Pharmacopeial quality of artemether–lumefantrine anti-malarial agents in Uganda

Abstract

Background Substandard anti-malarial agents pose a significant challenge to effective malaria control and elimination efforts especially in sub-Saharan Africa. The quality of anti-malarials in most low-and-middle income countries (LMICs) is affected by several factors including inadequate regulation and limited resources. In this study, the pharmacopeial quality of artemether–lumefantrine (AL) in low and high malaria transmission settings in Uganda was assessed. Methods This was a cross-sectional study conducted among randomly selected private drug outlets. The AL anti-malarials available in drug outlets were purchased using overt method. The samples were screened for quality using visual inspection, weight uniformity, content assay and dissolution tests. The assay test was done using liquid chromatography–mass spectrometry (LC–MS). The samples were considered substandard if the active pharmaceutical ingredient (API) content was outside 90–110% range of the label claim. Dissolution test was conducted following United States Pharmacopoeia (USP) method. Data was analysed using descriptive statistics and presented as means with standard deviations, frequencies, and proportions. Correlation between medicine quality and independent variables was determined using Fisher’s exact test of independence at 95% level of significance. Results A total of 74 AL anti-malarial samples were purchased from high (49/74; 66.2%) and low (25/74; 33.8%) malaria transmission settings. The most common batch of AL was LONART, 32.4% (24/74), with 33.8% (25/74) being ‘Green leaf’. Overall prevalence of substandard quality artemether–lumefantrine was 18.9% (14/74; 95% CI: 11.4–29.7). Substandard quality AL was significantly associated with setting (p = 0.002). A total of 10 samples (13.5%) failed artemether content assay test while, 4 samples (5.4%, 4/74) failed the lumefantrine assay test. One sample from a high malaria transmission setting failed both artemether and lumefantrine assay content test. Of the samples that failed artemether assay test, 90% had low (< 90%) artemether content. All the samples passed visual inspection and dissolution tests. Conclusion Artemether–lumefantrine agents, the recommended first-line treatment for uncomplicated malaria with APIs outside the recommended pharmacopeial content assay limit is common especially in high malaria transmission settings. There is need for continuous surveillance and monitoring of the quality of artemisinin-based anti-malarials across the country by the drug regulatory agency.

Application of hybrid failure mode effect analysis based on fuzzy AHP and fuzzy TOPSIS in quality risk assessment of fixed-dose artemether-lumefantrine tablets

“…The results of the survey may invoke a proactive risk mitigation plans systems for the management of product non-conformances, complaints, recalls, and continuous improvement plans [14]. The scientific literature on ACT quality assessment is fairly rich [3,[26][27][28]. However, only a few studies adopted a risk-based approach in ACT quality risk analysis [4].…”

“…The term quality is a broad term that summarizes multi-attribute criteria used to gauge the compliance level of the ACTs to fitness for intended clinical application throughout its lifecycle. ACTs critical product attributes include the drug's identification, purity, potency, shelf-life, dissolution kinetics, bioequivalence, disintegration, and compliance with labelling and packaging requirements, in addition to several other pharmacopoeial and regional regulatory specification [3][4][5][6] .The quality of ACTs is essential to both patient safety during the use of the product and successful therapy.…”

“…Unfortunately, forensic analysis has revealed the structural vulnerability of the pharmaceutical supply chain (both formal and informal) of Low and Middle-income Countries (LMICs) to counterfeit and substandard ACTs posing significant public health risks [3,7,8]. The presence of low-quality ACTs greatly jeopardizes the standards of the supply chain resulting in diminished confidence in the healthcare systems [8].…”

Copayment mechanism in selected districts of Uganda: Availability, market share and price of quality assured artemisinin-based combination therapies in private drug outlets

“…The sector thus plays an integral role in the fight against malaria [ 13 ]. Patients seeking malaria treatment in the private sector are however faced with multiple challenges including high cost, unreliable supply, and substandard antimalarial agents [ 10 , 14 ]. In most malaria affected countries price remains the leading contributor to limited access to antimalarial agents [ 10 , 15 ].…”

Availability, market share and price of quality assured artemisinin-based combination therapies in private drug outlets after over a decade of Copayment mechanism in Uganda

“…The sector thus plays an integral role in the fight against malaria (8). Patients seeking malaria treatment in the private sector are however faced with multiple challenges including high cost, unreliable supply, and substandard antimalarial agents (5,9). In most malaria affected countries price remains the leading contributor to limited access to antimalarial agents (5,10).…”