Abstract:
Within their Sustainable Development Goals (SDGs), the United Nations aim to achieve “access to safe, effective, quality and affordable essential medicines for all.” However, the occurrence of substandard and falsified (SF) medicines threatens the achievement of this goal, especially in low- and middle-income countries (LMICs). Often, the data on the occurrence of SF medicines in LMICs, like Nigeria, are very heterogeneous. Therefore, a study on the quality of 13 essential medicines in Enugu and Anambra states, Nigeria, was carried out in collaboration with the Nigerian partner organization Faith-Based Central Medical Foundation (FBCMF). In total, 260 samples were collected from licensed vendors and markets with unclear licensing status. They were investigated according to the United States Pharmacopeia (USP) for content and dissolution of their active pharmaceutical ingredient (API). Of all 260 samples, 25.4% did not comply with the USP specifications. Unexpectedly, no difference was observed in the proportions of out-of-specification medicines for samples collected from licensed vendors compared to markets. Four samples (1.5%), all collected in markets, were found to be falsified, as they did not contain any of the stated APIs. However, the percentage of falsified medicines found in this study is lower than previously reported in the media.
To fight SF medicines, the World Health Organization (WHO) promotes a “prevention, detection and response” strategy. The detection of these harmful products, which is particularly challenging in low-resource settings, can be improved through rapid, inexpensive and easy-to-use screening technologies. Therefore, the possibilities and limitations of detecting the API in tablets using a low-cost near-infrared (NIR) spectrometer were investigated. Spectra of 170 products were collected, comprising 41 different APIs, API combinations, placebos or falsified products. Chemometric models were built for 10 APIs using data-driven soft independent modelling of class analogy (DD-SIMCA) and subsequently tested with all other APIs and placebos, as well as the 20 falsified medicines. All developed models correctly identified samples containing a different API from the stated one, no API or grossly incorrect API amounts with 100% specificity, suggesting that the studied method is a promising technology for screening medicines for their quality in low-resource settings.
A widely used screening technology is the Global Pharma Health Fund (GPHF)-Minilab. Medicines collected during the medicine quality study in Nigeria were thus analyzed according to the GPHF-Minilab monographs with visual inspection, disintegration and TLC testing. The four falsified samples were flagged as suspicious during visual inspection and were readily identifiable with TLC analysis. However, only seven (35%) out of all 20 medicines deviating by more than 20% in USP assay analysis, which is the possible GPHF-Minilab detection limit, were detected as non-compliant in TLC analysis. To improve the quantitative evaluation of these TLC-analyses, a smartphone-based imaging software (TLCyzer) was developed in cooperation with the group of Hendrik Lensch (department of computer science, University of Tuebingen). The TLCyzer had shown promising results in a laboratory performance evaluation for 14 APIs and was subsequently tested in the course of this doctoral research in a real-life setting in Nigeria. Compared to analyzing the TLC plates visually, the detection of SF medicines was improved with the TLCyzer, but good quality samples were often incorrectly detected as non-compliant, indicating that the application needs further improvements before it is ready for field-use.
Since 2022, there has been an increase in the occurrence of pediatric medicines contaminated with diethylene glycol and ethylene glycol, leading to at least 300 fatalities in children worldwide. To improve the availability of suitable screening technologies to detect such contaminations, a target product profile (TPP) for screening devices to detect medicines contaminated with diethylene glycol and ethylene glycol was developed during this doctoral thesis and is in the process of being officially adopted by the WHO. The developed TPP may also be used as a template for further urgently needed TPPs for screening devices.
There is a general public opinion that higher costs for a medicine equate to better quality, yet there is little evidence on the relationship between prices and quality of medical products in LMICs. To address this research gap, the relationship between prices and quality of essential medicines collected in Cameroon, the Democratic Republic of the Congo and Nigeria was investigated. The 70 originator medicines and SRA generics (generic medicines manufactured in countries with stringent regulatory authorities [SRA]) were all within the pharmacopeial specifications for content and dissolution, whereas 21.1% of the 626 non-SRA generics (generic medicines manufactured in countries without an SRA) were outside the pharmacopeial specifications. Originators were thrice as expensive, and SRA generics twice as expensive, as non-SRA generics. Among the non-SRA generics, no positive correlation between medicine quality and medicine prices was established. Some criteria could be defined for the selection of manufacturers of good-quality medicines at affordable prices.
LMICs