Mohammad Sofiqur Rahman

Persistence of SARS-CoV-2 has been proposed as a biological driver of Long COVID, a disabling chronic illness with no proven treatments. We conducted an exploratory, placebo-controlled, double-blind, 2:1 randomized mechanistic trial (NCT05877508) of the SARS-CoV-2-specific monoclonal antibody AER002 in 36 participants who met the World Health Organization case definition of Long COVID. After baseline characterization, participants received a single infusion and were followed for 360 days. The primary endpoint was the PROMIS-29 Physical Health Summary Score (PHSS) at 90 days; secondary and exploratory endpoints included patient-reported and objective measures of physical and neurocognitive function as well as blood-, imaging-, and tissue-based biomarkers. While AER002 was safe and well tolerated, no significant differences in physical health, quality of life, objective measures of physical function or cognition, or blood-based biomarkers were demonstrated between the treatment and control arms. In a post-hoc analysis, participants with a lower baseline SARS-CoV-2 antibody level and higher drug exposure were more likely to perceive treatment benefit based on the Patient Global Impression of Change scale ( p < 0.05 for anti-S, S1, and RBD). Although AER002 was not efficacious in this proof-of-concept study, our findings could inform future trials using monoclonal antibodies to target viral persistence in Long COVID.

: Substandard and falsified medical products for treating COVID-19 have spread worldwide. These medicines have entered Japan through personal importation of products purchased via the Internet. In this study, we investigated the circulation of 19 COVID-19-related medicines on the Internet in Japan and evaluated the pharmaceutical quality and authenticity of 2 medicines (dexamethasone tablets and ivermectin tablets) obtained online. We purchased 23 samples of 0.5-mg dexamethasone tablets and 13 samples of 3-mg ivermectin tablets from the Internet in December 2020 and July 2022. We investigated the quality and authenticity of the obtained samples through visual observation and tested their authenticity. We conducted pharmacopoeia compliance testing (quantitative assay, content uniformity tests, and dissolution tests) using the high-performance liquid chromatography–photodiode array detector method. No prescription was ever required at the time of purchase. Visual observation revealed that most samples lacked a package insert and some samples had packaging deficiencies. In terms of authenticity, eight ivermectin samples were genuine; the authenticity of the other samples remained uncertain. Four dexamethasone samples and three ivermectin samples failed quality testing based on pharmacopeia validation standards. Our findings illustrate that dexamethasone and ivermectin tablets of poor quality are available online. It is important to increase consumer awareness and provide information about these medicines to prevent the purchase of substandard medicines via the Internet.

Comprehensive data are needed to prevent substandard and falsified (SF) medicines as they pose a major risk to human health. To assess the quality of selected medicines, samples were collected from random private drug outlets of Dhaka North and South City Corporation, Bangladesh. Sample analysis included visual observation of the packaging, authenticity of the samples, legitimacy and registration verification of the manufacturer, physicochemical analysis, and price. Chemical analysis of the samples was performed using a portable Raman spectroscopy and high-performance liquid chromatography according to the pharmacopoeia. Several discrepancies were noted in the visual observation of samples. Among the 189 collected samples of esomeprazole (ESM), cefixime (CFIX), and amoxicillin-clavulanic acid (CVA-AMPC), 21.2% were confirmed to be authentic, 91.3% manufacturers were confirmed legitimate, and 2.1% of all samples were unregistered. Chemical analysis of the samples revealed that 9.5% (95% CI 5.7–14.6) of samples were SFs. Falsified samples and quality variation in the same generic branded samples were both detected by Raman spectroscopic analysis. Overall, sample prices were satisfactory relative to the international reference price. This study documents the availability of poor-quality medicines, demonstrating the need for immediate attention by the national medicine regulatory authority.

The purpose of this study was to design a convenient, small-scale dissolution test for extracting potential substandard and falsified (SF) medicines that require full pharmacopoeial analysis. The probability of metronidazole samples complying with the US Pharmacopoeia (USP) dissolution test for immediate-release tablet formulations was predicted from small-scale dissolution test results using the following criteria: (1) 95% confidence interval lower limit (95% CI_low) of the average dissolution rate of any n = 3 of n = 24 units of each sample, and (2) average and minimum dissolution rates for any n = 3 of n = 24 units. Criteria values were optimized via bootstrap sampling with Thinkeye data-mining software. Compliant metronidazole samples in the USP first-stage and second-stage dissolution test showed complying probabilities of 99.7% and 81.0%, respectively, if the average dissolution rate of n = 3 units is equal to or greater than the monograph-specified amount of dissolved drug (Q; 85% of labeled content for metronidazole). The complying probabilities were 100.0% and 79.0%, respectively, if the average dissolution rate of n = 3 units is 91% or higher and the minimum dissolution rate is 87% or higher. Suitable compliance criteria for the small-scale dissolution test are: average dissolution rate of n = 3 units is Q + 6% or more and minimum dissolution rate is Q + 2% or more.

Comprehensive data are needed to prevent substandard and falsified (SF) medicines as they pose a major risk to human health. To assess the quality of select medicines, samples were collected from random private drug outlets of Dhaka North and South City Corporation, Bangladesh. Sample analysis included visual observation of the packaging, authenticity of the samples, legitimacy and registration verification of the manufacturer, physicochemical analysis, and price. Chemical analysis of the samples was performed using a portable Raman spectroscopy and high-performance liquid chromatography according to the pharmacopoeia. Several discrepancies were noted in the visual observation of samples. Among the 189 collected samples of esomeprazole (ESM), cefixime (CFIX), and amoxicillin-clavulanic acid (CVA-AMPC), 21.2% were confirmed to be authentic, 91.3% manufacturers were confirmed legitimate, and 2.1% of all samples were unregistered. Chemical analysis of the samples revealed that 9.5% (95% CI, 0.057–0.146) of samples were SFs. Falsified samples and quality variation in the same generic branded samples were both detected by Raman spectroscopic analysis. Overall, sample prices were satisfactory relative to the international reference price. Despite the relatively smaller proportions of SFs, this study documents the availability of poor-quality medicines, demonstrating the need for immediate attention by the national medicine regulatory authority.

Background: Poor quality medicines have serious implications for public health. The aim of this study was to explore the quality of the antidiabetic pioglitazone, using samples collected in China and Myanmar, and samples purchased online. Methods: In this cross-sectional study, we examined samples (n = 163) collected from hospitals in Shanghai, China in 2012 (n = 44), products purchased via the internet and imported into Japan in 2013 (n = 59), and samples purchased in shops in Yangon, Myanmar in 2015 (n = 60). Collected samples were subjected to visual inspection, authenticity investigation and quality testing (potency, content uniformity and dissolution test) by high-performance liquid chromatography. Samples were rated as compliant or non-compliant based on the relevant pharmacopoeial acceptance criteria. Results: Visual inspection of all samples revealed compliant products. However, responses from manufacturers during authenticity investigation were poor. Among the n = 44 samples from China, one was non-compliant in the potency test. Among the n = 59 samples personally imported into Japan, 38% of generic samples were found to be non-compliant. In Myanmar, 13.3% of samples were non-compliant. Non-compliant samples predominantly failed in the dissolution test. All non-compliant samples were generic. Conclusions: Despite the apparent satisfactory outcome on the samples from China, pioglitazone samples collected in Myanmar and purchased online for personal import into Japan included many substandard products, which failed quality assessment predominantly because of poor dissolution. Internet providers did not comply with Japanese regulations in various respects.

Background: substandard and falsified medicines (SFMs) are a threat to public health. The availability of SFMs in Myanmar was reported by the World Health Organization (WHO) in 1999, but there have been few systematic surveys on falsified medicines in Myanmar since then. The aim of this study is to examine the extent of SFMs for sale in Myanmar. Methods: target medicines were tablets of candesartan, metformin, and pioglitazone, and infusions of ciprofloxacin and levofloxacin. Samples were collected from hospitals, pharmacies, and wholesalers located in the Mandalay region in 2015. We carried out observation testing, authenticity investigation, and quality testing to search for SFMs, and analyzed the relationship between SFMs and the price and store type. Results: There were no falsified medicines found in the authenticity check, though there remained a problem due to low response rates from manufacturers and regulatory authorities. In the quality test, some tablets of metformin and pioglitazone made in India failed the dissolution test. Conclusions: although no serious problems were found, some substandard medicines were detected. Regular surveys to monitor SFMs are therefore recommended, together with further regulatory guidance to improve conditions in all medicine manufacturers, distributors, and pharmacies.

Although the issue of substandard and falsified medicines is quite well known, most research has focused on medicines used to treat communicable diseases, and relatively little research has been carried out on the quality of medicines for noncommunicable diseases (NCDs). This study was designed to assess the quality of seven widely used medicines for NCDs in Cambodia during 2011–2013. Medicines were collected from private community drug outlets in Phnom Penh (urban area), by stratified random sampling and in Battambang, Kandal, Kampong Speu, and Takeo (rural areas) by convenience sampling. Samples were subsequently analyzed by visual inspection, authenticity investigation, and pharmacopoeial analysis by high-performance liquid chromatography. Various discrepancies were observed in visual inspection of packages and medicines. Of 372 tablet/capsule samples from 64 manufacturers in 16 countries, the manufacturers confirmed 107 (28.8%) as authentic; the authenticity of other samples could not be verified. Three hundred sixty-four (97.8%) samples were registered in Cambodia. Among all samples, 23.4% (95% CI 19.2–28.0) were noncompliant in one or more of the quality tests: 12.9% (95% CI 9.7–16.7) contained an amount of active pharmaceutical ingredient outside the permitted range, including some showing extreme deviations, 14% (95% CI 10.6–17.9) failed because of content variation, and 10.8% (95% CI 7.8–14.4) failed to meet pharmacopoeial reference ranges in dissolution tests. Pharmaceutical quality appeared to be unrelated to storage conditions. Although no sample was obviously falsified, there is a high prevalence of substandard medicines for NCDs in Cambodia, indicating the need for focused regulatory action, including collaborative initiatives with manufacturers.

Objectives: To analyse and present the literature describing the health consequences of falsified medicines, focusing on mortality and morbidity, as well as the scale of the issue, the geographic extent, the medicines affected, and the harm caused at both the individual and population levels.Methods: We searched for articles in PubMed, using pre‐optimized keywords ‘(counterfeit OR fake OR bogus OR falsified OR spurious) AND (medicine OR drug)’. Searches up to February 2017 yielded 2006 hits, of which 1791 were full‐length articles in English. Among them, we found 81 papers that qualitatively or quantitatively described 48 incidents in which falsified medicines caused patients to suffer serious adverse effects, injury, symptoms or death.Results: The distribution of incidents was examined according to the economic status of the countries involved, regional location in the world, therapeutic category of the medicines, number of incidents and victims by year, and characteristics of the falsified medicines. Among the 48 reported incidents, 27 (56.3%) occurred in developing countries and 21 (43.7%) in developed countries. These incidents involved a total of approximately 7200 casualties including 3604 deaths.Conclusions: Despite the poor quality of much of the reported data, the results of this study indicate that all types of medications have been targeted for falsification, and falsified medicines have had a serious impact on the health of both adults and children worldwide, with similar numbers of incidents in developing and developed countries.