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Quality control of essential drugs
THE LANCET
Quality control of essential drugs SIR—Your Aug 30 editorial1 on quality control and essential drugs contains an erroneous statement that derives from Dr John Dunne. Between 1983 and 1989, when I was director of WHO’s Action Programme on Essential Drugs (DAP) and even later, DAP did not push for increased local production of essential drugs. In the General Assembly, in reports, and in advice to countries, DAP often did not advocate local production, particularly in countries with populations of less than 25 million. DAP’s concerns, based on experience in different countries, was that the value component in local-drug production was small and that quality and reliability of supplies were frequently questionable. When countries were eager to introduce local production of drugs, DAP recommended that they start with packaging from bulk and only gradually move towards simple formulation of drugs. Ernst Lauridsen Steglehylte, PL 620, 34030 Vislada, Sweden 1
Editorial. Quality control and essential drugs. Lancet 1997; 350: 601.
SIR—You draw much needed attention to the difficulties of pharmaceutical quality and price information in your Aug 30 editorial.1 You recognise the complexity of the issues, commend WHO for increased emphasis on quality assurance and regulatory capacity, and strongly endorse the concept of the Market New Service (MNS) as a source of current information on prices of raw materials for essential drugs. But you are also misleading with respect to WHO’s work in the area of quality assurance and pharmaceutical prices. Pharmaceutical quality and pharmaceutical prices are important public-health issues. In the example of tuberculosis, which you emphasise, control depends not only on the quality of antituberculars, but also on their availability at a reasonable price. The MNS is published by the United Nations International Trade Centre in collaboration with WHO. It is mainly used as a source of price information for pharmaceutical raw materials and also puts MNS subscribers in contact with potential supply sources; the service has never served as a broker. “Know your source” is a fundamental principle that applies equally to the procurement of pharmaceutical raw materials and finished products.
1106
Indeed, WHO’s guidelines on good manufacturing practices2 and procurement recommendations3 endorse this principle. The MNS does not promote individual suppliers in the newsletter, but clearly states that “information on the exact source” is available from the seller to subscribers who use the contact service.4 WHO condemns the sale of outdated products. The MNS prefers the current edition of pharmacopoeias, but specifications based on the previous edition are acceptable as a transition measure. This practice reflects the constraints of equipment, reagents, and training requirements for new tests. The practical implications of this approach vary according to the individual product. For example, you cite the use of the 1988 British pharmacopoeia (BP88) standards for rifampicin. Yet for rifampicin, as for many other drugs, BP88 and main edition BP93 standards are identical. Irrespective of which edition of a pharmacopoeia is used, the products themselves should be of recent manufacture. WHO guidelines on good manufacturing practice and WHO’s certification scheme provide specific measures to prevent the use of outdated and substandard ingredients. Contrary to the suggestion in your editorial, WHO contends that the production of essential drugs is appropriate only when drug quality can be assured. A producer who is unable to confirm the quality of raw materials as well as finished products should not be producing pharmaceuticals. The MNS was established as an information service. To address the issue of drug quality, WHO actively works with countries to strengthen the quality assurance capacity of national authorities and improve adherence to good manufacturing practice. Specific initiatives have also been undertaken in such areas as control of counterfeit drugs and certification of pharmaceutical raw materials. Since its inception in 1992, the MNS has evolved in light of comments received from MNS subscribers, WHO governing bodies, WHO experts, external evaluators, industry, and other concerned parties. WHO cannot accept the suggestion that the organization is anything but fully committed to promoting improved drug quality. *Jonathan Quick, Kari Bremer *Action Programme on Essential Drugs, World Health Organization, CH-1211 Geneva 27, Switzerland 1 2
Editorial. Quality control and essential drugs. Lancet 1997; 350: 601. WHO. Good manufacturing practices for pharmaceutical products. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Geneva: WHO, 1992 (technical report series 823).
3
4
WHO. Management Sciences for Health in Collaboration with World Health Organization Action Programme on Essential Drugs. In: Management drug supply. Hartford: Kumavian Press, 1997. Market News Service. Pharmaceutical Raw Materials/Essential Drugs, International Trade Centre, UNCTAD/GATT in collaboration with the World Health Organization. August, 1997.
SIR—You point to an independent control on quality of drugs at all stages in developing countries in your Aug 30 editorial.1 The manufacturers or control authorities could very well certify the potency of drugs, which would have to be supplemented by surveillance on quality and bioavailability of the drugs. However, formulations with optimum potency could then be stored and transported unsatisfactorily. Reports on a large-scale theft and black-market resale of expired and potentially toxic vaccines in Burma (Myanmar) is alarming: 10 000 doses of unrefrigerated vaccines were on sale in 1995. The vaccines were many months past the printed expiry date, had lost their potency, and were toxic when injected in laboratory animals.2 Another example is Sierre Leone where the use of expired drugs is an established practice and there is no organised system to monitor drug reaction.3 Roy’s analysis4 of 137 brands of ampicillin, cotrimexazole, and vitamin B2 preparations sold in Bangladesh, found 37 substandard formulations. Of the 16 brands of paracetamol and ten of ampicillin that were substandard, 11 and nine, respectively, had been assessed as satisfactory by regulatory authorities. The main obstacle in the control of essential drugs is the lack of trained manpower and equipment and inadequate funding for laboratories that monitor drug quality. To undertake quality control and test for malaria and tuberculosis, the laboratories would need to carry out infrared-absorption spectroscopy, thin-layer chromatography with silica gel, gas chromatography, and high-performance liquid chromatography. In less developed countries, the availability of simple, 1–2 step, assay procedures that do not require costly equipment and trained personnel is vital for strengthening quality control. A semiquantitative, paracetamol-specific spot test for screening paracetamol in the field,5 is promising. Screening of 38 brands of paracetamol enabled spotting of three spurious brands and 11 brands of borderline quality. Similar tests for drugs against tuberculosis would be invaluable. WHO’s Action Programme on Essential Drugs would be failing in its global commitments to ensure supply of potent drugs, if it does not
Vol 350 • October 11, 1997
Quality control of essential drugs SIR—Your Aug 30 editorial1 on quality control and essential drugs contains an erroneous statement that derives from Dr John Dunne. Between 1983 and 1989, when I was director of WHO’s Action Programme on Essential Drugs (DAP) and even later, DAP did not push for increased local production of essential drugs. In the General Assembly, in reports, and in advice to countries, DAP often did not advocate local production, particularly in countries with populations of less than 25 million. DAP’s concerns, based on experience in different countries, was that the value component in local-drug production was small and that quality and reliability of supplies were frequently questionable. When countries were eager to introduce local production of drugs, DAP recommended that they start with packaging from bulk and only gradually move towards simple formulation of drugs. Ernst Lauridsen Steglehylte, PL 620, 34030 Vislada, Sweden 1
Editorial. Quality control and essential drugs. Lancet 1997; 350: 601.
SIR—You draw much needed attention to the difficulties of pharmaceutical quality and price information in your Aug 30 editorial.1 You recognise the complexity of the issues, commend WHO for increased emphasis on quality assurance and regulatory capacity, and strongly endorse the concept of the Market New Service (MNS) as a source of current information on prices of raw materials for essential drugs. But you are also misleading with respect to WHO’s work in the area of quality assurance and pharmaceutical prices. Pharmaceutical quality and pharmaceutical prices are important public-health issues. In the example of tuberculosis, which you emphasise, control depends not only on the quality of antituberculars, but also on their availability at a reasonable price. The MNS is published by the United Nations International Trade Centre in collaboration with WHO. It is mainly used as a source of price information for pharmaceutical raw materials and also puts MNS subscribers in contact with potential supply sources; the service has never served as a broker. “Know your source” is a fundamental principle that applies equally to the procurement of pharmaceutical raw materials and finished products.
1106
Indeed, WHO’s guidelines on good manufacturing practices2 and procurement recommendations3 endorse this principle. The MNS does not promote individual suppliers in the newsletter, but clearly states that “information on the exact source” is available from the seller to subscribers who use the contact service.4 WHO condemns the sale of outdated products. The MNS prefers the current edition of pharmacopoeias, but specifications based on the previous edition are acceptable as a transition measure. This practice reflects the constraints of equipment, reagents, and training requirements for new tests. The practical implications of this approach vary according to the individual product. For example, you cite the use of the 1988 British pharmacopoeia (BP88) standards for rifampicin. Yet for rifampicin, as for many other drugs, BP88 and main edition BP93 standards are identical. Irrespective of which edition of a pharmacopoeia is used, the products themselves should be of recent manufacture. WHO guidelines on good manufacturing practice and WHO’s certification scheme provide specific measures to prevent the use of outdated and substandard ingredients. Contrary to the suggestion in your editorial, WHO contends that the production of essential drugs is appropriate only when drug quality can be assured. A producer who is unable to confirm the quality of raw materials as well as finished products should not be producing pharmaceuticals. The MNS was established as an information service. To address the issue of drug quality, WHO actively works with countries to strengthen the quality assurance capacity of national authorities and improve adherence to good manufacturing practice. Specific initiatives have also been undertaken in such areas as control of counterfeit drugs and certification of pharmaceutical raw materials. Since its inception in 1992, the MNS has evolved in light of comments received from MNS subscribers, WHO governing bodies, WHO experts, external evaluators, industry, and other concerned parties. WHO cannot accept the suggestion that the organization is anything but fully committed to promoting improved drug quality. *Jonathan Quick, Kari Bremer *Action Programme on Essential Drugs, World Health Organization, CH-1211 Geneva 27, Switzerland 1 2
Editorial. Quality control and essential drugs. Lancet 1997; 350: 601. WHO. Good manufacturing practices for pharmaceutical products. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Geneva: WHO, 1992 (technical report series 823).
3
4
WHO. Management Sciences for Health in Collaboration with World Health Organization Action Programme on Essential Drugs. In: Management drug supply. Hartford: Kumavian Press, 1997. Market News Service. Pharmaceutical Raw Materials/Essential Drugs, International Trade Centre, UNCTAD/GATT in collaboration with the World Health Organization. August, 1997.
SIR—You point to an independent control on quality of drugs at all stages in developing countries in your Aug 30 editorial.1 The manufacturers or control authorities could very well certify the potency of drugs, which would have to be supplemented by surveillance on quality and bioavailability of the drugs. However, formulations with optimum potency could then be stored and transported unsatisfactorily. Reports on a large-scale theft and black-market resale of expired and potentially toxic vaccines in Burma (Myanmar) is alarming: 10 000 doses of unrefrigerated vaccines were on sale in 1995. The vaccines were many months past the printed expiry date, had lost their potency, and were toxic when injected in laboratory animals.2 Another example is Sierre Leone where the use of expired drugs is an established practice and there is no organised system to monitor drug reaction.3 Roy’s analysis4 of 137 brands of ampicillin, cotrimexazole, and vitamin B2 preparations sold in Bangladesh, found 37 substandard formulations. Of the 16 brands of paracetamol and ten of ampicillin that were substandard, 11 and nine, respectively, had been assessed as satisfactory by regulatory authorities. The main obstacle in the control of essential drugs is the lack of trained manpower and equipment and inadequate funding for laboratories that monitor drug quality. To undertake quality control and test for malaria and tuberculosis, the laboratories would need to carry out infrared-absorption spectroscopy, thin-layer chromatography with silica gel, gas chromatography, and high-performance liquid chromatography. In less developed countries, the availability of simple, 1–2 step, assay procedures that do not require costly equipment and trained personnel is vital for strengthening quality control. A semiquantitative, paracetamol-specific spot test for screening paracetamol in the field,5 is promising. Screening of 38 brands of paracetamol enabled spotting of three spurious brands and 11 brands of borderline quality. Similar tests for drugs against tuberculosis would be invaluable. WHO’s Action Programme on Essential Drugs would be failing in its global commitments to ensure supply of potent drugs, if it does not
Vol 350 • October 11, 1997