The Single Convention on Narcotic Drugs, 1961 (as amended by the 1972 Protocol) and the Convention on Psychotropic Substances, 1971 contain specific control provisions for some psychoactive substances [321, 322]. Pursuant to these conventions, the Commission on Narcotic Drugs (CND) has the authority to decide, upon a recommendation from the World Health Organization, whether a substance should be scheduled as a narcotic drug or a psychotropic substance.
Methadone is currently scheduled as a “narcotic drug”, falling under the Single Convention on Narcotic Drugs and buprenorphine as a “psychotropic substance”, falling under the Convention on Psychotropic Substances.
The International Narcotics Control Board (INCB) is charged with monitoring the compliance by Governments with the above international treaties, ensuring on the one hand that controlled substances are available for medical and scientific use and on the other hand that diversion from licit sources to illicit traffic does not occur [321].
A7.1. Single Convention on Narcotic Drugs 1961
The Single Convention on Narcotic Drugs is the principal international treaty regulating the control of opioids. It seeks to limit exclusively to medical and scientific purposes the production, manufacture, export, import, distribution of, trade in, use and possession of narcotic drugs. Heroin, opium, morphine, oxycodone, methadone, and most other potent pharmaceutical opioids (with the exception of buprenorphine) are listed as narcotic drugs under the 1961 Single Convention.
To comply with the convention with regard to methadone, countries must:
estimate the annual medical and scientific requirements for methadone and submit their estimates to the INCB for confirmation
limit the total quantities of methadone manufactured and imported to the relevant estimates, taking into account the quantity exported
ensure that methadone remains in the hands of licenced parties from the point of manufacture or importation to dispensing
provide that methadone is dispensed against a medical prescription
report to INCB on the amount of methadone imported, exported, manufactured and consumed and of stocks held
maintain a system of inspection of manufacturers, exporters, importers, and wholesale and retail distributors of narcotic drugs and of medical and scientific institutions that use such substances; premises, stocks and records should be inspected
in addition, a country has a responsibility to ensure that diversion and abuse of methadone is prevented.
National estimates of medical need for opioids
Every year, national drug regulatory authorities must prepare estimates of the requirements for methadone of their country during the following year. The estimates must be submitted to the INCB six months in advance of the period for which they apply, but supplementary estimates may be submitted at any time. INCB publishes changes in the estimates received from governments on a monthly basis, as a guide for exporting countries. The responsibility for determining the amounts of opioids necessary to meet the medical and scientific requirements in a country rests entirely with the national governments, but the INCB must be informed of the method used. The INCB establishes estimates of annual requirements for narcotic drugs for countries which fail to do so. In case an estimate is established by INCB, the competent authorities of the country concerned are informed by the Board and requested to review the established estimates.
Obtaining a supply of methadone
After a country has received confirmation of its estimate from the INCB, it may commence manufacture or import procedures. In both cases, it is vital that the supply is reliable as interruptions to the supply of methadone are distressing for patients and place them at high risk of relapse to illicit opioid use.
Domestic manufacture
Some, or all of the methadone needed may be manufactured by enterprises in the country itself, under the regulation of the government. Regulation of manufacture of opioids includes licensing, requirements for record keeping and reporting, secure storage, and quality control.
The import/export system
A specific sequence of steps is stipulated in the convention for the import and export of narcotic drugs, although additional requirements may vary from country to country. Importation and exportation of methadone can only take place with the approval of the national drug regulatory authorities, and within the limits of the total of the estimates for the importing country. A copy of the export authorization must accompany each shipment.
The import and export authorization shall state:
the name of the drug
the international non-proprietary name (INN) of the drug, if any
the quantity of the drug to be imported or exported
the name and address of the importer and exporter
the period of validity of the authorization.
The export authorization shall also state the number and date of the import authorization and the authority by whom it has been issued.
The steps involved in the import/export process
The import/export process is outlined below in . Many countries also have an authorization/certification procedure to prevent marketing of pharmaceutical products that are falsely labelled, counterfeit or substandard.
Steps in opioid importation. Adapted from WHO 1996 [323]
The entity wishing to import a substance controlled under the Single Convention applies to its regulatory authority for an import authorization.
The regulatory authority considers whether the company is properly licensed and whether the drug and amount are within the national estimate; if approved, an original import authorization and the appropriate number of copies are issued. One copy should be sent to the competent authorities of the exporting country. The original and one copy should be sent to the importer who will send the original to the exporter and will keep one copy for the Customs declaration. One copy should be sent to the Customs authorities of the importing country and an additional copy should be kept in the records of the importing country's competent authority.
The importer sends the original of the import authorization to the company responsible for the export of the substance.
The exporter applies to its drug regulatory authority for an export authorization.
The regulatory authority in the exporting country checks that an import authorization has been issued and that the exporter is properly licensed, and that the estimate of the importing country is sufficient; if the application is approved, an export authorization is issued.
The regulatory authority in the exporting country sends a copy of the export authorization to the regulatory authority in the importing country. Two copies should be provided to the exporter, one of which must accompany the consignment. One copy should be sent to the Customs authorities of the exporting country and an additional copy should be kept in the records of the exporting country's competent authority.
The exporter ships the drugs to the importer, along with the copy of the export authorization.
The shipment must pass a customs inspection.
The importer sends the export authorization to its regulatory authority. The regulatory authority of the importing country shall return the accompanying export authorization to the regulatory authority of the exporting country with an endorsement certifying the amount actually imported.
The reporting system
National drug regulatory authorities must report to the INCB all imports and exports of methadone every quarter. They are also required to make an annual inventory and report the total amount of opioids manufactured, consumed and held in stock. The annual inventory does not include drugs stored in pharmacies, which for official purposes are considered to have been consumed.
Regulation of health-care workers
The convention recognizes that individual governments must decide the level of regulation of the individuals directly involved in dispensing opioids – pharmacists, physicians and nurses. However, it expresses several principles that should be observed:
individuals must be authorized to dispense opioids by their professional licence to practice, or be specially licensed to do so
movement of opioids may occur only between duly authorized parties
a medical prescription is required before opioids may be dispensed to a patient.
Drug abuse versus patient need
The convention recognizes that governments have the right to impose further restrictions if they consider it necessary, to prevent diversion and misuse of opioids. However, this right must be continually balanced against the responsibility to ensure opioid availability for medical purposes.
In deciding the appropriate level of regulation, governments should bear in mind the dual aims of the convention. The INCB has observed that, in some countries, fear of drug abuse has resulted in laws and regulations, or interpretations of laws and regulations, which make it unnecessarily difficult to obtain opioids for medical use.
“… prevention of availability of many opiates for licit use does not necessarily guarantee the prevention of the abuse of illicitly procured opiates. Thus, an overly restrictive approach to the licit availability of opiates may, in the end, merely result in depriving a majority of the population of access to opiate medications for licit purposes” [324].
A7.2. Convention on Psychotropic Substances, 1971
This convention establishes an international control system for psychotropic substances that balances their abuse potential and therapeutic value. Buprenorphine is listed as a psychotropic substance and is currently included in Schedule III of the convention.
To comply with the convention with regard to buprenorphine, countries must:
ensure that buprenorphine remains in the hands of licensed parties from the point of manufacture or importation to dispensing;
provide that buprenorphine is dispensed only with a medical prescription;
prohibit the advertisement of buprenorphine to the general public;
request that all operators manufacturing, trading or distributing buprenorphine keep records on each acquisition and disposal for at least two years;
report to INCB on the amount of buprenorphine imported, exported and manufactured on an annual basis;
maintain a system to inspect manufacturers, exporters, importers, and wholesale and retail distributors of psychotropic substances and of medical and scientific institutions that use such substances; premises, stocks and records should be inspected;
ensure diversion and abuse of buprenorphine is prevented.
Domestic manufacture
Some or all of the buprenorphine needed by a country may be manufactured by domestic enterprises, under the regulation of the government. Regulation of manufacture of psychotropic substances includes licensing, requirements for record keeping and reporting. Provisions relating to manufacture of pharmaceutical products in general, such as secure storage, and quality control, also apply.
Regulation of health-care workers
The convention recognizes that individual governments must decide the level of regulation of the individuals directly involved in dispensing psychotropic substances (i.e. pharmacists, physicians and nurses). However, it expresses several principles that should be observed:
individuals must be adequately qualified, and authorized to dispense psychotropic substances by their professional licence to practice, or be specially licensed to do so
movement may occur only between duly authorized parties
a medical prescription is required before psychotropic substances may be dispensed to a patient, except when individuals may lawfully obtain, use, dispense or administer such substances in the duly authorized exercise of therapeutic or scientific functions
prescriptions need to be issued in accordance with sound medical practice and subject to regulation to protect public health and welfare, particularly the number of times such prescriptions may be refilled and the duration of their validity.
Drug abuse versus patient need
The convention recognizes that governments have the right to impose further restrictions if they consider such restrictions necessary to prevent diversion and misuse of psychotropic substances. However, this right must be continually balanced against the responsibility to ensure the availability of psychotropic substances for medical purposes.
Obtaining a supply of buprenorphine
Reliable supply of buprenorphine is vital because interruptions to the supply are distressing for patients and place them at high risk of relapse to illicit opioid use. Although not required by the convention, most exporting countries will adhere to the additional voluntary control measures recommended by ECOSOC (see below). In practice, all importing countries should remember that they might encounter difficulties obtaining buprenorphine if they do not have an assessment (a simplified estimate of the annual requirements for a psychotropic substance, see below) covering the amount to be imported and an import authorization or ‘no objection’ certificate for each separate import.
Assessment of medical needs for buprenorphine in accordance with ECOSOC resolution 1993/38
National drug regulatory authorities should prepare an assessment of the annual requirements for buprenorphine of their country. INCB recommends that this assessment should be revised at least every three years. The assessment or its revision can be submitted at any time. The responsibility for determining the amounts of buprenorphine necessary to meet the medical and scientific need in a country rests entirely with the national governments. INCB publishes changes in the assessments received from governments on a monthly basis, as a guide to exporting countries.
The import-export system
A specific sequence of steps is specified in the convention for the import and export of psychotropic substances. Additional requirements have been recommended by ECOSOC, and they are adhered to by most governments.
1. Mandatory controls foreseen by the convention
The convention foresees mandatory import–export authorizations only for substances included in Schedules I and II.
When exporting Schedule III substances, such as buprenorphine, exporters have to submit two copies of an export declaration to the competent authorities of the exporting country, and the third copy of the export declaration has to accompany the consignment. The government of the exporting country must forward the export declaration to the competent authorities of the importing country as soon as possible, but not later than 90 days after the date of the dispatch. Countries may require the importer to transmit the copy accompanying the consignment, duly endorsed stating the quantities received and the date of receipt, to the competent authorities of the importing country.
The export declaration must include:
the international non-proprietary name (INN) of the substance, or failing such a name, the designation of the substance in the Schedule
the quantity and pharmaceutical form in which the substance is exported, and, if in the form of a preparation, the name of the preparation
the name and address of the importer
the name and address of the exporter
the date of the dispatch.
2. Voluntary controls foreseen by ECOSOC resolutions
In accordance with ECOSOC resolution 1996/30, most governments have extended the import-export authorization system to Schedule III and IV substances, including buprenorphine. An import can only take place with the approval of the national drug regulatory authorities of the importing country and should remain within the assessment for buprenorphine established by the importing country. Approved export authorizations must accompany each consignment.
The import authorization must include:
the authorization number
the date it was issued
the authority by whom it has been issued
the international non-proprietary name (INN) of the substance(s), or failing such a name, the designation of the substance(s) in the Schedule
the pharmaceutical form and quantity of the substance(s), and, if in the form of a preparation, the name of the preparation
the name and address of the importer
the name and address of the exporter
the period of validity of the authorization.
The steps involved in the import–export process, in accordance with the recommendations of the ECOSOC resolutions
The entity wishing to import buprenorphine applies to its regulatory authority for an import authorization.
The regulatory authority considers whether the entity is properly licensed and whether the substance and amount are within the assessment; if approved, an original import authorization or ‘no objection’ certificate and the appropriate number of copies are issued. (One copy should be sent to the competent authorities of the exporting country. The original and one copy should go to the importer who will send the original to the exporter and will keep one copy for the Customs declaration. One copy should go to the Customs authorities of the importing country and an additional copy should be kept in the records of the importing country's competent authority.)
The importer sends the original of the import authorization or certificate to the company responsible for the export of the substance.
The exporter applies to its drug regulatory authority for an export authorization.
The regulatory authority of the exporting country checks that an import authorization has been issued and that the exporter is properly licensed, and that the assessment of the importing country is sufficient; if the application is approved, an export authorization is issued.
The regulatory authority of the exporting country sends a copy of the export authorization to the regulatory authority of the importing country. Two copies should go to the exporter, one of which must accompany the consignment. One copy should go to the Customs authorities of the exporting country and an additional copy should be kept in the records of the exporting country's competent authority.
The exporter ships the drugs to the importer, along with the copy of the export authorization.
The consignment must pass a customs inspection.
The importer sends the export authorization to its regulatory authority. After receiving the consignment, the importing authority shall return the accompanying export authorization to the regulatory authority of the exporting country with an endorsement certifying the amount actually imported.
A7.3. Guidelines for regulation of health professionals
It is understood that regulatory requirements for physicians, nurses and pharmacists to dispense opioids to patients will differ from country to country. However, the following are general criteria that can be used to develop a practical system.
Legal authority. Physicians, nurses and pharmacists should be legally empowered to prescribe, dispense and administer opioids to patients in accordance with local needs.
Accountability. They must dispense opioids for medical purposes only and must be held responsible in law if they dispense them for non-medical purposes.
Appropriate records must be kept. If physicians are required to keep records other than those associated with good medical practice, the extra work incurred should be practicable and should not impede medical activities. Hospitals and pharmacists must be legally responsible for safe storage and the recording of opioids received and dispensed. Records of each individual acquisition and disposal of opioids must be preserved for a period of not less than two years.
Reasonable record keeping and accountability provisions should not discourage health-care workers from prescribing or stocking adequate supplies of opioids.
Prescriptions. Legal requirements for prescriptions vary by jurisdiction; however, in general a prescription for opioid agonist maintenance therapy should specify the following:
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name, address and telephone number of the prescribing doctor
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name of the pharmacy
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name and address of the patient
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date of the prescription
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preparation to be dispensed (i.e. methadone or buprenorphine)
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dose to be dispensed in milligrams (words and numbers)
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frequency of dispensing (daily, twice daily, alternate daily, three times a week)
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start and end dates of the prescription
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whether doses are to be supervised or taken away.
Patient access. Opioids should be available in locations that will be accessible to as many opioid-dependent patients as possible.
Medical decisions. Decisions concerning the type of drug to be used, the amount of the prescription and the duration of therapy are best made by medical professionals on the basis of the individual needs of each patient.
