Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Medicine Quality Research Group, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.
Nuffield Department of Medicine, Medicine Quality Research Group, University of Oxford Centre for Tropical Medicine and Global Health, Oxford, UK.
BMJ Glob Health. 2022 Aug;7(8). doi: 10.1136/bmjgh-2022-008564.
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.
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.
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.
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.
劣质和假冒（SF）兽用药品会影响动物健康、农业生产和食品安全，并会影响动物和人类的抗生素耐药性（AMR）。然而，我们对其范围和影响的了解还很有限。我们评估了有关 SF 兽用药品流行病学的现有公共领域证据，以更好地了解其流行程度和分布情况，以及它们对动物和人类的公共卫生影响。
截至 2021 年 2 月 28 日，在 Embase、PubMed、MEDLINE、全球卫生、Web of Science、CAB 摘要、Scopus、Google Scholar、Google 和对兽药质量感兴趣的网站上进行了检索。筛选出英文和法文的合格文章。使用《药品质量评估报告指南》评估流行率调查的质量。
共纳入 314 篇文献，其中失败频率（至少一项质量检测不合格的样本百分比）为 6.5%（2335/35733）。大多数样本来自韩国和中国药品监管部门对上市后药品的监测。一小部分（3.5%）的样本，均为抗感染药物，来自 20 项流行率调查，其中一半以上（53.1%，662/1246）来自非洲和亚洲低收入和中低收入国家。流行率调查样本量范围为 4 至 310 份（中位数（Q1-Q3）：50（27-80））；55.0%的调查采用便利抽样方法。在 20 项流行率调查中，超过一半的样本（52.0%，648/1246）至少有一项质量检测不合格。报告的最常见缺陷是活性药物成分（API）含量不符合规定、单位均匀性和崩解试验失败。几乎一半（49.7%，239/481）API 含量检测不合格的样本中至少含有一种药典限量以下的规定 API。52 份样本（所有样本的 4.2%）含有一种或多种不正确的 API。123 篇文献描述了 29 个国家的 SF 兽用药品不良事件（召回/扣押/病例报告）。
数据表明，SF 兽用产品可能是一个严重的动物和公共卫生问题，但尚未得到充分关注。然而，目前关于 SF 兽用药品的研究很少，而且地域限制很大。低于药典标准规定的 API 含量和崩解/溶解会导致治疗失败、动物痛苦，并导致 AMR。我们的研究结果强调需要进行更多的研究，采用更稳健的方法，以便更好地为政策提供信息，并采取措施确保供应链中兽用药品的质量。SF 兽用产品对动物和人类健康、农业生产、经济和 AMR 的影响及其机制需要更多跨学科研究。
