Novel approaches to the detection of substandard medicines

Trippe, Zahra Anita. Novel approaches to the detection of substandard medicines. 2018, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_13678

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This thesis addresses the serious implications of substandard medicines to public health care and describes attempts to bridge the apparent gap of detecting substandard medicines by exploring new detection approaches in pharmacovigilance and in analytical technologies as well as validating these methods in a field study.
Substandard medicines (SSMs) are licensed medicines, that most commonly contain either too little or too much active pharmaceutical ingredient (API). SSMs may be the result of negligence, error and/or low standard of quality control of the manufacturing process (non-good manufacturing accredited status) and/or distribution process (degradation of medicinal products through bad storage). The use of SSMs may result in severe adverse events (AEs) and even death and may promote antimicrobial resistance. Evidence of high increases of SSMs, predominantly in developing countries, reveals that there is a need for easy, rapid and affordable detection tools. Currently, there is no portable screening device in the market that can accurately measure the content of API of medicinal samples.
The only available device, currently under development, is PharmaChk, an innovative analytical instrument, that is able to quantify the amount of a number of APIs (e.g. artemisinin, tetracycline) and evaluate their dissolution profile. In collaboration with the Biomechanical Department of Boston University, we conducted further research on this device. The assay for essential antimalarial drug Coartem® (artemether and lumefantrine) was developed and used for a field study in Zimbabwe.
In addition to analytical detection, pharmacovigilance signal detection techniques have been shown to be effective in detecting SSMs. Preliminary research (conducted by the WHO Uppsala Monitoring Centre) exists on using data mining algorithms on the WHO Vigibase® data set of global individual case safety reports to identify SSMs. After validation of this pharmacovigilance screening tool and the assay of Coartem® on the PharmaChk device and in order to assess the efficiency of these two detection approaches of SSMs in real world practice, we initiated a field study on Coartem® and its generic versions in Zimbabwe. Malaria is a major health burden in this country with 8,000,000 people at risk (50% of the population). Previous studies have shown that Zimbabweans are at high risk from substandard and falsified medicines, resulting in increased mortality, morbidity, financial strain and long-term antimicrobial resistance. We collected samples from sites of the private health sector as well as from sites that were conveniently accessible. The purchase of samples was performed in 18 cities in areas with high risk for malaria.
The quality of purchased samples was tested through qualitative and quantitative measurements using different screening field devices including Raman, Near-Infrared spectrometry and X-Ray Fluorescence as well as spectrophotometer and high performance liquid chromatography (HPLC) analysis for confirmatory analysis in analytical laboratories in Zimbabwe, Switzerland and the United States. Data mining for the antimalarial drug Coartem® identified no excess reporting of AEs in Zimbabwe.
Analyses of all screening and confirmatory analytical technologies revealed a good quality of all collected samples. The PharmaChk device demonstrated comparable results of the collected samples to HPLC, which is the gold standard method. The analytical screening tool PharmaChk was able to determine that there was no unexpected risk with essential medicine artemether/lumefantrine in Zimbabwe. This pilot study highlighted the potential of these two detection methods (pharmacovigilance screening tool and analytical detection tool using the PharmaChk device). However, further research on a larger scale of samples and other therapeutic areas is required to validate these findings.
This thesis highlights the need and importance of collaborations in identifying SSMs. Without the partnership between academia, industry and private laboratory institutions this research may have not been possible. The complex issue of SSMs requires this kind of engagement to enhance safe and effective medical treatment by decreasing the number of circulating SSMs worldwide.
Advisors:Meier, Christoph and Gasser, Susan M.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Clinical Pharmacy (Meier)
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:13678
Thesis status:Complete
Number of Pages:1 Online-Ressource (161 Seiten)
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edoc DOI:
Last Modified:13 Aug 2020 08:40
Deposited On:13 Aug 2020 08:40

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