The quality of veterinary medicines and their implications for One Health.

OBJECTIVE: Substandard and falsified (SF) veterinary medicines affect animal health, agricultural production and food security and will influence antimicrobial resistance (AMR) in both animals and humans. Yet, our understanding of their extent and impact is poor. We assess the available public domain evidence on the epidemiology of SF veterinary medicines, to better understand their prevalence and distribution and their public health impact on animals and humans. METHODS: Searches were conducted in Embase, PubMed, MEDLINE, Global Health, Web of Science, CAB Abstracts, Scopus, Google Scholar, Google and websites with interest in veterinary medicines quality up to 28 February 2021. Identified articles in English and French were screened for eligibility. The Medicine Quality Assessment Reporting Guidelines were used to assess the quality of prevalence surveys. RESULTS: Three hundred and fourteen publications were included with a failure frequency (the percentage of samples that failed at least one quality test) of 6.5% (2335/35 733). The majority of samples were from post-marketing surveillance by medicines regulatory authorities of the Republic of Korea and China. A small proportion (3.5%) of samples, all anti-infectives, were from 20 prevalence surveys, with more than half (53.1%, 662/1246) collected in low-income and lower middle-income countries in Africa and Asia. The prevalence survey sample size ranged from 4 to 310 samples (median (Q1-Q3): 50 (27-80)); 55.0% of surveys used convenience outlet sampling methods. In 20 prevalence surveys more than half of the samples (52.0%, 648/1246) failed at least one quality test. The most common defects reported were out-of-specification active pharmaceutical ingredient(s) (API) content, failure of uniformity of units and disintegration tests. Almost half of samples (49.7%, 239/481) that failed API content tests contained at least one of the stated APIs below pharmacopoeial limits. Fifty-two samples (4.2% of all samples) contained one or more incorrect API. One hundred and twenty-three publications described incidents (recalls/seizures/case reports) of SF veterinary medicines in 29 countries. CONCLUSION: The data suggest that SF veterinary products are likely to be a serious animal and public health problem that has received limited attention. However, few studies of SF veterinary medicines are available and are geographically restricted. Lower API content and disintegration/dissolution than recommended by pharmacopoeial standards risks treatment failure, animal suffering and contribute to AMR. Our findings highlight the need of more research, with robust methodology, to better inform policy and implement measures to assure the quality of veterinary medicines within supply chains. The mechanism and impact of SF veterinary products on animal and human health, agricultural production, their economy and AMR need more transdisciplinary research.

The quality of medical products for cardiovascular diseases: a gap in global cardiac care.

OBJECTIVE: Good quality cardiovascular medicines and devices are crucial in the prevention and management of the ever-growing threats of cardiovascular diseases (CVDs) globally. Yet our current understanding of the extent and impact of substandard and falsified (SF) cardiovascular medical products is poor. Our objective was to review the available literature on SF cardiovascular medicines/devices, with a focus on prevalence studies to discuss their impacts on public health. METHODS: Searches were conducted in Embase, PubMed, Web of Science, Google Scholar, Google and websites with interest in medicines/devices quality up to 31 August 2020. Articles in English and French identified in these searches were screened for eligibility. The Medicine Quality Assessment Reporting Guidelines was used to assess the quality of prevalence surveys, and we report according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: A total of 279 articles were included, which were subcategorised into prevalence surveys (n=28), equivalence studies (n=118), stability studies (n=5), routine quality control analyses (n=15), bioavailability studies (n=2), recalls/seizures/case reports (n=77), general discussions (n=24) and reviews (n=10). A failure frequency (defined as the proportion of samples that failed at least one quality test described in the report) of 525 (15.4%) was observed for the 3414 samples tested for quality in the 27 prevalence surveys with sufficient information for inclusion in our quantitative analysis. Nineteen surveys (70.4%) used convenience outlet sampling. The majority (88.8%, 3032/3414) of samples included in prevalence surveys were collected from low-income and middle-income countries. The most common defects were out-of-specification active ingredient(s) content, impurity/contaminant content and impaired dissolution. We found 26 incidents describing SF cardiovascular devices with 181 related deaths but no prevalence surveys. CONCLUSION: The data suggest that SF cardiovascular products are likely to be a serious public health problem that has received limited attention. We do not suggest that 15.4% of cardiovascular medicines are SF, and our findings highlight the need for more research with robust methodology to provide more accurate prevalence estimates in order to inform policy and implement measures to ensure the quality of cardiovascular medicines and devices within the supply chain. Ensuring that CVD medical products are of good quality would help ensure effectiveness and that the benefits of therapy are realised in the prevention and treatment of CVDs.