Canada Gazette, Part I, Volume 146, Number 50: titre
December 15, 2012
Regulations Amending the Food and Drug Regulations (1688 — Arsenic Trioxide)
Food and Drugs Act
Department of Health
REGULATORY IMPACT ANALYSIS STATEMENT
(This statement is not part of the Regulations.)
Paragraph C.01.040(b) of the Food and Drug Regulations (Regulations) prohibits manufacturers or importers from selling a drug for human use that contains as an ingredient arsenic or any of its salts or derivatives. Clinical trials for the prohibited substance, arsenic trioxide, were conducted as permitted under C.05.004 of the Regulations, in anticipation that its use may result in a therapeutic benefit for a human being. The trials showed that arsenic trioxide is highly effective when used as a treatment for patients with relapsed acute promyelocytic leukemia (APL). Canadian sites have formally participated in five of these clinical trials using arsenic trioxide, three of which are still ongoing.
Currently, a sponsor wishing to market a product containing arsenic trioxide as a medicinal ingredient in Canada is deterred from filing a submission with Health Canada because of the prohibition contained in C.01.040(b). Consequently, physicians currently treating Canadians with relapsed APL or any other disease for which arsenic trioxide has proven beneficial must access the drug through Health Canada’s Special Access Program (SAP). Subsection C.08.011(2) of the Regulations exempts the sale of drugs accessed through the SAP from the provisions of the Food and Drugs Act and the Regulations. Thus, patients using arsenic trioxide accessed in this way do not benefit from the more comprehensive safety requirements contained in the Regulations.
However, if the sale of arsenic trioxide were to be exempted from the prohibition contained in C.01.040(b), then the degree of control over its sale must be addressed. To this end, arsenic trioxide was reviewed by Health Canada’s Drug Schedule Status Committee (DSSC) against a set of established and publicly available factors which include, but are not limited to, toxicity, pharmacological properties and therapeutic uses. The DSSC recommended that prescription status for arsenic trioxide would provide the proper degree of regulatory control over the risk factors associated with its use. Oversight by a practitioner would ensure that appropriate risk/benefit information is considered before a drug containing arsenic trioxide is administered and that the drug therapy is properly monitored.
The objectives of this proposal are as follows:
- Enable Health Canada to accept a new drug submission for arsenic trioxide; and
- Ensure that patients being treated with arsenic trioxide would benefit from appropriate regulatory control to mitigate against the risks associated with its sale and use.
Description and rationale
This proposed amendment would exempt the sale of a drug that contains arsenic trioxide as a medicinal ingredient from the prohibition contained in paragraph C.01.040(b) of the Regulations.
This amendment would also add arsenic trioxide when used as a medicinal ingredient to Part Ⅰ of Schedule F to the Regulations.
Drugs can only be sold in Canada once Health Canada has assessed them for safety, efficacy and quality, as required by the Food and Drugs Act and the Regulations. Final approval of the regulatory amendment adding a medicinal ingredient to Schedule F and its publication in the Canada Gazette, Part Ⅱ, means that prescription status for the drug can be enforced under provisions of the Regulations.
Market approval for arsenic trioxide sold pursuant to a prescription has been granted by the United States Food and Drug Administration, the European Medicines Agency and the Therapeutic Goods Administration of Australia.
Description of the medicinal ingredient arsenic trioxide
Presently, the major clinical use for arsenic trioxide is as an antineoplastic agent for the treatment of APL. However, clinical trials are underway to see if arsenic trioxide may also prove effective in the treatment of other serious cancers. Individualized instructions or direct supervision by a practitioner is required along with routine medical monitoring. As with all antineoplastic agents, there are potential or known undesirable or severe side effects at normal therapeutic dosage levels. These adverse effects are neither permanent nor irreversible nor do they usually require interruption of therapy. Arsenic is a carcinogen and is fetotoxic. Therapy with arsenic is contraindicated during pregnancy and lactation.
Regulatory burden — “One-for-One” Rule and small business lens
This proposed regulatory amendment does not add any regulatory burden to Canadian industry, including small business. Thus, the “One-for-One” Rule and small business lens would not apply. The amendment would remove the prohibition, presently contained in the Regulations, for the sale of arsenic trioxide as a medicinal ingredient and requires that arsenic trioxide be added to Schedule F so that if a Notice of Compliance were granted by Health Canada, its sale would be pursuant to a prescription.
On August 23, 2011, Health Canada consulted with the members of the Science Advisory Committee on Oncology Therapies (SAC-OT) on the issue regarding arsenic trioxide and its use, in conjunction with other chemotherapeutic agents, to treat APL. Specifically, the question posed to the committee revolved around paragraph C.01.040(b) of the Regulations that prohibits the sale of a drug for human use that contains arsenic, its salts or its derivatives as an ingredient. SAC-OT determined that there is no longer a justifiable scientific basis for the continued prohibition of the sale of drugs containing arsenic trioxide as a medicinal ingredient.
Strategic environmental assessment
It is estimated that a very small number of patients in Canada, approximately 50 patients per year, will receive treatment with arsenic trioxide. The average dose may be calculated assuming a 70 kg human receiving 0.15 mg/kg/day for up to 90 days total. This results in a total patient exposure of 945 mg of drug substance. The aggregate amount of drug that might be used per annum for the treatment of these individuals would be 47.25 g or 0.047 kg.
This proposal underwent a preliminary scan in accordance with the Strategic Environmental Assessment (SEA) Policy and a SEA Form was completed for arsenic trioxide. The scan determined that a detailed strategic environmental analysis is not required as the impact of arsenic trioxide when used as a drug and its resulting metabolites would have no impact or a neutral impact on the environment. The analysis supporting this conclusion is available on request from the contact below.
Implementation, enforcement and service standards
Following prepublication in the Canada Gazette, Part Ⅰ, the comments received during the 75-day comment period will be considered and addressed. If it is decided to go forward with the amendment, it would be implemented by notifying the general public through publication in the Canada Gazette, Part II, and by notifying both internal and external stakeholders via email of this publication.
This amendment does not alter existing compliance mechanisms under the provisions of the Food and Drugs Act and the Regulations enforced by the Health Products and Food Branch Inspectorate.
Refer to Project No. 1688
Bureau of Policy, Science and International Programs
Therapeutic Products Directorate
Holland Cross, Tower B, 2nd Floor
1600 Scott Street
Address Locator: 3102C5
PROPOSED REGULATORY TEXT
Notice is given that the Governor in Council, pursuant to subsection 30(1) (see footnote a) of the Food and Drugs Act (see footnote b), proposes to make the annexed Regulations Amending the Food and Drug Regulations (1688 — Arsenic Trioxide).
Interested persons may make representations concerning the proposed Regulations within 75 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 Theresa Burke, Bureau of Policy, Science and International Programs, Therapeutic Products Directorate, Health Products and Food Branch, Department of Health, 1600 Scott Street, Holland Cross, Tower B, 2nd Floor, Address Locator 3102C5, Ottawa, Ontario K1A 0K9 (tel.: 613-957-6469; fax: 613-941-6458; email: email@example.com).
Ottawa, December 6, 2012
Assistant Clerk of the Privy Council
REGULATIONS AMENDING THE FOOD AND DRUG
(1688 — ARSENIC TRIOXIDE)
1. Paragraph C.01.040(b) of the Food and Drug Regulations (see footnote 1) is replaced by the following:
- (b) arsenic or any of its salts or derivatives, other than arsenic trioxide.
2. Part Ⅰ of Schedule F to the Regulations is amended by adding the following in alphabetical order:
COMING INTO FORCE
3. These Regulations come into force on the day on which they are registered.