Anti-malarial medicine quality field studies and surveys: a systematic review of screening technologies used and reporting of findings

Abstract

Background: Assessing the quality of medicines in low-middle income countries (LMICs) relies primarily on human inspection and screening technologies, where available. Field studies and surveys have frequently utilized screening tests to analyse medicines sampled at the point of care, such as health care facilities and medicine outlets, to provide a snap shot of medicine quality in a specific geographical area. This review presents an overview of the screening tests typically employed in surveys to assess anti-malarial medicine quality, summarizes the analytical methods used, how findings have been reported and proposes a reporting template for future studies. Methods:A systematic search of the peer-reviewed and grey literature available in the public domain (including national and multi-national medicine quality surveys) covering the period 1990-2016 was undertaken. Studies were included if they had used screening techniques to assess the quality of anti-malarial medicines. As no standardized set of guidelines for the methodology and reporting of medicine quality surveys exist, the included studies were assessed for their standard against a newly proposed list of criteria. Results:The titles and abstracts of 4621 records were screened and only 39 were found to meet the eligibility criteria. These 39 studies utilized visual inspection, disintegration, colorimetry and Thin Layer Chromatography (TLC) either as components of the Global Pharma Health Fund (GPHF) MiniLab ® or as individual tests. Overall, 30/39 studies reported employing confirmatory testing described in international pharmacopeia to verify the quality of anti-malarials post assessment by a screening test. The authors assigned scores for the 23 criteria for the standard of reporting of each study. Conclusions:There is considerable heterogeneity in study design and inconsistency in reporting of field surveys of medicine quality. A lack of standardization in the design and reporting of studies of medicine quality increases the risk of bias and error, impacting on the generalizability and reliability of study results. The criteria proposed for reporting on the standard of studies in this review can be used in conjunction with existing medicine quality survey guidelines as a checklist for designing and reporting findings of studies. The review protocol has been registered with PROSPERO (CRD42015026782).

Quality of the antimalarial medicine artemether – lumefantrine in 8 cities of the Democratic Republic of the Congo

“…Nevertheless, a chemical analysis is always necessary to confirm any suspicion. TLC is a widely used technique for the identification of poor‐quality pharmaceutical compounds and finished products and has been applied in numerous quality surveys worldwide . It is cost‐effective, simple, and rapid.…”

“…However, TLC is a mainly qualitative technique and less sensitive than HPLC, which nowadays represents the gold standard in pharmaceutical analysis . Although it requires a laboratory with sophisticated equipment, it has several advantages such as higher accuracy, precision, and resolution capability.…”

“…TLC is a widely used technique for the identification of poor-quality pharmaceutical compounds and finished products and has been applied in numerous quality surveys worldwide. 30 It is cost-effective, simple, and rapid. In most of the studies conducted in Africa and Asia, the Global Pharma Health Fund (GPHF) Minilab protocols were used as a semi-quantitative assessment tool.…”

“…However, TLC is a mainly qualitative technique and less sensitive than HPLC, which nowadays represents the gold standard in pharmaceutical analysis. 30,34 Although it requires a laboratory with sophisticated equipment, it has several advantages such as higher accuracy, precision, and resolution capability. Using a slightly modified version of the method described in the monograph of The International Pharmacopoeia, HPLC-UV analysis permitted to confirm all the suspected cases, i.e., samples with only 1 or none of the 2 declared ingredients, and to discriminate substandard from good-quality medicines.…”

“…Using a sonication time shorter than 120 minutes resulted in a very high intra-individual deviation of the respective contents of more than 20%. Thus, different sonication times were evaluated(30, 60, and 120 minutes) and a duration of 120 minutes was eventually chosen to ensure complete extraction of the API from the tablet or from the powder for oral suspension matrices.Moreover, HPLC-UV analysis permitted classification of the samples by their chromatographic impurity profiles: Apart from the peaks corresponding to the active pharmaceutical ingredients, i.e., artemether and lumefantrine, 15 (10%) and 28 (18.7%) samples had 2 and 3 additional peaks, respectively, eluting near the artemether peak (Figure 5).3.5 | LC-MS analysisHPLC analysis in combination with diode array detection (HPLC-DAD) and MS investigations (LC-MS) revealed that the online ultraviolet and mass spectra of the additional compounds were related to degradation products of lumefantrine (viz., m/z = 406, 420, and 436) (Supporting Information), with molecular weights corresponding to degradation products already reported in the literature 24. By-products related to the chemical synthesis of lumefantrine have recently been found in AL drug samples collected in Nigeria 25.…”