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Objective: Previous studies have demonstrated quality concerns with misoprostol. Mifepristone, however, has not been extensively assessed for quality. Between 2020 and 2021, Concept Foundation and the International Planned Parenthood Federation conducted a study to determine the quality of these medical abortion drugs in low‐ and middle‐income countries (LMIC). Methods: The collection of batch samples of misoprostol and mifepristone was carried out by trained sampling agents in selected LMIC. Single drug packs and combipacks were sampled. A World Health Organization prequalified laboratory conducted testing method verifications and subsequent sample analysis. Tests included identification, assay, related substances, and content uniformity for misoprostol, and identification, assay, related substances, and dissolution for mifepristone. Results: Samples were collected from Burkina Faso, Cambodia, Democratic Republic of Congo, India, Kyrgyzstan, Moldova, Nepal, Nigeria, Pakistan, Uganda and Vietnam. Sixty‐four pooled batch samples were tested, consisting of 31 combipacks, 26 misoprostol‐only and seven mifepristone‐only products. Overall, 54.7% of samples were non‐compliant with one or more of the specifications, representing 51.6% of combipack products, 57.1% of misoprostol tablets analyzed and 23.7% of mifepristone tablets. One falsified misoprostol‐only product was found. Conclusion: The present study confirms that a significant problem still exists in relation to the quality of medical abortion drugs in LMIC. For misoprostol, our findings suggest that historical concerns around primary packaging may have been largely resolved but that manufacturing processes for both finished product and active pharmaceutical ingredient need to be improved. The present study also provides evidence of mifepristone quality issues. Synopsis: Over half of mifepristone, misoprostol, and combipack samples collected and tested did not meet one or more requirements. One product was falsified. [ABSTRACT FROM AUTHOR]

Simple, quick, cost-effective, and environmentally friendly analytical methods for quality assurance and control roles for different medicines, including Tetrcyclines, are most significantly needed. Also, different thin layer chromatography (TLC)-based methods for tetracycline identification exist, but high performance thin layer chromatography methods based on modern state- of- the art equipment are still nonexistent. Thus, in this study, analytical method development and verification were done by high performance thin layer chromatography (HPTLC) (using an automated equipment model) using glass plates coated with silica gel 60 F254 after treating with 10% Na2EDTA. Validation was carried out according to International Council for Harmonization (ICH) guidelines. A mobile phase formed from ethyl acetate, acetonitrile, methanol, and 1% aqueous ammonia in the composition of 4.4:19.6:10:6 volume to volume ratio (V/V) was used. Rf value, percentage recoveries, linearity ranges, limit of detection (LOD), and limit of quantitation (LOQ) for the developed HPTLC method were 0.28, 100.83–106.25%, 160–560 ng/band (r2 values of 0.9999), 31.9 ng/band, and 96.7 ng/band, respectively. The results of the sample assays conducted using the new method and the United States Pharmacopoeia (USP) high performance liquid chromatography (HPLC) method were 91.59% to 108.3% and 90.83% to 102.85%, respectively. The F test for the aforementioned methods was 2.01, which is smaller than the tabulated F value of 5.05 with 5 degrees of freedom at a 95% confidence range, proving that the newly developed HPTLC and HPLC pharmacopoeial methods can be used interchangeably.The newly developed HPTLC method is easy, economical, specific, accurate, and roboust, thus it can be employed in a range of settings that require quality control and assurance activities of tetracycline hydrochloride (TC-HCl) in bulk and ointment dosage forms. [ABSTRACT FROM AUTHOR]

We explored whether isotope ratio mass spectrometry (IRMS) is useful to investigate the origin of falsified antimalarials. Forty-four falsified and genuine antimalarial samples (artesunate, artemether-lumefantrine, dihydroartemisinin-piperaquine and sulphamethopyrazine-pyrimethamine) were analyzed in bulk for carbon (C), nitrogen (N), and oxygen (O) element concentrations and stable isotope ratios. The insoluble fraction ("starch") was extracted from 26 samples and analyzed. Samples of known geographical origin maize, a common source of excipient starch, were used to produce a comparison dataset to predict starch source. In both an initial (n = 18) and a follow-on set of samples that contained/claimed to contain artesunate/artemether (n = 26), falsified antimalarials had a range of C concentrations less than genuine comparator antimalarials and δ13C values higher than genuine comparators. The δ13C values of falsified antimalarials suggested that C4 plant-based organic material (e.g., starch derived from maize) had been included. Using the known-origin maize samples, predictions for growth water δ18O values for the extracted "starch" ranged from − 6.10 to − 1.62‰. These findings suggest that IRMS may be a useful tool for profiling falsified antimalarials. We found that C4 ingredients were exclusively used in falsified antimalarials versus genuine antimalarials, and that it may be possible to predict potential growth water δ18O values for the starch present in falsified antimalarials. [ABSTRACT FROM AUTHOR]

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low- and middle-income countries (LMICs). Oxytocin and misoprostol are used for the prevention and treatment of PPH. However, both medicines are chemically unstable and sensitive to environmental conditions. Previous studies reported a high prevalence of substandard oxytocin and misoprostol preparations in LMICs.Methods: In randomly selected health facilities of four districts of Malawi, the availability of oxytocin and misoprostol was determined, and the knowledge of health workers on storage requirements and use of oxytocics was assessed. Temperature loggers were used to record the storage temperature of oxytocics. Samples of oxytocin injections and misoprostol tablets were collected from the health facilities and from wholesalers. Oxytocin samples were analysed for identity, assay (= quantity of oxytocin) and for pH value according to United States Pharmacopeia 40. Misoprostol samples were analysed for identity, assay, dissolution and related substances according to the International Pharmacopeia 2017.Results: All visited hospitals and health centers had oxytocin available. At non-refrigerated storage sites, the recorded mean kinetic temperature exceeded the oxytocic's storage temperature stated on the labels in 42% of the sites. At refrigerated storage sites, the required temperature of 2-8 °C was exceeded in 33% of the sites. Out of 65 oxytocin samples, 7 (11%) showed moderate deviations from specification, containing 82.2-86.8% of the declared amount of oxytocin. Out of 30 misoprostol samples, 5 (17%) showed extreme deviations, containing only 12.7-30.2% of the declared amount. The extremely substandard misoprostol was reported to the national authorities and to WHO, leading to an immediate recall of the respective brand in Malawi. The UK-based distributor of this brand closed its business shortly thereafter.Conclusion: Availability of oxytocin was excellent in Malawi, and its quality was better than reported in previous studies in other LMICs. However, storage conditions at the health facilities often did not meet the requirements. Extremely substandard misoprostol tablets were found, representing a serious risk to maternal health. This shows the need for continued efforts for quality assurance in medicine procurement and registration, as well as for post-marketing surveillance. [ABSTRACT FROM AUTHOR]

An direct injection ESI-Q-TOF-MS analysis method was developed to value the chemical constituent in Salvia miltiorrhiza (Danshen) coming from Shangzhou, Luonan, Dali, Danfeng and Tongchuan in Shaanxi Province, through analyzing the MS abundance ol water soluble and lipid soluble extracts and obvious variation in chemical constituent. The comparison among different abundances was beneficial to select the optimum planting urea ol Danshen. The results showed that all Danshen samples from five different regions had nine kinds ol lipid soluble chemical constituent (Tanshi-none I, Tanshinone llA, Tanshinone IlB, Cryptotanshinone, Dihydrotanshinone, Danshenxinkun A, Danshenxinkun D, 2-Isopropyl-8-methylphenanthrene-3,4-dione and 7-beta-hydroxy-8-13- abietadiene-11, 12-dione) and nine kinds ol water soluble chemical constituent (danshensu, caffeic acid, ferulic acid, rosmarinic acid, prolithospermic acid, litho-spermic acid, protocatechuic acid, salvianolic acid A and salvianolic acid B). The contents ol danshensu, lithospermic acid, salvianolic acid B and cryptotanshinone were higher than other chemical constituent with a MS abundance ol 30% at least. However, with the change of planting environment, the content of the same chemical constituents in Danshen varied greatly in different regions. More tanshinones with important biological activity existed in Danshen coming from Shangzhou, especially the MS abundance of Tanshinone I was as high as 72.6% , which was much higher than that in other four regions ranging from 1.8% to 11.3%. According to the comprehensive comparison, the quality of Danshen was ranged by Shangzhou > Tongchuan > Dali> Luonan> Danfeng. The direct injection ESI-Q-TOF-MS method was not easily affected by the growth environment and extraction conditions of the medicinal materials. It provides a scientific, reliable and convenient way to evaluate the medicine quality and a new way to formulate the specifications and grades of traditional Chinese medicine. The system is suitable for the chemical constituent ol Danshen in Shaanxi Province. [ABSTRACT FROM AUTHOR]

Abstract To assess drug quality and pharmaceutical care in South Africa, “mystery” (i.e., anonymous) customers collected 316 samples from July to September 2016. Solid dosage forms containing amoxicillin alone or in combination with clavulanic acid as well as analgesics containing paracetamol alone or in combination with other drugs were sampled in a randomized fashion from the formal market (pharmacies) and by convenient sampling from the informal market. Visual inspection, uniformity of dosage units, and dissolution testing were performed to evaluate adherence to pharmacopoeial quality standards and to identify counterfeit, degraded, or substandard drugs. Although no counterfeited products were identified, only 55.4% (173/312) of samples were able to fulfill all pharmacopeial requirements for quality. Most of the 139 samples that failed were unable to pass the visual inspection due to inappropriate labeling and packaging. In addition, several substandard products were identified: 17 (5.4%) samples failed dissolution testing and 15 (4.8%) failed the content uniformity test. To improve drug quality and the quality of pharmaceutical care, better education of pharmaceutical professionals and monitoring of the pharmaceutical supply chain in South Africa are needed. Further field studies are necessary to evaluate risks and quality issues for other drug classes and distribution channels. [ABSTRACT FROM AUTHOR]

Background: Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector. Results: In 2014/15, non-QAACT were most commonly available in Kinshasa (83%), followed by Katanga (53%), Nigeria (48%), Kenya (42%), and Uganda (33%). Non-QAACT accounted for 20% of the market share in the private sector in Kenya, followed by Benin and Uganda (19%), Nigeria (12%) and Zambia (8%); this figure was 27% in Katanga and 40% in Kinshasa. Public sector non-QAACT availability and distribution was much lower, with the exception of Zambia (availability, 85%; market share, 32%). Diverse generics and formulations were available, but non-QAACT were most commonly artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA PPQ), in tablet formulation, imported, and distributed in urban areas at either pharmacies or drug stores. The number of unique manufacturers supplying non-QAACT to each country ranged from 9 in Uganda to 92 in Nigeria. Conclusions: Addressing the availability and distribution of non-QAACT will require effective private sector engagement and evidence-based strategies to address provider and consumer demand for these products. Given the variation in non-QAACT markets observed across the eight study countries, active efforts to limit registration, importation and distribution of non-QAACT must be tailored to the country context, and will involve addressing complex and challenging aspects of medicine registration, private sector pharmaceutical regulation, local manufacturing and drug importation. These efforts may be critical not only to patient health and safety, but also to effective malaria control and protection of artemisinin drug efficacy in the face of spreading resistance. [ABSTRACT FROM AUTHOR]

Background: Assessing the quality of medicines in low-middle income countries (LMICs) relies primarily on human inspection and screening technologies, where available. Field studies and surveys have frequently utilized screening tests to analyse medicines sampled at the point of care, such as health care facilities and medicine outlets, to provide a snap shot of medicine quality in a specific geographical area. This review presents an overview of the screening tests typically employed in surveys to assess anti-malarial medicine quality, summarizes the analytical methods used, how findings have been reported and proposes a reporting template for future studies. Methods: A systematic search of the peer-reviewed and grey literature available in the public domain (including national and multi-national medicine quality surveys) covering the period 1990–2016 was undertaken. Studies were included if they had used screening techniques to assess the quality of anti-malarial medicines. As no standardized set of guidelines for the methodology and reporting of medicine quality surveys exist, the included studies were assessed for their standard against a newly proposed list of criteria. Results: The titles and abstracts of 4621 records were screened and only 39 were found to meet the eligibility criteria. These 39 studies utilized visual inspection, disintegration, colorimetry and Thin Layer Chromatography (TLC) either as components of the Global Pharma Health Fund (GPHF) MiniLab ® or as individual tests. Overall, 30/39 studies reported employing confirmatory testing described in international pharmacopeia to verify the quality of anti-malarials post assessment by a screening test. The authors assigned scores for the 23 criteria for the standard of reporting of each study. Conclusions: There is considerable heterogeneity in study design and inconsistency in reporting of field surveys of medicine quality. A lack of standardization in the design and reporting of studies of medicine quality increases the risk of bias and error, impacting on the generalizability and reliability of study results. The criteria proposed for reporting on the standard of studies in this review can be used in conjunction with existing medicine quality survey guidelines as a checklist for designing and reporting findings of studies. The review protocol has been registered with PROSPERO (CRD42015026782). [ABSTRACT FROM AUTHOR]

Background: Recent studies alluded to the alarming scale of poor anti-malarial drug quality in malaria-endemic countries, but also illustrated the major geographical gaps in data on anti-malarial drug quality from endemic countries. Data are particularly scarce from Central Africa, although it carries the highest burden of malaria. The aim of this medicine quality field survey was to determine the prevalence of poor-quality anti-malarial drugs in Gabon. Methods: A field survey of the quality of anti-malarial drugs in Gabonese pharmacies was conducted using the Global Pharma Health Fund Minilab® tests, following the Medicine Quality Assessment Reporting Guidelines. Antimalarial drugs were purchased randomly from selected pharmacies in Gabon. Semi-quantitative thin-layer chromatography (TLC) and disintegration testing were carried out to measure the concentration of active pharmaceutical ingredients (APIs). The samples failing the TLC test were analysed by high-performance liquid chromatography. Following the collection of anti-malarial drugs, a street survey was conducted to understand where people purchase their anti-malarial drugs. Results: A total of 432 samples were purchased from 41 pharmacies in 11 cities/towns in Gabon. The prevalence of poor-quality anti-malarial drugs was 0.5% (95% CI 0.08-1.84%). Two out of 432 samples failed the MiniLab® semiquantitative TLC test, of which a suspected artemether-lumefantrine (AL) sample was classified as falsified and one sulfadoxine-pyrimethamine (SP) sample as substandard. High performance liquid chromatography with ultraviolet photo diode array detection analysis confirmed the absence of APIs in the AL sample, and showed that the SP sample did contain the stated APIs but the amount was half the stated dose. Of the people interviewed, 92% (187/203) purchased their anti-malarial drugs at a pharmacy. Conclusion: Using the GPHF Minilab®, the prevalence of poor-quality anti-malarial drugs is far lower than anticipated. The findings emphasize the need for randomized and robust sampling methods in order to collect representative data on anti-malarial drug quality. [ABSTRACT FROM AUTHOR]

• Rifampicin Quinone undergoes temperature dependent chemical conversion to Rifampicin. • Chemical conversion occurs in physiologically relevant temperatures and timescales. • Conversion is observable through absorbance spectroscopy, HPLC and LC–MS. • Conversion of Rifampicin Quinone to Rifampicin results in increased antimicrobial activity. Rifampicin is an antibiotic used as a first line treatment for tuberculosis, as well as in the treatment of other infectious diseases. Drug quality is essential for drug efficacy. Determining the stability and activity of Rifampicin Quinone in solution is important in its role as a standard against which to determine Rifampicin quality and in its effect on treatment and AMR development. Poor quality medicines, such as antimicrobials not only increase mortality and morbidity, but can also contribute to the development of antimicrobial resistance (AMR). One common marker of poor quality in Rifampicin samples is the presence of the degradation product Rifampicin Quinone. In this study we have found that Rifampicin Quinone in solution undergoes a chemical conversion to Rifampicin that is temperature dependent. This conversion occurs in physiologically relevant temperatures (30−50 °C) and time scales (24−120 h) and was verified using HPLC and LC–MS methods. Additionally, the conversion of Rifampicin Quinone to Rifampicin results in an increase in antimicrobial activity. We believe that ours is the first study reporting the instability of Rifampicin Quinone, and this instability in solution at these temperatures and time scales raises concerns for its use as a standard in quality testing using liquid chromatography methods and in studies of the effect of Rifampicin Quinone on AMR. Due to the use of Rifampicin Quinone as a standard in determining Rifampicin quality, the instability of Rifampicin Quinone also poses public health concerns, as the incorrect determination of medicine quality risks patient health and may promote the development of AMR. [ABSTRACT FROM AUTHOR]

Regulatory enforcement of product safety standards given health concerns, whether it is in romaine lettuce, smartphones or cars, is emerging to be a challenge for global public health. This is particularly true for developing economies with fragile institutions. In this context, recent studies on Indian pharmaceutical markets provide evidence suggesting that the sector is a hub for substandard quality of medicines. Departing from these prior studies which use randomly collected samples, we reinvestigate this question using novel pan-India market sales data of banned medicines from 0.75 million pharmacists and chemists in India. We find that indeed such medicines get sold in India even after bans are imposed on them in the period 2007 to 2013. However, there is a general decline in demand post ban for our focal molecules suggesting broad adherence to bans. We also observe regional heterogeneity in prevalence of banned medicines sold between rich and poor regions of India with the former counterintuitively showing more sales. That said, while Ozawa et al. (2018) argue that prevalence of substandard medicines is around 13% in low and middle-income countries, we find an infringement ratio which is more muted in India at about 5%. Finally, a regression-based examination suggests that prior firm presence in therapeutic markets and popularity of molecules positively impact the likelihood of sale of banned medicines in India. Our results are robust to alternative explanations and are substantiated with a theoretical set up examining firm trade-offs in the decision to infringe. India has recently been under the lens of the global access to medicines debate and our findings have important policy implications for global health. • Developing economies face enforcement challenges to implement pharmaceutical bans. • In India we find regional heterogeneity in enforcement of bans on medicines. • Richer regions of India counterintuitively see more sales of banned medicines. • Medicines sold post ban in India were worth some USD 2 million between 2007 and 2013. • A new metric, the infringement ratio by firms was about 5% in most regions. [ABSTRACT FROM AUTHOR]

Where regulation is weak, medicine transactions can be characterised by uncertainty over the drug quality and efficacy, with buyers shouldering the greater burden of risk in exchanges that are typically asymmetric. Drawing on in-depth interviews (N = 220) and observations of medicine transactions, plus interviews with regulators (N = 20), we explore how people in Ghana negotiate this uncertainty and come to trust a medicine enough to purchase or ingest it. We identify two mechanisms – attempts to mitigate uncertainty through seeking observable signs of quality and attempts to reduce informational asymmetry – that underpin cognitive assessments of a medicine's trustworthiness. However, these 'cognitive' forms of trust assessment have limited traction where uncertainty is high and trustworthiness remains unknowable, so a third mechanism comes into play: one based on affective relationships within which transactions are socially embedded. Even these, however, cannot eliminate uncertainty, because of the dispersed and under-regulated nature of wider supply chains. In conclusion, we reflect on the need for careful research on actors' practices and decision-making across supply chains to inform more effective policy and regulation. • Weakly regulated medicine supply chains create significant trust issues. • Buyers must negotiate uncertainty and come to trust a medicine enough to purchase or ingest it. • Cognitive and affective based assessments of trustworthiness are used by purchasers of medicine. • Uncertainty about medicine quality is not eliminated but managed. [ABSTRACT FROM AUTHOR]