Vol. 151, No. 26 — December 27, 2017
SOR/2017-277 December 8, 2017
CONTROLLED DRUGS AND SUBSTANCES ACT
P.C. 2017-1523 December 8, 2017
Her Excellency the Governor General in Council, on the recommendation of the Minister of Health, pursuant to section 60 (see footnote a) of the Controlled Drugs and Substances Act (see footnote b), considering that it is necessary in the public interest, makes the annexed Order Amending Schedules I and VI to the Controlled Drugs and Substances Act (U-47700).
Order Amending Schedules I and VI to the Controlled Drugs and Substances Act (U-47700)
1 Schedule I to the Controlled Drugs and Substances Act (see footnote 1) is amended by adding the following after item 25:
- 26 U-47700 (3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide), its salts, derivatives, isomers and analogues, and salts of derivatives, isomers and analogues, including
- (1) Bromadoline (4-bromo-N-(2-(dimethylamino)cyclohexyl)benzamide)
- (2) U-47109 (3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)benzamide)
- (3) U-48520 (4-chloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide)
- (4) U-50211 (N-(2-(dimethylamino)cyclohexyl)-4-hydroxy-N-methylbenzamide)
- (5) U-77891 (3,4-dibromo-N-methyl-N-(1-methyl-1-azaspiro[4.5]decan-6-yl)benzamide)
2 Part 1 of Schedule VI to the Act is amended by adding the following after item 30:
- 31 N1,N1,N2-trimethylcyclohexane-1,2-diamine and its salts
Coming into Force
3 This Order comes into force on the day on which it is published in the Canada Gazette, Part II.
REGULATORY IMPACT ANALYSIS STATEMENT
(This statement is not part of the Order or the Regulations.)
Opioid-related overdoses and deaths have emerged as one of North America’s leading public health and safety concerns. In 2016, there were 2 816 apparent opioid-related deaths in Canada. Opioids are a highly addictive class of drugs and users cannot know what type or strength of opioid is contained in an illegally purchased product. Fentanyl, and a range of other strong new synthetic opioids, have been identified in illegal drugs, and are associated with substantial harms, including deaths.
U-47700 is one such synthetic opioid. Internet user reports describe the effects of U-47700 use as similar to that of opioids that are known to be misused recreationally (e.g. oxymorphone, hydromorphone). Although no animal or human studies related to the potential addictive properties of U-47700 are available, internet user reports describe cases of chronic use of, dependence on, and problematic use of U-47700.
In March 2017, the United Nations Commission on Narcotic Drugs voted in favour of controlling U-47700 under Schedule I to the Single Convention on Narcotic Drugs of 1961 (1961 Convention). As a party to the 1961 Convention, Canada is obligated to impose controls on this substance.
The Controlled Drugs and Substances Act (CDSA) provides a legislative framework for the control of substances that can alter mental processes and that may cause harm to the health of an individual or to society when diverted or misused. Currently, over 300 such substances are expressly listed in Schedules I to IV to the CDSA.
U-47700 was initially conceived as a potential pharmaceutical ingredient in the late 1970s; however, it was never developed for use as a medicinal drug in Canada or internationally. There is no known evidence demonstrating that U-47700 has any legitimate use apart from potential scientific research. Based on a search of medical and scientific literature, U-47700 is not currently used for research in Canada. (see footnote 2)
Over 130 internet user reports and over 40 reports of fatal and non-fatal overdoses demonstrate that U-47700 is being used recreationally in Canada and internationally.
In the last year or so, five Canadian deaths from U-47700 overdoses were reported in the media.
U-47700 appears to be used by illegal drug manufacturers in counterfeit prescription medications and other drug mixtures (e.g. cocaine, heroin). U-47700 was detected in 254 law enforcement drug seizure exhibits provided to Health Canada’s Drug Analysis Service (DAS) in 2016. (see footnote 3) In 2017, there were 223 exhibits submitted to DAS from January through August 29th that were associated with U-47700. Health Canada has identified one Canadian company that sells U-47700 in Canada.
Bromadoline, U-47109, U-48520, U-50211 and U-77891 are analogues of U-47700. They have a similar pharmacology to U-47700 and have no known legitimate uses. Based on a search of the medical and scientific literature, bromadoline, U-47109, U-48520, U-50211, and U-77891 are not currently used for research in Canada. (see footnote 4)
Health Canada has not identified any Canadian businesses currently selling these substances to the Canadian market; however, they are available to Canadians through international internet retailers.
The substances used to synthesize U-47700 are not controlled under the CDSA and are commercially available in Canada. One of these substances, namely N1,N1,N2-trimethylcyclohexane-1,2-diamine, has no identified legitimate use in Canada and is involved in the final step of the U-47700 synthesis. By placing controls on this one chemical, the risk of the unauthorized production of U-47700 could be further limited. Health Canada has identified one company that sells N1,N1,N2-trimethylcyclohexane-1,2-diamine in Canada.
The objective of this regulatory proposal is two-fold:
- meet Canada’s international obligations with respect to controlling U-47700; and
- protect the health and safety of Canadians from the negative impacts of U-47700 misuse by making U-47700 subject to the controls of the CDSA and designating N1,N1,N2-trimethylcyclohexane-1,2-diamine, as a class A precursor, under the CDSA and the Precursor Control Regulations (PCR).
The Order adds a new entry to Schedule I to the CDSA for U-47700 and its salts, derivatives, isomers and analogues, and the salts of its derivatives, isomers and analogues. In the interest of clarity, five analogues of U-47700 (bromadoline, U-47109, U-48520, U-50211 and U-77891) are being specifically listed under the entry for U-47700.
For substances listed in Schedule I to the CDSA, the Act prohibits activities such as possession, production, trafficking, possession for the purpose of trafficking, importation, exportation, and possession for the purpose of exporting these substances, unless authorized under the regulations to the CDSA or through an exemption issued under the CDSA.
The Order also adds N1,N1,N2-trimethylcyclohexane-1,2-diamine and its salts to Schedule VI to the CDSA. Schedule VI contains two parts: Part 1 for Class A precursors and Part 2 for Class B precursors. N1,N1,N2-trimethylcyclohexane-1,2-diamine is listed in Part 1, as a Class A precursor.
For substances listed in Schedule VI to the CDSA, the Act prohibits any person from conducting the activities of importation, exportation and possession for the purpose of exportation unless authorized by regulation or exempted in accordance with the Act. With these amendments, any person who is not authorized to import, export or possess for the purpose of exporting this precursor chemical will be subject to the offences and penalties set out in section 6 of the CDSA.
The Regulations add U-47700 and its salts, derivatives, isomers and analogues, as well as the salts of its derivatives, isomers and analogues to Part I of the Schedule to Part J of the Food and Drug Regulations (FDR) to ensure that it is accessible for any future scientific/research activities. Bromadoline, U-47109, U-48520, U-50211 and U-77891 are also listed under the entry for U-47700 in Part I of the Schedule to Part J of the FDR.
Persons intending to conduct certain activities (e.g. selling, importing or exporting) with U-47700 or its related substances must seek authorization to do so under Part J of the FDR by applying for a dealer’s licence, or for an amendment to their existing licence. In addition, licensed dealers who intend to import or export these substances must obtain an import and/or export permit in order to do so.
Researchers affiliated with institutions engaged in research who intend to use U-47700 or its related substances for research purposes must, depending on their circumstances, have an authorization from Health Canada under Part J of the FDR, or become a licensed dealer under Part J of the FDR, to obtain, possess and use these substances for research purposes.
The Regulations also add N1,N1,N2-trimethylcyclohexane-1,2-diamine and its salts to column 1 of the Schedule to the PCR and sets out in column 2 a maximum quantity of “0” for this chemical. This means that an end-use declaration must be obtained by the licensed dealer when selling or providing this chemical to a person who is not a licensed dealer, and licensed dealers must adhere to record-keeping requirements related to transportation. Any person who is authorized to produce, sell, provide, import, export, and possess for the purposes of export this precursor chemical will have to be in compliance with the PCR. Contraventions of the PCR are punishable offences in accordance with section 46 of the CDSA.
The “One-for-One” Rule applies to this proposal; however, in order to fulfill Canada’s international obligations, an exemption has been granted because this proposal implements non-discretionary obligations. As a signatory to the 1961 Convention, Canada is obligated to impose controls on U-47700, as it has been controlled internationally. Notwithstanding that the proposal is exempt from the “One-for-One” Rule, Health Canada has estimated the impact of the proposal on the administrative burden for two Canadian businesses, should they wish to continue to sell U-47700 or N1,N1,N2-trimethylcyclohexane-1,2-diamine after these substances become subject to the CDSA.
The first company, which offers U-47700 as part of its inventory, is already a licensed dealer. In order to continue to undertake activities with U-47700, it would need to submit a one-time application (45 minutes to prepare the application) for an amendment to its existing licence to include U-47700.
Additional administrative costs with regard to the completion of import and/or export permit applications (45 minutes per application) may be incurred if the company intends to import and/or export U-47700. There is no information available regarding this company’s activity with U-47700; therefore, for the purpose of this analysis, a conservative approach has been taken and it is assumed that a maximum of four permits could be requested by the company every year for the next 10 years. (see footnote 5) The company would also need to keep records of import/export activities and make the information available to Health Canada upon request. It is assumed, to meet ongoing requirements as a licensed dealer, that the company already keeps such records and, therefore, would not incur any related incremental cost. Assuming an employee in the natural or applied science field would be filling out these application forms at an average cost of $48 per hour, the total administrative burden cost to the companies (estimated over 10 years, from 2017–2026, and discounted to 2012 using a 7% discount rate) would amount to $765 (2012 dollars) or an annualized value of $109.
The second company, which offers N1,N1,N2-trimethylcyclohexane-1,2-diamine as part of its inventory, is not a licensed dealer. In order to continue to undertake activities with N1,N1,N2-trimethylcyclohexane-1,2-diamine, it would need to complete an application for a licence (approximately 3 hours to complete), and to renew its licence every year thereafter (1.5 hours to complete). Furthermore, the company may incur additional administrative costs associated with submitting permit applications (45 minutes per application) if they decide to import or export N1,N1,N2-trimethylcyclohexane-1,2-diamine. For the purposes of this analysis, it is assumed that businesses may require as many as four permits per year. The company would also need to keep records of import/export activities and make the information available to Health Canada upon request. Using an average cost of $48 per hour, the total administrative burden cost to the company (estimated over 10 years, from 2017–2026, and discounted to 2012 using a 7% discount rate) would amount to $2,953 (2012 dollars) or an annualized value of $420.
The present value of the total annualized incremental administrative costs to these two businesses is estimated to be $529.
Small business lens
There were no small businesses identified as dealing with U-47700 or N1,N1,N2-trimethylcyclohexane-1,2-diamine. Therefore, the small business lens does not apply.
On June 3, 2017, Health Canada published a notice to interested parties (NTIP) in the Canada Gazette, Part I, to notify stakeholders and the general public of the government’s intent to control U-47700 and that N1,N1,N2-trimethylcyclohexane-1,2-diamine was also being considered for control (link: http://gazette.gc.ca/rp-pr/p1/2017/2017-06-03/html/notice-avis-eng.php#na4). Health Canada notified potential stakeholders regarding the publication of the NTIP, including licensed dealers, health professional associations and regulatory bodies, as well as stakeholders listed in Health Canada’s Consultation and Stakeholder Information Management System. Health Canada also posted information about the NTIP on both the Health Canada and Government of Canada websites.
There were three stakeholder responses as a result of these consultations. One comment expressed support for the scheduling of U-47700, one comment was neutral and the third comment expressed concern that the scheduling of U-47700 would create barriers for researchers. Health Canada is of the view that this is unlikely, given that there is no known research with U-47700 being undertaken in Canada, and that any legitimate future scientific/research activities can be authorized under Part J of the FDR. No comments were received with respect to N1,N1,N2-trimethylcyclohexane-1,2-diamine.
U-47700 is a synthetic opioid and is not known to be used for any legitimate industrial or medical purpose. Based on recreational user reports, many of the effects of U-47700 appear to resemble those of oxymorphone or hydromorphone. Reports indicate that U-47700 is being sold and used for recreational purposes both internationally and in Canada. There are numerous reports of intoxication and deaths linked to U-47700 use.
Adding U-47700 and related substances to Schedule I of the CDSA is intended to impose controls on these synthetic opioids. Listing them in the Schedule to Part J of the FDR ensures that access is possible for legitimate scientific and research uses. These amendments also allow Canada to meet its international obligations under the 1961 Convention.
Placing controls on N1,N1,N2-trimethylcyclohexane-1,2-diamine, which has no identified legitimate use in Canada and is involved in the final step of the U-47700 synthesis, further limits the risk of unauthorized production of U-47700.
The recreational use of U-47700 can result in a range of fatal and non-fatal negative health effects. The fact that these substances are currently sold to Canadians poses risks to their health and safety. Furthermore, individuals may be tempted to experiment with U-47700, mistakenly believing that it is safer than controlled opioids.
It is expected that regulating U-47700 and related substances under the CDSA will limit their availability and prevent potential cases of misuse and negative health incidents. Controlling U-47700 and related substances as well as N1,N1,N2-trimethylcyclohexane-1,2-diamine will also enable law enforcement agencies to take action against illegal activities involving these substances.
Costs for business
Health Canada has identified one business that currently indicates that they supply U-47700 as a research chemical. (see footnote 6) This company is a licensed dealer and, therefore, will not incur any compliance costs, but will incur a one-time administrative cost to amend its licence. (see footnote 7) In addition, should the licensed dealer wish to import and/or export U-47700, they would need to complete import/export permit applications and submit them to Health Canada. It is assumed that a maximum of four permits could be requested by the company every year. The present value of the total administrative cost burden to this company over the 10-year period of analysis (2017–2026, and discounted to 2017 using a 7% discount rate) would be approximately $1,073. Annually, the incremental administrative burden is expected to be approximately $153.
Health Canada has also identified one company that currently sells N1,N1,N2-trimethylcyclohexane-1,2-diamine in Canada. This company is not a licensed dealer, so should it choose to continue to sell N1,N1,N2-trimethylcyclohexane-1,2-diamine, it would need to meet all applicable regulatory requirements under the PCR, which include obtaining a dealer’s licence. Although there is no fee to apply for or renew a dealer’s licence under the PCR, there are some compliance costs associated with ensuring the precursor in their possession is secure. This one-time compliance cost is not expected to exceed $100. There would also be administrative costs associated with filling out the licence application and renewal forms, keeping records of transactions involving the precursor for up to two years, and filling out import and/or export permit applications, if needed. The present value of the total cost to this business over a 10-year period, using a 7% discount rate, is estimated to be $4,242, or an annualized cost of $604.
Cost to researchers
Based on a search of medical and scientific literature, U-47700 as well as its analogues U-47109, U-48520, U-50211, U-77891, and bromadoline are not currently used for research in Canada. Should there be institutions that want to access U-47700 or its related substances for research purposes in the future, they would have to submit an application to Health Canada for an authorization to use a restricted drug and meet security requirements. Although the application form is relatively short, and there is no fee associated with the application, these research institutions would incur administrative burden costs associated with completing the form and submitting required supporting information, determining the relevant security level needed, as well as keeping records for a period of two years regarding the amount of restricted drug(s) received, and full clinical data of the use of the restricted drug(s). Should the research institution need to also import U-47700, they would need to submit the required documentation to a licensed dealer, who would then import on their behalf. While there is a potential for this burden to occur in the future, it is not possible to estimate the related cost because no potential research institutions that could be impacted have been identified, and the level of potential research activity cannot be estimated. (see footnote 8)
No research involving N1,N1,N2-trimethylcyclohexane-1,2-diamine in Canada or internationally was identified in the published literature and Health Canada is not aware of any research actively occurring in Canada at this time. Given the lack of information regarding research, it is not possible to make reasonable assumptions with respect to potential research in the future. However, should there be researchers who wish to access N1,N1,N2-trimethylcyclohexane-1,2-diamine in the future, they will incur a negligible administrative cost, as they will need to fill out an end-use declaration form in order to purchase N1,N1,N2-trimethylcyclohexane-1,2-diamine from a licensed dealer under the PCR (30 minutes). Should a researcher need to import this substance for research purposes, they can
- ask a licensed dealer under the PCR to import the substance on their behalf. An end-use declaration form would need to be filled out and provided to the licensed dealer (30 minutes);
- request that Health Canada import it on their behalf. This would require that they fill out an exemption application (3 hours) and complete an import application form (45 minutes); or
- apply for a Class A Precursor Licence (3 hours) and then apply for a import permit from Health Canada (45 minutes).
Given the uncertainty around research activities with this substance, these administrative costs have not been accounted for in the estimates. (see footnote 9)
There are no additional costs expected for the government. Health Canada already has a licensing system in place for restricted drugs and precursor chemicals. Providing licences, authorizations and permits for U-47700 and its related substances, as well as N1,N1,N2-trimethylcyclohexane-1,2-diamine, would be part of its normal activities, and is not expected to result in any increase in resource requirements. Costs associated with compliance activities are negligible, and would be absorbed by existing Health Canada programs. Similarly, any costs associated with law enforcement will be managed within existing budgets.
Overall, the present value of the total compliance and administrative costs (estimated over 10 years) to be incurred by the two identified companies to meet the applicable requirements as a result of the amendments will amount to $5,315 or $757 annually.
Implementation, enforcement and service standards
As part of the implementation of the amendments, Health Canada will notify stakeholders of the changes to Schedules I and VI to the CDSA, and to the schedules to Part J of the FDR and to the PCR. Information will also be provided on Health Canada’s website.
These regulatory amendments will come into force upon publication. At that time, Health Canada will be responsible for authorizing activities with these substances and for monitoring compliance with regulatory requirements.
Federal, provincial and local law enforcement agencies are responsible for taking enforcement action in response to contraventions of the CDSA. Under the CDSA, a range of penalties apply to the offences associated with U-47700. For certain offences associated with U-47700 and their related substances, listed in Schedule I of the CDSA, there is a maximum penalty of life imprisonment (mandatory minimum penalties of one, two or three years may apply if certain conditions are met).
There are no additional service standards other than those that already exist for issuing authorizations, licences and permits under regulations to the CDSA.
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- Footnote a
S.C. 2017, c. 7, s. 45
- Footnote b
S.C. 1996, c. 19
- Footnote 1
S.C. 1996, c. 19
- Footnote 2
The only recent published research with respect to U-47700 was in a 2017 article examining several substances, including U-47700. However, the article was published by American scientists.
- Footnote 3
U-47700 was not identified in any drug seizure exhibits submitted to Health Canada’s DAS, prior to 2016.
- Footnote 4
No evidence for the use of U-47109, U-48520, U-50211, U-77891 exists in the publicly available basic scientific literature since they were developed by the Upjohn Company in the 1980s. Bromadoline use in scientific research was reported by an English team in 1987 and no published medical and scientific literature has been found on bromadoline since 1987.
- Footnote 5
Based on 2016 data of import/export permits for eight restricted drugs, the number of permits varied from none to four.
- Footnote 6
There are no known Canadian companies that supply bromadoline, U-47109, U-48520, U-50211 or U-77891 as a research chemical.
- Footnote 7
This company would incur a one-time administrative cost of $36 (0.75 hour at an average cost of $48 per hour) associated with filling out the licence amendment form and submitting it to Health Canada.
- Footnote 8
However, for illustration purposes, it is estimated that the administrative burden cost would amount to $108 on a per-application basis, assuming these administrative activities would be undertaken at an average wage of $43 per hour. The compliance cost for the research institution to meet a level 1 security requirement would amount to a one-time cost of $40. These costs were not included in estimating the impacts of this regulatory initiative.
- Footnote 9
These administrative activities would be undertaken at an average cost of $43 per hour.