Vol. 144, No. 11 — May 26, 2010

Registration

SOR/2010-105 May 13, 2010

FOOD AND DRUGS ACT

Regulations Amending the Food and Drug Regulations (743 — Non-Medicinal Ingredients)

P.C. 2010-571 May 13, 2010

Her Excellency the Governor General in Council, on the recommendation of the Minister of Health, pursuant to section 30 (see footnote a) of the Food and Drugs Act (see footnote b), hereby makes the annexed Regulations Amending the Food and Drug Regulations (743 — Non-Medicinal Ingredients).

REGULATIONS AMENDING THE FOOD AND DRUG REGULATIONS (743 — NON-MEDICINAL INGREDIENTS)

AMENDMENTS

1. Subsection C.01.001(1) of the Food and Drug Regulations (see footnote 1) is amended by adding the following in alphabetical order:

“flavour” means a non-medicinal ingredient or combination of non-medicinal ingredients added to a drug solely to produce or mask a particular taste. It does not include an ingredient or combination of ingredients that impart only a sweet taste to the drug; (saveur)

“fragrance” means a non-medicinal ingredient or combination of non-medicinal ingredients added to a drug to produce or mask a particular odour; (parfum)

“non-medicinal ingredient” means a substance — other than the pharmacologically active drug — that is added during the manufacturing process and that is present in the finished drug product; (ingrédient non médicinal)

“pharmaceutical ink” means a non-medicinal ingredient or combination of non-medicinal ingredients used to imprint the drug with marks or symbols; (encre pharmaceutique)

2. (1) Section C.01.004 of the Regulations is amended by adding the following after subsection (1):

(1.1) In addition to the requirements of subsection (1), when a drug is intended for human use, its outer label must contain a list of all non-medicinal ingredients, or, if the outer label is too small, the list must appear on a tag, tape or card that is attached to the package.

(1.2) The non-medicinal ingredients must be listed in alphabetical order or in descending order of predominance by their proportion in the drug, preceded by words that clearly distinguish them from the medicinal ingredients.

(1.3) In the case of flavour, fragrance or pharmaceutical ink, the expressions “flavour/saveur”, “fragrance/parfum” and “pharmaceutical ink/encre pharmaceutique”, respectively, may be included in the list to indicate that such ingredients have been added to the drug, instead of listing those ingredients or combinations of them individually.

(1.4) When the composition of the drug varies from one lot to another, the outer label must include a reference to all non-medicinal ingredient alternatives that may be present in the drug, preceded by the symbol “+/–” or “±” or the expression “or/ou” or “may contain/peut contenir”.

(1.5) Subsections (1.1) to (1.4) do not apply to

(a) a drug that is required to be sold pursuant to a prescription;

(b) a drug that is not required to be sold pursuant to a prescription but is administered only under the supervision of a practitioner;

(c) a drug that is represented as being solely for use as a disinfectant on hard non-porous surfaces; or

(d) a drug for veterinary use.

(2) The portion of subsection C.01.004(2) of the Regulations before paragraph (a) is replaced by the following:

(2) In addition to the requirements of subsection (1) and, if applicable, subsections (1.1) to (1.4), the outer label of a drug must show all of the following information:

COMING INTO FORCE

3. These Regulations come into force two years after the day on which they are registered.

REGULATORY IMPACT
ANALYSIS STATEMENT

(This statement is not part of the Regulations.)

Executive summary

Issue

Certain non-medicinal ingredients (NMIs) present in nonprescription drugs can cause adverse reactions in individuals with sensitivities or allergies. Consequently, individuals may wish to avoid consuming certain NMIs for health reasons, or for reasons of personal preference. This regulatory amendment requires the labelling of NMIs on the outer labels of nonprescription drugs for human use (with some exceptions). This may result in a positive impact on consumer health and safety, by allowing individuals to avoid life-threatening allergens and agents for which they have a history of adverse reactions. Furthermore, this will enable consumers to make informed choices when purchasing nonprescription medications.

This amendment is similar to mandatory NMI labelling requirements already in place in the United States, Europe and Australia. In Canada, the Natural Health Products Regulations and the Cosmetic Regulations have required the mandatory listing of all NMIs since January 2004 and November 2006, respectively.

This amendment to the Food and Drug Regulations will require that all NMIs be listed on the outer labels of drugs for human use. However, the amendment does not apply to

(i) prescription drugs;

(ii) nonprescription drugs that are only administered under the supervision of a practitioner;

(iii) drugs that are represented as being solely for use as disinfectants on hard, non-porous surfaces; or

(iv) drugs for veterinary use.

Objectives

The requirements to list NMIs on the outer labels of nonprescription drugs for human use will assist individuals in avoiding life-threatening allergens and agents for which they have a history of adverse reactions.

This amendment may result in a positive impact on consumer health and safety which, in turn, may allow for a reduction in the costs to provincial health care systems as a result of reduced adverse drug reaction incidents.

In addition, increased consumer awareness may cause manufacturers to amend product formulations to remove ingredients known to be sensitizers, or ingredients which are otherwise unacceptable to some consumers.

Description

NMI labelling proposals were pre-published in the Canada Gazette, Part I, on four separate occasions: December 2, 1989, February 5, 1994, May 22, 1999, and June 6, 2009. Whereas extensive comments were received during the first three consultation periods, only 10 responses were received during the most recent consultation. Overall, stakeholders were in agreement with the principle behind the first three proposals, but were not in agreement with some of the more technical details. By eliminating much of the technical detail that was a source of concern in the 1999 proposal, the June 6, 2009, proposal addressed stakeholder concern, while maintaining the fundamental objective of disclosing NMIs on drug product labels. This regulatory amendment is written to ensure that NMI information is available at the time of product purchase so that consumers can make informed choices.

The following identifies the issues that were raised in previous proposals.

(1) Which drugs?

This amendment is less prescriptive than the first three proposals. Its scope is nonprescription drugs for human use. This includes those products purchased off the store shelf, as well as those products located behind a pharmacist’s counter that can be purchased without a prescription. Exemptions include (1) prescription drugs; (2) nonprescription drugs only administered under the supervision of a practitioner; (3) low-level disinfectants; and (4) veterinary drugs. Drugs as defined in Division 4 of the Regulations are already exempt from this amendment as per the current provisions of section C.04.019.

(2) Which NMIs?

As in the first three proposals, the amendment mandates that all NMIs be labelled except for the sub-ingredients of flavours and fragrances. Sub-ingredients of pharmaceutical inks are also not required to be labelled under this amendment.

Substances used during the manufacturing process that are present in the finished drug product are also to be included on the label.

(3) Which labels?

This amendment is the same as the third proposal, pre-published in 1999, with respect to the labels affected: NMIs are required to be listed on the outer label.

(4) What names?

This amendment is less prescriptive than the first three proposals: the type of NMI names is not specified, thereby allowing the use of proper, common, or international nomenclature.

(5) What order?

This amendment is less prescriptive than the first three proposals: NMIs are required to be listed on the label either in alphabetical order or in descending order of drug proportion. A heading is not required to identify the type of order for NMI listing.

(6) Drug formulation

This amendment is less prescriptive than the first three proposals in that it focuses only on NMI labelling. The removal of requirements around NMI formulation is one of the key differences between this amendment and previous proposals. NMI formulation is being undertaken as a separate initiative.

(7) Other technical details

Other technical details were mandated in past proposals, such as how NMIs were to be distinguished on the label from medicinal ingredients and how variations in NMIs among drug lots were to be indicated. As described below, this amendment is less prescriptive in these areas as well as others.

The changes to the Food and Drug Regulations are as follows:

1. Amend C.01.001(1): Define four terms.

“flavour” means any non-medicinal ingredient or combination of non-medicinal ingredients in a drug used solely to impart a taste to the drug, but does not include an ingredient or combination of ingredients that imparts only a sweet taste to the drug; (saveur)

“fragrance” means any non-medicinal ingredient or combination of non-medicinal ingredients in a drug used solely to impart a smell to the drug; (parfum)

“non-medicinal ingredient” means any substance other than the pharmacologically active drug or prodrug which is included in the manufacturing process and is present in the finished drug product; (ingrédient non medicinal)

“pharmaceutical ink” means any non-medicinal ingredient or combination of non-medicinal ingredients in a drug used to imprint the drug with marks or symbols; (encre pharmaceutique)

2. Amend C.01.004(1):

2.1. Mandate the following rules regarding NMI labelling:

— list all NMIs on the outer label of the drug; and

— if the outer label is too small, clearly and prominently affix NMI labelling to the product so that it is readily discernible to the purchaser or consumer under the customary conditions of purchase and use.

2.2. Exempt the following from NMI labelling:

— prescription drugs;

— nonprescription drugs only administered under the supervision of a practitioner;

— low-level disinfectants; and

— drugs for veterinary use.

2.3. Mandate the following rules regarding NMI labelling details:

— list NMIs in alphabetical order or in descending order of drug proportion;

— precede NMIs with clear wording that distinguishes them from medicinal ingredients;

— list flavours, fragrances, and pharmaceutical inks, but not their sub-ingredients; and

— use the terms “may contain”, “+/-” or “or” to indicate that lot composition of NMIs varies from one to the other.

3. Amend C.01.004(2): Update to ensure congruence of the numbering of amended subsections in C.01.004(1).

4. Mandate an implementation date of two years following publication of this regulatory amendment in the Canada Gazette, Part II.

Regulatory and non-regulatory options considered

Option 1: Status quo

The status quo would be that NMIs are not required to be listed on drug labels.

Option 1 was rejected because consumers with sensitivities and allergies are not provided with information to pre-empt adverse reactions caused by NMIs, nor are consumers able to exercise personal preference with respect to certain NMIs.

Furthermore, other lower-risk regulated product categories covered under the Food and Drugs Act, such as cosmetics, natural health products, and foods, have their own NMI labelling requirements and their own food ingredient labelling requirements, respectively. Finally, prior to this amendment, Canada did not mandate NMI labelling for drugs, whereas international regulators such as the U.S. Food and Drug Administration, the European Medicines Agency, and Australia’s Therapeutic Goods Administration do mandate some degree of NMI labelling for drugs.

Option 2: Voluntary labelling

In 1985, voluntary guidelines for the disclosure of selected NMIs were adopted by the Nonprescription Drug Manufacturers Association of Canada. This information was to be made available on the labels of nonprescription drug products.

Since that time, there has been increased voluntary labelling of NMIs on drugs. However, option 2 was rejected because the labelling has been inconsistent in application and selective in disclosure. As such, it has not completely satisfied the information needs of the consumer.

Option 3: Partial labelling

Partial labelling is NMI listing of only those ingredients known to cause reactions.

Option 3 was rejected because not all potential sensitizing agents or allergens are known. The 1994 Regulatory Impact Analysis Statement (RIAS) stated that “[d]etermining and communicating a list of sensitizers to manufacturers for subsequent disclosure would be an unwieldy, time-consuming process, unresponsive to consumers’ needs”. Furthermore, the 1999 proposal stated that “[p]artial label disclosure of only those ingredients known to cause reactions has not been proven to be a reasonable alternative. Not all potential sensitizing agents are identified. Full label disclosure will eliminate the difficulties associated with the identification of ingredients which are suspected or most likely to be the cause of adverse effects, or those which individual consumers may wish to avoid.”

Option 4: NMI information disclosure from sources other than a label

Strategies that are designed to provide NMI information to consumers from a source other than a label have been considered. Though considered appropriate for drugs that require the intervention of a practitioner, option 4 was rejected for nonprescription drugs directly accessible to consumers because it does not provide information disclosure to consumers at time of purchase. Alternate strategies could provide for valuable supplemental methods of making available NMI information, but these would not negate the need for ready access to the information by the consumer at the point and time of purchase. Furthermore, any decision that requires that NMI information be made available through sources other than labelling would not take advantage of the voluntary labelling activity that is presently occurring.

Option 5: The NMI labelling amendment, described above

The NMI labelling amendment, option 5, was selected. This amendment addresses comments received in past consultations with stakeholders, specifically much of the technical detail that was the source of stakeholder concern. The amendment is built on the premise that a performance standard of full NMI labelling takes priority over prescriptive standards in the technical details.

Benefits and costs

The amendment is expected to have an impact on the following sectors:

Public

Consumers will be provided with ready access to meaningful information concerning the NMI content of nonprescription drugs. The listing of NMI content will allow consumers to make an informed choice when purchasing nonprescription drugs. Furthermore, it is anticipated that mandatory NMI labelling should lead to fewer repeat adverse reactions. Thus, by allowing individuals to avoid life-threatening allergens and agents for which they have a history of adverse reactions, this amendment may result in a positive impact on consumer health and safety.

Industry

While any costs associated with these regulations would be largely borne by the pharmaceutical industry, and to some extent the personal care product industry, these are anticipated to be minimal. Furthermore, costs will be reduced by deferring the implementation of the regulatory amendment to two years after publication in the Canada Gazette, Part II.

The two-year implementation period was extended from the one-year period proposed in earlier consultations. This extension will assist manufacturers with low-volume specialty products for which labels are not often reprinted.

This transition period will also allow the depletion of existing label supplies and allow packaging companies to introduce the changes within a normal label life-cycle, hence reducing cost. For further cost-effectiveness, manufacturers may voluntarily precede the implementation date for NMI labelling at the next label printing for individual products, thereby avoiding relabelling to comply with the regulation at the effective date. Many pharmaceutical companies are already in voluntary compliance with this amendment and hence will have minimal additional cost.

Increased consumer awareness may cause manufacturers to amend product formulations to remove ingredients known to be sensitizers, or ingredients which are otherwise unacceptable to some consumers. This would result in increased availability of products which are less likely to cause undesirable side effects.

Provincial health care systems

There are no expected costs to the provincial health care systems. However, there may be a reduction in the costs to health care systems as a result of reduced adverse drug reaction incidents, meaning there may be a decrease in practitioner visits due to a decrease in adverse reactions.

The practice of pharmacy may benefit from the increasing amount of drug product information that will become available on outer labels. Although currently versed in counselling consumers with regard to NMI information for some products, pharmacists may see a decrease in the number of NMI enquiries.

Federal Government

There will be minimal increases in Government costs to ensure compliance.

In sum, the benefits of the amendment outweigh and justify the costs. There is general support for NMI labelling in the industry, and the amendment builds upon the progress made by previous regulatory proposals (described below).

Rationale

The NMI labelling amendment is less prescriptive than previous proposals with respect to the manner of compliance. More specifically, it does not require the rigid and prescribed manner of labelling that was proposed in 1989, 1994, and 1999, none of which built upon industry’s 1985 voluntary labelling guidelines. As detailed below, this amendment eliminates much of the technical detail that was the source of stakeholder concern while ensuring that NMI information is made available to consumers.

(1) Prescription drugs

NMIs listed on the manufacturers’ labels of prescription drugs generally do not reach the consumer, because prescription drugs are routinely repackaged and relabelled for the individual patient by the pharmacist. The responsibility for the selection of the medication most often lies with the individual who writes the prescription. This individual is a practitioner who is familiar with the health status of the consumer in question, and is well positioned to contextualize risk involved (including risks relating to allergens and sensitizers) in prescribing a specific treatment to a patient. At the point of sale, a pharmacist may also counsel consumers regarding the selection of medication.

Currently, NMI information for prescription drugs is typically available to health care practitioners by means of the Product Monograph and the Compendium of Pharmaceuticals and Specialties. A Product Monograph is a factual, scientific document about a drug that (a) describes the drug’s properties, claims, indications, and conditions of use, and (b) contains any other information that may be required for optimal, safe, and effective use of the drug; the Product Monograph is devoid of promotional material. “Part I: Health Professional Information” of the Product Monograph requires an alphabetical listing by proper or common name of all NMIs for each strength of each dosage form of the drug. Product Monographs authorized after January 2004 are now posted on the Health Canada Web site and are also available upon request.

The Compendium of Pharmaceuticals and Specialities is a drug product information source for health care practitioners and is published annually by the Canadian Pharmacists Association. It is also available to practitioners through the Canadian Pharmacists Association website. Product information that is published in the Compendium of Pharmaceuticals and Specialties is obtained either directly from the manufacturer or is a direct transcription of the prescribing information in the Health Canada-authorized Product Monograph.

Given that NMI information is generally available for prescription drugs through counsel with a practitioner, a risk-based approach does not support the high level of regulatory scrutiny and burden which would result if the NMI labelling requirements were applied to prescription drugs. It has been determined through earlier consultations that this would be an overly rigid requirement without a commensurate increase in consumer safety.

Prescription drugs were included in the proposal during the first two consultations (1989 and 1994) but were exempted in the third proposal. For reasons described above, prescription drugs remain exempt from this amendment.

(2) Nonprescription drugs only administered under the supervision of a health care practitioner

NMIs listed on the manufacturers’ labels of nonprescription drugs only administered under the supervision of a practitioner would not reach the intended recipient, the patient, because these drugs are usually administered to the patient in non-self-care settings such as hospitals and dental offices. The practitioners who administer these drugs are well-positioned to contextualize the risk involved. The general principle behind the NMI labelling amendment is that no self-administered non-prescription drug product should be exempt.

Furthermore, NMI information for nonprescription drugs only administered under the supervision of a health care practitioner is typically available to practitioners through the Product Monographs and through the Compendium of Pharmaceuticals and Specialties. Consequently, these drugs are exempt from this amendment.

Issues around classification for these drug products as well as their current exemption status will be examined further in the future as well as through legislative and regulatory modernization initiatives.

(3) Low-level disinfectants

Low-level disinfectants are disinfectants that kill pathogenic and potentially pathogenic microorganisms on hard, non-porous, inanimate surfaces. The issue of labelling for these products will be examined and addressed under a separate policy initiative, and therefore, these drugs are exempt from this amendment.

(4) Veterinary-use drugs

The scope of this amendment is human-use drugs, consumer safety through decreasing the potential for adverse reactions in humans, and personal choice in self-care. Veterinary-use drugs are outside of this scope; therefore they are exempt from this amendment.

Consultation

As described in considerable detail in the RIAS which was pre-published in the Canada Gazette, Part I, on June 6, 2009, NMI labelling has been the subject of extensive informal discussions and formal consultations with interested parties. The proposed regulatory amendment was pre-published on June 6, 2009, and differs from the previous proposals with respect to the following:

• Sub-ingredients of pharmaceutical inks were added to the list of the already exempted sub-ingredients of flavours and fragrances;
• Pharmaceutical ink is added to the definitions and fabricator is no longer defined;
• Nomenclature includes proper, common or internationally accepted names, therefore, less prescriptive than the previous proposal;
• A heading is not required to identify the type of order for NMI listing (alphabetical order versus descending order of proportion);
• The reference to any composition variation is more generalized;
• Formulation is no longer required; and,
• Affixing of labels for small containers is required.

Overall, stakeholders are supportive of this amendment. Following pre-publication, 10 responses were received during the 75-day comment period. These responses came from academia, parents and consumers, regulatory and pharmaceutical manufacturing associations and the medical profession. Health Canada has given consideration to all of the comments, which addressed a range of issues, including: labelling requirements; whether the amendment should also apply to prescription drugs; whether the amendment should also apply to all nonprescription drugs; the inclusion of NMI information in Health Canada databases; flexibility with respect to nomenclature; and the length of the transition period. Responses were also received from stakeholders seeking clarity with respect to terminology and the impact of this amendment on the practice of pharmacy. The comments did not result in any changes between the pre-published proposal and the final version of the amendment. Other comments received related to issues that fall outside of the scope of this amendment and, therefore, are not addresses here. A more detailed and complete description of comments is available upon request.

Implementation, enforcement and service standards

This amendment does not alter existing compliance mechanisms under the provisions of the Food and Drugs Act and the Food and Drug Regulations enforced by the Health Products and Food Branch Inspectorate.

Implementation of the regulatory amendment will be deferred to two years after publication in the Canada Gazette, Part II. This transition period will allow the depletion of existing label supplies and allow packaging companies to introduce the changes within a normal label life-cycle, hence reducing cost.

Performance measurement and evaluation

Not applicable.

Contact

Refer to Project No. 743
Bureau of Policy, Science and International Programs
Therapeutic Products Directorate
Health Canada
Holland Cross, Tower B, 2nd Floor
1600 Scott Street
Address Locator: 3102C5
Ottawa, Ontario
K1A 0K9
Telephone: 613-948-4623
Fax: 613-941-6458
Email: regaff-affreg@hc-sc.gc.ca

Footnote a
S.C. 2005, c. 42, s. 2

Footnote b
R.S., c. F-27

Footnote 1
C.R.C., c. 870

Footnote 2
For details on the reasoning behind the proposed exemptions for these products, please see the updated Rationale section of the Regulatory Impact Analysis Statement (RIAS).

NOTICE:
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