In a random study of drugs from 713 pharmacies from 19 countries, 9.1% of anti-tuberculosis drugs analysed failed basic quality control testing using thin layer chromatography (TLC) for the required level of active pharmaceutical ingredient (API), according to a recent study published in the International Journal of Tuberculosis and Lung Disease.1
The samples were taken from private-sector pharmacies in Angola, Brazil, China, Democratic Republic of Congo, Egypt, Ethiopia, Ghana, India, Kenya, Nigeria, Russia, Rwanda, Thailand, Turkey, Uganda, United Republic of Tanzania and Zambia.
The authors believe this preliminary investigation may underestimate the actual numbers of fake and substandard TB drugs available. Previous research by the group using TLC and high performance liquid chromatography (HPLC) indicated that better quality fakes can be missed.2
In 2011, 8.7 million new cases of TB were reported with 1.4 million fatalities, according to the World Health Organization (WHO).3 The target set by WHO to halve the TB mortality rate of 1990 globally by 2015 is on track, however, this trend is reversed in African and European regions. Nearly half of TB cases reported worldwide (40%) are in Africa and Asia2 and increasing rates of multidrug-resistant TB (MDR-TB) strains are a key factor.
The length and complexity of TB treatment is a big problem. Recommended treatment is over a course of six months, and combines the dosage of two antibiotics, isoniazid (INH) and rifampicin (RMP). WHO recommends that patients attend government-run clinics for TB treatment, but in reality, this is not always an option for patients in the third world and many turn to the private sector for advice and medication, encouraging the production of non-registered drugs.
“Falsified drugs made up a small but still significant portion of the failing drugs in our study,” said the authors, noting that it is not yet known to what extent poor quality drugs—whether substandard or counterfeit—are contributing to drug resistance on a global scale. “The research simply hasn't been done to quantify that, but we hope that large-scale studies of this problem will be forthcoming. Our study, as a preliminary field analysis, does suggest that poor quality TB drugs are a problem both for individual patients and for populations.”
The focus of the investigation suggests that this is mainly a third-world problem, but the authors say that it has implications for the US and other developing countries, and that a high level of vigilance is needed to avoid counterfeiting of newly developed drugs against TB.
The authors commented: “The FDA just approved the first new drug to treat MDR-TB, Sirturo, and we may see another MDR-TB drug be approved as early as this year. “ said the authors. “Authorities should be vigilant to ensure counterfeit versions of these new drugs don't make their way into the supply chain.”
Larger public health agencies need to put more resources into further investigations to measure the full extent of the problem. Supply chains of TB drugs need to be improved to prevent degradation, and enforcement of regulations increased to bring counterfeiters to justice, according to the authors. Analytical chemistry will be essential to the future safety testing of TB drug supply chains.
1. R. Bate, P. Jensen, K. Hess, L. Mooney and J. Milligan, International Journal of Tuberculosis and Lung Disease, DOI: http://dx.doi.org/10.5588/ijtld.12.0355 (2013).
2. R. Bate, K. Hess, R. Tren, L. Mooney, F. Cudjoe, T. Ayodele, F. Cudjoe, T. Ayodele and A. Attaran, Research and report in Tropical Medicine, DOI: http://dx.doi.org/10.2147/RRTM.S33690 (2012).
3. World Health Organisation (WHO) Global Tuberculosis Report 2012, http://www.who.int/tb/publications/global_report/en
4. Health Protection Agency, UK http://www.hpa.org.uk/infections/topics_az/tb/