Date Published: March 08, 2018
Publisher: The American Society of Tropical Medicine and Hygiene
Author(s): Benedetta Schiavetti, Evelien Wynendaele, Bart De Spiegeleer, Geremie J. Mbinze, Nicodème Kalenda, Roland Marini, Vera Melotte, Epco Hasker, Bruno Meessen, Raffaella Ravinetto, Josiane Van der Elst, Daniel Mutolo Ngeleka.
Poor-quality medicines are a threat to public health in many low- and middle-income countries, and prospective surveys are needed to inform corrective actions. Therefore, we conducted a cross-sectional survey on a sample of products used for children and available in the private market in Kinshasa, Democratic Republic Congo: amoxicillin (AX) and artemether/lumefantrine (AL), powders for suspension, and paracetamol (PC) tablets 500 mg. Overall, 417 products were covertly purchased from 61 wholesalers. To obtain a representative sample, the products were weighted on their market shares and a subset of 239 samples was randomly extracted to undergo in-depth visual inspection locally, and they were chemically assessed at two accredited laboratories in Belgium. Samples were defined of “poor-quality” if they failed to comply with at least one specification of the International Pharmacopoeia (for AL) or United States Pharmacopoeia 37 (for AX and PC). Results are reported according to the Medicine Quality Assessment Reporting Guideline. The visual inspection detected nonconformities in the aspects of antimalarial powders for suspension, and poor-quality labels across all medicine types. According to chemical analysis, 27.2% samples were of poor quality and 59.5% of AL samples were underdosed in artemether. Poor quality was more frequent for locally manufactured antimalarials (83.3%, P = 0.021; 86.4%, P = 0.022) and PC (4.8%, P = 0.000). The poor quality of the surveyed products may decrease the treatment’s efficacy and favor the development of resistances to antimalarials. It is hoped that these findings may guide the corrective actions of the Democratic Republic of Congo Regulatory Authority, which was the main partner in the research.
There is growing evidence that poor-quality medicines represent an important problem,1–7 which may cause therapeutic inefficacy and prolonged illness or death,8 toxicity,9 increased drug resistances,10–12 as well as loss of trust in health-care systems. They are particularly prevalent in low- and middle-income countries (LMICs).13–15 Although the interpretation of existing data is blurred by the lack of harmonization in the methodologies and definitions used,16 two recent reviews suggested respectively that among antimalarials tested over a span of 67 years, 30.1% were of poor quality16 and that the rate of poor-quality medicines in sub-Saharan Africa ranges from 12% to 48%.17 The global supply chain is increasingly complex18 and the price competition may foster the trade of non-quality–assured products, whereas the under-resourced national medicines regulatory authorities (NMRAs) struggle to control their markets.19–21 Children in LMICs have often been the victims of poor-quality medicines22,23; a recent modeling study estimates that 3.75% of all malaria deaths in children aged less than 5 years in sub-Saharan Africa are due to poor-quality antimalarials.24 However, few studies have formally assessed the quality of pediatric formulations.25
The definitions used in this survey are provided in Box 1.
The chemical analysis could not screen for degradation, but no samples were expired at the time of the purchase and analysis. The chemical analysis could also not screen for falsification. However, all the samples contained the stated active ingredients; the high-performance liquid chromatography analyses did not reveal suspect peaks and the visual inspection did not find gross signs of mislabeling. This means that we did not find any suggestion of “falsified” medical products, that is, products that “deliberately or fraudulently misrepresent their identity, composition, or source.” Therefore, we tentatively classified the poor-quality samples as substandards, that is, medicines that are “authorized by national regulatory authorities but fail to meet either national or international quality standards or specifications, or in some cases, both.” Noteworthy, according to the new WHO definitions of poor-quality medicines that were approved by the World Health Assembly on May 29, 2017, a part of our samples were not registered in DRC, so they should now be classified as “unregistered or unlicensed medical products,” that is, medicines that “have not been assessed or approved by the relevant national or regional regulatory authority for the market in which they are marketed, distributed, or used.”