Report of the first meeting of the Programme Planning Working Group on WHO's new procedures for the review of dependence producing psychoactive substances for international control. Geneva, 12-16 March 1984

• WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE REPORT OF THE FIRST MEETING OF THE P~RAMME PLANNING WORKING GROUP ON WHO'S NEW PROCEDURES FOR THE REVIEW OF DEPENDENCE PRODUCING PSYCHOACTIVE SUBSTANCES FOR INTERNATIONAL CONTROL , /)et./ C ~· ( ( IS 7 Geneva, 12-16 March 1984 ·wHoooc ~ / _5 CONTENTS 1. Introduction .......................................................................... 2 2. 3. 1.1 Introductory Remarks . ........................................................•.. 2 1.2 Activities of Relevant WHO Divisions and other Organizations •••••••••••••••••••• 2 Role 2.1 2.2 2.3 of WHO Activities relevant to the Review Process •••••••••••••••••••••••.••••••••• 4 Division of Mental Health ••••••••••••••••••••••••••••••••••••••••••••••••••••••• 4 Other Divisions and Progrannnes •••••••••••••••••••••••••••••.•••••••••••••••••••• 6 WHO Regional Offices and Country Progrannne Coordinators ••••••••••••••••••••••••• 7 Role of Non-governmental Organizations and Other Groups ••••••••••••••••••••••••••••••• 7 4. Development of Guidelines for the WHO Review Process ••······•·····•••••••••·••••·•·••8 4 .1 Basic Framework . .......•..........................•.................•........... 8 4.2 WHO Collaborating Centres ••••••••••••••••••••••••••••••••••••••••••••••••••••••• 9 4.3 Expert Panels ................................................................... 9 4.4 Progranune Planning Working Group •••••••••.••••..•. 4••••··•··••••••••·•••••··••·•9 4.5 Procedural Steps in the Review Process •••••••••••••••••••••••••••••••••••••••••• 9 4.6 Criteria for Selection of Substances for Review •••.••......•••...••.•••••.•••.. 12 5. Special Issues .•.............•............•.......•.................................. 12 5.1 Conflict of Interest ......•...........•........................................ 12 5.2 Confidentiality ................................................................ 12 5.3 Provisional Control .•............•........................................•.... 13 6. Future Review Activities ..............•.•..•......................................... 13 7. Special Items for Second PPWG . ....•........................•..........••........•.... 14 8. Agenda for 22nd Expert Connnittee on Drug Dependence and List of substances to be reviewed .. .............•.•.....•................................... . 14 9. Reco1D1D.enda t ions . .•..............•................................•.......•........ • .. 14 Annexures Annex 1 List of Participants ••••••••••••••••••••••.•••••••••••.•••••••••••••• 15 Annex 2 Annex 3 List of Background Documents ••••••••••••••••••••••••••••••••••••••••• 17 Annex 4 Draft Agenda for 22nd Expert Connnittee on Drug Dependence ••··••••••·l8 List of Substances for Review by the 22nd Expert Committee on Drug Dependence • .•..............•••......•.•.........•.•••.•...•.•.•• 20 The issue of this document does not constitute formal publication. It should not be reviewed. abstracted or quoted without the agreement of the World Health Organization. Authors alone are responsible for views expressed in signed articles. Ce document ne constitue pas une publication. II ne doit faire l'objet d'aucun compte rendu ou resume ni d'aucune citation sans l'autorisation de !'Organisation mondiale de la Sante. Les opinions exprimees dans les articles signes n'engagent que leurs auteurs. MNH/PAD/84.2 " • Pa3e 2 . INTRODUCTION 1.1 Introductory Remarks Dr Norman Sartorius, Director of the Division of Mental Health, addressed the participants on behalf of Dr Mahler, Director-General of the World Health Organization. He underlined the importance WHO attaches to the fulfilment of its obligations under the international drug control treaties. He thanked Dr B. Rexed, of Sweden, for his numerous and important contributions in the process of developing a comprehensive strategy for the review process, and reminded the Group of the need to balance treatment requirements and the control of substances with dependence producing properties. The present meeting was convened to advise the Organization on the best way to develop its progrannne concerned with the Treaty obligations in accordance with the mandate given by the Executive Board of WHO (EB73R.ll). In this respect the Group was requested to make recommendations about the selection of substances to be reviewed by WHO next year, about criteria which might be useful for the future selection of substances for review as well as the priorities to be followed in the selection of substances, and to review procedures which will ensure that the recommendations of the DG can be based on the best scientific basis possible. With a view to ensuring that the views of the various groups involved in the review process were represented, participants were drawn from a variety of institutional sources. These included representatives of the scientific connnunity; WHO governing bodies; the United Nations Commission on Narcotic Drugs (CND) and government drug regulatory agencies. Representatives of the United Nations Division of Narcotic Drugs (DND), the International Narcotics Control Board (INCB) and Interpol participated throughout the meeting. Representatives of WHO collaborating centres were invited to help plan how their activities could contribute to the review process. Finally, NGO's in official relations with WHO such as the International Federation of Pharmaceutical Manufacturers Associations (IFPMA),and the International Council on Alcohol and Addictions (ICAA), as well as others such as the International Organizaton of Consumer Unions (ICX:U) were invited to address the Group and express their views about the review process and the manner in which they could contribute to it. The full list of participants is given in Annex 1. The Group elected Dr Bror Rexed as the Chairman, Dr D.B. Bisht as the Vice-Chairman and Dr Charles R. Schuster as the Rapporteur for this meeting. 1.2 Activities of Relevant WHO Divisions and Other Organizations Following Dr Sartorius' presentation on the interaction of the various units and progrannnes within WHO, Dr B. Sankaran, Director of the Division of Diagnostic, Therapeutic and Rehabilitative Technology (DTR) addressed the meeting. He expressed his support to promote the interaction of various progrannnes in his Division which had relevance to the substance review process. The Division of DTR and in particular, the Pharmaceutical and Traditional Medicine Units have an important role in the substance review process outlined in the guidelines for the review of substances. These include providing data on adverse reactions, including dependence; therapeutic efficacy; and availability of psychoactive substances in various Member States. The Traditional Medicine Unit (TRM) has responsibilities towards identification of traditional medicinal plants with psychoactive properties. This is of particular importance in developing countries where the abuse potential of such plants or plant derivatives may present probl~ms. This concern has been expressed by the World Health Assembly in a recent resolution(lJ. Mr F. Ramos-Galino, Deputy Director of the Division of Narcotic Drugs (DND), addressed the Group highlighting the interaction between DND and WHO. He emphasized that there had been continuing cooperation between WHO and DND in the performance of their respective functions under the international drug control treaties in the matter of scheduling. ( 1) Resolution WHA33 .27, paragraph 7(3) ( ( I • MNH/PAD/84.2 Page 3 For a number of years, the international community had.found the procedures followed by WHO quite satisfactory for reviewing substances for international control and in making its recommendations to the Secretary-General of the United Nations for possible inclusion of substances in one of the schedules of either the Single Convention on Narcotic Drugs, 1961 or the Convention on Psychotropic Substances 1971. In the last few years, however, difficulties had arisen in obtaining the requisite majority of votes, particularly with respect to recommendations for the scheduling of a large number of benzodi~zepines. During its thirtieth session, the CND adopted by consensus a resolution (2 J establishing the procedures to be followed by the Commission in matters of scheduling substances. Following the thirtieth session of CND, efforts were made by DND and WHO to step up their cooperation with a view to streamlining procedures along the lines requested by CND. Concrete positive results of this increased cooperation could be seen in the following meetings: (a) Working Group held in Geneva 3-4 March 1983 which adopted the guidelines for the WHO review of psychoactive substances; (b) The 8th Review of Psychoactive Substances for International Control held in Geneva from 12-16 September 1983 which recommended the scheduling of 33 benzodiazepines; (c) The 73rd session of the Executive Board of WHO which approved, in principle, the new procedures prepared by the Director General for the review of psychoactive drugs for international control; and (d) the eighth special session of CND, where all recommendations concerning the scheduling of substances received from WHO were accepted by the Commission. The need to have a two-thirds majority of the members of CND required for scheduling under the Convention on Psychotropic Substances made it highly desirable to continue to seek the further improvement of the procedures to be followed by WHO in the review of substances for international control and the contents of the reports submitted during the various stages of the review. It should be noted however that it is not always possible to get the necessary information to enable WHO to fulfil its responsibilities under the Conventions. For instance, the collection of data on illicit traffic concerning substances not under national or international control presents very difficult problems. Efforts have to be made, therefore, to facilite the collection of data. It was suggested that data be required by governments on the dependence-producing properties of a given substance prior to its registration. This would then constitute an additional source of useful data. The Secretary of the International Narcotics Control Board (INCB), Mr A. Bahi, mentioned the long-standing cooperation between the Board and the World Health Organization. He expressed his regret that Professor Kaymak~alan whose contributions in the field of drug dependence were well known, had unfortunately been prevented from participating in the meeting. The main responsibility of the INCB is with the monitoring of drugs once they are placed under control. Mr Bahi expressed the Board's satisfaction with the new review procedures adopted by WHO which, among other advantages, gave advance notice to those in charge of implementing the Conventions, to plan the necessary arrangements for such control. Mr Walter Leamy of Interpol spoke to the Group about the role of his Organization in the WHO review process. The general secretariat of !CPO/Interpol, at the request of WHO, assists in the collection of data regarding psychoactive substances under consideration for international control. It is the adopted policy of Interpol to collaborate with, and support the work of other international organizations engaged in the suppression of drug abuse and the trafficking in drugs. In furtherance of this activity, the Interpol general secretariat requests, through the Interpol National Centres, relevant information for each substance under study, from every member country. The information requested covers all relevant illicit trafficking and related data assembled by police and customs authorities in the countries. For example, for each substance under study, the following items of data and information are sought: (a) Seizures in the country; number of seizures and total quantity seized for the period specified. (b) Diversion of the substance from licit to illicit channels; thefts from pharmacies and/or other stockholding establishments; falsified or counterfeit prescriptions, etc. Quantitative reporting is requested (i.e. number of thefts, quantity of drugs involved, etc.). 2. Resolution 4(XXX) MNH/PAD/84.2 Page 4 (c) Information concerning possible clandestine production of the substance, as well as illegitimate trade in precursor chemicals. (d) Other relevant data concerning the role of the substance in illicit traffic (for example, the frequency of the substance in counterfeiting or "look-alike" activity). Through this process Interpol seeks to make available to the reviewing bodies an accurate summary of illicit activity, if such exists, relating to the substance. 2.0 2.1 Review of WHO Activities Relevant to the Review Process Division of Mental Health Medium-Term suhstances. and planned The Division of Mental Health (MNH) has initiated three projects as part of its Programme (1984-89) which are concerned with the use and abuse of psychoactive These projects are described below in relation to their objectives and ongoing activities: PROJECT A. Assessment of the Efficacy and Side Effects of Psychoactive Drugs If Consumed in ( Combination with Other Drugs or Alcohol. The objectives of this project are: (i) ( ii) ( iii) (iv) (v) to promote the development of guidelines, obtain evidence to evaluate the role of other drugs and alcohol when used concommitantly with a single psychoactive substance in a formulated speciality or when taken individually; to assess the benefit and risk ratio of an active psychoactive substance when consumed in a product containing other ingredients; to advise the Secretary-General of the UN as to the validity of exemptions granted by Member States; to keep records of the past decisions taken by the UN Commission on Narcotic Drugs for easy retrieval and comparison in future work; and to advise authorities and members of health professions on the possible risk involved. A number of activities in connection with this project are either underway or planned for the immediate future. Among them are (l)the WHO meeting from 23-27 April 1984 at its Regional Office in Washington, D.C. (WHO/PAHO), to develop the guidelines further and to review in a preliminary way, the pending notifications from four countries in preparation for a full review of these at the next PPWG meeting, (2) A survey of the existing literature on this subject to help in advising public health officials and members of the health professions. PROJECT B. Assessment of the Therapeutic Usefulness and Public Health Effects of the Widespread Use of Specific Psychoactive Drugs with A View to Making Recommendations to Countries and UN Bodies One of the oldest responsibilities assigned to WHO at its inception was that it should recommend narcotic drugs obtained both from natural sources and from synthetic material, for national and international control, under the existing international drug control treaties. This was done on the basis of the drugs' dependence liability, abuse potential and actual abuse. The bases of WHO recommendations are: (i) the capacity to produce dependence, and abuse; (ii) the associated public health and social problems; (iii) the therapeutic usefulness. , • MNH/PAD/84,2 Page 5 So far WHO has produced 21 reports of Expert Connnittees on Drug Dependence, one report on the implementation of the 1971 Convention, and a number of other reports addressing themselves to the development of methodology related to the dependence potential of psychoactive drugs, and the assessment of public health and social problems. On the recommendation of WHO 104 single narcotic substances are included in the 1961 Convention, and 44 single psychotropic substances in the 1971 Convention. Efforts have already been made to create awareness of the need to obtain data required to schedule psychoactive drugs. The objectives of this Project are; 2. to promote the development and application of methods for the: (i) assessment of the dependence liability and the public health and social problems associated with the use of narcotic and psychotropic substances. (ii) assessment of the therapeutic usefulness of psychoactive substances. establishment of the benefit and risk ratio of psychoactive substances. 3. based on the benefit and risk ratio of psychoactive substances, the recommendation to schedule or deschedule a single substance or group of substances at national and international levels. 4. promotion of the rational use of psychoactive substances through cooperation between government, members of health professions through their professional associations, medical schools, and the pharmaceutical industry. WHO has planned a number of review meetings to establish the benefit and risk ratio of specific substances and groups of substances under the international drug control treaties, e.g., an expert committee in 1985, to reivew uncontrolled amphetamines (see 8.0). The following are the other activities to be undertaken in 1984-85: (a) Meeting on "Assessment of Therapeutic Usefulness of Psychotropic Drugs", scheduled to be held in Oslo from 1-5 October 1984. (b) Meeting on "Evaluation of Methods and Data Related to Public Health and Social Problems Associated with the Use of Psychotropic Drugs", scheduled to be held in Bangkok from 25-30 March 1985. {c) In accordance with the resolution of the Executive Board (EB69R9, 1982) that educational efforts for improvement of knowledge for the physicians and other health care professionals are necessary for achieving rational use of psychoactive drugs, a meeting has been planned in the USSR from 8-16 October 1984, titled "Education of Health Care Professionals for Improving Prescription, Delivery and Utilization of Psychoactive Drugs". PROJECT C. Development of Guidelines in The Context of International Drug Control Treaties and Obligations The use and abuse of drugs of natural origin have been known since antiquity. It was the large-scale use of some of these natural products which drew attention to the need for control of such dependence-producing substances, and for achieving at the same time a reduction in their demand. Efforts to provide an international legal framework for the control of psychoactive drugs began by the International Opium Commission in Shanghai in 1909, have resulted in a number of international treaties. The formulation of the 1961 Convention and its amending protocol, and the 1971 Convention, have been the major achievements in the development of coordinated international control of dependence-producing drugs. These are instruments which provide a framework for MNH/PAD/84.2 Page 6 the regulation of a number of defined narcotic drugs and psychotropic substances, the most dangerous of which are eliminated from use. The potentially beneficial ones are subjected to controls in production, manufacture, trade and distribution. The treaties embody a policy and indicate the type of controls needed in legislation and drug regulatory work, thus helping to promote the rational utilization of the controlled substances and the prevention of their abuse, and to counteract illicit international traffic. A rational drug policy concerning psychoactive drugs is essential for the accomplishment of WHO's progrannne of Health for All by the Year 2000. WHO stimulates and supports the continuing education of members of the health professions in the therapeutic use of these drugs to prevent any harm they can produce. The on-going WHO progratRIDe for selecting a list of essential drugs offers another opportunity to nations to screen psychoactive drugs available in their countries and to evaluate their benefit-risk ratio in the spirit of the drug control treaties. The 33rd World Health Assembly, in Resolution WHA33.27, in its operative paragraph 7(3) requested the Director-General to promote the initiation and strengthening of national and international programmes for the assessment, scheduling, control and appropriate use of narcotic and psychotropic substances, including those of plant origin, and to support such progra1TU11es by the development of appropriate guidelines in consultation with the UN Division of Narcotic Drugs, the INCB and other UN organs concerned. WHO has carried out an extensive study of 13 countries centring on the setting up and functioning of national drug policy, drug laws and drug control systems, and the assessment of actual drug use and abuse. A set of guidelines has been prepared by Rexed et al, and is available. This project now is to implement the wishes contained in the above resolultion, once these guidelines are available. The objectives of this Project are: (i) to facilitate the ratification of the international drug control treaties by those nations which have not yet done so; (ii) to facilitate national efforts to carry out their functions and responsibilities assigned by the ratification of the treaties, using WHO's guidelines; (iii) to facilitate further national efforts to promote the rational use of psychoactive substances, using WHO's guidelines. With the availability of the guidelines, WHO plans to provide yet another publication facilitating the implementation of the guidelines at national level. It is planned to relate the guidelines to a few national situations, indicating how these guidelines have been and can be translated into action. This will involve review of the existing national legislative policies, progra1TU11es and the infrastructure including facilities, in providing health care in practical terms in the selected countries. The existing situations in individual countries will also be evaluated in the light of the guidelines to identify gaps and ways and means of filling them. The review will be based on published material within WHO, UNDND, INCB, Interpol and !CAA and other agencies. After field testing the material prepared by WHO will be made available as a supplement to the guidelines for wide use by the UN agencies concerned, national authorities and others. 2.2 Other Divisions and Programmes MNH has a number of projects in collaboration with other WHO Divisions which are relevant to the Review Process. Collaboration with the Division of Diagnostic, Therapeutic and Rehabilitative Technology (DTR) is essential since many of their progra1TU11es involve data acquisition and decisions of critical importance. As mentioned on pages 4 and 5, the Pharmaceutical Unit (PHA) can provide data on:the general acceptability of psychoactive substances; adverse drug reactions in general and particularly those related to dependence potential and drug utilization. In addition, MNH can assist the PHA by providing it with information on the dependence producing properties of psychoactive substances being considered for inclusion on the list of essential drugs. I ' MNH/PAD/84.2 Page 7 MNH can also provide data on the dependence producing properties of psychoactive substances to assist the DAP 1n their efforts to educate members of health teams in their use of psychoactive substances. Finally MNH can collaborate with the Traditional Medicine Unit (TRM) to obtain data on the dependence producing properties of herbal remedies. 2.3 WHO Regional Offices and Country Programme Coordinators WHO Regional Offices have a unique role which permits them to make an important contribution to the WHO review process. Using their contacts with national authorities, the Regional Offices can obtain reports on governments' plans and programmes, identify drugs of abuse warranting international control and call attention to possible formal notifications in appropriate cases. They can be in touch with regional drug control organizations and obtain scientific and other relevant information from them. Through collaborating centres, country contacts and links with non-governmental organizations, the Regional Offices can obtain information about new developments in psychopharmacology and results of epidemiological and other studies of relevance to the WHO Review Process. Furthermore, through contacts with national drug regulatory agencies, the Regional Offices can obtain lists of registered drugs, information about changes in the control of substances and results of clinical trials. In all this work it should be of central importance to maintain close contact with WHO Country Programme Coordinators, who will have to receive all relevant information enabling them to facilitate the governments' programmes in this area. In order to be able to perform these roles, the WHO Regional Offices will have to give additional attention to these matters, further develop their programmes dealing with drug dependence and drug abuse, facilitate the systematic collection of relevant data and ensure regular linkages with other relevant WHO activities at regional level (e.g., dealing with essential drugs). 3.0 Role of Non-Governmental Organizations and Other Groups Representatives of the International Federation of Pharmaceutical Manufacturers Associations (IFPMA) and the International Organization of Consumer Unions (IOCU) and the International Council on Alcohol and Addictions (ICAA) addressed the Group. These organizations welcomed the new WHO Review Procedures and were in general agreement with the principles outlined in the principal background paper, It was underlined f that the industry and consumer perspectives should be adequately reflected during all relevant stages in the review process. The representatives expressed willingness to participate in the meetings convened in the course of the WHO review process as well as to pa~ticipate in any other manner. Several possibilities of collaboration involving the Programme Planning Working Group (PPWG), the Expert Committee on Drug Dependence (ECDD) and the Secretariat, on the one hand, and the industry and consumer groups, on the other, were considered. It was agreed that prior to PPWG meetings the Secretariat may consider convening an informal consultation to identify, inter alia, possibilities of supplementing the information and data to be made available to the ECDD. IFPMA indicated that it would, in particular, be pleased to arrange informal consultations with individual manufacturers if information and data of drugs manufactured by such manufacturers would be useful to the WHO review process. On account of the wide spectrum of issues which have a bearing on the need to make psychotropic substances available for therapeutic purposes whilst at the same time preventing their misuse or abuse, it was felt that future collaboration should cover areas such as judicious prescribing habits; educational programmes for professionals and the public; restrictive labelling and advertising practices etc. An informal consultation on the development of possible programmes in the area of prescriptions and education is to be convened at an early date. Drug abuse preventive education programmes are of particular importance to consumer groups. These groups would also be able to provide information regarding problems relating to marketing and availability. MNH/PAD/84.2 Page 8 A potentially rewarding contact with scientific sources might be through the national medical research councils and corresponding institutions. A continuing relationship with these councils and institutions should be built up with a view to define new trends in psychoactive drug development, to identify scientists and institutions for WHO collaboration, and to help organize symposia, seminars and working groups in priority areas of the WHO Review. CIOMS (Council for International Organizations of Medical Sciences) may be an important partner in this effort. The International Council of Scientific Unions is a special group worthy of attention. It unites the national societies of scientists working in the various disciplines. There are a number of international, regional and national organizations which have already assisted WHO in its evaluation of substances for possible international control. WHO has had a long-standing contact with the Committee on Problems of Drug Dependence, an independent US research organization originally associated with the National Academy of Sciences. This Committee is likely to remain an important source of scientific information in the future. Special mention should be made of its active drug testing programme concerning the dependence potential and abuse liability of drugs as a basis for advance warning of potential drug problems, and its specialized scientific meetings which produce data on substances of interest to WHO. There are many international organizations assembling scientific disciplines, special activities or related institutions in the different areas relevant to the WHO Review. On account of the different interests which they represent they may serve as an informative group in following the developments relating to the use and misuse of psychoactive substances. WHO collaboration with them should take constructive forms, and it may be worth while to assemble a WHO Conference of international organizations involved in the study of dependence-producing drugs. Obviously the nongovernmental organizations in official relations with WHO form a special group in this context. 4.0 Development of Guidelines for the WHO Review Process 4.1. Basic Framework The Group began its most important task by thanking Dr Rexed, Dr Khan and Mr Jayasuriya for providing a background document outlining a possible comprehensive strategy for the WHO review of psychoactive substances. The underlying principle of the procedure anticipated a formalized system of administrative and scientific decisions. WHO's work would be shaped taking into careful \ consideration the guidance provided by the Programme Planning Working Group (PPWG). The Expert Committee on Drug Dependence (ECDD) makes recommendations for international control to the Director-General. The Group recommended that there generally should be no overlap between the members of the PP~ and ECDD in order to avoid individual views dominating the Review Process. By having separate membership a diversity of views can be better represented. The Secretariat will provide the necessary liaison function between these two groups.In effecting the new procedure, ample time shall be made available for contributions of necessary data by the various United Nations organs the NGO's and other interested parties. The new procedure would allow for more visibility and openess in the decision-making process. The discussions by the Group re-emphasized the role of the CND as laid down by the Single Convention on Narcotic Drugs as well as the Convention on Psychotropic Substances. While WHO assessed the scientific and medical factors, the CND has to take into account legal, administrative, economic, social and other factors in addition. The group seriously considered the question of confidentiality of information at the disposal of the PPWG and ECDD. Member States expect to have access to documents received by WHO.* * See also 5.2 below ' • MNH/PAD/84,2 Page 9 The level at which the various NGO's and especially IFPMA would participate in the meetings of the review groups was also discussed, It was felt that participation of these organizations would be most valuable at the time of the meeting of the PPWG, Members of the Group briefly examined the problem in the event a participating expert might have a conflict of interest. It was felt that even though such cases might occur very rarely, it might be advisable to have members make a prior written declaration of their interest in relation to spP.cific issues on the agenda, (see also 5.1) 4.2 WHO Collaborating Centres The Group examined the role which the WHO Collaborating Centres might play in the new procedure. It was felt that these centres were in a unique position to collect data on basic research, clinical studies and epidemiology of use and abuse of substances. The Collaborating Centres would be encouraged to provide such essential data. They often have the capability of collecting and collating relevant abuse and therapeutic use data which would be helpful to the PPWG in identifying psychoactive substances for review by ECDD. Special projects may be implemented by some centres in technical areas on which relevant information could be generated for use by PPWG or ECDD, Each Collaborating Centre is a source of candidates for consultants and for members of PPWG and ECDD. 4.3 Expert Panels The Group examined the role of WHO Expert Panels in the Review Process. The need to have as members scientists of international standing selected from among disciplines such as behavioural science, pharmaceuticals, pharmacology, medical, biological and epidemiological sciences, public health and administration was emphasized, The participation of experts in other fields which may be relevant to the review process was also suggested when appropriate. 4.4 Programme Planning Working Group The PPWG will make recommendations about; i) Long-range plans of the WHO Review of Dependence Producing Psychoactive Substances. ii) Procedures used in the review of psychoactive substances. iii) Establishment of Ad-hoc groups, involvement of consultants, support of development of collaborating centres or other matters concerning the infrastructure for the conduct of activities relevant to the review process at national and international levels. iv) psychoactive substances for review by ECDD in the following year(s). v) Acceptability of the background documents and Critical Review of substances for review by the ECDD, The PPWG will meet annually. The terms of reference of the PPWG were discussed and criteria for selection of substances for the PPWG meetings were agreed upon. 4,5 Procedural Steps in the Review Process Preparation of the sununary review leading to WHO's reconunendation on control of psychoactive substances should proceed sequentially as shown in the following diagram; MNH/PAD/84.2 Page 10 DIAGRAM I. - SEQUENTIAL PROCEDURE FOR PREPARATION OF WHO RECOMMENDATIONS ON INTERNATIONAL CONTROL OF PSYCHOACTIVE SUBSTANCES WITH TIME-SCHEDULES AND ASSIGNMENT OF RESPONSIBILITIES Time Schedule Responsible Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 St<!p 10 Step 11 Step 12 * February March August Sept (end) Sept/Oct/Nov December Feb/March Apr i l April April May May/June Identification of substances Request for information Information received Information organized and categorized Information critically reviewed and a draft Critical Review produced Draft Critical Review Sent to PPWG, Industry and relevant parties Decision on completeness and quality of Critical Review Supplementary information, if any added Critical Reviews sent to ECDD members Meeting of ECDD to produce Recommendations accompanied by a +Summari Review (each substance) provided to DG Report of ECDD prepared and submitted for publication* Recommendations to SG PPWG Sec Sec Sec Sec Sec PPWG PPWG/Sec Sec ECDD DG The Report contains the Recommendations, with relevant summary reviews as well as any other comments and findings. ' ' MNH/PAD/84.2 Page 11 The steps to be followed in the above procedure are described below: Step 1) During the PPWG meeting substances will be identified for review Step 2) The Secretariat is responsible for requesting, collecting and organizing the information for each substance from all relevant sources. Step 3) To receive information Step 4) Ideally and where feasible, the data should be organized for each substance under the following categories of information. 1. Substance Identification International Non-proprietory Name (INN) Chemical or other common name Identification characteristics, Chemical Abstract Service (CAS) Registry Number 2. Chemistry 3. General pharmacology 4. Toxicology - including adverse reactions in humans 5. Pharmacokinetics 6. Dependence potential 7. Nature and magnitude of public health and social problems 8. Epidemiology of drug use and abuse 9. National control 10. Therapeutic usefulness 11 Production, consumption, and international trade 12. Illicit manufacture and illicit traffic and related information It is realised that not all of these categories of information can be covered in all instances or to the same extent. For example, it may not be possible to cover categories (4), (5), (7), (8), (10), (11) for new hallucinogenic substances. Indeed, the concept of generating certain data in such circumstances may not be justifiable on ethical grounds. Likewise, extensive epidemiological data may not be available. Thus in such instances, the ECDD may have to base its decisions primarily on preclinical data. Step 5) The Secretariat should prepare a draft Critical Review to be sent to the PPWG, pharmaceutical industry and other relevant parties for review and comments. The information under each heading, with salient references should be limited to that which is essential and consistent with the need to facilitate the review by PPWG. Care must be exercised in preparing the Critical Review so as not to include data which may be sensitive or otherwise damaging to its source, and every effort should be made to respect the confidentiality of information when so requested. Step 6) The draft should be submitted to PPWG, industry and relevant parties at least two months prior to the February/March meeting of PPWG. MNH/PAD/84.2 Page 12 Step 7) PPWG should examine the critical review for such characteristics as clarity, accuracy, completeness and utility for recommendation-making. PP~ should have access to all information collected by the Secretariat and may incorporate such information into any possible revision of the critical review. Step 8) Once approved by PPWG the Critical Review should be made available to ECDD. A reasonable period of time between steps 7) and 10) should be available to permit adequate review. Step 9) Critical Review transmitted to members of ECDD. Step 10) ECDD will; evaluate the critical review and comments received - prepare a Summary Review and Reconnnendation for each substance Step 11) The summary review and recommendations will be submitted to the Director-General. Step 12) The recommendations of the D.G. will be transmitted to the S.G. 4.6. Criteria for selection of substances for review One of the important tasks for the PPWG is to select substances for review by WHO and to assign priorities to the group of drugs listed. The guidelines document formulated by the Group also discusses criteria for selecting these drugs, taking into account that WHO will have one expert committee a year. Besides, there are considerations such as the wishes of the governments and in particular, those who are parties to a relevant treaty; the wishes of Member States expressed during the UN Commission on Narcotic Drugs; and the fact that a drug or a class of drugs may have created public health and social problems warranting review by WHO. If a Government provides a notification which identifies an abuse problem of extreme urgency which requires immediate international action, the evidence will be reviewed at the next PPWG meeting to determine whether ECDD should consider the substance as a matter of high priority. 5.0 Special Issues 5.1 Conflict of Interest Members discussed the issue of conflict of interest at some length. It was pointed out that Expert Committee members might have vested interest both for and against drug control. Such issues as contracts for research, interest in advancing personal hypotheses or theories, simultaneous membership in scientific evaluations and policy deciding groups, and even employment by a drug control agency or industry have the potential for generating external perception of conflict of interest. The group felt that it was not possible to eliminate all such perceptions since they are based on subjective factors. It was decided that to minimize potential criticism and allegations of partiality, members of both PP~ and ECDD should be requested to sign statements confirming that there is no conflict of interest in their participation in the review of a specific substance or in the general activity. 5.2 Confidentiality The issue of confidentiality of data was raised by several participants. Release of sensitive or otherwise confidential data may prove injurious to its source. Moreover, the potential release of information could present a barrier to data collection as parties would refrain from submitting relevant documents. To avoid this problem it was suggested that requests for confidentiality should be honoured to the maximum extent possible and feasible. Member States, of course, cannot be denied access to any documents. As for access by other interested parties, confidential information could be screened or re-arranged so as to protect the source at the time the Critical Review is prepared by the Secretariat. Thus this document should be prepared as if it was a public document. , ' MNH/PAD/84.2 Page 13 5.3 Provisional Control In reply to a query from the Chairman relating to the provisional control of substances under the international drug control treaties, Mr Ramos Galino stated that to speak of a system of provisional control of substances under the treaties was not really justified. No such provisional control system had been established either under the Single Convention on Narcotic Drugs, 1961 or the Convention on Psychotropic Substances, 1971. What had been established under both Conventions was the obligation for States Parties to consider the possibility of provisionally applying to a given substance all measures of control applicable to Schedule I in the 1961 Convention or those applicable to Schedule I or II as appropriate in the 1971 Convention. This was contemplated under the treaties only following receipt by the Secretary-General of a notification for scheduling either from a State Party or from WHO. The legal provisions governing this question were not exactly the same under the two conventions. Thus under the terms of article 3, para (3) of the Single Convention, the Parties following receipt of a notification relating to a substance not already in Schedule I or II shall examine in the light of the available information the possibility of the provisional application to the substance of all measures of control applicable to drugs in Schedule I. Furthermore, the Connnission on Narcotic Drugs, pending its decision on scheduling may decide that the Parties should apply provisionally to that substance all measures of control applicable to drugs in Schedule I. This decision of the CND is mandatory on all Parties to the Single Convention. Under the 1971 Convention, upon receipt of a notification for inclusion of a substance in Schedule I or II, the Parties are obliged to examine the possibility of the provisional application to the substance of all measures of control applicable to substances in Schedule I or II as appropriate. Moreover, it would seem that the provisions of these Conventions are quite adequate to meet any emergency situation which might arise with regard to any given substance. Should an emergency arise, either a Party or WHO can notify the Secretary General who in turn would notify the Parties, thus making it necessary for the Parties to consider the possibility of provisional control. 6.0 Future Review Activities The Group next considered the review act1v1t1es to be carried out by WHO in the next year. It was agreed that the Amphetamine-type stimulant and hallucinogenic substances should be reviewed. A number of such substances were suggested for this review (Annex 2). It was noted that many of these substances had no recognized medical usefulness and that there was evidence of public health and social problems resulting from their abuse in various regions of the world. It was for this reason that this group of drugs was selected for review in 1985. A tentative list of classes of substances which would need review in the future was also drawn up by the Group. These include; -Barbiturates not currently controlled Congeners of THC and related synthetic substances. -Mixed agonist-antagonist analgesics -Anxiolytics and sedative-hypnotics (non-barbiturates) not currently controlled. -Exempted preparations It was recognized that notifications by Member States and unforeseen emergencies caused by specific substances may have to take precedence over the substances scheduled for review on a long term progrannne. Nevertheless, such long-range planning allows the initiation of data collection far enough in advance to develop the comprehensive data base for decisions. MNH/PAD/84.2 Page 14 7.0 Special Agenda Items for the Second PPWG The Group decided that working papers on the following issues should be prepared so that they can be presented to the PP~ at the next meeting: 1. Collaboration in data collection by UNDND, Interpol and WHO. 2, Classes of drugs to be reviewed by WHO in future. 3. Exempted preparations and the role of WHO. 4. The impact of scheduling psychoactive substances on the practice of medicine S. Ways of stimulating epidemiological investigations regarding use and abuse of psychoactive substances to facilitate WHO's decision-making process. 6. The practical problems relating to the long-term storage of information used in the review process. 8.0 Agenda for Expert Committee on Drug Dependence The Group drew up a tentative agenda for the 22nd meeting of the Expert Committee on Drug Dependence scheduled for 22-27 April 1985 (see Annex 3), and a list of 28 substances for review 10. RECOMMENDATIONS Finally, the Group agreed on the following two recommendations~ 1. Since reliable data on the public health and social problems caused by psychoactive drugs are essential to the WHO Review, efforts must be made to improve national epidemiological studies. With this aim WHO and DND should discuss how they, individually or in collaboration, might support national health authorities to increase the quality and scope of ongoing studies on the epidemiology of drug abuse, and to initiate new studies in other countries. 2. It is important to consider the relation of national drug control to the scope of control of the Conventions. A number of psychoactive drugs registered for medical use in a country, and a number of those used only with a physician's prescription, are in most countries not yet included in the schedules of the Convention. Some of the drugs nationally controlled are those likely to produce public health and social problems in the future. Information as to changes in national control from year to year would be a valuable input to WHO's Review in its screening phase. The WHO regional offices should compile and annually update a list of controlled psychoactive drugs in the contries of their regions indicating the level of control for each of them. 3. The paucity of data on the dependence potential of newly marketed therapeutic agents has rendered the task of WHO psychoactive substances review groups very difficult. It is rather anomalous that sufficient data appears to be available to allow registration and national scheduling of these compounds while similar information is lacking for international drug control purposes. The Group considers that it would be advisable for national regulatory authorities to formalize requests for dependence potential data within their new drug reeistration process. Failing that it would seem equally advisable to exercise caution and prudence in ascribing levels of controls to such new drugs. Thus the Group asks the DG of WHO to share this concern with member countries. 4. The Panel on Drug Dependence and Alcohol should be revised and enlarged. ( ' • MNH/PAD/84.2 Page 15 LIST OF PARTICIPANTS 1. Dr D.B. Bisht, Director-General of Health Services, Government of India, New Delhi 11011, India. (Vice-Chairman) 2. *Dr Smail Bouzer, Deputy Director of Pharmacy, Ministry of Public Health , Algiers, Algeria Annex l 3. *Mr Neil A. Boyer, Agency Director, Health and Narcotics Progra11Dnes, Bureau of International Organization Affairs, Department of State, Washington, D.C. 20520, USA 4. 5. Dr V.M. Bulaev, Deputy Chief, Department for the Introduction of New Drugs and Medical Technology, Ministry of Health of the USSR, Rahmanovskij per. 3, 1011431 GSP Moscow N-51, USSRl Professor E.A. Carlini, Department of Psychobiology, Paulista School of Medicine, Rue Botucatu 862 - 1 Andar, 040233 Sao Paulo SP, Brazil. 6. *Mr Mairaj Husain, Chaiman, Pakistan Narcotics Control Board, Islamabad, Pakistan, and Vice-Chairman UN Commission on Narcotic Drugs 7. Dr A. Lafontaine, Directeur honoraire de l'Institut d'Hygiene et d'Epidemiologie, Ministere de la Sant~ publique et de la Famille, rue Juliette Wytsman, 14, 1050 Brussels, Belgium 8. Dr Jacques G. LeCavalier, Director, Bureau of Dangerous Drugs, Health Protection Branch, Ottawa, Canada 9. Dr O. Ogunremi, Professor of Behavioural Sciences, Faculty of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, Nigeria 10. Professor Bror Rexed, Thomas Heftyes Gate 14C, Oslo 2, Norway (Chairman) 11. Dr C.R. Schuster, Director, Drug Dependence Research Centre, Department of Psychiatry, University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA (Rapporteur) 12 Dr T. Yanagita, Director, Preclinical Research Laboratories, Central Institute for Experimental Animals, Kawasaki, Japan REPRESENTATIVES OF OTHER ORGANIZATIONS United Nations Division of Narcotic Drugs Mr P.K. Bailey, Chief, Treaty Implementation and Commission Secretariat Section , United Nations Division of Narcotic Drugs, Vienna International Centre, Vienna, Aus tr i a International Narcotics Control Board Mr A. Bahi, Secretary, International Narcotic Control Board, Vienna International Centre, Vienna, Austria International Criminal Police Organization Mr Walter J. Leamy, Head, Drugs Sub-Division, International Criminal Police Organizat ion, 26 rue Armengaud, Saint-Cloud, France. Mr Helge De Fine, Specialist Officer, Drugs Sub-Division, International Criminal Police Organization, 26 rue Armengaud, Saint-Cloud, France MNH/PAD/ 81+. 2 Page 16 International Council on Alcohol Addiction Dr Eva Tongue, Deputy-Director, International Council on Alcohol Addiction, Case postale 140, 1001 Lausanne, Switzerland International Federation of Pharmaceutical Manufacturers Associations Dr R.B. Arnold, Executive Vice-President, International Federation of Pharmaceutical Manufacturers Associations, rue de St-Jean 67, 1201 Geneva, Switzerland Miss Margaret Cone, Vice-President, International Federation of Pharmaceutical Manufacturers Associations, rue de St-Jean 67, 1201 Geneva Switzerland. International Organization of Consumers Unions Dr A. Herxheimer, Department of Phamarcology, 12th Floor, Laboratory Block, Charing Cross Hospital Medical School, London W6 8RF, England. WHO COLLABORATING CENTRES National Institute of Drug Abuse Dr James Cooper, Assistant Director for Medical Affairs, National Institute of Drug Abuse, Department of Health and Human Services, 5600 Fishers Lane, Rockville, Maryland 20857, USA *Addiction Research Foundation, Toronto, Canada *Instituto Mexicano de Psiquiatria, Mexico *Health Research Institute, Chulangkorn University, Bangkok, Thailand *National Drug Dependence Clinical Research Centre, Universiti Sains, Penang, Malaysia WHO SECRETARIAT Dr A. Arif, Senior Medical Officer in charge of Drug Dependence Programme, Division of Mental Health, WHO, Geneva, Dr Michael c. Gerald, Consultant, Division of Mental Health, WHO, Geneva Mr T. Ito, Pharmacist, Division of Mental Health, WHO, Geneva Dr Inayat Khan, Senior Medical Officer, Division of Mental Health, WHO, Geneva (Secretary) Dr Norman Sartorius, Director, Division of Mental Health, WHO, Geneva Dr B. Sankaran, Director, Division of Diagnostic, Therapeutic and Rehabilitative Technology, WHO, Geneva Dr J.F. Dunne, Chief, Pharmaceutical Unit, WHO, Geneva Mrs M. Helling-Borda, Senior Scientist, Programme on Essential Drugs, WHO, Geneva Mr D. Devlin, Senior Legal Officer, Office of the Legal Counsel, WHO, Geneva Mr D.C. Jayasuriya, Attorney-at-Law, 40/12 Swarnadisi Place, Nawala, Sri Lanka (Temporary Adviser) * Invited but unable to attend ' • 1. 2 3. 4. 5. 6. 7. 8. 9. 10. 11. LIST OF BACKGROUND DOCUMENTS "Action in Respect of International Conventions on Narcotic Drugs and Psychotropic Substances" (Report of the DG to EB73) - ditto - Resolution on EB73/19 (Agenda Item 15) Provisional Sunnnary Record of the 12th Meeting of EB73 Provisional Summary Record of the 13th Meeting of EB73 Provisional Summary Record of the 15th Meeting of EB73 The New Procedures for the Review of Psychoactive Drugs with Dependence Liability by WHO - Guidelines for Future Action by Bror Rexed et al The Eighth Special Session of the United Nations Connnission on Narcotic Drugs ; Report by Dr Inayat Khan Guidelines for the Exemption of Preparations Under the Provisions of Article 3 of the 1971 Convention by Dr. Khan Consultation on the Convention on Psychotropic Substances; Review of Articles 3 and 10 WHO Consultation on Development of Further Guidelines for the Exemption Preparations under Article 3 of the Convention on Psychotropic Substances 1971 12. Provisional Control of Substances under the 1971 Convention on Psychotropic Substances - Considerations for National Governments and International Agencies - by Dr Inayat Khan and Mr D.C. Jayasuriya 13. Selection of Psychoactive Substances for WHO Review by Dr I. Khan 14. Selection of Psychoactive Substances for WHO Review by Dr C.R. Schuster 15. Review of Uncontrolled Amphetamines for Provisional International Control by Dr Michael C. Gerald 16. "Note for the Record" of Discussions between Dr Khan and Representatives of IFPMA dated 22/2/84 17. Statement by IFPMA dated 14/3/84 18 Copy of Letter from Dr V. Navaratnam of Penang, dated 1/3/84 19. Report Compiled by UNDND for Use at the AD HOC WHO Review of Psychoactive Substances for International Control, 17 March 1984 WHO REFERENCE DOCUMENTS 1. Guidelines for the Review of Psychoactive Substances 2. Eighth Review of Psychoactive Substances for International Control MNH/PAD/84.2 Page 17 Annex 2 EB73/19 EB73/19.Add.l EB73 .Rll EB73/SR/12 EB73/SR/13 EB73/SR/15 MNH/PAD/83.3 MNH/PAD/84.6 MNH/PAD/84.8 MNH/78.1 MNH/82.51 MNH/PAD/84.9 MNH/PAD/84 .10 MNAR/1984/4 MNH/83.13 MNH/83.28 MNH/PAD/84.2 Page 18 DRAFT AGENDA FOR THE 23ND EXPERT COMMITTEE ON DRUG DEPENDENCE 22-27 APRIL 1985 I. Welcoming Remarks II. Introduction III. Review of Substances 1. Drugs to be reviewed: see Annex 1 2. Chemistry, preparations and availability in different countries 3. Basic pharmacology and toxicity: i. Spectrum of action: Isolated organs, CNS, cardiovascular and respiratory systems, tolerance, physical dependence, antagnoism studies, etc. ii. Toxicity: acute and chronic 4. Behavioural pharmacology: i. Profile of behavioural effects compared to amphetamine ii. Self-administration studies iii. Drug discrimination studies 5. Clinical pharmacology: L. Human pharmacology and toxicology compared to amphetamine ii. Dependence potential in man: physical and psychological iii. Therapeutic efficacy 6. Public health and social consequences: i. Extent and pattern of consumption and utilization ii. Abuse liability iii. Public health problems iv. Social problems v. Information from WHO regional offices and countries vi. Data from INTERPOL vii. Data from the United Nations Division of Narcotic Drugs viii. Data from DEA (USA) ' • 7. Decisions regarding control of individual drugs; i. The need for control ii. Under what Convention should the drug be controlled? iii. Degree of control warranted IV. Consideration of Future Programme V. Notification if received from the Secretary-General of the UN VI. Any other matter for consideration MNH/PAD/84.2 Page 19 MNH/PAD/84.2 Page 20 Annex 4 List of Substances for Review by the 22nd Expert Connnittee on Drug Dependence 1. Cathine (norpseudophedrine) 2. Cathinone 3. Clobenzorex 4. Dimethoxyamphetamine 5. Dimethoxybromoamphetamine (DOB) 6. Etilamfetamine (ethylamphetamine) 7. Fenbutrazate 8. Fencamfamine 9. Fenetylline 10. Fenproporex 11. Furfenorex 12. Levamfetamine 13. Levomethamphetamine 14. Mefenorex 15. Methoxyamphetamine (PMA) 16. Methylenedioxyamphetamine (MDA) 17. Morazone 18. para-methoxyamphetamine 19. Pemoline 20. Propylhexedrine 21. Pyrovalerone 22. Trimethoxyamphetamine (TMA) 23. 4-Bromo-2,5-dimethoxyphenethylamine 24. 2,5-Dimethoxy-4-ethylamphetamine (DOET) 25. N,N-Dimethylamphetamine (dimetamfetamine) 26. N-Ethyl-3,4,Methylenedioxyamphetamine (N-Ethyl-MDA) 27. 5-Methoxy-3,4-methylenedioxyamphetamine (MMDA) 28. 3,4-Methylenedioxymethamphetamine (MDMA)