ANNEX 6OPIOID ANALGESICS AND INTERNATIONAL CONVENTIONS

A6.1. UN drug conventions and their governance system

There are three international drug control treaties: the United Nations Single Convention on Narcotic Drugs, 1961, as amended by the 1972 Protocol (94); the United Nations Convention on Psychotropic Substances, 1971 (119); and the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, 1988 (120). These conventions represent a global effort to prevent drug abuse, while enabling access to these substances as medicines for the relief of pain and suffering. By signing these treaties, countries have made a commitment to implement a number of drug control measures in their territories without unduly restricting medicines access.

The Commission on Narcotic Drugs (CND), which represents the States that are Parties to these international drug conventions, 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. The process for developing the recommendations for scheduling drugs under these two conventions is described in the Guidance for the WHO review of psychoactive substances for international control (121). The International Narcotics Control Board (INCB) is charged with monitoring governments' compliance with the above international treaties, and ensuring, on the one hand, that controlled substances are available for medical and scientific use and, on the other hand, that the drugs are not diverted from licit sources to illicit markets.

A6.2. The Single Convention on Narcotic Drugs and opioid analgesics

The Single Convention on Narcotic Drugs, 1961, as amended by the 1972 Protocol (94) is the principal international treaty regulating the control of opioids. It seeks to limit the production, manufacture, exportation, importation, distribution, trade, use and possession of narcotic drugs exclusively to medical and scientific purposes. The Single Convention distinguishes among four types of classification: Schedule I, Schedule II, Schedule III and Schedule IV. Each schedule refers to a number of control measures to be applied according to the gravity of drug abuse and dependence produced by the listed substances.

Morphine and the other strong opioids considered for safe switching in children with persisting pain (fentanyl, hydromorphone, oxycodone and methadone) are listed under Schedule I. In order to comply with the Single Convention, countries should take the following measures for narcotic substances listed under Schedule I:

• estimate the annual medical and scientific requirements and submit their estimates to the INCB for confirmation;
• limit the total quantities manufactured and imported to the estimates, taking into account the quantity exported;
• ensure they remain in the hands of licensed parties for trade and distribution within the country;
• require a medical prescription be dispensed for their use;
• report to the INCB on the amount imported, exported, manufactured, consumed and on the 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; and ensure premises, stocks and records are inspected;
• take steps to prevent the diversion and abuse of these substances.

The Single Convention states in its preamble: “recognizing that the medical use of narcotic drugs continues to be indispensable for the relief of pain and suffering and that adequate provision must be made to ensure the availability of narcotic drugs for such purposes.” Thus, this puts an obligation on the countries that are Parties to the international conventions to ensure the medical availability of the controlled substances.

A6.3. Drug misuse versus patient need

The Single 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 Single Convention. The INCB has observed that, in some countries, fear of drug misuse 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. (122)

In its annual report of 2004, the INCB furthermore acknowledged that there was a huge disparity in countries' access to opioid analgesics for pain relief. It reported that six developed countries accounted for 79% of the global consumption of morphine. Conversely, developing countries, which represent 80% of the world's population, accounted for approximately 6% of the global consumption of morphine (123). A study on the adequacy of opioid consumption around the world concluded that 5 683 million people live in countries where the consumption level of strong opioid analgesics is below adequate, against 464 million in countries with adequate consumption of strong opioids. An additional 433 million people live in countries for which no data are available (124).

Drug control conventions were established to enhance public health, which is affected positively by the availability of controlled medicines for medical treatment and negatively by misuse and dependence. Countries should seek the optimum balance in order to attain the best outcomes for public health.

Governments should examine their drug control legislation and policies for the presence of overly restrictive provisions that affect delivery of appropriate medical care involving controlled medicines. They should also ensure that provisions aim at optimizing health outcomes and take corrective action as needed. Decisions which are ordinarily medical in nature should be taken by health professionals. For doing so, they can use the WHO policy guidelines mentioned earlier in this annex (95), in particular the Country Check List comprised in that publication.

A6.4. Competent national authorities under the international drug control treaties

The national legislation in countries that have ratified the Single Convention on Narcotic Drugs, 1961, as amended by the 1972 Protocol, designates a competent national authority to liaise with the INCB and the competent authorities of other countries. These competent national authorities also administer national regulations relating to controlled substances for medical use. The office of the competent national authority is usually located in the national medicines regulatory authority and/or in the ministry of health. In certain countries, the competent national authority is a separate government agency; in others, it is an office located in another ministry, such as the ministries of justice, police or finance.

The identification of the competent national authority is a necessary step for any manager and officer involved in the planning of the procurement and supply of opioid analgesics. A list of country competent authorities and their contact details is available at: http://www.painpolicy.wisc.edu/internat/countryprofiles.htm

A6.5. The Convention's requirements for national estimates of medical need for opioids

Every year, competent national authorities must prepare estimates for the following calendar year of their requirements for Schedule I narcotic drugs (morphine and other strong opioid analgesics considered for safe switching in children with persisting pain) and Schedule II (125). These estimates are submitted to the INCB and set the yearly limits for the amount of strong opioids to be procured for medical use. The estimates must be submitted to the INCB by 30th June, six months in advance of the period for which they apply. The Board notifies confirmed estimates to the competent national authorities by December of the same year.

Under the Single Convention on Narcotic Drugs, 1961, as amended by the 1972 Protocol, the quantity of controlled substances manufactured or imported into a country must not exceed the official government estimates. Therefore, the submission of adequate estimates to the INCB is crucial when importing controlled substances, as exporting countries will refuse to export additional narcotic substances to a country that has used up the quantity it is allowed to import for the calendar year.

The responsibility for determining the amount of opioids needed to meet medical and scientific requirements in a country rests entirely with the government, although the Board may examine the estimates and request additional information and clarification. If countries fail to establish estimates of annual narcotics requirements, the INCB determines them on their behalf. In such cases, the Board informs the competent national authority of the country concerned of their estimates and requests the authority to review them.

A6.6. The importance of reliable estimates

The World Health Organization and the International Narcotics Control Board are working on a joint guide for estimating requirements for substances under international control. This is a particularly important step in the supply cycle of opioid analgesics as it ensures the uninterrupted supply of these essential medicines. Countries introducing or enlarging the coverage of pain relief services will need to forecast adequately the quantities of opioid analgesics that will be increasingly supplied in the health system.

If an annual estimate proves to be inadequate, the competent national authority can submit supplementary estimates to the INCB at any time during the course of the year. However, the competent national authority will be requested to provide an explanation of the circumstances necessitating additional drug quantities. As far as possible, such supplementary estimates should only be used in the case of unforeseen circumstances and for the introduction of new treatments (126).

The market availability of controlled substances is confined to the estimates submitted to the INCB. Hence, it is crucial for managers and other parties concerned with the procurement of strong opioids to be aware of national estimates for the relevant drugs. The Board publishes changes in the estimates received from governments on a monthly basis on the Internet (www.incb.org), or on a quarterly basis in the form of a hard copy technical report sent to governments, as a guide to exporting countries.

A6.7. Domestic manufacture of strong opioid analgesics

After a country has received confirmation of its estimates from the INCB, it may start manufacturing or importing procedures for opioid analgesics under Schedule I. The Single Convention requires governments to license individuals and enterprises involved in the manufacture of opioid medicines. In order to prevent the diversion of these strong opioids to illicit markets, manufacturers must make resources available for record-keeping and security procedures, and for the provision of secure facilities from the moment the raw materials are acquired until the finished products are distributed.

In addition, governments should assure the quality of the manufactured medicines, such as through enforcing Good Manufacturing Practices, and the requirement of a market authorization by the national medicines regulatory authority.

Special reporting to INCB is additionally requested regarding the:

• quantities of opioid medicines to be used in the manufacturing of other medicines;
• number of industrial establishments that will manufacture opioid medicines;
• quantities of opioid medicines to be manufactured by each establishment.

A6.8. The import/export system for strong opioids

The principles governing the procurement and supply of strong opioid medicines are similar to other pharmaceutical products, but require additional steps as mandated by the Single Convention and national legislation.

Generally, each country has its own importation procedures, which may require approval from different authorities in the country, such as the ministry of health, the national medicines regulatory authority and other entities (e.g. for import duties).

Specifically, the Single Convention requires additional steps and approvals for the importation and exportation of narcotic drugs. These steps, outlined below and in Figure A6.1 below, are broadly applicable across countries, although specific requirements may vary from country to country.

Figure A6.1

Steps in opioid import/export procedures. See A6.8 for explanation of the numbered steps. Source: (127)

1. The licensed importing entity (e.g. private or public company) applies for an import authorization from the importing country's competent authority.²
2. The competent authority considers whether the entity is properly licensed and whether the amount of drug required is within the national estimate. If so, the competent authority issues an original import certificate and the appropriate number of copies. The original and one copy are for the importer, one copy is for the competent authority of the exporting country, and an additional copy is to be kept in the records of the issuing competent authority.
3. The importer sends the original of the import authorization to the company responsible for the export of the substance.
4. The exporter applies to its competent authority for an export authorization and encloses the import authorization to the application.
5. The competent authority in the exporting country checks that an import authorization has been issued and that the exporter is properly licensed. If the application is approved, an export authorization is issued and the original import authorization is returned.
6. The competent authority in the exporting country sends a copy of the export authorization to its counterpart competent authority in the importing country.
7. The exporter ships the drugs to the importer, along with the copy of the export authorization and the original import authorization.
8. The shipment must pass two customs inspections: one in the exporting country and one in the importing country.
9. The importer sends the export authorization to its competent authority in the importing country.

A6.9. Requirements for import/export authorizations or certificates

Both import and export authorizations should include the:

• international non-proprietary name (INN) of the medicine
• quantity of the medicine to be imported or exported
• name and address of the importer and exporter
• period of validity of the authorization.

The export authorization should also state the reference number and date of the import authorization, and the issuing authority. The forms for import and export applications may vary from country to country, INCB model forms for these authorizations are available in Guidelines for the import and export of drugs and precursor references standards for use by national drug testing laboratories and competent national authorities (128).

Import and export authorizations are normally required for each shipment.³

The authorization process for the importation and exportation of opioid medicines can be very lengthy and subject to errors. Therefore, the procurement of controlled medicines requires careful planning.

Managers and officers involved in the procurement of opioid analgesics should use the steps outlined here as a starting point to develop comprehensive plans specific to their countries' situations. Since the importation of controlled medicines involves decision-making and authorizations from several departments/agencies, it is crucial that strong coordination and partnerships are established among all parties.

A6.10. The reporting system following exportation, importation and consumption of opioids

The competent national authority in the country must send quarterly reports to the INCB of all imports and exports of opioid analgesics classified under Schedule I. It is also mandatory to make an annual inventory and report the total amount of opioids manufactured, consumed and held in stock at central level (e.g. licensed central warehouses, manufacturers' warehouses). The annual inventory does not include medicines stored in retail pharmacies, retail distributors or other health services which, for official purposes, are considered to have been consumed.⁴

A6.11. Distribution of strong opioids

The Single Convention requires countries to ensure that trade and distribution can be performed only by licensed parties. The competent national authority normally provides trade and distribution licences for private companies, either manufacturers or wholesalers. A manufacturer or wholesaler may distribute the finished products directly to licensed pharmacies or hospitals. Wholesalers must also be licensed by the competent national authority, and must comply with rules concerning security and record keeping. The Single Convention neither requests countries to provide exclusive rights for the storage, distribution and trade of controlled medicines to one single state agency or private company, nor suggests that opioids be managed within a special or separate medicine distribution system.

However, some countries have separated the storage and distribution of controlled medicines from the distribution system for other medicines. They have also established additional requirements to those mandated by the Single Convention. These may sometimes have a negative impact on the accessibility to strong opioids and increase distribution costs.

A6.12. Usual requirements for prescribing and dispensing opioids

The Single Convention requires medical prescriptions to prescribe and dispense controlled medicines to individuals. Legal requirements for prescriptions vary from country to country. However, in accordance with most prescription medicines, a prescription for an opioid analgesic should specify the following:

• name and business address of the prescribing health professional
• name of the patient
• date of the prescription
• preparation to be dispensed (e.g. morphine tablet)
• dose to be dispensed in milligrams (words and numbers)
• frequency of dispensing (e.g. daily, twice daily)
• signature of the prescribing doctor or health professional.

Requirements for duplicate prescriptions and special prescription forms increase the administrative burden both for health-care workers and drug control authorities. The problem is compounded if forms are not readily available, or if health professionals need to pay for them. The conventions allow for duplicate prescriptions and special prescription forms if countries consider them necessary or desirable. Governments should ensure that this system does not impede the availability and accessibility of controlled medicines. No limit is set on the quantity of medicines or the length of the treatment inscribed in a prescription.

Footnotes

2

It should be noted that, while the competent authorities in some countries are different from the national medicines regulatory authority, in others they may be one and the same authority.

3

One import authorization can allow for more shipments (for which exportation authorization needs to be granted on a single basis).

4

“Stock” is defined in Article 1 of the Single Convention on Narcotic Drugs 1961 as amended by the 1972 Protocol.