Characterizing Medicine Quality by Active Pharmaceutical Ingredient Levels: A Systematic Review and Meta-Analysis across Low- and Middle-Income Countries

Abstract

Substandard and falsified medicines are often reported jointly, making it difficult to recognize variations in medicine quality. This study characterized medicine quality based on active pharmaceutical ingredient (API) amounts reported among substandard and falsified essential medicines in low- and middle-income countries (LMICs). A systematic review and meta-analysis was conducted using PubMed, supplemented by results from a previous systematic review, and the Medicine Quality Scientific Literature Surveyor. Study quality was assessed using the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). Random-effects models were used to estimate the prevalence of medicines with < 50% API. Among 95,520 medicine samples from 130 studies, 12.4% (95% confidence interval [CI]: 10.2-14.6%) of essential medicines tested in LMICs were considered substandard or falsified, having failed at least one type of quality analysis. We identified 99 studies that reported API content, where 1.8% (95% CI: 0.8-2.8%) of samples reported containing < 50% of stated API. Among all failed samples (N = 9,724), 25.9% (95% CI: 19.3-32.6%) reported having < 80% API. Nearly one in seven (13.8%, 95% CI: 9.0-18.6%) failed samples were likely to be falsified based on reported API amounts of < 50%, whereas the remaining six of seven samples were likely to be substandard. Furthermore, 12.5% (95% CI: 7.7-17.3%) of failed samples reported finding 0% API. Many studies did not present a breakdown of actual API amount of each tested sample. We offer suggested improved guidelines for reporting poor-quality medicines. Consistent data on substandard and falsified medicines and medicine-specific tailored interventions are needed to ensure medicine quality throughout the supply chain.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) diagram.

Figure 2.

Forest plot of overall prevalence of substandard and falsified medicines. Sample size includes all medicine quality study samples tested. Antimalarials include studies that examined antimalarials but not antibiotics. Antibiotics exclude studies that examined antimalarials. Antimalarials and antibiotics category includes studies that examined both together. Sample sizes of 1) antiretrovirals, 2) antihypertensives, 3) analgesics and anti-inflammatories, and 4) uterotonics include studies that investigated the specific therapeutic category but not antibiotics or antimalarials, and may or may not include other therapeutic categories.

Figure 3.

Proportion of samples that failed medicine quality tests by active pharmaceutical ingredient (API) levels. Sample size (99 studies, N = 9,724) includes studies with enough information to distinguish proportions of failed samples for no or incorrect API, > 50% API, and > 80% API.

Figure 4.

Medicines with < 50% active pharmaceutical ingredient (API) among samples that failed medicine quality tests. Sample size includes medicines found to be substandard or falsified across medicine quality studies. Classifications among therapeutic classes are the same as in Figure 2.