Drugs in medicine [full issue]

WORLD HEALTH THE MAGAZINE OF THE WORLD HEALTH ORGANIZATION • DECEMBER 1985 Drugs in medicine ' Cover: A chemical structure in stylised form. Design by Peter Davies IX ISSN 0043-8502 World Health is the official illustrated magazine of the World Health Organization. Editor : John Bland Deputy Editor : Christiane Viedma This Issue's Theme Editor: Diana Gibson Art Editor : Peter Davies News Page Editor : Peter Ozorio World Health appears ten times a year in English, French,.German, Portuguese, Russian and Spanish, and four times a year in Arabic and Farsi. Articles and photographs not copyrighted may be repro- duced provided credit is given to the World Health Organization. Signed articles do not necessarily reflect WHO's views. World Health, WHO, Av. Appia, 1211 Geneva 27, Switzerland. Ph ot o W H O /C . St au ff e r harmaceutical innovation has transformed the practice of medicine in the industrialised world within the lifetime of a single generation of clinicians. Less than 50 years ago, no specific treatment existed for the bacterial infections. Tuberculosis, syphilis and rheumatic heart disease were rampant in count- less large cities ; erysipelas and scarlet fever were potentially lethal diseases ; anaesthesia was rudimentary and many patients who underwent elec- tive surgery were consigned to septic wards with serious postoperative in- fections. There were no effective drugs to treat hypertension or the oedema of cardiac failure. Mentally disturbed patients were likely to be committed to an institutional life in perpetuity. All this and much more has changed dramatiCally for the better, and furth- er advances are in prospect. Promis- ing progress is being made in vitally important fields including cancer chemotherapy, antiviral chemothe- rapy and immunosuppressive therapy, and on many other fronts. In the more distant future, the striking advances now being made in the biosynthesis of highly complex peptides and proteins seem clearly destined to open up new vistas in therapeutic fields as diverse as vaccine development and psychi- atric medicine. As the simpler thera- peutic challenges are met, however, the pace of advancement that fol- lowed the application of synthetic organic chemistry to therapeutic medicine is unlikely to be sustained, and cost may become a decisive deter- minant of progress. Very large sums of high-risk capital are invested in the development of new drugs and the research-based com- panies that undertake the work need, in the interests of corporate survival, to consider the eventual return on investment. The result is that consider- able activity has been focused on the major health problems of affluent WORLD HEALTH, December 1985 societies, while diseases of major im- portance, endemic in the developing world, hive been neglected by de- fault. The routine management of filariasis, onchocerciasis and trypa- nosomiasis remains much as it was 40 years ago. The prevalence of malaria has probably doubled over the past decade, as both the parasites and the vectors have developed resistance against the available drugs and insecti- cides. Conditions such as measles and the diarrhoeal diseases, which rarely result in death in affluent countries, remain major causes of mortality among infants in developing countries. The need to foster socially orien- tated approaches to new drug devel- opment is also appreciated now in developed countries, where it has be- come evident that research on a drug intended to capture a share of an established market may hold more attraction than a bolder venture into innovation. Duplicative research with- in competing companies draws critic- ism for being ill-adapted to global therapeutic needs. The thesis that molecular manipulation not infre- quently offers dividends in terms of improved therapeutic performance is a valid but vulnerable argument. Large numbers of essentially inter- changeable marketed products render effective therapeutic comparison im- practicable. They create a situation in which therapeutic choice is deter- mined by advertising pressure rather than by objective evidence and, in the longer term, threaten to frustrate evalu- ation of therapeutic performance. Times are hard, but the recent emergence of AIDS and legionnaire's disease in the highly developed world serves as a salutary reminder that disease will never remain a static target. Innovative potential must be encouraged, but every practicable in- itiative should be explored to ensure that the development of new drugs is aligned as closely as possible with real health needs. ■ Contents A moving target by John Dunne 3 Advantages of an EDL by A. W. El-Borolossy 4 The naming ceremony by Robert Moreau 7 Quality control — think small by James Y. Binka and Witold Wieniawski 10 A bestseller for WHO? by C. A. Johnson and Andrei Mechkovski 14 Centrespread : Drugs in medicine . 16 An importer's guarantee by Agathe Wehrli 18 Safety first by Kjell Strandberg 21 A vital service by Bengt 0. Ohrner 23 How medicines are controlled by Norman M. Hale 24 Fore-warned is fore-armed by John Dunne 26 • Departments: Appropriate Technology 13 Education and Training 15 Books and Publications 28 News Page 30-31 A moving target by John Dunne Advantages of an EDL Adoption by countries of an Essential Drug List (EDL) brings scientific, educational and economic benefits, especially in conjunc- tion with the advisory services offered by WHO and other UN agencies by A. W. El-Borolossy ou have to be a citizen of the Third World to grasp the import- ance of an Essential Drug List (EDL). In many Third-World coun- tries, where physicians are in short supply, most health care is obtained from traditional healers or by self- medication. The medicines available are nearly all imported; vast quan- tities of them, not necessarily related to the community's needs, are thrown onto the market with little information about their proper use, leaving the field open for the sometimes unwar- ranted promotional activities of the manufacturing firms. This in turn cre- ates more unjustified demand for drugs, draining most of the meagre budget available for the health services. Some developing countries have an established system of health care de- livery, a national health policy and even a drug policy governing the pro- curement, control, distribution and use of medicines. However, others do not, and the availability of drugs and vaccines may be erratic. Many Third- World countries, therefore, require a system whereby drugs essential for the prevalent diseases become available at a reasonable cost whenever they are needed. This is not a purely technical matter concerned only with the choice of drugs : in many instances, there is a lack of experience in quality assu- rance, procurement procedures, and proper storage and drug distribution facilities. In 1975, the World Health Assem- bly debated the main problems facing the developing countries in securing the essential drugs required for their 4 WORLD HEALTH, December 1985 particular health problems. Con- troversy broke out between the Third- World countries — eager to seek help in drawing up an EDL relevant to their needs — and the major drug producers, who thought that a list would limit the number of drugs circulating in the international market, leading to a fall in profits. The following year, a WHO commit- tee drew up guidelines for establishing an EDL : the response of WHO Member States and several nongovernmental organizations then allowed WHO to draw up and publish the first WHO Model List of Essential Drugs in 1977. It has since been revised and updated every two years, on the last occasion in 1985 (see page 28). In most small developing countries nearly all medicines are imported; supplies may be erratic. Photo WHO/M. Jacot The guidelines are flexible enough to allow each Member State to use the EDL as appropriate for health prob- lems and the health care delivery system. WHO's Model List is taken as an example which can be modified by additions or deletions ; different drugs may be substituted if they make for greater efficacy or a more favourable cost/benefit ratio. One country, to take an example, set up a technical drug committee com- prising physicians, pharmacists and pharmacologists whose task was to suggest, on the basis of the Model List, a drug list for each level of health care delivery. Three lists have been drawn up. The first is for use in primary health care centres, with 100 generi- cally named drugs to be prescribed by the general practitioner managing that centre. The second list contains 160 generic names for the more corn- prehensive health centres, where some specialist advice is available. The third list, containing 200 generic sub- stances, is intended for use in the general hospitals where consultants and more advanced diagnostic units are to hand. For comparison, the num- ber of trade-marks registered in that country and sold in community phar- macies amounts to 1,850 items, pre- sented in 2,800 pharmaceutical forms ! In some places, the Model List has been used as the basis of a National Drug Formulary, a task made easier by the "information sheets" prepared by WHO on drugs listed in the EDL. These sheets contain the basic, concise and accurate pharmacological and therapeutic information needed by the treating physician and other members of the health team. The Action Programme The WHO Action Programme on Es- sential Drugs and Vaccines helps less developed countries to utilise the Model List : in association with UNICEF, WHO responds to requests from Mem- ber States for procurement of drugs contained in the list at a very reason- able cost, much lower than the market price. Moreover, the two agencies en- courage group purchasing, which further reduces prices. An experiment in group purchasing with obvious ad- vantages in terms of cost has been under way for several years in the Gulf States. The Action Programme provides, in addition, other useful services in the drug field, including helping Member States to formulate their National Drug Policies, assure the quality of imported drugs and train personnel. wHo has also, through its Certification Scheme, been active in helping de- veloping countries which lack quality control facilities to ensure the quality of imported products. Other UN agencies cooperate in ex- panding the services provided through the Action Programme. UNCTAD and UNIDO, for example, are offering their expertise in technology transfer and in other areas of local pharmaceutical production. A further development arising from use of the Model List is the encourage- ment to use generic names of drugs WORLD HEALTH, December 1985 The midwife discusses patient records with her trainee during a home visit in Yemen (above) ; below, praziquantel tablets provide a one-dose cure for schisto- somiasis. Third-World countries need a system including quality assurance, procure- ment, storage and distribution to make essential drugs available for local conditions at reasonable cost. Photos WHO/M. Jacot _ ,cout,t1,,t SILFADIMIDINE BP KG rern t NNE Phas CHLOROQUINE Phosphate 40 mg ml B.P. IChlaroquirunni Establishment of local quality con- trol facilities to guarantee safety and efficacy of drugs. In some cases, regional cooperation may be estab- lished. Improvement of systems of pro- curement, storage and distribution of drugs, to ensure ready availabil- ity at the lowest cost. Encouragement of local production of pharmaceuticals, within the framework of the National Drug Policy, starting with simple formu- lations which may gradually be de- veloped as feasible. Some Third- World countries already produce over 80 per cent of their drug consumption ; some have also intro- duced production of certain phar- maceutical chemicals and packaging materials. Promotion of research capabilities in various pharmaceutical, phar- macological and clinical fields. Sim- ple pharmaceutical research in- cludes investigation of the stability of dosage forms under local weath- er conditions, and the most suitable and economic packaging. Phar- macological research includes as- pects of drug behaviour in the body, effects and adverse reactions. Clini- cal research requires the coopera- tion of clinical pharmacologists and clinicians to evaluate the therapeu- tic effects and cost/benefit ratio of drugs when used by the local popu- lation under specific genetic and environmental conditions. Experience so far with the Model List has been more than gratifying : the advantages are scientific, educa- tional and economic. On the scientific and educational side, an EDL leads to a more rational use of drugs and facilitates the production of a national drug formulary. On the economic side, an EDL reduces expenditure on medicines, avoids drug misuse, en- courages local production of phar- maceuticals, and increases the propor- tion of the health care budget that can be devoted to other items. Already, a large number of Third- World countries have their own EDLs ; many of them have national formularies, and some are enjoying certain of the above-mentioned ad- vantages. To say the least, the concept of the EDL has been widely accepted, the Action Programme has been well utilised and the rational use of drugs has been gaining ground. ■ Generic drug names are used in WHO's Model 2. List of Essential Drugs and for national essential drug programmes. They make it easier to recognise a drug, and to procure it at a favourable price. Photo WHO/T. Farkas 3. instead of trade-names. A generic name is an approved official name for a certain chemical entity ; it relieves the user of the need to memorise a 4. multitude of trade-names for the same drug. It also facilitates, to a great extent, the work of procurement of- ficers, enabling them to choose the best available medicine at the most reasonable price ; and it largely re- lieves the pressures exerted by manu- facturers at the moment of tender. Benefits for countries The extent to which a country is 5. able to use the Model List and benefit from the Action Programme depends largely on its stage of development. At least some, if not all, of the following advantages should be obtainable : 1. Assistance in formulating a Nation- al Drug Policy which satisfies the needs of the national health policy and reflects the country's socio- economic conditions. 6 WORLD HEALTH, December 1985 The naming ceremony INNs are simplified, universal names for chemical substances that make it easier for professionals and public alike to identify drugs and use them with safety. Obligatory in some countries, INNs are increasingly used for generic purchasing and prescribing by Robert Moreau A s X suffers from a chronic con-dition and her doctor prescribes a drug to be taken regularly. On going abroad, she fails to take a large enough supply with her. The drug she takes is sold under another name in the country she is visiting ; as she doesn't know that name, she cannot get hold of it. All this is because a drug's commer- cial name is a trade-mark, the exclu- sive property of a given pharmaceuti- cal manufacturer ; the same drug is nearly always sold under a different name in different countries, and often under several different names in the same country. So Ms X may well be at some risk, which could be avoided if her drug had only one name, freely usable and known throughout the world. Such a name does in fact exist : the systematic chemical name, standar- dised by international bodies. How- ever, although this has the merit of clearly defining a precise chemical substance, it is very difficult to use in medical practice. It is usually long, sometimes several lines long ; it means practically nothing to non-chemists ; and it gives the prescriber no indica- tion of the drug's therapeutic activity. Because of these difficulties, WHO launched a programme in the 1950s designed to identify every phar- Confusing for consumers: drugs tend to be sold under a different name in each country —often they have several different brand names in the same country. Photo WHO/A. W. El-Borolossy maceutical substance by a single, com- mon, universal term : the international nonproprietary name (INN). The first step was to establish a procedure, that came into force in 1955 and is still in use today, for assigning international nonproprietary names to drugs, in collaboration with the pharmaceutical industry, trade- mark registration offices, and the legal division of WHO. As a rule, pharmaceutical manufac- turing laboratories submit their appli- cations to WHO through the national nomenclature authorities, on applica- tion forms giving all the information required : the brand name, chemical name, molecular structure and thera- peutic category. WHO then submits these applications to Members of the Expert Advisory Panel of the Inter- national Pharmacopoeia and Phar- maceutical Preparations. These mem- bers come from various countries (cur- rently from the Federal Republic of Germany, France, Indonesia, Japan, WORLD HEALTH, December 1985 The naming ceremony Left : Contents of a village pharmacy in Niger. The INN (international nonpropri- etary name) is a true generic name. It distin- guishes one drug from another, and shows its relationship to a pharmacological group— unlike a brand name, which gives no such information. Right : A Guatemalan health worker gives contraceptive advice in her living-room clinic. INNs are only recommended by WHO, not enforced—but they are gaining favour with international bodies and governments for use in conventions, pharmacopoeias and essential drug lists. Photos WHO/R. da Silva and J. Matthews/Format © Nigeria, Poland, the United Kingdom, the United States of America and the USSR). The experts, following well defined general principles, examine the proposed name, make corrections to it or, if appropriate, put forward a better name. Once the name has been accepted by all the experts, it becomes a "proposed INN", and is widely publicized through the WHO Chronicle and by letters to Member States. During the next four months com- ments may be sent to WHO, for exam- ple if the proposed INN sounds too much like an existing trade-mark. Should an objection be raised, WHO may intervene to attempt to have it withdrawn, or may submit the dis- puted name to re-examination. In the absence of any objection, the prop- osed INN becomes a "recommended INN " and is once again publicized through the same channels. Two basic principles are involved in the recommendation of an INN. The first is that it should be clearly distin- guishable from other INNs in both sound and spelling, should not be inconveniently long and should not be liable to confusion with names already in common use. The second principle is that if the substance is one of a pharmacologically related group, the INN should so far as possible show this relationship, but be free from any anatomical, physiological, pathologi- cal or therapeutic suggestion. The second principle involves the presence of a "stem" common to the names of substances that are chemical- ly or, especially, pharmacologically related. For example, the INNs of all hypoglycaemic sulfonamides have to begin with gli- (glibenclamide, glicla- zide, gliquidone, glisoxepide) while those of antibiotics derived from penicillin must end in -cillin (azlocillin, cloxacillin, meticillin, ticarcillin). An INN indicating that a substance be- longs to a particular group in this way becomes a true generic name, as op- posed to a trade-mark, which conveys no such information. The spelling of INNs should also be simple, so as to make them easy to pronounce and to translate. At the outset, INNs were formed primarily by the contraction of their chemical names or by reference to structural features, which often led to long and unpleasant-sounding names. Nowadays, apart from the the obliga- tory key stem, there is no longer any 8 WORLD HEALTH, December 1985 directive for selecting the rest of the name, the primary requirement being that the different INNs of the same group should be well distinguished. As a result the names adopted are easier to pronounce and better adapted to the prescribing of generic drugs. INNs versus trade names One of the main reasons for possibly not adopting an INN is that it may clash with a trade name, which neces- sitates a very meticulous search, ini- tially by the applicant at the time of submitting the request, then by the national nomenclature authorities, and subsequently by each expert in the course of the adoption procedure. The publication of proposed INNs pro- vides an opportunity for final verifica- WORLD HEALTH, December 1985 tion ; at this stage, any disagreement may give rise to an " objection ". The WHO procedure allows for op- position by the pharmaceutical indus- try to the adoption of INNs that close- ly resemble a trade name, even if they are not exactly the same. The opposite does not apply, since the only protec- tion possessed by INNs is against iden- tical trade names. This often leads to difficulties in the formulation of new INNs; WHO is therefore examining means of extending the protection of complete INNs to the key stems. WHO merely recommends that Member States should adopt INNs, but some Member States issue regula- tions making it compulsory to use them, especially on the labels of phar- maceutical dosage forms, side by side with the trade name, so that the drug is immediately recognizable by any- one, whatever trade name it carries. Recommended INNs have now been officially adopted for narcotics and for psychotropic substances cov- ered by the 1971 Convention. The Council of Europe and the European Economic Community stipulate their general use ; many pharmacopoeias do the same. Increasingly, the INNs are now used in the marketing and dis- tribution of generic drugs. WHO's programme on international nonproprietary names for phar- maceutical substances has gradually become more of a generally accepted agreement on the naming of drugs. Safety in use has undoubtedly been increased, and this in itself fully jus- tifies the active continuation of the programme. ■ 9 Quality control think small Even a small quality control lab, run by an analyst with only four or five technicians, can prevent potentially serious accidents by detecting poor quality, mislabelling or deterioration of drug products by James Y. Binka and Witold Wieniawski 13 ine-drinkers often go through the ritual of having the bottle opened in front of them and a small quantity of wine poured into the glass to taste— a connoisseur can dis- tinguish a bad wine from a good one. Most people can also tell whether or not there is salt in a soup. But it is much more difficult to tell the differ- ence between good and bad drugs. If given some capsules or an injection, for example, a patient has little or no chance of assessing whether the drug they contain is of acceptable quality. If a drug contains other chemicals such as breakdown products or conta- minants, poisoning can result. Or a dosage form may contain no drug at all, as recently detected in some of the West African countries, where cap- sules being offered for sale contained cassava starch and nothing else. In cases like these, the patient may get worse and have to attend the clinic again, obtaining a fresh prescription for a now aggravated condition. This chain of events causes extra health care expenditure, while endangering the health of the individual. Some episodes have occurred in our generation where the use of poorly evaluated drugs has led to national and international havoc. The contami- nated sulfonilamide incident in the USA in the 1930s and the thalidomide disaster of the 1960s are still in every- one's memory. These major events, which had devastating effects on peo- ple's lives, provoked international concern about the quality of commer- cial drugs. The World Health Organization re- sponded by providing materials and guidelines for the control of drug qual- ity. These include the International Pharmacopoeia (IPh), guidelines for Good Manufacturing Practices (GMP), which give recommendations for qual- ity control of drugs during their manu- facture, and the WHO Certification Scheme on the Quality of Pharmaceut- ical Products Moving in International Commerce, which provides an attesta- tion by the competent regulatory au- thority in the country of export that the drug in question has been pro- duced in accordance with GMP. The various measures are intended to ensure the availability of good- quality drugs. In developed countries, drugs are usually assessed for their efficacy, safety and quality before they are accepted for use by the popu- lation. Quality control surveillance is maintained by monitoring the quality of drugs in circulation, using sophisti- cated and expensive national quality control laboratories. However, the picture may be different in developing countries, where personnel and infra- structure are not available, or where there is no quality control for register- ing and testing drugs because develop- ing countries cannot afford expensive laboratories. How then can the quality of drugs manufactured in poor de- veloping countries, or imported by them, be guaranteed, bearing in mind that both the poor and the rich alike require good-quality drugs? Before we try to find a solution to the plight of developing countries The small-scale drug control lab tests pro- ducts for identity, potency and purity, in- cluding possible deterioration—and saves foreign exchange. Photo Roche WORLD HEALTH, December 1985 Quality testing in progress in Tanzania. How do poor-quality drugs enter developing countries? Sometimes through dishonest dealers who falsify the expiry date, through bad manufacture or mislabelling, or through exposure to high temperature and humidity. All such problems can be eliminated by quality control surveillance. Photo WHO/J. Hasfeldt without quality control systems, let us examine how poor-quality drugs can enter developing countries. The WHO essential drug concept is being adopted by many developing countries which are now limiting their drug purchases to a national essential drugs list of a little over 200. Due to their serious financial situation in the present economic recession, many of the developing countries go to inter- national tender in order to obtain good prices for the drugs they buy. In Africa, for example, Ghana, Tanzania and Liberia tender regularly, as does WORLD HEALTH, December 1985 Lesotho to a limited extent : the Carib- bean countries also do group purchas- ing on international tender. Such ten- ders are, of course, usually won by the suppliers offering the lowest prices. Poor-quality drugs may well be supplied to countries with limited quality control facilities. Wholesale drug companies are now springing up in Europe and America : sometimes drugs pass through the hands of about four dealers before they get to the final purchaser, the developing coun- try. In such a situation it can be difficult to obtain a wHo certificate from the quality control authority in the exporting country. A recent inves- tigation by the Lesotho drug au- thorities into the issue of the wHo certificate led to the discovery that some drugs they were importing had passed through about five dealers. Sometimes, a drug bought by the " middleman " may be near its expiry date (the end of the guaranteed effi- cacy period as recommended by the original manufacturer). But the mid- dleman may falsify the expiry date of the drug and sell it to a developing country at a very low price. Both imported and locally manufac- tured drugs can also deteriorate in storage, due to adverse environmental conditions. In the tropics, where most of the developing countries are lo- cated, warehouse temperatures can go as high as 50°C, or even more, during the hot season. High temperature and high humidity can speed up the break- down process of some drugs if they are not kept in air-conditioned premises. Misleading labels Another danger is that a manufac- tured drug may be wrongly labelled —for example, a sulfonamide drug designed to combat a bacterial infec- tion has been known to be labelled "paracetamol" (an analgesic). On the 11 other hand, a tablet or capsule may be so poorly manufactured that it passes straight through the patient's gut with- out being absorbed. Most of these problems leading to poor-quality drugs circulating in a country can be eliminated if com- prehensive quality control surveil- lance is maintained. A national quality control system should include : a drug registration scheme for all drugs enter- ing the market, regular inspection of drug manufacturing plants, and sys- tematic monitoring of the quality of drugs as they are distributed in the country. The small-scale lab To check the quality of drugs in circulation, a laboratory facility is a necessity. The report of the WHO Ex- pert Committee on Specifications for Pharmaceutical Preparations (wHo Technical Report Series, No. 704) con- tains a proposal for setting up a small- scale quality control laboratory, de- signed to enable developing countries with limited funds to have some small- scale drug testing. The equipment sug- gested is simple yet, used effectively, it is quite adequate for the majority of the quality tests for drugs indicated in the International Pharmacopoeia. The ideal would be for every coun- try to have a well-equipped national laboratory capable of performing all the tests required to assess the quality of the drugs people are taking. This is " crying for the moon " for some de- veloping countries ; yet it is amazing how much a model small-scale laboratory, as recommended by WHO, can do to prevent accidents. Some time ago a hospital pharmacist in an African country, preparing a syrup for children, used salt wrongly labelled sodium carbonate instead of sodium bicarbonate; reports from other coun- tries indicate that this incident, which claimed several victims, is not unique. A drug can sometimes break down during storage and become ineffec- tive : if this happens with an important drug like penicillin syrup for children, one can imagine how many children might suffer the consequences. Testing in a small-scale laboratory can detect such mistakes as well as unaccept- able products, saving both hard- earned foreign exchange—and lives. A small-scale drug control labora- tory, sometimes called a first-stage laboratory for drug surveillance, will need a building, equipment, and staff. The building need not be large—a one- storey pavilion will do, some 60 metres square, situated ideally on the Health workers and patients alike must be able to rely on the safety and efficacy of the drugs they use. Ideally, every country should have a well-equipped national laboratory—but a model small-scale lab as recommended by wHo can work wonders. Photo WHO/Unesco/P. Almasy premises of a large hospital, or adjoin- ing a university, with consequent ac- cess to existing technical installations and utilities such as electricity, water supply, drainage and sewerage. A piped gas supply is not necessary— a propane gas tank will do. Access to an existing library, whether medical or chemical, will be a bonus. Equipment and staff The empty building has to be equip- ped with laboratory furniture, tables, benches and hoods, the benches suit- ably enclosed and provided with an exhaust system which permits safe work when noxious fumes are given off in the course of chemical tests. The technical equipment must perform analytical procedures that confirm the identify of chemical drugs, test their potency, and detect possible deterio- ration. The staff of a small laboratory need not be large : four or five people at the most. The key person is the analyst, who must be well trained (in phar- macy or chemistry) to select the prop- er analytical method, to supervise the technicians who actually do the analy- sis, and to judge whether the product samples sent in to the laboratory can be pronounced satisfactory. The ana- lyst also needs a strong personality : negative verdicts sometimes lead to considerable losses for drug manufac- turers or dealers. Small-scale laboratories can be link- ed up to a reference laboratory lo- cated in the same region, so that suspect drugs requiring more detailed analysis can be referred to the refer- ence lab from the whole region. This concept of regional laboratories has been under serious consideration by some countries : one has been estab- lished in the Caribbean area ; East and West African countries are also discus- sing a similar facility. The author of a feasibility study made on behalf of the West African Pharmaceutical Federa- 12 WORLD HEALTH, December 1985 Appropriate technology Stability of Drugs ome drugs are liable to degrade during storage, particularly under tropical conditions. WHO has identified those drugs appearing on its Model List that are most vulnerable to deterioration, and has developed a series of simple or so-called "basic" tests to detect gross degradation of stocks. Unfortunately, far greater investment is needed to prevent deterioration than to detect it. However, unless medicines are stored with the same care with which they are manufactured, the quality of medical care is jeopardised. ■ Photo WHO/W. Wieniawski Basic Tests part from the need to test for absence of gross degradation, inspectors may want to check the identity of a drug consignment at any point in the distribution chain. Containers can become mislabelled by accident or by fraud. WHO's series of simple identification tests for substances on the Model List of Essential Drugs can be performed without recourse to specialised laboratory facilities, and with a small number of the most commonly used reagents, available 'even in remote areas. The drug is treated in a test-tube with an appropriate reagent ; the coloration, formation of a precipitate or the appearance of a characteristic odour confirms its identity. When the results of two or three such reactions are positive, it can be safely assumed that the substance in the container is in fact the one named on the label. ■ 13 tion has proposed that countries like Gambia, Sierra Leone and Liberia could establish their own small-scale national quality control laboratories— for example, at the Royal Victoria Hospital, Banjul, Gambia, where cer- tain analytical facilities could be shared with the existing clinical biochemical laboratory. A similar one may be established in Sierra Leone, using the central government hospital in Freetown. These small-scale quality control laboratories are expected ulti- mately to become independent and grow into larger and more sophisti- cated labs, if the resources are avail- able and the demands on them justify the expansion. It is important for a country to announce in the national drug policy its intention of supplying good-quality essential drugs to its citizens. It must then be prepared to allocate money for the establishment of a quality con- trol system. To calculate the financial commitment involved, a feasibility study should be conducted to spell out both the capital and recurrent expen- ditures, and the manpower involved. For countries with limited budgetary provision, it may be necessary to phase the project over a certain length of time. Making a start Once there is a national drug policy to protect people from poor-quality drugs, the drug testing programme can begin by making special arrangements to use the facilities of existing national laboratories in another country—an example of technical cooperation among developing countries (TCDC). An interesting arrangement has been made among Member States within the West African Pharmaceutical Fed- eration. Drug samples from Gambia, Sierra Leone and Liberia, where at present there are no national quality control laboratories, are sent to Ghana or Nigeria for testing. It is better for countries to start somewhere, using available resources —the WHO Certification Scheme, and existing laboratory facilities—than to have no scheme at all and risk wasting any of the drugs they have purchased at such high cost to the nation and its people. ■ WORLD HEALTH, December 1985 WORLD HEALTH, December 1985 A bestseller for WHO? by C. A. Johnson and Andrei Mechkovski n olden times, medicines were always prepared on the spot ac- cording to the client's need, so the pharmacopoeias (from the Greek pharmakon—a drug, and poiein—to make) of three of four centuries ago were recipe books for the compound- ing of medicines, with descriptions of their ingredients, mostly of herbal but also of animal or mineral origin. The finished preparations were never sub- ject to examination, since they were made by or under the direct supervi- sion of the apothecary. With the pas- sage of time, however, more and more medicines have been made on a large scale by industrial suppliers and the nature of the ingredients has changed, with increasing emphasis on synthetic organic compounds. These factors have influenced the content of pharmacopoeias to the ex- tent that the " recipe " aspects have diminished, while the descriptions of the ingredients and the dosage forms, such as tablets and capsules, have become more searching. Meanwhile, advances in the sciences of chemistry, physics and biology have provided methods that enable modern, highly potent drugs to be precisely analysed and controlled. Confidential matters By the early 1960s, many govern- ments were beginning to set up sys- tems to register or license all marketed drugs. To obtain a licence each com- pany has to settle all details of the analytical control of every product that it manufactures with the govern- mental authority. These controls re- main confidential, however, because they could well provide clues to secret manufacturing processes to compet- itors, since they are adapted to the particular method of synthesis and 14 preparation used in the factory con- cerned. There is still a need for a published pharmacopoeial monograph for each product, however—even though it may be less exacting—since this provides a means of checking the quality of stocks long after they have left the factory. Provided a copy of the appropriate pharmacopoeia is avail- able, a sample of the product can be properly analysed at any time in any suitably equipped laboratory any- where in the world. This woman of the Yucatan peninsula makes her own plant remedies, as did the ancient apothecaries. Modern pharmacopoeias give precise standards for analytical purposes, rather than recipes. Photo WHO/P. Almasy The old adage that quality cannot be tested into a product applies to phar- maceuticals no less than to other mate- rials. Good quality pharmaceuticals depend on the application of good manufacturing practices and on ap- propriate in-process controls. The final testing of the finished product simply gives an added assurance that it is satisfactory. The fact that many similar drug products and their active ingredients are in use throughout the world has, for a long time, led governments to consider the feasibility of producing internationally recognised norms and requirements for the quality of drugs. In principle, such unification would greatly simplify both the establish- ment of requirements for quality con- trol and the tasks of drug regulatory Education and training Learning from one another All countries need to create some system for controlling the drugs on their market, and to enforce its provi- sions by law. They must be realistic in their aims, however : several have failed in their basic objectives by intro- ducing over-ambitious plans. Each country needs to devise its own sys- tem according to local circumstances and the number of qualified staff available. To perform effectively, the doctors and pharmacists who will run the system must undergo relevant training. Traditionally, WHO used to place the greatest emphasis on training phar- macists to be responsible for quality assurance. Now, it is arranging courses on the administrative princi- ples of drug distribution and supply, t-h. ilPr," to. P- Si Photo WHO/R. da Silva drug selection, and registration sys- tems, in collaboration with donor agencies, governments, professional organizations and the pharmaceutical industry. These courses will be held largely in developing countries, and on a regional basis, in order to foster collaboration between neighbours and ensure that "appropriate techno- logy" is applied. Wherever they may be in the world, drug regulators need reassurance that they are not alone in their task and that their responsibilities are continu- ously evolving. They also need to realise that no country is entirely inde- pendent . in its regulatory apparatus. For this reason WHO has not confined its attention to basic training : in creat- ing the forum of the International Conference of Drug Regulatory Au- thorities it has given regulators worldwide the opportunity to learn from each other and to appreciate each others' problems. ■ authorities, particularly if global agreement could be achieved. It would also promote international commerce in pharmaceutical products. Among the various steps taken to- wards unification of quality require- ments for drugs, one can mention the Brussels Protocol of 1902, the Brussels Agreement of 1925, the creation in 1937 by the League of Nations of a Technical Commission of Phar- macopoeial Experts, and finally the publication of the International Phar- macopoeia by the World Health Organization. The first edition of the International Pharmacopoeia, published in three consecutive issues between 1951 and 1959, contained 337 monographs on raw materials and 187 monographs on finished pharmaceutical forms (mostly tablets and injections). The 2nd edi- tion (1967) together with the supple- ment (1971) provided specifications for 375 raw materials and 229 dosage forms. It must be admitted that these two editions of the International Phar- macopoeia enjoyed only limited success. There is little evidence that they were actively used for drugs moving in international commerce. No doubt they had some effect on nation- al pharmacopoeias, but this was mod- est when measured against expecta- tions (the Expert Committee of WHO created in 1948 to advise on the programme was originally called " Ex- pert Committee on the Unification of Pharmacopoeias "). The new edition It is difficult to judge why they were not more successful — but one impor- tant factor is that, unlike national and certain regional pharmacopoeias that have legal status, the International Pharmacopoeia simply offers recom- mendations, without legal recognition unless a particular Member State so decides. With these considerations in mind, a new approach was taken to the 3rd edition, now in publication in several volumes. Whereas earlier editions re- lied heavily on material taken from certain 'national pharmacopoeias, the 3rd edition aims to accommodate the needs of developing countries by of- fering sound standards for essential drugs which rely, wherever possible, on readily applicable methods of test- ing, and analyses that are appropriate for the facilities available in control laboratories in developing countries. In addition to the substances of the WHO Model List of Essential Drugs, specifications will be provided for widely used dosage forms and some of the more important non-active materials that are utilised in their production. The considerable work involved in this endeavour is willingly contributed by advisers from many parts of the world. As befits such a broad-based project, they are drawn from several scientific disciplines, and from academic, governmental and indus- trial organizations. The work they do, both in small groups and by corres- pondence, is consolidated within the WHO Secretariat and circulated for cri- tical and constructive comment to members of the panel of experts on Specifications for Pharmaceutical Pre- parations, and to governments. Work on the International Phar- macopoeia, stimulated by the Alma- Ata Declaration on Primary Health Care, is now being carried out in such a way as to provide maximum support to the WHO Action Programme on Essential Drugs. At the present time monographs have been developed for all drug substances in the WHO Model List; a number of these are not yet included in any national or regional pharmacopoeia. In addition, the revi- sion of requirements for dosage forms has begun. To be a really effective instrument which supports wHo policies, how- ever, the International Pharmacopoeia should be recognised as providing the preferred standards to be used in connection with the WHO Drug Action Programme, the UNICEF pro- curement programme, joint WHO/ UNICEF projects, and UNIDO and UNDP projects for the development of local drug manufacture. This would be a real "field test" for the concept of an International Phar- macopoeia. If, as we believe, the work now being produced passes the test, wider recognition by many Member States and manufacturers will surely follow. ■ WORLD HEALTH, December 1985 15 DRUB National Drug Regulatory Authorities No drug should be offered for sale unless persuasive assurances can be offered regarding its quality, efficacy and safety. It is the responsibility of national drug regulatory authorities to ensure that qual- ity, efficacy and safety are rigorously maintained. Close contacts between these authorities and WHO serve as an important channel for the exchange of information. Essential Drugs Countries with limited resources need to rationalise drug procurement in order to make their health care systems effective. WHO has produced a Model List of some 250 Essential Drugs to meet basic health care needs. Countries are invited to adapt the model list to their own specific nation- al needs. Drug Monitoring Everyone who prescribes or uses drugs should be aware that they are biologically active agents which are never totally devoid of risk. Adverse effects of drugs need to be closely monitored to make sure that unexpected hazards are iden- tified. For many years, countries with highly evolved monitoring facilities have been coordinating their activities under the aegis of WHO. Drug Names A single drug is often sold under many brand names, possibly differing from country to country. The drug may also be combined with other drugs in yet more branded products. Some widely used drugs are available globally in well over 100 products with totally different names. There should never be any doubt, how- ever, about the composition of a medi- cine. Every proprietary product should carry, in addition to the brand name, an officially approved non-proprietary or generic name for each ingredient. WHO'S list of 5,000 international non-proprietary names (INNs), compiled over the last 30 years, has brought about the world-wide standardization of drug nomenclature. Photo Roche WORLD HEALTH, December 1985 Photo Roche IS IN MEDICINE .. • Photo WHO/UNIDO WORLD HEALTH, December 1985 Good Manufacturing Practice (GMP) Drug manufacture is a complex and ex- acting task : every stage must be carefully controlled. WHO has therefore issued a code for Good Practices in the Manufac- ture and Quality Control of Drugs (GMP). The guidance given sets a standard for government inspectors. No aspect of the process escapes attention : the GMP code covers not only the manufacturing opera- tions themselves, but the layout of pre- mises, hygiene and sanitation, staffing, measures taken to assure quality, label- ling and packaging routines, and mainte- nance of records and procedures for handling complaints. The WHO Certification Scheme Countries importing drugs need to know that they have been produced according to the WHO guidelines on good manufac- turing practice. The WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Com- merce was devised to provide this assur- ance. The governments of most drug exporting countries have acceded to this scheme by agreeing to provide, on re- quest, an attestation on whether a factory has been inspected, and whether a pro- duct is available for sale in the country of origin. Quality Control Laboratories There is usually no simple way of detect- ing a sub-standard, degraded or spurious drug. The countries most vulnerable to unacceptable products are those without a national drug quality control laboratory that would be a cost-effective investment in virtually every country. The International Pharmacopoeia In producing the International Phar- macopoeia, WHO has aimed to support the concept of the modest quality control laboratory. The IPh provides for a full analysis of all the drugs on WHO'S Model List; 70 per cent of these tests can be performed in the simplest of the recom- mended laboratories. Photo WHO/A. S. Kochar Photo WHO/A. S. Kochar Photo WHO/D. Henrioud An importer's guarantee Ineffective or harmful drugs are a total waste of money. By adhering to the WHO Certification Scheme, drug-importing countries acquire the right to ask questions about what they're buying by Agathe Wehrli \Ij hen we buy a headache re- medy or get a physician's pre- scription filled in a pharmacy in a developed country, we do it with full confidence. Doubts about the quality of the product wouldn't even cross our mind. Are we right to be so sure? Yes, because no drug can be put on the market until it has been regis- tered with the drug regulatory author- ity, and no manufacturer may have a product registered until the authorities are satisfied that every necessary pre- caution has been taken to assure its quality; similar types of regulatory control are exercised in all developed countries. Furthermore, rigorous con- trols are applied to the sale of these drugs, since in affluent countries pre- scription medicines and most—if not all—other medicines can only be sold under the supervision of a qualified pharmacist. But what is the situation in develop- ing countries, which depend largely on the import of drugs and lack the infra- structure for regulatory and quality control of drugs ? The quality of their imported products can also be readily attested—thanks to the WHO Certifica- tion Scheme on the Quality of Phar- maceutical Products Moving in Inter- national Commerce. This Scheme, adopted by the World Health Assembly in 1975, allows de- veloping countries to benefit from the highly developed regulatory struc- tures in the industrialised countries. It works like this : 1) Any country wishing to join the Scheme informs WHO of its intention and provides the address of its respon- sible drug regulatory authority. WHO regularly publishes the names and addresses of the responsible au- thorities in all participating countries. The initiative for using the Scheme has to come from the regulatory au- thority of the importing country. The objective of the Scheme is to provide an official channel of com- munication between the responsible authorities of importing and exporting countries, and to provide a simple A drug's quality is composed of three elements: 1) its efficacy; 2) its safety; 3) its chemical iden- tity, purity, potency and stability administrative mechanism whereby importing countries can know whether or not a drug is registered in the exporting country, and also have con- firmation that the manufacturer is reg- ularly inspected and complies to the WHO requirements for good manufac- turing practices (GMP). The WHO code of good manufactur- ing practices provides comprehensive guidance to governments and manu- facturers on important aspects of drug manufacture including personnel, pre- mises, equipment, sanitation, starting materials, manufacturing operations, labelling and packaging, quality con- trol system, self-inspection, distribu- tion records, complaints and reports of adverse reactions. It consequently provides a documentary framework for the inspection of manufacturing premises. Information supplied In practice, when issuing a certifi- cate on a drug's regulatory status and the manufacturer's compliance with GMP as described above, many coun- tries also provide approved labelling information—for example, on the use of a drug and its contra-indications. In other words, the Scheme can provide sufficient information on a drug to enable the importing country to assume full responsibility for its distribution ; it also gives the import- ing country the right to ask questions from the regulatory authority in the exporting country. This is most impor- tant, since the information provided by the manufacturer may not always be objective. Some countries now require certifi- cation of all imported drugs, and by this regular use they have established easy contact and mutual trust between the persons responsible in the import- ing and exporting country. More infor- mal contacts, like telephone calls and telexes, can be of great help to a drug controller in an importing country who has a particular problem. How widely is the Scheme used? At the time of writing, 110 countries are participating in it, among them almost all the major drug exporting countries. 18 WORLD HEALTH, December 1985 Rigorous regulatory controls are applied to the sale of drugs in all developed countries. By using the WHO Certification Scheme, developing countries can also be confident that imported products are produced according to WHO good manufacturing practices (GmP) in regularly inspected factories. Photos Roche and WHO/A. S. Kochar 19 It did take some time for some of them to join because they had to adjust their legislation in order to be able to comply with the requirements of the Scheme for issuing export cer- tificates. Exporting countries also have to ensure that they have appropriate drug registration and quality assur- ance systems. Some 30 developing countries, for which the Scheme was originally de- vised, still do not formally participate. However, the importance of the issue has been reflected in several reso- lutions that have been adopted by the UN General Assembly in New York on protection against products harmful to health and the environment, request- ing the UN Secretary-General to pro- vide information on banned, with- drawn, severely restricted or non-ap- proved pharmaceuticals. If the provi- sions of the Scheme had really been used to the maximum, there would have been no need for this resolution to extend to pharmaceuticals since, thanks to the certificate, the importing country would know when a product was banned or not registered in the country of export, and the reasons for this would be stated on the certificate. The reasons may be perfectly legiti- mate, as in the case of drugs for tropical diseases for which there is no need in the exporting country, since the diseases do not occur. On other occasions, an importing country may have good reasons to refuse the im- port of a drug which is not registered in the country of export. The decision should remain the prerogative of the importing country, based on informa- tion obtained from the exporting country's drug regulatory authority or also, for example, from WHO. Problem countries The usefulness of the Scheme is beyond any doubt. Why, then, is it not used systematically by all developing countries, and what should be done to promote its use? Firstly, some de- veloping countries still lack any ad- ministrative infrastructure for drug control, or even for making use of the simple administrative mechanism underlying the use of the Certification Scheme—so it is urgent to support these countries in developing a legal WORLD HEALTH, December 1985 Sub-standard, ineffective drugs—a hazard that can be eradicated—are harmful to the patient and a complete waste of money. About 30 developing countries have still to join the WHO Certification Scheme. Photo WHO/J. Mohr framework for drug registration and control of imports, giving priority to the import of essential drugs. The strengthening of these national drug regulatory capacities will allow them to benefit fully from the Scheme. Secondly, some countries which have the basic structure still have to be encouraged to use the Scheme, which can be done by spreading information through publications and workshops. The International Conferences of Drug Regulatory Authorities strongly support the Scheme, and provide a particularly suitable forum for its promotion as they bring together the people responsible for issuing the cer- tificates and those requesting them. Also, the conference held in Nairobi at the end of November 1985 on the Rational Use of Drugs provided a further opportunity to discuss the Scheme and its advantages. Quality control Is use of the Certification Scheme alone enough to ensure the quality of drugs? It certainly provides assurance that a given drug product is adequate when it leaves the exporting country. However, for assurance that the qual- ity is maintained until the drug reaches the customer, proper storage facilities at the port of entry and throughout the distribution system are vital, since many drug products, even when spe- cially packed, are unstable under cer- tain climatic conditions. Certificates and good storage practices are the first steps towards complete drug quality assurance ; the next step within the grasp of developing countries is the setting up of a small quality control laboratory which makes it possible to assess the quality of products, whether imported or locally produced. Such simple mechanisms, used effectively, can go a long way to eliminating sub- standard drugs in developing coun- tries. In addition, they are highly cost- effective, since any money spent on sub-standard drugs—which are not only ineffective but also harmful to the patient—is completely wasted. ■ 20 WORLD HEALTH, December 1985 Safety first Some 26 countries report all suspected adverse drug reactions to the WHO Collaborating Centre at Uppsala, Sweden. There, 400,000 case reports form a unique data-base for further investigation by KjeII Strandberg cj h he continuous search for more potent and selective medicines has highlighted not only the ben- efits of drug treatment, but also some of its unpredictable hazards, known as adverse drug reactions (ADRs). Prompted by the thalidomide disaster, many governments introduced strict safety regulations for the marketing of new medicines, and also set up post- marketing surveillance schemes in an attempt to get early warning of new potential hazards to patients. Begun in 1968 as a pilot study in 10 countries, the WHO International Moni- toring Programme for human drugs was intended to make it easier to detect adverse drug reactions not revealed during clinical trials. A few years later, the Swedish government took on operational and financial re- sponsibility for the programme and a WHO Collaborating Centre for Interna- tional Drug Monitoring was created at Uppsala, staffed by a medically qual- ified director, three pharmacists, a computer programmer and two part- time physicians. Today, 24 developed and two de- veloping countries are participating in the WHO programme. A national centre in each country processes and evaluates adverse reaction reports, feeding them back to the medical profession. They also send their case reports to the WHO Centre, either on forms or on magnetic tape. A compu- ter checks them for completeness and technical accuracy before adding them to the data-base, which now contains around 400,000 items. Four times a year, the material re- ceived is screened for serious reactions and associations not previously re- ported. Reports are then sent back to the national centres on : all drugs associated with death, fetal malformations, neoplasms or dependence adverse drug reaction associations not previously reported follow-up on the reporting frequen- cy of interesting associations chosen by the national centres or by WHO Centre staff. Countries often ask for the adverse reaction profile of a specific drug before putting it on the market. Photo WHO/M. Jacot In addition, the national centres re- ceive an annual reference document containing summary data on all sus- pected reactions occurring within the last four years. This is probably the most extensively used printout. In retrospect, it seems that the origi- nal expectations for the scheme—that is, that it should serve mainly as an early warning system—were set too high, largely due to the delays that occur at different stages in report- processing. It was thought that by applying carefully designed statistical analysis to the large amount of data, it would be possible to identify new, unex- pected reactions of medical signifi- cance. However, a purely statistical approach does not identify important problems : well-known effects of a drug and obvious nonsense associa- tions cannot be sorted out by a compu- ter programme, however sophisti- cated. A combination of automatic signalling devices and scanning of the data base by experienced medical personnel is crucial to successful inter- pretation. An increasingly important part of the Centre's work is to act as a com- munication centre—a clearinghouse for information on drug safety. Its backbone is the accumulated collec- tion of 400,000 adverse reaction case reports, a unique reference source used for strengthening or refuting sus- picions about new adverse reactions arising at national centres. On aver- age, two or three requests are received each week for special data-base searches and investigations. Through searches in the WHO register, direct communication can be established be- tween centres with a similar drug problem. The fastest way for a nation- al centre to gain access to international experience is through an on-line con- nection to the WHO Centre computer. Countries often ask for the adverse reaction profile of a specific drug, especially when thinking of registering a product previously marketed else- where. A summary of all reported reactions is then provided, in the form of a table and a graph. It is often WORLD HEALTH, December 1985 21 The national reporting centre investigates case reports on adverse reactions and feeds them back again to the medical profession. Photo WHO/A. S. Kochar interesting to compare the ADR spec- trum of newer drugs with that of the older-established therapies. For the past three years, the WHO Collaborating Centre has been dis- tributing an Adverse Reaction News- letter to participating centres, with reviews of national adverse reaction bulletins, news of drug problems being investigated in the various countries and figures from the WHO register. Since 1978, representatives of na- tional centres have been enthusiasti- cally attending annual meetings that greatly help to maintain international communication. They discuss current drug problems and methodological and technical issues. These meetings help to harmonise definitions and methodology in drug monitoring, and promote the international monitoring programme. Subtle interpretation The proper interpretation of data produced by spontaneous monitoring systems requires a clear insight into the nature of the information. The extent of underreporting by the medi- cal profession can only be estimated. Knowledge about the actual number of patients treated with a certain drug is often lacking or incomplete : inter- national disclosure of sales figures would be a tremendous advantage in this respect. Other factors also have to be considered with international data, since the methodology differs between countries. Some receive all or a major- ity of their reports from hospitals, while others get them mainly from general practitioners or through phar- maceutical manufacturers. Although a majority of countries evaluate the casualty in each individual case, most reports received at the Centre lack such an assessment. Furthermore, dif- ferences in therapeutic traditions may result in different adverse reaction patterns from country to country for the same substance. Only an interna- tional monitoring programme can de- tect these inter-country differences and investigate their causes. ■ WORLD HEALTH, December 1985 A vital service by Bengt 0. Ohrner ecent progress in analytical chemistry has been remarkable and the identity, purity and strength of any pharmaceutical pro- duct can now be established or con- firmed with great accuracy. Unfortu- nately, though, there is a snag. In many cases, to obtain really precise results, the product has to be com- pared with a well-defined reference sample of the same substance. Pharmacopoeial methods for assur- ing drug quality depend heavily, in fact, on the availability of reference substances. With the aim of giving all countries access to adequate supplies of these materials, the WHO Col- laborating Centre for Chemical Refer- ence Substances was set up in 1956 to collect, store and distribute them, at the Central Laboratory of the Swedish Pharmacies, already internationally recognised in drug quality control. The Centre began on a modest scale, but from the outset work started on developing new reference sub- stances, not merely distributing exis- ting ones. The priorities were clearly laid down in the second edition of the International Pharmacopoeia (1967), which required about 40 chemical re- ference substances to support its specifications. Today, the Centre of- fers about 120 different reference materials, while work is in progress to establish about 60 others for sub- stances included in the wrio Model List of Essential Drugs. Like everything else, the cost of processing, evaluating, and distribut- ing International Chemical Reference Substances has risen over the years. Indeed, costs now threaten to jeopar- dize the future of the service. The bulk substances are usually donated by pharmaceutical manufacturers, but the additional exacting analysis needed to demonstrate beyond any doubt that they are suitable for their intended purpose is demanding and time-con- suming; their stability must be moni- tored by regular re-examination. The Centre's annual budgetary deficit is now well in excess of US$ 150,000; several possibilities are being consi- dered to alleviate the situation. It may be possible, for instance, to replace many expensive reference substances with a unique " thumb- print " that identifies a compound on the basis of a tracing showing the extent to which it absorbs light throughout the infra-red spectrum. The question has also been raised of levying charges on government labora- Chemical reference materials have been supplied free of charge to laboratories around the world for nearly 30 years. Photo WHO/D. Henrioud tories, which so far have received reference substances free, but the risk is obvious that such laboratories, particularly in developing countries, might then be deprived of necessary reference materials due to lack of allotments in convertible currencies. The Centre currently distributes about 2,500 packages of International Chemical Reference Substances each year; at present, the stocks of most are sufficient to meet demand. However, laboratories needing large quantities of chemical reference substances are encouraged to establish their own working standards, not an easy task. The calibration must be done with utmost care and it is advantageous if several laboratories can pool their resources and do the work together. The Centre supports such initiatives by offering consultancy advice and laboratory training The future is difficult to predict. Analytical chemistry may progress to the point where reference substances will no longer be needed. For the foreseeable future, however, well de- fined reference substances will remain of vital importance, not least for the developing countries, which are now making great efforts to establish their own pharmaceutical industries. WHO itself is urging these countries to es- tablish small quality control labora- tories. It would indeed be frustrat- ing if these laboratories could not be efficiently used because they lacked reference substances. ■ WORLD HEALTH, December 1985 23 How medicines are controlled Drug regulation is concerned with quality, safety and efficacy. Under the umbrella of ICDRA, exporting and importing countries can discuss such questions as hazards, advertising and labelling in a world context by Norman M. Hale \I‘j e notice medicines mainly when we need to take them or when there is publicity in the media; the latter is usually be- cause of a new medicine with great promise or because a medicine in use shows unexpected problems. Medi- cines have been used for thousands of years with many attempts to control their safety and quality. But only in this century have scientific systems of regulating drugs—although I prefer the less ambiguous word " medicines " —been created. Countries have de- veloped their own regulatory systems, especially since the thalidomide tragedy of the 1960s. Now, in the 1980s, the regulatory authorities of the world are meeting to exchange Analysis of herbal medicines, Mexico. Scientific drug regulation began only in this century. Photo WHO/J. Bland views. With a medical colleague, I attended the third such International Conference of Drug Regulatory Au- thorities (ICDRA) in a hotel at Salts- jobaden, outside Stockholm, last year —with representatives from over 50 countries. Let me first explain what a regula- tory authority is, taking my country as an example. Under the legislation of the United Kingdom and the European Community, United Kingdom Health Ministers are responsible for licensing and controlling the supply of medi- cines. They are supported by the Medicines Division of the Department of Health and Social Security. The Division is concerned with the safety, quality and efficacy of medicines—but not with their price—including control and inspection of the manufacture, labelling and advertising of old as well as new medicines. Most senior staff in the Medicines Division are professionally qualified doctors, pharmacists, scientists or lawyers, with wide experience of the National Health Service or the phar- maceutical industry. But there are also some senior administrators whose main experience is, like mine, not in medicines but in running a public service within a Government Depart- ment. I believe that, as non-profes- sionals, we can help to interpret com- plex issues on medicines for other non-professionals, whether they are Ministers, members of legislatures, or the most important people of all—the patients for whose benefit medicines are provided. When I arrived in Stockholm, I knew that the first Conference in An- napolis, USA, in 1980 had been at- tended mainly by members of regula- tory authorities from the developed world, to explore the possibilities of international cooperation. At the sec- ond meeting in 1982 in Rome, rep- resentatives from 44 countries had explored the differences in various systems of regulation. Now at the third Conference—and my first—we hoped to be able to explore together some of our problems. We realised the difficulties. The 50 or more countries represented at Salts- jobaden were very diverse, with a wide variety of diseases and health problems. Economically, they in- cluded both developed countries and an increasing representation from less developed countries. A special feature of the Conference was the help it gave all of us in thinking more deeply about our health priorities. For some of us these might be adverse reactions to medicines and the control of old medicines. For others, it was how to WORLD HEALTH, December 1985 start a simple regulatory scheme, and obtain reliable information about medicines imported into their country. Politically too, the Conference in- cluded countries with widely differing ideologies. Stockholm showed that, despite all these differences, we had much of value to exchange. The seclusion of Saltsjobaden, and the splendid organisation of our Swed- ish hosts, gave us time for detailed discussions, in the " workshops " on particular topics, and more informally. The final plenary sessions produced useful reports to help both regulatory authorities in individual countries and international bodies such as WHO and the United Nations. A theme common to several work- shops was the need for better dis- semination of information about medicines. The emphasis is on quality because, otherwise, countries are overwhelmed with information from overseas which they either cannot use at all or use incorrectly. WHO provides a Certification Scheme for the quality of medicines imported from another country and we suggested how this might be improved. We also consi- dered a United Nations list of banned and restricted products and how, espe- cially through WHO, countries could obtain better information, in a form they could use, on the hazards of medicines, and on advertising and labelling them. While much of this work was directed to the needs of less developed countries, most of the is- sues were common to us all. A particu- lar topic was the review of ' old ' medicines—those already on the mar- ket when regulatory schemes begin to ensure that they really are safe and effective for the public. What therefore is the future role of these Conferences — the next in 1986 likely to be? Let me start by stating what I be- lieve these Conferences could not—or should not—become. They are not the first step towards an international regulatory body for medicines. The differences between countries are too Setting up an intravenous drip, Niger. The use of medicines knows no national bound- aries—all countries need to learn from each other. Photo WHO/M. Jacot WORLD HEALTH, December 1985 great and the importance of safety in each country is too strong to permit this—even if it was desired. Nor, for similar reasons, can the Conferences replace the existing groups of countries who meet regular- ly because of their close common interests in the regulation of medi- cines. For example, there is the Phar- maceutical Committee of the Euro- pean Community, which is concerned with Community legislation on medicines, and the Nordic Council, which produces guidelines for its members. Countries with similar prob- lems on medicines must continue to meet together. These groupings are, however, not enough. The use of medicines, and scientific knowledge about them, knows no national boundaries and we all need to learn from each other. There is a major role for WHO in collecting and disseminating informa- tion about medicines on a systematic basis and the International Conference of Drug Regulatory Authorities can support this in two ways. First, the Conference enables reg- ulators from many countries to con- centrate every two years on the issues then of current interest and to set them in a world-wide context. The Conference brings together major pharmaceutical exporting countries and countries mainly dependent on imported medicines. It enables us to prepare—as experts in medicines con- trol—for the wider debates in the World Health Assembly and the United Nations. 1986 will undoubt- edly bring further special issues for consideration. The second form of support the Conferences give to WHO is less easy to define but is even more important. If the specific topics for the Conferences are the bricks, the cement needed to create the building is the informal contact and off the record discussions between regulators which can come only from a meeting such as that in Stockholm. Some of us there knew each other well and were able to discuss mutual problems in depth. Some of us were strangers until we met there and yet were able to gain greater insights into our own problems and into the anxieties of countries with quite different problems. Above all, the Conference enabled both de- veloped and less developed countries to recognise together that the safe use of medicines, to cure or alleviate hu- man ills and to prevent disease, is a shared responsibility for us all. The 1986 Conference will renew the pro- cess and, I hope, enable new col- leagues to share in the benefits the Conferences bring. ■ Fore-warned is fore-armed Now that many widely used drugs are available all over the world, the efficient transfer of information between countries is of prime importance to ensure drug safety by John Dunne rugs are biologically active sub- stances. Used imprudently they may do harm rather than good, but considerable efforts are made to ensure that marketed products meet the claims which are made for them, and that they are acceptably safe. It would be misleading to suggest that absolute safety is attainable, or that every potential danger can be spotted before a new drug is released for general use. Indeed, from time to time, drugs are withdrawn from use because they are found to hold previ- ously unsuspected dangers. But it would also be wrong to cast into question the undeniable benefits that pharmaceutical innovation has yielded since organic synthetic chemistry be- came established some 50 years ago. Life is beset by hazards, but drug- induced injury holds a particular pathos. Clinicians mindful of their Hippocratic oath are concerned not with statistics but with individuals. Their first consideration is never to do harm. However, in reality, they are concerned in virtually every interven- tion with an assessment of benefit and risk. It is ultimately for society, rather than the professions, to judge what risks are acceptable in the conquest of naturally occurring disease. The congenital deformities induced by thalidomide some 25 years ago provided an indelible reminder that some risks are totally unacceptable. The response of many governments was immediate. No drug was to be released on to the market until its safety had been assessed by inde- pendent experts ; suspicions of drug- induced adverse reactions were to be reported to a central authority ; and a systematic review was to be under- taken of the safety and efficacy of all previously marketed products. The scale of the task involved was such that very few national drug reg- ulatory authorities have, as yet, com- pleted a full review of the products marketed under their jurisdiction. However, this of itself created a basis for international collaboration : no na- tional authority could any longer re- gard itself as totally self-sufficient in its regulatory responsibilities. Widely used drugs are available in many countries and it became important to exchange information on their per- formance. It was.also immediately evident that many countries had neither the finan- cial resources nor the technical exper- tise to undertake the complex multi- disciplinary assessments that are re- quired in drug evaluation, since these make demands upon clinicians, phar- macologists, toxicologists, statisticians A health worker in India makes sure his patient takes the medicine. All countries should be able to test the drugs that are put on the market, whether they are manufac- tured at home or abroad. Photo WHO/A. S. Kochar 26 WORLD HEALTH, December 1985 pharmacists, chemists and lawyers. Ef- ficient transfer of information be- tween countries thus became of prime importance to the assurance of drug safety. Over the years, the governing bodies of WHO have adopted many resolutions calling for the strengthen- ing and further elaboration of interna- tional collaboration to assure the qual- ity, safety and efficacy of drugs mov- ing in international commerce. The contribution of WHO to this exchange of information comprises a variety of elements which appear at first sight to bear little relationship to one another. In fact, each element makes an important contribution to the process of drug regulation, and each helps to increase national self- reliance in a highly complex technical responsibility. Some of this information is nor- mative in character. Thus, a drug has to be identifiable by a single non- proprietary name that is recognised throughout the world, and it is wHo's responsibility to select and assign these names. Similarly, a country needs to be in a position to test the quality of the products on its markets, whether they are manufactured domestically or imported. wHo pro- vides standards for the requisite anal- yses in its International Pharma- copoeia, and these are based on classi- cal methods of analysis which can be performed in a modest quality control laboratory. Lastly, countries with too little to spend on the drugs that they desperately need have to rationalise their procurement policies ; WHO has provided an approach to this task in creating and updating its Model List of Essential Drugs. Most developing countries are largely dependent upon imported drugs, in which case the governments of the exporting countries have a dual responsibility. They need to attest that the product is of good quality, that it has been manufactured in accordance with WHO's guidelines for good manu- facturing practice, and whether or not it is available for the domestic market. They also need to ensure as far as is practicable that the export of unac- ceptable products is frustrated. This is far from simple in an imperfect world. A prudent importing country will do well to insist on formal certification of Nursing care for mother and child in Ethiopia. Most developing countries are largely dependent on imported drugs, so they have to make sure that the product is of good quality. Photo WHO/P. Almasy its imports in accordance with WHO's Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce. Certification by the regulatory au- thority in the exporting country is not, of itself, an absolute safeguard in so far as drug assessment is an open- ended process. Hazards are occasion- ally identified after a product has been marketed that may call for restrictions in its use, additional warnings on the label, or even its removal from the market. Action of this nature taken in one country needs to be conveyed immediately to every other country in which the drug is marketed. For this reason each national drug regulatory authority has nominated an informa- tion officer with a responsibility to keep WHO informed of such develop- ments, which are then rapidly com- municated to all Member States. In practice, regulatory authorities often need to consult each other and to share relevant information before such regulatory decisions are taken. The potential for inter-agency collab- oration in this regard is enhanced by the existence of the voio Collaborating Centre for International Drug Moni- toring, which is located within the Department of Drugs in Sweden. On a broader front, collaboration and mutual understanding between reg- ulators from both developed and de- veloping countries has been greatly encouraged by the biennial meetings of the International Conference of Drug Regulatory Authorities. Drug control now has a well-defined inter- national dimension which offers valu- able support to all countries, but par- ticularly to developing nations which are concerned to put a fully effective system in place. ■ WORLD HEALTH, December 1985 27 Books and Publications Model List brought up to date he use of essential drugs, no. 722 in WHO'S Technical Re- port Series*, contains the latest version of the WHO Model List of Essential Drugs. The Model List is revised periodically by the members of the WHO Expert Committee on the Use of Essential Drugs. Besides giving the Model List in full with explanatory notes, The use of essential drugs also includes guidelines for establishing a national essential drugs programme, criteria for selection of drugs and dosage forms, and a list of information ser- vices offered by WHO. The following are some interesting extracts from this new WHO publi- cation. Criteria for the selection of essential drugs Essential drugs are those that satis- fy the health care needs of the majori- ty of the population ; they should therefore be available at all times in adequate amounts and in the approp- riate dosage forms. The choice of such drugs depends on many factors, such as the pattern of prevalent diseases ; the treatment facilities ; the training and experience of the available personnel ; the finan- cial resources and genetic, demo- graphic, and environmental factors. Only those drugs should be selected for which sound and ad- equate data on efficacy and safety are available from adequate clinical studies and for which evidence of performance in general use in a vari- ety of medical settings has been obtained. Each selected drug must be avail- able in a form in which adequate quality, including bioavailability, can * Obtainable from: Distribution and Sales, WHO, 1211 Geneva 27, Switzerland. Price: US$ 3.00. be assured ; its stability under the anticipated conditions of storage and use must be established. Where two or more drugs appear to be approximately similar in the above respects, the choice between them should be made on the basis of a careful evaluation of their relative effi- cacy, safety, quality, price, and avail- ability. In cost comparisons between drugs the cost of the total treatment, and not only the unit cost of the drug, must be considered. In some cases the choice may also be influenced by other factors, such as comparative pharmacokinetic properties, or by lo- cal considerations such as the avail- ability of facilities for manufacture or storage. In the great majority of cases es- sential drugs should be formulated as single compounds. Fixed-ratio combi- nation products are acceptable only when the dosage of each ingredient meets the requirements of a defined population group and when the com- bination provides a proven advantage over single compounds administered separately in therapeutic effect, safe- ty, or compliance. Essential drugs and primary health care Criteria for the selection of drugs for primary health care The Expert Committee on the Selection of Essential Drugs in its first report recommended the compilation of a separate list of drugs appropriate for use in primary health care. After broad consultation, and having regard to situations in which a traditional healer or community health worker rather than a qualified doctor is the patients' first point of reference, the present Expert Committee has selected 23 substances from the main list that might be considered for this purpose. They are listed below. It cannot be emphasized too strongly that, in practice, the selection must be determined nationally since the train- ing and responsibilities of these work- ers vary within wide limits. The fol- lowing factors, however, will inevit- ably influence the content of the list. Existing systems of medecine. The establishment of primary health care services should not result in abrupt disruption of prevailing cultural pattern8 in rural communities, but the work of traditional healers should be adapted and supplemented in such a way as to ensure that innovation is successfully integrated into existing systems of care. The national health infrastruc- ture. The type of primary health care service that a country requires is de- pendent upon the proximity and na- ture of the first referral facilities. It is still not unusual in some countries for the nearest permanently manned health post to be one or more days' travelling time from isolated villages in its catchment area. Training and supplies. The num- bers of trained personnel, the facilities placed at their disposal, and the sup- plies entrusted to them determine both the scope and the limitations of the primary health care system. Workers with one or more year's vocational training can obviously ac- complish more than personnel reliant upon an intensive course of practical instruction lasting only a few weeks. But, whatever the circumstances, lit- tle can be accomplished unless con- tinuity of essential supplies and infor- mation is assured. WORLD HEALTH, December 1985 Photo WHO/C. Stauffer (4) The pattern of endemic dis- ease. The prevalence of major en- demic infections and parasitic dis- eases may vary from region to region within a country in conformity with climatic, geographical, topographical, social, economic, and occupational factors. Careful planning and, in some cases, epidemiological surveys are re- quired to ensure that the most effec- tive drugs are provided, and to obtain full benefit from limited resources. A model list of drugs for primary health care acetylsalicylic acid activated charcoal an antacid an antihaemorrhoidal drug atropine (antispasmodic) benzoic acid + salicylic acid 'benzyl benzoate calamine lotion chlorhexidine solution chloroquine chlorphenamine ephedrine (asthma) ergometrine (postpartum haemor- rhage) gentian violet, also known as crystal violet (International Nonproprietary Name: methylrosanilinium chloride) iodine ipecacuanha iron/folic acid (nutritional supplement during pregnancy) lindane mebendazole oral rehydration salts paracetamol piperazine tetracycline eye ointment The selected drugs, which should be available in the dosage forms specified in the main list, can be used effectively and safely by responsible individuals with little formal medical knowledge. The list is adapted to the needs of a malarious area (free from chloroquine resistance) where hel- minthic infections are also endemic, and the instructions for using the drugs can be based upon the recogni- tion of a few basic clinical signs and symptoms. Highly trained workers might use a wider range of drugs appropriate to their diagnostic skills with acceptable safety. However, where there is no scarcity of medical manpower, the provision of comprehensive emergen- cy and domiciliary services involves the use of many potent drugs. Deci- sions regarding the availability of specific drugs to community health workers can be taken only when all relevant locally operative factors have been taken into account. In ideal circumstances antibiotics, for instance, should be used only by individuals with advanced diagnostic skills and with access to appropriate microbiological facilities. However, the need for these drugs is as great in isolated rural communities as else- where, and health administrators have a prime responsibility to ensure that, as far as possible, basic medical services are brought within the reach of the whole population. ■ WORLD HEALTH, December 1985 29 0** 00* 000 000 000 000 00* ****** 00* 000 00* 000000 00* 1000 000*00 oo• 000::: ..0. . . 000 MOO 000 000 000 *00 00* 000 000 000 000 000 6 • 000 000 000 00.000 00• *0* 000 00• *00 OOOOOO *00 00* 00* 00• 041 0 000 *00 *00 00* *00 080 000 000 * 0* 000 00* SOO Malaria Control through Primary Health Care A significant and long-lasting improvement in the global malaria situation is urgently needed as we approach the fi- nal decade of this century, ac- cording to Dr S. K. Litvinov, Assistant Director-General of WHO. He was addressing the Organization's 18th Expert Committee on Malaria which met recently in Geneva. A resolution adopted by the World Health Assembly last May urged Member States to undertake an immediate review and appraisal of the malaria situ- ation and recommended that malaria control be developed as an integral part of national pri- mary health care systems. Un- fortunately, the implementation of malaria control strategies as part of primary health care has been slow, and it is becoming increasingly difficult to cope with the disease. As a result, The success of malaria control activities depends on education and involvement of the com- munity. Photo WHO/PAHO/J. Moquillaza the malaria situation worldwide continues to deteriorate steadily. At their meeting, the experts stressed the need for an epidemiological approach to the problem, taking into account the local variability not only in the intensity of malaria but in its response to control measures. But they recognised the limita- tions that might be imposed on such an approach by the lack of resources and the potential of the infrastructure to maintain control activities. Two substantially different approaches were identified at extreme ends of the spectrum. The first would require as an abosolute minimum the provi- sion of diagnosis and treatment, prophylaxis throughout pre- gnancy, and improved educa- tion of the public. The second approach, calling for planned in- terference in malaria transmis- sion on a large scale, should only be considered if it will pro- duce a significant improvement in the malaria problem that could be maintained. This would involve designing appropriate strategies, identifying suitable control measures, monitoring and evaluating results, manag- ing problems such as parasite resistance to drugs, or vector resistance to insecticides, and developing malaria control ac- tivities within the framework of primary health care in con- sideration with other disease problems. Since operational respon- sibilities would be transferred to the general health services, the district medical officer must be in a position to decide on the approach and on the appropriate technology to be used in malaria 'control in his area, bearing in mind socio-economic and be- havioural factors. The experts also recom- mended that training of health workers should provide them with precise lines of action, not only in performing control ac- tivities but also in educating people and stimulating com- munity involvement, including some contribution by the com- munity towards the resources needed for malaria control oper- ations. All this will require research and development studies to ascertain how best to apply the principles of malaria control as part of primary health care to the wide variety of ecological and social situations where malaria is a serious problem. Malaria can be cured com- pletely through prompt diag- nosis and adequate treatment with appropriate antimalarial drugs. Reducing the toll and death caused by this disease will require the development of appropriate diagnostic, thera- peutic and preventive action against malaria as an integral part of a community-based health programme. ■ Aids Cases Reported to European Centre WHO•s Weekly Epidemiological Record continues to give periodic up-dates on the fast- moving situation of AIDS, the Acquired Immune Deficiency Syndrome. WER's issue No. 40, dated 4 October, for instance, showed that the 17 countries taking part in the surveillance of AIDS in Europe by reporting data to the WHO Collaborating Centre in Paris (the Pasteur In- stitute) had an average increase of 22 new cases per week over a three-month period. Luxem- bourg became the 18th country to join the surveillance group, reporting one single case. A total of 1,226 cases had then been reported, and 626 deaths—a case-fatality rate of 51 per cent. Males accounted for 91 per cent of the cases, a sex ratio of 11 to one. Forty-two per cent of the cases were in the 30-39-year group, and there were 29 paediatric cases (chil- dren below the age of 15 years); 18 of these were chil- dren of parents suffering from AIDS or belonging to groups at high risk. For seven others (four haemophiliacs and three reci- pients of blood transfusions), transmission of the disease was connected with contaminated blood. No risk factor was notified in four cases. Distribution by geographical origin showed four distinct groups. Of the 1,011 Euro- peans, 976 patients were living in Europe before the onset of the first symptoms of the dis- ease; 35 cases were living out- side Europe (Zaire : 11 ; USA: 10 ; Haiti : 2 ; Bermuda : 1 ; Burundi : 1 ; Congo : 1 ; Gabon : 1 ; Ghana : 1 ; Malaysia : 1 ; Nicaragua : 1 ; South Africa : 1 ; Togo : 1 ; Venezuela : 1 ; for two patients the country of resi- dence was not specified). Of 36 Caribbean cases, 34 were living in Europe before the onset of the first symptoms : 30 Haitians were diagnosed in France and one in Belgium ; one patient from Dominica and one Jamaican were resident in the United Kingdom ; one case of unspecified origin was resident in Switzerland. Two other Hai- tian cases diagnosed in France were resident in Haiti. 30 WORLD HEALTH, December 1985 Newsbriefs More for the Least. The United Nations Development Programme has announced that it is increasing its contribu- tion to the poorer countries, especially those on the list of Least Developed Countries, in both real and relative terms. Besides making continuous efforts to channel increasing resources to these countries, UNDP will increase the propor- tion of its own funds distributed to LDCs from 37 per cent to 41.4 per cent beginning in 1987. Smallpox rumours. Between January 1980 and June 1985, no fewer than 117 rumours of smallpox cases have been notified to the surveillance programme established by WHO after the disease was eradicated from the world five years ago. Every rumour has turned out to be false—usually they were cases of chickenpox or measles—thus confirming the continued absence of this once dreaded disease since December 1979, when the Global Commission for the Certi- fication of Smallpox Eradicated concluded that "smallpox is dead." Threatened forests. Smoking poses a threat not only to human health but also to the world's great forests. Ceres, the journal of the Food and Agriculture Organization (FAO), has pointed out that it takes between two and three hectares of forest timber to smoke-cure one ton of tobacco. To quote just one tobacco-producing country among many: the annual tobacco production in Kenya requires the felling of from 5,000 to 8,000 hectares of forest each year. Ceres com- mented: "At present rates of felling, there may be no trees left in Kenya by the year 2000." Drought and strife in EMRO. Drought, famine and civil strife in a number of countries in WHO's Eastern Mediterra- nean region have overshadowed the normal priorities and impeded progress during the past year. Dr Hussein A. Gezairy, regional director for EMRO, speaking at the opening of the EMRO regional committee, held this year in Geneva, said : "Time and again, the governments, and WHO and its sister agencies, have been forced to meet emergencies—and it is well-known that emergencies are, in economic terms, wasteful of funds. I am, however, pleased that WHO was able to respond effectively to the urgent requests of the needy." In the next issue The January-February issue of World Health will be devoted to the slogan for World Health Day 1986: "Healthy living : everyone a winner." This theme reflects the growing conviction—not only in WHO—that greater emphasis should be placed on the positive actions that individuals and communities can take to protect and promote health. The 141 African cases were diagnosed in seven European countries and originated from 21 African countries ; 87 cases were from Zaire and 14 cases from the Congo. Among the remaining 19 countries, the number of cases ranged from 1 to 5. The origin of one case was unknown ; 75 patients were liv- ing in Europe before the onset of the first symptoms ; 61 were living in Africa ; one in the USA. Two patients from Zaire, one from Burundi, and one from Rwanda were living in other parts of the world. Most of the 38 patients of other origins came from the American continent (USA : 19 ; Canada : 1 ; Argentina : 3 ; Brazil : 3 ; Chile : 1 ; Nicaragua : 1 ; Peru : 1 ; Uruguay : 1). One patient was from Australia, 1 from Lebanon, 1 from Pakistan, 1 from Thailand, 1 from Turkey : the origin of three patients was unknown. Thirteen of these pa- tients were not living in Europe before the onset of the first symptoms (USA: 10: Africa : 1 ; unknown : 2). Among the 1,011 Europeans, 80 per cent (809 cases) are homosexuals or bisexuals ; five per cent (48 cases) are drug abusers and 1.5 per cent (15 cases) are both homosexuals and drug abusers. Four per cent (38 cases) are haemophiliacs, and for 2 per cent (20 cases), the only risk factor found was blood transfusion. Among the patients from the Caribbean (36 cases), four are homosexuals : 31 present no risk factor (sex ratio 2.5 : 1); and no information was obtained for one case. Among the Africans (141 cases), ten are homosexuals ; five have had blood transfu- sions ; one is both homosexual and a drug abuser; 112 present no risk factor (sex ratio 2 : 1); and no information was ob- tained for one case. Among the patients from other geographical areas (38 cases): 30 are homosexuals ; two are both homosexuals and drug abusers (one Canadian diagnosed in the United King- dom ; one American diagnosed in Spain); one is haemophiliac (American diagnosed in Swe- den); two present no risk fac- tors; and no information was obtained for three. ■ Authors of the Month Dr John DUNNE is Chief of WHO's Pharmaceuticals unit, in the Division of Diagnostic, Therapeutic and Re- habilitative Technology. Dr A. W. El-BoRoLossY is Professor of Pharmacology and Vice President at the University of Jordan in Amman. Professor Robert MOREAU is with the Chemical Therapy Laboratory at the Faculty of Pharmaceutical and Biological Sciences, Universite Rene Descartes, in Paris. Dr James Y. BINKA is Head of Qual- ity Control with the Ministry of Health in Accra, Ghana, and Profes- sor Witold WIENIAWSKT is Chairman of the Polish Pharmacopoeia Com- mission and Deputy Director of the Institute of Drug Research and Con- trol in Warsaw. Dr C. A. JOHNSON is Secretary and Scientific Director of the British Pharmacopoeia Commission Sec- retariat in London, and Dr Andrei MECHKOVSKI is a Scientist with WHO'S Pharmaceuticals unit. Miss Agathe WEHRLI is a Scientist with WHO's Pharmaceuticals unit. Dr Kjell STRANDBERG iS Director of the WHO Collaborating Centre for International Drug Monitoring in Uppsala, Sweden. Dr Bengt 0. OHRNER is Director of the WHO Collaborating Centre for Chemical Reference Substances in Solna, Sweden. Mr Norman M. HALE is Head of the Medicines Division, Department of Health and Social Security, London, and is an Under Secretary in the UK Civil Service. WORLD HEALTH For readers everywhere 1985 Subscription Rates One year Two years Three years USS 12.50 22.50 30. Sw. fr. 25.— 45.— 60. ORDER FORM Please enter my subscription to "World Health" as follows : One year Two years Three years I enclose cheque/international postal order in the amount of • Name • Street • City • Country • World Health, WHO, Avenue Appia, 1211 Geneva 27, Switzerland World Health is also distributed through the network of international bookstores and sub- scription agencies. For payment in national cur- rencies, please contact your usual bookseller. WORLD HEALTH, December 1985 31 Pr in te d in S w itz er la nd — R o to -S a da g G e ne ve November Sexually transmitted diseases and AIDS • Nutrition • Diabetes in youth • Caring care WORLD HEALTH ISSUES IN 1984 January-February World Health Day: Children's health— tomorrow's wealth March This wormy world : intestinal para- sites April Down from the ivory tower: the universities and Health for all May Rehabilitation for all June Population and health July Essential drugs for the world August-September Handle with care! Chemical safety October Nutrition : facts and hopes November Healthy mouths • Smallpox • Radiation • Water • Blindness • Guinea worm • UNRWA • Accidents December Schistosomiasis : new goals WORLD HEALTH ISSUES IN 1985 January-February World Health Day: Healthy youth —our best resource March Partners in health: NGOs and Health for all April Women : the next ten years May Tropical diseases research June Technology for health July Animals and man : veterinary pu- blic health August-September Protecting the mind : preventing mental ill health October A decade of onchocerciasis control December Drugs in medicine 111 JULY SALUD MUNDIAL Tratese con cuidado ! AUGUST- SEPTEMBER A WOE DO hil.AIDO Esquistossamiase: novosobjectives DECEMBER SAME DU !WOKE Une jou nosse sairte r ■ otna meal eur FISOUt JANUARY- FEBRUARY AUGUST- SEPTEMBER World Health Index 1958-1983 is available on demand from WHO Regional Offices or WHO headquarters in Geneva.