Evaluation of portable devices for medicine quality screening: Lessons learnt, recommendations for implementation, and future priorities.

Céline Caillet and co-authors discuss a Collection on use of portable devices for the evaluation of medicine quality and legitimacy.

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.

Substandard and falsified antibiotics: neglected drivers of antimicrobial resistance?

OBJECTIVES: Antimicrobial resistance (AMR) is a significant global health threat with substandard and falsified (SF) antibiotics being neglected contributing factors. With their relationships poorly understood, more research is needed in order to determine how interventions to reduce SF antibiotics should be ranked as priorities in national AMR action plans. We assessed the evidence available on the global prevalence of SF antibiotics, examined the quality of the evidence and discussed public health impact. MATERIALS/METHODS: We searched PubMed, Embase, Google and Google Scholar for publications on antibiotic quality up to 31 December 2020. Publications reporting on the prevalence of SF antibiotics were evaluated for quantitative analysis and assessed using the Medicines Quality Assessment Reporting Guidelines. RESULTS: Of the 10 137 screened publications, 648 were relevant to antibiotic quality. One hundred and six (16.4%) surveys, published between 1992 and 2020 and conducted mainly in low-income and middle-income countries (LMICs) (89.9% (480/534) of the data points), qualified for quantitative analysis. The total number of samples tested for quality in prevalence surveys was 13 555, with a median (Q1-Q3) number of samples per survey of 47 (21-135). Of the 13 555 samples, 2357 (17.4%) failed at least one quality test and the median failure frequency (FF) per survey was 19.6% (7.6%-35.0%). Amoxicillin, sulfamethoxazole-trimethoprim and ciprofloxacin were the most surveyed antibiotics, with FF of 16.1% (355/2208), 26.2% (329/1255) and 10.4% (366/3511), respectively. We identified no SF survey data for antibiotics in the WHO 'Reserve' group. The mean Medicine Quality Assessment Reporting Guidelines score was 11 (95% CI 10.1 to 12.2) out of 26. CONCLUSIONS: SF antibiotics are widely spread with higher prevalence in LMICs. The quality of the evidence is poor, and these data are not generalisable that 17.4% of global antibiotic supply is SF. However, the evidence we have suggests that interventions to enhance regulatory, purchasing and financial mechanisms to improve the global antibiotic supply are needed. PROSPERO REGISTRATION NUMBER: CRD42019124988.

A comparative field evaluation of six medicine quality screening devices in Laos.

BACKGROUND: Medicine quality screening devices hold great promise for post-market surveillance (PMS). However, there is little independent evidence on their field utility and usability to inform policy decisions. This pilot study in the Lao PDR tested six devices' utility and usability in detecting substandard and falsified (SF) medicines. METHODOLOGY/PRINCIPAL FINDINGS: Observational time and motion studies of the inspections by 16 Lao medicine inspectors of 1) the stock of an Evaluation Pharmacy (EP), constructed to resemble a Lao pharmacy, and 2) a sample set of medicines (SSM); were conducted without and with six devices: four handheld spectrometers (two near infrared: MicroPHAZIR RX, NIR-S-G1 & two Raman: Progeny, Truscan RM); one portable mid-infrared spectrometer (4500a), and single-use paper analytical devices (PAD). User experiences were documented by interviews and focus group discussions. Significantly more samples were wrongly categorised as pass/fail with the PAD compared to the other devices in EP inspections (p<0.05). The numbers of samples wrongly classified in EP inspections were significantly lower than in initial visual inspections without devices for 3/6 devices (NIR-S-G1, MicroPHAZIR RX, 4500a). The NIR-S-G1 had the fastest testing time per sample (median 93.5 sec, p<0.001). The time spent on EP visual inspection was significantly shorter when using a device than for inspections without devices, except with the 4500a, risking missing visual clues of samples being SF. The main user errors were the selection of wrong spectrometer reference libraries and wrong user interpretation of PAD results. Limitations included repeated inspections of the EP by the same inspectors with different devices and the small sample size of SF medicines. CONCLUSIONS/SIGNIFICANCE: This pilot study suggests policy makers wishing to implement portable screening devices in PMS should be aware that overconfidence in devices may cause harm by reducing inspectors' investment in visual inspection. It also provides insight into the advantages/limitations of diverse screening devices in the hands of end-users.