Vol. 147, No. 11 — May 22, 2013

Registration

SOR/2013-89 May 2, 2013

FOOD AND DRUGS ACT

Regulations Amending the Food and Drug Regulations (1431 — Schedule F)

P.C. 2013-524 May 2, 2013

His Excellency the Governor General in Council, on the recommendation of the Minister of Health, pursuant to subsection 30(1) (see footnote a) of the Food and Drugs Act (see footnote b), makes the annexed Regulations Amending the Food and Drug Regulations (1431 — Schedule F).

REGULATIONS AMENDING THE FOOD AND DRUG REGULATIONS (1431 — SCHEDULE F)

AMENDMENT

1. Part I of Schedule F to the Food and Drug Regulations (see footnote 1) is amended by adding the following in alphabetical order:

Quinine and its salts and derivatives, except when sold in oral dosage form that provides 50 mg or less of quinine base per dosage unit or per daily dose

Quinine, ses sels et dérivés, sauf lorsque vendus en unité posologique orale fournissant 50 mg ou moins de quinine basique par unité posologique ou par dose quotidienne

COMING INTO FORCE

2. These Regulations come into force six months after the day on which they are registered.

REGULATORY IMPACT ANALYSIS STATEMENT

(This statement is not part of the Regulations.)

Background

Before a drug can be sold in Canada, Health Canada assesses its safety, efficacy and quality as required by the Food and Drugs Act and associated regulations. Sections C.01.041 to C.01.049 of the Food and Drug Regulations control the sale of medicinal ingredients that are listed in Schedule F. Schedule F designates prescription drug status, and contains two Parts: Part I of Schedule F lists medicinal ingredients that require a prescription for human and veterinary use, and Part II of Schedule F lists medicinal ingredients that require a prescription for human use.

Determining the prescription status of a medicinal ingredient (or classes of drugs) depends upon the risk factors associated with their use; any revisions to prescription status listings are also based on the risk factors and a scientific assessment. Health Canada’s Drug Schedule Status Committee (DSSC) makes recommendations for prescription status and bases the scientific assessment of each medicinal ingredient against established and publicly available risk factors, such as the need for direct practitioner supervision, the toxicity profile, the pharmacological properties and therapeutic uses of the medicinal ingredients. A complete list of the factors may be accessed at www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/pol/schf_annf_fact_pol-eng.php.

Quinine is a naturally sourced medicinal ingredient that was originally made from the bark of several species of the cinchona tree and was used for centuries as the primary treatment for malaria. The use of quinine as a malaria treatment has declined over the years, as new synthetic derivatives of the drug (such as chloroquine and mefloquine) were developed and used. However, with increasingly drug-resistant strains of malaria appearing, there has been renewed interest in the use of quinine to treat malaria. Quinine is now being used in combination with other drugs such as antibiotics to treat non-severe malaria infections caused by specific organisms that are resistant to other anti-malarial drugs.

Currently, quinine products are available without a prescription as natural health products under the Natural Health Products Regulations; however, quinine is regulated provincially as a prescription drug. Health Canada’s DSSC recommends prescription status for this medicinal ingredient with a threshold limit, such that products over the limit that need direct practitioner oversight and monitoring would require a prescription while products under the limit could be sold without a prescription and considered as natural health products under Canada’s Natural Health Products Regulations.

Other countries, such as the United States, the United Kingdom and Australia, consider quinine as a prescription medicinal ingredient. In addition, currently in Canada, medicines containing quinine are already dispensed by pharmacists only upon receipt of a prescription.

Issues and objectives

The use of quinine to treat malaria is already designated prescription status provincially, as it is associated with a number of risk factors that support direct practitioner supervision. However, at a federal level, the Food and Drug Regulations currently permit oral dosage forms of quinine to be sold without a prescription regardless of level. This broad permission does not reflect the DSSC recommendation for prescription status at certain dosages.

The objective of this proposal is to add quinine to Schedule F with a specific strength threshold for oral dosage forms. This level has been assessed to be an appropriate margin of safety and practitioner intervention is not required to allow products in oral dosage form under this safe limit (i.e. of 50 mg or less per dosage unit or per daily dose) to be available without a prescription. The amendment would enable those products that fall under the limit to be licensed as natural health products and not require a prescription.

Any potential safety concerns associated with quinine when used as a natural health product would be mitigated by the threshold limit of 50 mg per dosage unit or per daily dose. All other aspects related to safety, efficacy and quality would be considered during the premarket review process under the Natural Health Products Regulations. It would also ensure that any risk associated with higher dosages would have consistent requirements for practitioner oversight, through prescription status.

Description

This regulatory amendment adds quinine, its salts and derivatives (except in oral dosage form that provides 50 mg or less of quinine base per dosage unit or per daily dose) to Part I of Schedule F to the Food and Drug Regulations.

Products for oral use containing 50 mg or less of quinine per dosage unit or per daily dose will not require a prescription but instead be regulated as a natural health product under the Natural Health Product Regulations. Foods containing quinine as a food flavouring agent are not subject to Schedule F of the Food and Drug Regulations or the Natural Health Products Regulations, and are therefore not affected by this regulatory change.

“One-for-One” Rule

The “One-for-One” Rule does not apply to this proposal as there is no change in administrative costs on business.

Small business lens

The small business lens does not apply to this proposal, as there are no costs (or insignificant costs) on small business.

Consultation

Advance notice of the proposed change in regulatory status was communicated through notices of intent (NOIs) in 2004, 2006 and 2011. This advance notice plus a 90-day transition period is intended to provide manufacturers of affected products with sufficient time to transition and obtain approval of their Drug Identification Number (DIN) submission. In addition, guidance and draft labelling information has been sent to manufacturers of products affected by this regulatory amendment to assist in preparing the required prescription labelling.

The initial Letter to Stakeholders published on October 25, 2004, followed by a 30-day comment period resulted in six responses from stakeholders, and proposed adding quinine to Schedule F with no qualifiers or threshold: three respondents expressed support for the amendment; two respondents raised questions regarding the use of quinine as a flavouring in food products such as tonic water; and one respondent objected to the amendment as worded, expressing concern about the ability of naturopathic doctors to treat patients with quinine.

The second Letter to Stakeholders published on May 30, 2006, followed by a 75-day comment period also proposed adding quinine to Schedule F with no qualifiers or tolerance limits, and resulted in four responses from stakeholders: three respondents supported the proposal, and one respondent requested that there be an exemption provided in the listing that would allow naturopathic doctors to continue to treat patients with quinine. The latter request led to further review of information on quinine and a revised proposal to include a threshold limit (i.e. exemption from prescription status for oral dosage forms that provide 50 mg or less of quinine base per dosage unit or per daily dose).

A revised Notice of Intent (NOI) regarding this regulatory proposal was provided to provincial and territorial ministries of health, medical and pharmacy licensing bodies, and industry, consumer and professional associations. The NOI was published in the Canada Gazette, Part I, on March 26, 2011, and was sent subsequently to stakeholders on May 20, 2011, followed by a 75-day comment period. This initiative was also posted on the Health Canada and Consulting with Canadians Web sites. Four comments were received from stakeholders: two respondents expressed support for the proposal, and two respondents opposed the regulatory proposal.

Comment

The two respondents opposing the regulatory proposal expressed concern that the regulatory proposal would result in a prescription being required to sell quinine-containing foods such as “tonic water.”

Response

To clarify the respondents’ misunderstanding, the regulatory proposal only pertains to drugs, and not to any foods or food substances under Health Canada’s food framework. While quinine is present in both drugs and food, the addition of quinine, its salts and derivatives (except in oral dosage form that provides 50 mg or less of quinine base per dosage unit or per daily dose) to Schedule F only applies to drugs; quinine used as a flavouring agent in foods is only subject to the food provisions of the Food and Drug Regulations.

Rationale

This amendment to add quinine with a qualifier to Schedule F listing is based on Health Canada’s scientific assessment and recommendation, given the potential benefits, harms and uncertainties related to its use at different strengths and dosages. Stakeholders have been provided extensive notification and opportunity to comment. This proposal will permit the sale of drugs containing quinine above the specified threshold while ensuring that appropriate safety measures are in place.

The impacts in terms of expected benefits and costs are as follows.

Public

Accessing this medicinal ingredient through a prescription from a practitioner will benefit Canadians by decreasing the risks of improper use, and by ensuring the guidance and care of a health professional. In addition, medicinal ingredients listed in Schedule F may be covered by both provincial and private health care plans.

Health insurance plans

Drug products for human use containing medicinal ingredients listed in Schedule F may be a cost covered by both provincial and private health care plans.

Provincial health care services

Potential additional costs for health care services should be minimal since it is already current practice for pharmacists to dispense only upon receipt of a prescription.

Manufacturers

Going forward, drugs containing quinine, its salts and derivatives (except in oral dosage form that provides 50 mg or less of quinine base per dosage unit or per daily dose) will require a valid Drug Identification Number (DIN) and prescription labelling. Notice of the impending change in regulatory status was communicated to the pharmaceutical industry through the Notice of Intent, and additional guidance has been provided to assist in meeting the requirements for this transition. The advanced notice, in addition to a delayed coming into force, is intended to provide manufacturers of affected products with sufficient time to transition.

Implementation and enforcement

This amendment will come into force six months after publication in the Canada Gazette, Part II.

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

Contact

Brian Fuerst
Refer to Project Number: 1431
Office of Legislative and Regulatory Modernization
Policy, Planning and International Affairs Directorate
Health Canada
Holland Cross, Tower B, 5th Floor
1600 Scott Street
Address Locator: 3105A
Telephone: 613-946-7268
Fax: 613-941-7104
Email: lrm-mlr@hc-sc.gc.ca