Analytical Strategies for the Determination of the Prevalence of Poor-Quality Anti-Infective Medicines in Cameroon

Summary
Substandard and falsified (SF) medicines represent a global pandemic, which poses a threat to populations from a socio-economic and public health point of view. To combat this scourge, it is essential, on the one hand, to have a clear understanding of the extent of the situation in terms of prevalence, and on the other hand to develop efficient control strategies that consider the socio-economic realities of the target geographical areas. The main goal of our thesis was to propose an efficient analytical strategy implementable during pharmaceutical post-market surveillance in limited-resource countries. To achieve this, several projects were carried out.
The first task consisted in a literature review of alerts and studies on SF medicines in Cameroon. We found that the problem of SF medicines is insufficiently studied in this country, since only 92 publications consisting of alerts and medicine quality studies (MQSs) were issued between 1995 and 2020. Among the MQSs, there was 4 reporting cases of falsified medicines, and 19 field surveys. Based on the field surveys, a prevalence of 26.9% of SF medicines was determined, mostly from the informal sector. The poor-methodological quality of these studies, and the non-uniformity of their national coverage, were the main shortcomings that could potentially bias the determination of the prevalence of SF medicines.
Secondly, we conducted a prevalence study in accordance with existing guidelines for field studies. The aim was to assess the quality of anti-infective medicines in 3 Cameroonian cities, using ciprofloxacin and metronidazole tablets as models. The visual inspection test, disintegration test and HPLC assay were implemented on 292 samples collected from the formal and the informal sectors. The prevalence of SF medicines was 7.9%, and the prevalence of facilities distributing SF medicines was 14.6%. These proportions were high in the informal sector.
Thirdly, we implemented three low-cost portable screening tools - the simplified visual inspection checklist, portable near-infrared equipment (NIR-S-G1) and paper analytical devices - on the 292 samples of the previous study. Their usefulness in this screening phase was demonstrated for the detection of SF medicines in limited-resource countries since advantages and limitations of each device were underlined. The obtained results can be used as guide for future users regarding the type of screening tool to be implemented.
Finally, we developed and successfully validated in Liège (temperate oceanic climate), PLS regression models intended to detect substandard ciprofloxacin and metronidazole samples in tablet dosage forms, using low-cost portable NIR equipment in transmission mode (NIR-M-T1). These rapid and cheaper methods were designed to be easily applied in field settings in limited resources countries. Therefore, the obtained models were implemented in Cameroon (tropical climate), adopting a transfer strategy to reduce the influence of environmental factors linked to climatic differences with Belgium. In view of the obtained results, low-cost handheld NIR devices can be used for in-field dosages in resource-limited countries to reduce the number of samples that need to be analyzed using confirmatory laboratory methods.
In light of these findings, we proposed a two-stage analytical strategy based on the use of field methods upstream of laboratory ones. This one can be implemented in limited-resource settings to strengthen the capacity of NMRAs for pharmaceutical market surveillance and monitoring, and thus help to rapidly reduce the prevalence of SF medicines and their negative impact on the population.