By Pierre Massat – QUAMED Program Manager, Institute of Tropical Medicine
When people talk about the quality of medicines, they almost invariably end up pronouncing the word “counterfeit”. The problem stretches far beyond, though, and the consequences on the global public health are substantially bigger than in the case of fake sneakers or sunglasses. Although quite technical, the essence of the subject is not that difficult to understand, provided that someone takes the trouble to frame the problem with precision and show you the big picture.
This is precisely what the Institute Of Medicine, the “health arm” of the US National Academy of Sciences managed to do in a report published last March. Entitled “Countering the problem of falsified and substandard drugs”, it was mandated by the US-Food and Drug Administration to a committee of experts led by Lawrence O. Gostin and Gillian J. Buckley, with the aim of providing a complete overview of the current knowledge on poor quality medicines and their impact on public health.
In the introduction, the authors review the standards against which quality is assessed, the role of the pharmacopeia and of national medicines regulatory authorities and provide definitions. The report strongly advocate against the use of the term counterfeit which, by focusing on pure intellectual property concerns, have diverted the international discussions: as they put it in chapter 7, “an emphasis on the public health risks of illegitimate drugs is central to framing this problem; protecting drug companies’ proprietary interests is not.” Thus the authors propose to classify poor quality medicines into three categories: substandard (“fails to meet national specifications cited in an accepted pharmacopeia or in the manufacturer’s approved dossier”), falsified (“falsely represent the product’s identity or source or both”) and unregistered medicines (“lack market authorization from the national regulatory authority”). This last category only means that medicines are illegally marketed, and does not provide any information on their quality a priori.
Through striking real-life cases, chapter 2 illustrates the public health consequences of poor quality drugs. From a strictly chemical perspective poor quality medicines may contain wrong ingredients, in some cases toxic (such as an ingredient of anti-freeze which was found in syrups and killed over 300 people in Nigeria, Panama and China), the active ingredient may be overdosed, underdosed, or there can simply be no active ingredient at all. Although the deadly cases are the most reported, the most worrying effect on global public health on the long run is the drug resistance induced by underdosed active ingredients (affected diseases include TB and malaria).
From a socio-economic perspective, poor quality drugs are extremely costly: their lower efficacy leads to longer treatments or treatment failure, which increases the financial burden on both households and the health system and put pressure on the ever more expensive development of new substances. Last but not least, poor quality medicines (often the result of poor regulation), are a threat to governments by reducing the confidence of the population in the health system, and by financing criminal activities and corruption.
Although scientific studies have tackled the issue and a few international initiatives exists that centralize reported cases , data is difficult and costly to obtain, and the actual prevalence of poor quality medicines worldwide is unknown. The authors suggest a methodology for conducting surveys, and stress the need for raising awareness, and for capacity building to improve case reporting.
The causes of poor quality drugs are mainly economic and political. Assuming that manufacturers have no intention to produce poor quality medicines, it is costly to meet the international best manufacturing practices, and access to loans is nearly impossible in low-income countries. Manufactures can intentionally “cut corners” by marginally reducing the content in active ingredient, which can lead to a substantial increase in the profit margin, as well as by investing in “parallel production” (producing the same medicine, with lower requirements on quality, through subcontracted manufacturers established in cheaper environments). Medicines can be shipped in bulk and be repacked by wholesalers, making it difficult to trace their origin, thus creating opportunities for poor quality medicines to enter the legitimate supply chain. This is all the more true in developing countries, where the distribution of medicines is fragmented through thousands of small wholesalers, pharmacies and street-shops. At the very end of the distribution chain stand the consumers, who mostly have to buy medicines out of pocket in unregulated drug shops due to the frequent shortages in the public health system.
The majority of these weaknesses are the result of poor national and international regulation, with insufficient control on manufacturers and weak monitoring of the distribution chain. The low probability of being caught, associated with insignificant punishment ( falsification of medicines in the US is punished by up to 1 year in prison and a $ 1 000 fine), creates incentives for ill-intentioned actors. The authors also mention that retailers selling medicines on the internet will be a major challenge for regulators in the coming years.
In weakly regulated country, one mid-term solution is the strengthening of the procurement system, by increasing transparency in tenders, strengthening the donors’ rules, and helping national procurement agencies implement the WHO’s Model Quality Assurance System (MQAS). Incidentally, this is precisely what QUAMED advocates for, and a substantial part of our activities are targeted at bringing partner procurement agencies up to standards.
The authors conclude with a call for an “international code of practice for falsified and substandard medicines”, the development of which should be led by the WHO and that is intended to act as “soft law” (“the committee does not believe that the time is ripe for hard low solutions”) providing guidelines on surveillance, regulation and law enforcement. The ultimate goal is to be able to better combat the global issue of drug quality with more coordination and harmonized regulation policies.
This report is roughly 250 pages long, and it would be too ambitious to accurately summarize all its keys messages . Yet I hope that this blog post will stir enough interested for you to read at least part of it. I personally believe that this is a must read for anybody working not only in the field of the quality of medicines, but also for those interested in health policy, health economics, and more generally in the interactions between the world economy, the regulators and the global public health.