assist them in selecting products that meet their particular needs and expectations.
Product Licensing Scheme
Comments:
(a) that the product licensing scheme should be simplified and streamlined
(b) that specifications be dropped from product licensing scheme
(c) that shelf life be dropped from product licensing scheme
(d) that non-medicinal ingredients be declared qualitatively, if at all, in the product licence application
(e) that most product changes be made annual notifications or 60-day notifications, and that few changes be amendments
(f) that one product licence be issued for multiple brand names
Response:
(a) The NHPD has simplified the proposed product licensing scheme, including clarification on the types of changes that need only be notified.
(b) The NHPD has narrowed the definition of specifications based on recommendations that were made.
(c) The NHPD has accepted this recommendation and has dropped the requirement for shelf life in the product licence application. It should be noted, however, that there is a requirement under good manufacturing practices for a stability determination to be made, i.e. to ensure that a product will continue to meet its specifications until its expiration date.
(d) The NHPD has included these recommendations in the Regulations: a proposed qualitative list is to be provided with the product licence application and notification and amendment provisions apply to some changes to non-medicinal ingredients.
(e) The NHPD has decreased the number of changes that require amendments. Also, performance targets will reflect the types of product changes being made.
(f) The NHPD has decided that one product licence can be issued for more than one brand name.
Product Licensing Delays
Comment:
(a) that resources be sufficient to avoid long delays in product licensing
Response:
Three systems are envisioned in which parallel product submission reviews could occur simultaneously:
- DIN products, since they have been previously reviewed, would essentially be transferred over to the new regulatory framework after a quick review;
- non-DIN products currently on the market would remain on the market while the submissions for a product licence are processed; and
- new products not currently on the market will be reviewed concurrently.
Resources will be augmented in the NHPD to deal with the initial intake of products. As well, the graduated or staged implementation or coming into force of the Regulations will lessen the impact on resourcing and allow for planning for peak intake periods.
In addition, through the 60-day disposition clause, the NHPD will review certain NHP licence applications within 60 days, assuring lengthy delays are avoided in these cases.
Site Licensing
Comments:
(a) that wholesalers not be required to hold site licences
(b) that a site licence application not include a list of products that will be handled at each site
(c) that the requirement to supply product samples, if required, at the application stage be dropped
(d) that site licensing requirements be the same for foreign and domestic sites
Response:
(a) The NHPD has accepted this recommendation and has crafted the definition of distributor to exclude a wholesaler, as the name of the wholesaler is not usually on the product (see definitions).
(b) This recommendation was also accepted. The product list need not be provided as part of the application, though a list of products being handled at the site must be maintained under GMPs (Records).
(c) The NHPD accepted this recommendation.
(d) This recommendation was accepted, as shown in the GMP and site licensing sections.
Compliance and Enforcement
Comments:
(a) that the stop sale provision be dropped
(b) that there be an adequate amount of inspectors
(c) that inspectors be properly trained for NHPs
Response:
(a) The NHPD is of the view that the stop sale provision is a key regulatory tool. A stop sale could prevent the sale of a contaminated or otherwise adulterated lot or batch of a product before it reaches store shelves. It could also allow Health Canada and the NHPD to react to post market data (e.g. a new adverse reaction or contraindication is noted) by allowing a reassessment of the safety and efficacy in light of new information. A product licence suspension is not desirable in all cases. The stop sale would enable Health Canada to ensure a label change or other corrective measure, while not having to suspend or cancel a product licence, which would prevent all retail sales of the product.
(b) The NHPD will work with the Health Products and Food Branch Inspectorate to ensure that compliance and enforcement is carried out in a timely and appropriate manner, and that activities are sufficiently resourced. The Inspectorate will be responsible for the delivery of inspection, investigation, site licensing and related laboratory analysis for the NHPD.
(c) The NHPD will work with the Inspectorate to ensure that inspectors are properly trained in the application of the good manufacturing practices (GMPs) specific to NHPs.
Implementation
Comments:
(a) that key guidance documents be available to stakeholders at the time of pre-publication in the Canada Gazette, Part I
(b) that the transition time be shortened for certain elements, e.g. that labelling requirements be met within six months to one year of publication in the Canada Gazette, Part II
Response:
(a) The following guidance documents will be released on the Health Canada Web site: good manufacturing practices, standards of evidence for evaluating safety and claims, filing of a product licence application and filing of a site licence application.
(b) The NHPD has shortened the time frame for implementation, based on comments received from industry and consumers. Specifically, the NHPD is proposing that product licences be obtained within two years, and labelling and packaging requirements be met within two years, in comparison to the three years that were proposed for each of these requirements in the Phase II consultation documents.
Progress on Standing Committee on Health's 53 Recommendations
Comment:
(a) that work continue as quickly as feasible to implement the recommendations of the Standing Committee on Health
Response:
The NHPD is continuing to make progress on the 53 recommendations made by the Standing Committee on Health. To view the progress, please visit the NHPD Web site.
Cost
Comment:
The impact of the Regulations on the cost of the product was a concern. The issue of cost recovery was often raised.
Response:
The NHPD is currently not cost recovered. If the NHPD is required to move to cost recovery, it would do so in an open and consultative manner similar to the consultation process we used to develop these Regulations.
Additional Consultation
Working Groups
The Natural Health Products Directorate held two 2-day workshops, one in March of 2001, and one in October, in which knowledgeable individuals were brought together to assist in the development of the good manufacturing practices (GMP) and standards of evidence (SOE) guidance documents, respectively. Approximately 50 people were involved in the GMP workshop, including industry, academics, researchers, consumers and others. At the SOE workshop, industry, academics, researchers, consumers, practitioners and others represented the approximately 40 participants.
Performance Measure
The NHPD will assess the effectiveness of the present regulatory initiative after some experience has been gained under the new framework.
Education and Outreach
The NHPD plans to initiate a public awareness campaign, to make both stakeholders and consumers aware of the Regulations, and what they will mean. In particular, the Directorate will work with industry to educate them about the new requirements.
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
The NHPD will work with the Health Products and Food Branch Inspectorate to ensure compliance and enforcement is carried out. The Inspectorate will be responsible for the delivery of inspection, investigation, site licensing and related laboratory analysis for the NHPD.
The Inspectorate will, for the purpose of site licensing, carry out inspections at the request of the Directorate to ensure that good manufacturing practices (GMPs) are met. Site licence issue and withdrawal will therefore be accomplished with full participation from the Inspectorate.
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. However, to be cost-efficient, this random sampling would be on an occasional basis only, and not all products would be tested.
Non-compliance could result in several actions, depending on whether the non-compliant party is the product licence holder, manufacturer, distributor, importer, labeller, or packager. Enforcement activities could include a stop sale order for a specific product, the suspension or cancellation of a product licence, or the suspension or cancellation of a site licence.
Contacts
Kyra Paterson, Policy and Regulatory Affairs, Natural Health Products Directorate, Health Products and Food Branch, Health Canada, Address Locator 3709B, 171 Slater Street, Ottawa, Ontario K1A 0L3, (905) 690-7651; Phil Waddington, Director General, Natural Health Products Directorate, Health Products and Food Branch, Health Canada, Address Locator 3709B, 171 Slater Street, Ottawa, Ontario, K1A 0L3, (613) 952-2558.
PROPOSED REGULATORY TEXT
Notice is hereby given that the Governor in Council, pursuant to subsection 30(1) (<Reference a> S.C. 1999, c. 33, s. 347) of the Food and Drugs Act, proposes to make the annexed Natural Health Products Regulations.
Interested persons may make representations with respect to the proposed Regulations within 90 days after the date of publication of this notice. All such representations must cite the Canada Gazette, Part I, and the date of publication of this notice, and be addressed to Philip Waddington, Director General, Natural Health Products Directorate, Health Products and Food Branch, Department of Health, Address Locator 3709B, 171 Slater Street, 9th Floor, Ottawa, Ontario K1A 0L3 (tel.: (613) 952-3128; fax: (613) 946-1615; e-mail: ONHP_Consultations@hc-sc.gc.ca).
Persons making representations should identify any of those representations the disclosure of which should be refused under the Access to Information Act, in particular under sections 19 and 20 of that Act, and should indicate the reasons why and the period during which the representations should not be disclosed. They should also identify any representations for which there is consent to disclosure for the purposes of that Act.
Ottawa, December 13, 2001
RENNIE M. MARCOUX
Acting Assistant Clerk of the Privy Council
*** TABLE EXTRACTED ***
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
(a) that is used to distinguish the natural health product; and
(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)
"common name" means, in respect of an ingredient contained in a natural health product, the name in English or French
(a) by which it is commonly known; and
(b) that has been assigned to it in a scientific or technical publication, other than a publication referred to in Schedule B to the Act. (nom usuel)
"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, bearing a label showing that person's name and address, to another person for the purpose of further sale by that other person. (distributeur)
"expiration date" means the earlier of
(a) the date, expressed at minimum as a year and month, up to and including which a natural health product maintains its potency, purity and physical characteristics, and
(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 preparation or a traditional medicine, that is manufactured, sold or represented for use in
(a) the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state or its symptoms in humans;
(b) restoring or correcting organic functions in humans; or
(c) maintaining or promoting health or otherwise modifying organic functions in humans.
However, a natural health product does not include a substance set out in Schedule 2 or any combination of substances that 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 microflora indigenous to humans. (probiotique)
"proper name" means, in respect of an ingredient contained in a natural health product, one of the following names:
(a) if the ingredient is a vitamin or a salt or derivative of a vitamin, a 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 fungus, a non-human animal material or a probiotic, the Latin name of its genus and species;
(c) if the ingredient is other than one described in paragraph (a) or (b) and an English or French name is assigned to it in any publication referred to in Schedule B to the Act, that name in English or French; and
(d) if the ingredient is other than one described in paragraphs (a) to (c), the chemical name of the ingredient. (nom propre)
"recommended conditions of use" means, in respect of a natural health product,
(a) its recommended use or purpose;
(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 34(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) Subject to subsection (2), these Regulations apply to
(a) the sale of natural health products;
(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, a homeopathic preparation or a traditional medicine is not considered to be a natural health product if there is a narrow margin of safety between its recommended dose and its toxic dose, as determined by observing the following factors on the basis of the information referred to in subsection (3) that is available:
(a) the lowest dose at which it produces toxicity in humans; and
(b) the highest dose at which it does not produce toxicity in humans.
(3) For the purposes of subsection (2), the information in respect of the substance or combination of substances, the homeopathic preparation or the traditional medicine is as follows:
(a) its recorded history of use in humans;
(b) its clinical experience data;
(c) its adverse reaction reports; and
(d) its toxicological effects in any animal species tested.
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 that 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 of time that the sale of that natural health product is directed to be stopped under section 15.
(3) No person shall sell a natural health product for which a product licence is issued
(a) during the period of any suspension of the licence under section 16 or 17; or
(b) after cancellation of the licence under paragraph 18(b).
Licence Application
5. An application for a product licence shall be submitted to the Minister and shall contain the following information and documents:
(a) the name, address and telephone number, and if applicable, the facsimile number and electronic mail address of the applicant;
(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) in respect of each manufacturer, packager, labeller, importer and distributor
(i) the person's name, address and telephone number, and if applicable, the person's facsimile number and electronic mail address, if that information is different from that submitted under paragraph (a),
(ii) if the activity is conducted in Canada, the number assigned to the site licence issued to the person in respect of that activity, and
(ii) if the activity is conducted outside of Canada, the number assigned to any site licence issued to the person in respect of that activity;
(d) the address of each building in which the natural health product is manufactured, packaged or labelled;
(e) the address of each building in which the natural health product is stored for the purposes of importation or distribution;
(f) for each medicinal ingredient contained in the natural health product,
(i) its proper name and, if any, its common name,
(ii) its strength or potency,
(iii) a description of its source material, if any, and
(iv) a statement indicating whether it is synthetically manufactured;
(g) a qualitative list of the non-medicinal ingredients contained in the natural health product and for each ingredient listed, a statement that indicates the purpose for which the ingredient is included in the natural health product;
(h) each brand name under which the natural health product is proposed to be sold;
(i) the recommended conditions of use for the natural health product;
(j) information that supports the safety and efficacy of the natural health product when it is used in accordance with the recommended conditions of use;
(k) the text of each label that is proposed to be used in conjunction with the natural health product;
(l) a copy of the specifications to which the natural health product will comply; and
(m) one of the following attestations, namely,
(i) if the natural health product is imported, an attestation by the applicant, as well as 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, or
(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.
60-Day Disposition
6. (1) Subject to subsection (2), the Minister shall dispose of an application submitted under section 5 within 60 days after the date on which it is submitted if, in support of the application, the only information submitted by the applicant under paragraph 5(j) is that which is
(a) in the case of an application respecting a natural health product that has only one medicinal ingredient, contained in a monograph for that medicinal ingredient in the Compendium; and
(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 12, 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.
Issuance
7. (1) The Minister shall issue the applicant a product licence if
(a) the applicant has submitted to the Minister an application that is in accordance with section 5;
(b) the applicant has submitted to the Minister any additional information or samples requested under section 12;
(c) the applicant has not made a false or misleading statement in the application; and
(d) the issuance of the licence to the applicant would not result in injury to the health of a purchaser or consumer.
(2) If the Minister issues a product licence in accordance with subsection (1), the Minister shall assign the natural health product a product number.
Licence Contents
8. (1) A product licence shall set out the following information:
(a) the name and address of the licensee;
(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) in respect of each medicinal ingredient contained in the natural health product
(i) its authorized strength or potency, and
(ii) its authorized source material;
(g) the recommended use or purpose that is authorized for the natural health product; and
(h) the date on which the licence was issued.
(2) Within 60 days after the date on which the licensee commences sale of the natural health product in Canada, the licensee shall notify the Minister in writing of any information set out on the product licence that the licensee knows to be incorrect.
Notification
9. (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 date of the change, provide the Minister with
(a) written notification of the change; and
(b) the text of each label used in conjunction with the natural health product after the date of the change, if the change is any of those described in paragraphs (2)(b) to (e).
(2) For the purposes of subsection (1), changes in respect of a natural health product are
(a) a change to the information submitted under any of paragraphs 5(a) to (e);
(b) an addition or substitution of any of its non-medicinal ingredients, the addition or substitution of which does not affect its safety or efficacy;
(c) its sale under a brand name other than one submitted under paragraph 5(h);
(d) a change of the common or proper name of any of its medicinal ingredients; and
(e) 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.
Amendment
10. (1) If the licensee makes any of the following changes in respect of the natural health product, the licensee shall not sell any of the natural health products affected by the change until the product licence is amended:
(a) a change to its recommended dose;
(b) a change to its recommended duration of use;
(c) the deletion or modification of risk information shown on any 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) a change affecting its safety or efficacy that does not arise as a result of
(i) a change to the strength or potency of any of its medicinal ingredients, or
(ii) a change to its dosage form or its recommended route of administration; or
(g) one or more of the following changes to its specifications, namely,
(i) the removal of a test set out in the specifications,
(ii) the modification of a test set out in the specifications in a manner that widens the tolerances associated with the properties or qualities of the natural health product, or
(iii) the modification of a test method set out 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:
(a) the product number of the natural health product;
(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 date of the change, if the change is any of those described in paragraphs (1)(a) to (f); and
(e) a copy of the revised specifications, if the change is any of those described in paragraph (1)(g).
(3) The Minister shall amend a product licence if
(a) the applicant has submitted an application for amendment that is in accordance with subsection (2);
(b) the applicant has submitted to the Minister any additional information or samples requested under section 12;
(c) the applicant has not made a false or misleading statement in the application for amendment; and
(d) the amendment of the licence would not result in injury to the health of a purchaser or consumer.
Sale After Change
11. If the licensee makes a change in respect of the natural health product, the licensee may not sell any of the natural health product affected by that change
(a) if the change is to the strength or potency of any of its medicinal ingredients;
(b) if the change is to its dosage form or its recommended route of administration; or
(c) until the product licence is amended, if the change is any of those described in subsection 10(1).
Additional Information or Samples
12. If the information and documents submitted in respect of a product licence application under section 5 or an application for amendment under subsection 10(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 submit such additional information or samples of the natural health product as are necessary to make the determination.
Reaction Reporting
13. (1) A licensee shall provide the Minister with
(a) a case report for each serious adverse reaction in respect of the natural health product that occurs inside Canada, within 15 days after becoming aware of the reaction; and
(b) a case report for each serious unexpected adverse reaction in respect of the natural health product that occurs inside or outside Canada, within 15 days after becoming 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
(a) all adverse reactions in respect of the natural health product that have occurred inside Canada; and
(b) all reactions for which a case report is required to be provided under subsection (1), that have occurred
(i) during the previous 12 months, and
(ii) at a dose used or tested for the diagnosis, treatment or prevention of a disease or for maintaining or promoting health or otherwise 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 the licensee
(a) provide to the Minister, within 30 days after receiving the request, a copy of any summary report prepared under subsection (2); or
(b) prepare and provide to the Minister, within 30 days after receiving the request, an interim summary report containing a concise and critical analysis of
(i) all adverse reactions in respect of the natural health product that have occurred inside Canada, and
(ii) all reactions for which a case report is required to be provided under subsection (1), that have occurred
(A) since the date of the most recent summary report prepared under subsection (2), and
(B) at a dose used or tested for the diagnosis, treatment or prevention of a disease or for maintaining or promoting health or otherwise modifying organic functions in humans.
Safety Information
14. 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 receiving the request, with information and documents demonstrating that the natural health product is safe when used under the recommended conditions of use.
Direction to Stop Sale
15. (1) The Minister may direct the licensee, manufacturer, importer and distributor to stop their sale of a natural health product if
(a) the licensee does not provide the Minister with the information and documents requested in accordance with section 14;
(b) the information and documents submitted by the licensee in accordance with section 14 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 submits to the Minister information and documents demonstrating that
(a) in the case of a direction to stop sale arising under either paragraph (1)(a) or (b), the natural health product is safe when used under the recommended conditions of use;
(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
16. (1) Subject to subsection (2), the Minister shall suspend a product licence if the Minister has reasonable grounds to believe that
(a) the licensee has contravened these Regulations or any provision of the Act relating to the natural health product; or
(b) the licensee has made a false or misleading statement in the application submitted under section 5 or the application for amendment under subsection 10(2).
(2) Subject to section 17, the Minister shall not suspend a product licence unless
(a) the Minister has sent the licensee a written notice of the intention to suspend the licence that sets out the reason for the intended suspension; and
(b) the licensee has not, within 90 days after receiving the notice referred to in paragraph (a), provided the Minister with information or documents demonstrating that the licence should not be suspended on the grounds that
(i) the situation giving rise to the intended suspension did not exist, or
(ii) the situation giving rise to the intended suspension has been corrected.
17. The Minister shall suspend a product licence before giving the licensee an opportunity to be heard if 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.
18. If the Minister suspends a product licence under section 16 or 17, the Minister shall send the licensee a written notice of the suspension setting out the reasons for and the effective date of the suspension, and the Minister shall
(a) reinstate the licence if, within 90 days after the effective date of the suspension, the licensee provides the Minister with information or documents demonstrating that the situation giving rise to the suspension did not exist or that it has been corrected; or
(b) cancel the licence if, within 90 days after the effective date of the suspension, the licensee has not provided the Minister with the information or documents referred to in paragraph (a).
19. If the Minister cancels a licence under paragraph 18(b), the Minister shall send the licensee a written notice of the cancellation setting out the reasons for and the effective date of the cancellation.
PART 2
SITE LICENCES
Prohibition
20. (1) Subject to subsection (2), no person shall manufacture, package, label or import a natural health product for sale or distribute a natural health product unless
(a) the person holds a site licence;
(b) the person conducts the activity in accordance with the requirements set out in Part 3; and
(c) if the person is importing a natural health product in dosage form for sale, the person has a representative in Canada who is responsible for the sale of the natural health product.
(2) No person who holds a site licence shall manufacture, package, label or import a natural health product for sale or distribute a natural health product
(a) during the period of any suspension of the licence under section 29 or 30; or
(b) after cancellation of the licence under paragraph 31(b).
Licence Application
21. An application for a site licence shall be submitted to the Minister and shall contain the following information and documents:
(a) the name, address and telephone number, and if applicable, the facsimile number and electronic mail address of the applicant;
(b) a statement specifying which one or more of the following activities, namely, manufacturing, packaging, labelling, importing or distributing 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 or distribute 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)
(i) a report from an inspector indicating that they comply with the requirements set out in Part 3; or
(ii) an audit report indicating that they comply with the requirements set out in Part 3 and that is signed and dated by a person who, in respect of each activity for which the audit report is made, has technical expertise and training relating to the activity and to the requirements set out in Part 3.
Issuance
22. (1) The Minister shall issue the applicant a site licence if
(a) the applicant has submitted to the Minister an application that is in accordance with section 21;
(b) the applicant has submitted to the Minister all additional information requested under section 28;
(c) the applicant has not made a false or misleading statement in the application; and
(d) the issuance of the licence to the applicant would not result in injury to the health of a purchaser or consumer.
(2) If the Minister issues a site licence in accordance with subsection (1), the Minister shall assign that licence a site licence number.
Licence Contents
23. A site licence shall set out the following information:
(a) the name and address of the licensee;
(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 or distribute a natural health product, the address of each building in which the licensee is authorized to store that natural health product.
Notification
24. If the licensee makes any of the following changes, the licensee shall, within 60 days after the date of the change, provide the Minister with written notification of the change:
(a) a change to the information submitted under paragraph 21(a); and
(b) a change that substantially alters any building, equipment, practice or procedure in respect of which a report from an inspector or an audit report was submitted under paragraph 21(f).
Amendment
25. (1) A licensee shall not conduct any of the following activities unless the site licence is amended:
(a) conduct any activity for a which a site licence is required that the licensee is not authorized to conduct;
(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 or distribute a natural health product, store that 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 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:
(a) the licence number;
(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 indicating 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.
(3) The Minister shall amend a site licence if
(a) the applicant has submitted to the Minister an application for amendment that is in accordance with subsection (2);
(b) the applicant has submitted to the Minister all additional information requested under section 28;
(c) the applicant has not made a false or misleading statement in the application for amendment; and
(d) the amendment of the licence would not result in injury to the health of a purchaser or consumer.
Expiry
26. (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 27.
(2) A site licence that is renewed in accordance with section 27 expires on the day on which the renewal period ends unless the licence is further renewed in accordance with section 27.
Renewal
27. (1) The Minister shall renew a site licence if
(a) the licensee has submitted to the Minister, no later than 30 days before the day on which the licence expires, a written request to renew the licence;
(b) the licensee has submitted to the Minister any additional information requested under section 28; and
(c) the renewal of the licence would not 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
(a) one year, 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 less than three years;
(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
28. If the information and documents submitted in respect of an application under section 21, an application for amendment under subsection 25(2) or an application for renewal under section 27 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 submit to the Minister such additional information as is necessary to make the determination.
Suspension and Cancellation
29. (1) Subject to subsection (2), the Minister shall suspend a site licence if the Minister has reasonable grounds to believe that
(a) the licensee has contravened these Regulations or any provision of the Act relating to the natural health product; or
(b) the licensee has made a false or misleading statement in the application submitted under section 21 or the application for amendment under subsection 25(2).
(2) Subject to section 30, the Minister shall not suspend a site licence unless
(a) the Minister has sent the licensee a written notice of the intention to suspend the licence that sets out the reason for the intended suspension; and
(b) the licensee has not, within 90 days after receiving the notice referred to in paragraph (a), provided the Minister with information or documents that demonstrate that the licence should not be suspended on the grounds that
(i) the situation giving rise to the intended suspension did not exist, or
(ii) the situation giving rise to the intended suspension has been corrected.
30. The Minister shall suspend a site licence before giving the licensee an opportunity to be heard if 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.
31. If the Minister suspends a site licence under section 29 or 30, the Minister shall send the licensee a written notice of the suspension setting out the reasons for and the effective date of the suspension, and the Minister shall
(a) reinstate the licence if, within 90 days after the effective date of the suspension, the licensee provides the Minister with information or documents that demonstrate that the situation giving rise to the suspension did not exist or that it has been corrected; or
(b) cancel the licence if, within 90 days after the effective date of the suspension, the licensee has not provided the Minister with the information or documents referred to in paragraph (a).
32. If the Minister cancels a site licence under paragraph 31(b), the Minister shall send the licensee a written notice of the cancellation setting out the reasons for and the effective date of the cancellation.
PART 3
GOOD MANUFACTURING PRACTICES
Prohibition
33. (1) Subject to subsection (2), no person shall sell a natural health product unless it is manufactured, packaged, labelled, imported, distributed and 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 and 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
34. (1) Every natural health product available for sale shall comply with the specifications submitted in respect of that natural health product under paragraph 5(l) and with every change to those specifications made by the product licence holder.
(2) The specifications shall be in writing and shall contain the following information:
(a) detailed information respecting the identity and purity of the natural health product, including statements indicating the identity and purity tolerances of the natural health product;
(b) if a representation relating to the potency of the natural health product is to be shown on any of its labels, detailed information respecting the potency of the natural health product, including statements indicating the potency tolerances of the natural health product; and
(c) 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
35. (1) Every natural health product must 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
(a) permits the premises to be kept clean and orderly;
(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 must be stored under conditions that will maintain the quality and safety of the natural health product.
Equipment
36. Every natural health product must be manufactured, packaged, labelled and stored using equipment that is designed, constructed, maintained, operated and arranged in a manner that
(a) permits the effective cleaning of its surfaces;
(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
37. Every natural health product must be manufactured, packaged, labelled and stored by personnel who are qualified by education, training or experience to perform their respective tasks.
Sanitation Program
38. Every natural health product must be manufactured, packaged, labelled and stored in accordance with a written sanitation program that sets out
(a) procedures for effectively cleaning the premises in which the activity is conducted;
(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
39. Every natural health product must be manufactured, packaged, labelled and stored in accordance with written standard operating procedures that are designed to ensure that the activity is conducted in accordance with the requirements of this Part.
40. Every manufacturer, packager, labeller, importer and distributor shall establish and maintain a system of control that permits the rapid recall of every lot or batch of the natural health product that has been made available for sale.
Quality Assurance
41. (1) Every manufacturer, packager, labeller, importer and distributor shall
(a) have a quality assurance person who is responsible for assuring the quality of the natural health product before it is made available for sale; and
(b) investigate and record every complaint received in respect of the quality of the natural health product and, if necessary, take corrective action.
(2) Every natural health product must be manufactured and packaged 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 must be manufactured, packaged, labelled and stored using methods and procedures that, prior to their implementation, have been examined and approved by a quality assurance person.
(4) Every lot or batch of a natural health product must 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, must be approved by a quality assurance person before that natural health product may be made available for resale.
Stability
42. Every manufacturer and 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
(a) it is stored under its recommended storage conditions; or
(b) if it does not have recommended storage conditions, it is stored at room temperature.
Records
Manufacturers
43. Every manufacturer who sells a natural health product shall maintain the following records at the site at which the natural health product is manufactured:
(a) the master production document for the natural health product;
(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 42 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; and
(i) a list of all natural health products that are being manufactured at the site.
Packagers
44. Every packager who sells a natural health product shall maintain the following records at the site at which the natural health product is packaged:
(a) records of any testing conducted in respect of the material used to package the natural health product;
(b) records demonstrating that each lot or batch of the natural health product was packaged in accordance with the requirements of this Part; and
(c) a list of all natural health products that are being packaged at the site.
Labellers
45. Every labeller who sells a natural health product shall maintain the following records at the site at which the natural health product is labelled:
(a) records demonstrating that each lot or batch of the natural health product was labelled in accordance with the requirements of this Part; and
(b) a list of all natural health products that are being labelled at the site.
Importers
46. Every importer who sells a natural health product shall maintain the following records:
(a) the master production document for the natural health product;
(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 42 and the information that supports that determination; and
(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.
Distributors
47. Every distributor shall maintain, at the site at which the natural health product is stored, 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.
Product Licence Holders
48. Every product licence holder who sells a natural health product shall maintain 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.
Record Maintenance
49. Every person required to maintain a record under this Part shall maintain that record for a period of one year following the expiration date of the natural health product to which that record relates.
Sterile Natural Health Products
50. Every natural health product that is intended to be sterile shall be manufactured and packaged
(a) in a separate and enclosed area;
(b) under the supervision of a person trained in microbiology; and
(c) using a method scientifically proven to ensure its sterility.
Ophthalmic Use
51. (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
(a) the words "or parenteral"; and
(b) the words "or to its common name if there is no proper name" set out in paragraph (a) to that section.
Lot or Batch Samples
52. (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) A sample provided under subsection (1) must 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 of a natural health product referred to in subsection (1) if, at the time of the request, more than one year has elapsed since the expiration date of that natural health product.
Recall Reporting
53. Every manufacturer, importer or distributor who commences a recall of a natural health product shall submit the following information in respect of that natural health product to the Minister within three days after commencing the recall:
(a) the proper name of each medicinal ingredient that it contains;
(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, if any, 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 the manufacturer or importer and the distributor; 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
54. 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)
"clinical trial investigator" means the person responsible to the sponsor for the conduct of the clinical trial at a clinical trial site, who is a health professional regulated by the laws of the province where the clinical trial site is located, and whose scope of practice under those laws is directly related to the subject-matter of the clinical trial. (chercheur d'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 65. (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 on the natural health product that are described in paragraph 57(e). (brochure du chercheur)
"protocol" means a document that describes the objectives, design, methodology, statistical considerations and organization of a clinical trial. (protocole)
"research ethics board" means a body that is not affiliated with the sponsor, and
(a) the principal mandate of which is to approve the initiation of, and conduct periodic reviews of, biomedical research involving human subjects in order to ensure the protection of their rights, safety and well-being; 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
(i) two members whose primary experience and expertise are in a scientific discipline, who have broad experience in the methods and areas of research to be approved and one of whom is from a medical discipline or, if the clinical trial is in respect of a natural health product to be used for dental purposes only, is from a medical or dental discipline,
(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
55. (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 56(1)(a), subsection 56(2), section 59, paragraphs 65(a) to (i), subsections 66(1) and 67(1) and (2), paragraphs 67 (3)(a) to (d) and (f) to (h), subsection 67(4) and sections 68 and 71 to 74, 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 59.
Prohibition
56. (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
(a) the person is authorized under this Part;
(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
(a) during the period of any suspension of the authorization under section 71 or 72; or
(b) after cancellation of the authorization under paragraph 73(b).
Application for Authorization
57. 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:
(a) a copy of the protocol for the clinical trial;
(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
(i) the title of the protocol and the clinical trial number,
(ii) the brand name or the code for the natural health product,
(iii) a quantitative list by proper name that sets out all medicinal ingredients contained in the natural health product,
(iv) a qualitative list of the non-medicinal ingredients contained in 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 clinical trial investigator,
(x) for each clinical trial site, a summary of the education, training and experience of the clinical trial investigator that is relevant to the conduct of the clinical trial,
(xi) 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 protocol referred to in paragraph (a) and approved an informed consent form containing the statement referred to in paragraph (b),
(xii) for each clinical trial site, 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 the protocol referred to in paragraph (a), its reasons for doing so and the date on which the refusal was given, and
(xiii) a statement
(A) that the clinical trial will be conducted in accordance with good clinical practices and these Regulations, and
(B) that all information contained in, or referenced by, the application is complete and accurate and is not false or misleading;
(d) an attestation, signed and dated by the research ethics board for each clinical trial site, that it has reviewed and approved the protocol referred to in paragraph (a) and an informed consent form containing the statement referred to in paragraph (b) and that the board carries out its functions in a manner consistent with good clinical practices;
(e) an investigator's brochure that contains the following information, namely,
(i) the physical, chemical and, if any, the pharmaceutical properties of the natural health product,
(ii) the chemistry and manufacturing information of each synthetically manufactured medicinal ingredient contained in 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
(f) the proposed date for the commencement of the clinical trial at each clinical trial site.
Authorization
58. (1) The Minister shall authorize a sponsor to sell or import a natural health product for the purposes of a clinical trial if
(a) the sponsor has submitted to the Minister an application that is in accordance with section 57;
(b) the sponsor has submitted to the Minister any additional information or samples requested under section 64; and
(c) the Minister has reasonable grounds to believe, based on an assessment of the application, an assessment of any information submitted under section 64 or a review of any other information that
(i) the use of the natural health product for the purposes of the clinical trial will not endanger the health of a clinical trial subject or other person, and
(ii) the clinical trial is not contrary to the best interests of the clinical trial subjects.
(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 written notice of the authorization.
59. 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 was issued a product licence.
60. Within 15 days after the date on which the clinical trial commences at a clinical trial site, the sponsor shall notify the Minister in writing of the commencement.
Notification
61. 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 notifies the Minister in writing within 15 days after the date of the change:
(a) a change to the information referred to in subparagraph 57(e)(ii) that does not affect the quality or safety of the natural health product; and
(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 62.
Amendment
62. (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:
(a) an amendment to the protocol that affects the selection, monitoring or dismissal of a clinical trial subject;
(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 57(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 date of the amendment.
(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 57, shall contain the following information and documents:
(a) if as a result of the amendment, it is necessary to amend the statement referred to in paragraph 57(b)
(i) a copy of the amended statement that indicates the new information, and
(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;
(b) if the application is in respect of an amendment referred to in any of paragraphs (1)(a) to (e)
(i) a copy of the amended protocol that indicates the amendment,
(ii) a copy of the protocol submitted under paragraph 57(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;
(c) if the application is in respect of an amendment referred to in paragraph (1)(e), a copy of the amended investigator's brochure or an addendum to the investigator's brochure that indicates the new information, including supporting toxicological studies and clinical trial safety data, if any; and
(d) if the application is in respect of an amendment referred to in paragraph (1)(f), a copy of the amended chemistry and man-ufacturing 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
(a) the sponsor has submitted to the Minister an application for amendment that is in accordance with subsection (3);
(b) the sponsor has submitted to the Minister any additional information or samples requested under section 64; and
(c) the Minister has reasonable grounds to believe, based on an assessment of the application for amendment, an assessment of any information submitted under section 64 or a review of any other information that
(i) the use of the natural health product for the purposes of the clinical trial will not endanger the health of a clinical trial subject or other person, and
(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 written notice of the amendment.
63. If the authorization to sell or import a natural health product for the purposes of the clinical trial has been amended in accordance with subsection 62(5), the sponsor shall
(a) before commencing to sell or import the natural health product in accordance with the amended authorization
(i) cease to sell or import the natural health product in accordance with the existing authorization, and
(ii) maintain records concerning the information referred to in subparagraph 57(c)(ix), if any of that information has changed since it was submitted, and the information referred to in paragraph 57(f); and
(b) conduct the clinical trial in accordance with the amended authorization.
Additional Information and Samples
64. If the information and documents submitted in respect of an application under section 57 or an application for amendment under subsection 62(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 submit to the Minister, within two days after receipt of the request, 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
65. 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
(a) the clinical trial is scientifically sound and clearly described in a protocol;
(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 clinical trial investigator;
(f) at each clinical trial site, medical care in respect of the clinical trial is provided to the clinical trial subjects;
(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
(i) the risks and anticipated benefits to his or her health arising from participation in the clinical trial, and
(ii) all other aspects of the clinical trial that are necessary for that person to make the decision to participate in the clinical trial;
(i) the requirements respecting information and records set out in section 67 are met; and
(j) the natural health product is manufactured and stored in accordance with the requirements set out in Part 3 except for section 52.
Labelling
66. (1) The sponsor shall ensure that the natural health product bears a label that sets out the following information in both official languages:
(a) a statement indicating that the natural health product is an investigational natural health product to be used only by a clinical trial investigator;
(b) the brand name or code of the natural health product;
(c) the expiration 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 75 to 84 do not apply to a natural health product used for the purposes of a clinical trial.
Records
67. (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
(a) a copy of all versions of the investigator's brochure for the natural health product;
(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 clinical trial investigator that is signed and dated by the clinical trial investigator prior to the commencement of his or her responsibilities in respect of the clinical trial, that states that
(i) the clinical trial investigator will conduct the clinical trial in accordance with good clinical practices, and
(ii) the clinical trail investigator will immediately, on discontinuance of the clinical trial by the sponsor, in its entirety or at a clinical trial site, inform 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;
(g) for each clinical trial site, a copy of the protocol, informed consent form and any amendment to the protocol or informed consent form that have been approved by the research ethics board for that clinical trial site; and
(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
68. (1) The Minister shall require a sponsor to submit, within two days after receipt of the request, 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
(a) 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;
(b) the clinical trial is contrary to the best interests of a clinical trial subject;
(c) a clinical trial investigator is not respecting the undertaking referred to in paragraph 67(3)(f); or
(d) information submitted in respect of the natural health product or the clinical trial is false or misleading.
(2) The Minister may require the sponsor to submit, within seven days after receipt of the request, any information or records kept under section 67, 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
69. (1) During the course of a clinical trial, the sponsor shall inform the Minister of any serious adverse reaction and any serious unexpected adverse reaction in respect of the natural health product that has occurred inside Canada as follows:
(a) if it is neither fatal nor life threatening, within 15 days after becoming aware of the information; and
(b) if it is fatal or life threatening, within seven days after becoming aware of the information.
(2) The sponsor shall, within eight days after having informed the Minister under paragraph (1)(b), submit to the Minister 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
70. (1) If a clinical trial is discontinued by the sponsor in its entirety or at a clinical trial site, the sponsor shall
(a) inform the Minister no later than 15 days after the date of the discontinuance;
(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, inform all clinical trial 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 date 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 has discontinued the 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 a clinical trial in its entirety or at a 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 57(c)(ix) to (xi) and paragraphs 57(d) and (f).
Suspension and Cancellation
71. (1) Subject to subsection (2), 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, if the Minister has reasonable grounds to believe that
(a) the sponsor has contravened these Regulations or any provisions of the Act relating to the natural health product;
(b) any information submitted 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 provide
(i) information or samples of the natural health product as required under section 64 or 68, or
(ii) information or a report under section 69.
(2) Subject to section 72, the Minister shall not suspend the authorization unless
(a) the Minister has sent the sponsor a written notice of the intention to suspend the authorization that indicates whether the authorization is to be suspended in its entirety or at a clinical trial site and the reason for the intended suspension; and
(b) the sponsor has not, within 30 days after receipt of the notice referred to in paragraph (a), provided the Minister with information or documents demonstrating that the authorization should not be suspended on the grounds that
(i) the situation giving rise to the intended suspension did not exist, or
(ii) the situation giving rise to the intended suspension has been corrected.
72. 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 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.
73. If the Minister suspends the authorization under section 71 or 72, the Minister shall send the sponsor a written notice of the suspension setting out the reasons for and the effective date of the suspension and indicating whether the authorization is suspended in its entirety or at a clinical trial site, and the Minister shall
(a) reinstate the authorization if, within 30 days after the effective date of the suspension, the sponsor provides the Minister with information or documents demonstrating that the situation giving rise to the suspension did not exist or that it has been corrected; or
(b) cancel the authorization if, within 30 days after the effective date of the suspension, the sponsor has not provided the Minister with the information or documents referred to in paragraph (a).
74. If the Minister cancels the authorization under paragraph 73(b), the Minister shall send the sponsor a written notice of the cancellation setting out the reasons for and the effective date of the cancellation.
PART 5
GENERAL
Labelling and Packaging
General
75. (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 pursuant to a prescription or is to a manufacturer or distributor.
76. (1) Subject to subsection (2), the statements, information and declarations required by these Regulations to be shown on a label of a natural health product shall be in either English or French in addition to any other language, if any.
(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 if the natural health product is not required by these Regulations to be sold on prescription:
(a) its recommended use or purpose;
(b) its recommended route of administration;
(c) its recommended dose;
(d) its recommended duration of use; and
(e) its risk information, including any cautions, warnings, contra-indications or known adverse reactions associated with its use.
77. The statements, information and declarations required by these Regulations to be shown on a label of a natural health product shall be
(a) clearly and prominently displayed; and
(b) readily discernible to the purchaser or consumer of the natural health product under the customary conditions of purchase and use.
78. 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.
79. 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:
(a) "Lot number";
(b) "Lot Number";
(c) "Lot"; or
(d) "(L)".
80. Every product 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:
(a) "NHP"; or
(b) "PSN".
81. 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.
82. A natural health product that is required by these Regulations to be sold on prescription is exempt from section 3 of the Act to the extent that the labels on and leaflets that accompany the natural health product mention a disease, disorder or abnormal physical state referred to in Schedule A to the Act when the mention is necessary in order to provide the recommended conditions of use.
83. (1) Subject to section 84, the inner and outer labels shall show the following information in respect of a natural health product:
(a) on the principal display panel,
(i) a brand name,
(ii) its product number,
(iii) its dosage form,
(iv) if it is sterile, the words "sterile" and "stérile",
(v) if it is one that is required by these Regulations to be sold on prescription, the designation "Pr" in boldface type in the upper left quarter of the principal display panel, and
(vi) the net amount in the immediate container in terms of weight, measure or number; and
(b) on any panel,
(i) the name and address of the product licence holder,
(ii) if it is imported, the name and address of the importer,
(iii) the proper name and, if any, the common name of each medicinal ingredient that it contains,
(iv) a list by proper name that sets out the strength or potency of each medicinal ingredient contained in each dosage unit,
(v) its recommended use or purpose,
(vi) its recommended route of administration,
(vii) its recommended dose,
(viii) its recommended duration of use, if any,
(ix) its risk information including any cautions, warnings, contra-indications or known adverse reactions associated with its use,
(x) its recommended storage conditions, if any,
(xi) its lot number,
(xii) its expiration date, and
(xiii) a description of the source material of each medicinal ingredient that the natural health product contains, if any.
(2) In addition to the requirements set out in subsection (1), the outer label shall show
(a) a qualitative list of all non-medicinal ingredients that are contained in the natural health product; and
(b) if the natural health product contains mercury or any of its salts or derivatives, a quantitative list by proper name that sets out all preservatives contained in the natural health product.
Small Package Labelling
84. (1) If the immediate container is not large enough to accommodate an inner label that complies with the requirements of section 83, the natural health product shall be labelled as follows:
(a) the inner label shall show the following in respect of the natural health product, namely,
(i) a brand name,
(ii) a qualitative list by proper name that sets out in descending order of quantity, all medicinal ingredients that it contains,
(iii) its recommended dose,
(iv) its recommended duration of use, if any,
(v) its lot number,
(vi) its expiration date,
(vii) its product number,
(viii) if it is sterile, the words "sterile" and "stérile",
(ix) if it is one that is required by these Regulations to be sold on prescription, the designation "Pr" in boldface type in the upper left quarter of the principal display panel,
(x) the net amount in the immediate container in terms of weight, measure or number,
(xi) its recommended use or purpose, and
(xii) 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
(b) the outer label, if any, shall be labelled as required under section 83.
(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 83 shall be shown in a leaflet that is affixed or attached to the immediate container.
Security Packaging
85. (1) Subject to subsection (2), no person shall sell or import a natural health product that is packaged and that is not required by these Regulations to be sold on prescription 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
(a) on the inner label; and
(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
86. 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
87. 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
88. Section C.01.012 of the Food and Drug Regulations applies in respect of natural health products.
Inspectors
89. 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
90. 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
91. 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
92. Sections A.01.050 and A.01.051 of the Food and Drug Regulations apply in respect of natural health products.
Standards and Grades
93. Section C.01.009 and subsections C.01.011(1) and (4) of the Food and Drug Regulations apply in respect of natural health products.
Tablet Disintegration Times
94. 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.
Natural Health Products Recommended Solely for Children
95. Section C.01.037 of the Food and Drug Regulations applies in respect of natural health products.
Prescription Natural Health Products
96. (1) Sections C.01.041 to C.01.046, C.01.048 and C.01.049 of the Food and Drug Regulations and Schedule F to those Regulations apply in respect of natural health products.
(2) Whenever the expression "these Regulations" occurs in the provisions of the Food and Drug Regulations referred to in subsection (1), it shall be interpreted as a reference to the Food and Drug Regulations.
PART 6
AMENDMENTS, TRANSITIONAL PROVISIONS AND COMING INTO FORCE
Amendments
Food and Drug Regulations
97. Section C.01.030 (<Reference 1> SOR/88-323) of the Food and Drug Regulations (<Reference 2> C.R.C., c. 870) is repealed.
98. Division 4 (<Reference 3> SOR/93-64; SOR/2001-181) of Part D of the Regulations is repealed.
99. Sections D.05.001 to D.05.007 (<Reference 4> SOR/81-196; SOR/97-228; SOR/80-546) of the Regulations are repealed.
100. Section D.05.010 of the Regulations is repealed.
Transitional Provisions
101. (1) Subject to section 107, a person may, without complying with these Regulations, sell a drug to which these Regulations apply that is being sold in Canada before these Regulations come into force until the earlier of
(a) the day on which an application for a product licence in respect of the drug is disposed of or withdrawn, and
(b) the expiry of two years after the day on which these Regulations come into force.
(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.
102. A person may, for a period of two years after the day on which these Regulations come into force, sell a lot or batch of a drug referred to in section 101 that is not packaged or labelled in accordance with the requirements of Part 5, if the lot or batch is packaged and labelled in accordance with the Food and Drug Regulations before the earlier of
(a) the day on which an application for a product licence in respect of the drug is disposed of or withdrawn, and
(b) the expiry of two years after the day on which these Regulations come into force.
103. (1) A person who submits an application for a product licence within two years after the day on which these Regulations come into force is not required to submit the information referred to in subparagraphs 5(c)(ii) and (iii) if that information is unavailable at the time the application is submitted.
(2) If the information referred to in subsection (1) is unavailable at the time of the product licence application and the applicant is issued the licence, the licensee shall provide that information to the Minister within two years after the day on which these Regulations come into force.
104. (1) A person who, before these Regulations come into force, manufactures, packages, labels or imports for sale a drug to which these Regulations apply or who distributes that drug may conduct that activity without complying with the requirements of Parts 2 and 3 until the earlier of
(a) the day on which that person's application for a site licence to conduct that activity in respect of the drug is disposed of or withdrawn, and
(b) the expiry of two years after the day on which these Regulations come into force.
(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.
105. For greater certainty, a person who, at the time these Regulations come into force, holds an establishment licence issued under the Food and Drug Regulations to wholesale or test a drug to which these Regulations apply shall continue to conduct that activity in accordance with the requirements of the Food and Drug Regulations until the establishment licence expires.
106. A person may sell a lot or batch of a drug referred to in section 101 that is not imported and that is not manufactured, packaged, labelled, distributed and stored, as the case may be, in accordance with the requirements of Part 3 if
(a) the lot or batch is manufactured, packaged and labelled within two years after the day on which these Regulations come into force; and
(b) any manufacturing, packaging, labelling, distributing or storage of the lot or batch that is not conducted in accordance with the requirements of Part 3 is conducted in accordance withthe requirements of Division 2 of Part C of the Food and Drug Regulations.
107. A sale or importation of a drug to which these Regulations apply that is authorized for the purposes of a clinical trial under Division 5 of Part C of the Food and Drug Regulations before these Regulations come into force shall continue to be regulated under that Division.
Coming into Force
108. These Regulations come into force on the day on which they are registered.
SCHEDULE 1 (Subsection 1(1))
INCLUDED NATURAL HEALTH PRODUCT SUBSTANCES
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SCHEDULE 2 (Subsection 1(1))
EXCLUDED NATURAL HEALTH PRODUCT SUBSTANCES
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