The uncertain role of substandard and falsified medicines in the emergence and spread of antimicrobial resistance

Cavany, Sean; Nanyonga, Stella; Hauk, Cathrin; Lim, Cherry; Tarning, Joel; Sartorius, Benn; Dolecek, Christiane; Caillet, Céline; Newton, Paul N.; Cooper, Ben S.

doi:10.1038/s41467-023-41542-w

Cited by 9 publications

(6 citation statements)

References 72 publications

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“…Slightly lower than permitted dissolution of antibiotics may also place the product in the mutation selection window, favouring the development and spread of antibiotic-resistant bacteria. 5,[36][37][38] In our study, poor dissolution of cefixime is especially worrying, since WHO assigns it to the "Watch" category of antibiotics prone to resistance. 39 Our findings were comparable with other studies in Indonesia, Cambodia, India and Togo in finding that quality did not vary by price.…”

Section: Discussionmentioning

confidence: 99%

A randomised survey of the quality of antibiotics and other essential medicines in Indonesia, with volume-adjusted estimates of the prevalence of substandard medicines

Pisani,

Rahmawati,

Mulatsari

et al. 2023

Preprint

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IntroductionMost substandard and falsified medicines are at best not optimally effective, and at worst fatal. While the World Health Organisation and others warn they are a major threat to public health in low and middle income countries, little is known about their true prevalence. Authors of meta-analyses universally warn that survey data are not generalisable, because of unrepresentative study designs and variations in medicines included; tests performed; reference standards and pharmacopeia used; and definitions used when translating multiple quality parameters into a single pass/fail measure.We hypothesised that weighting for sales volume of different products and brands would increase accuracy of estimates of medicine quality.Methods and FindingsWe collected samples of allopurinol, amlodipine, cefixime and dexamethasone, as well as amoxicillin in 2 formulations in seven districts across Indonesia, the world’s fourth most populous country. Outlets, including retail pharmacies, over the counter medicine shops, public and private hospitals, primary health centres, doctors and nurses were randomised. We also sampled from the internet. Retail samples were collected by mystery shoppers, other samples overtly.We tested 1274 samples for identity and assay, and all relevant samples for dissolution and uniformity of content, using USP reference standards and monographs. Samples that failed any laboratory test were considered out of specification. We calculated prevalence per product and brand, and weighted the results by the sales volume of each product, using sales data from IQVIA and the national public procurement system.The weighted prevalence of out-of-specification products was 4.9%, 40.3% lower than the raw estimate (8.2%). Antibiotics were more likely to be substandard (weighted prevalence 6.8 vs 3.1; raw prevalence 13.6 vs 4.9, p<0.000). There was no relationship between quality and any of the following: price; branded status; public procurement status; outlet type. Our estimate compared with the Indonesian medicine regulator’s estimate of 4.0%, calculated based on unweighted analysis of 13,539 samples of a wider variety of medicines, collected overtly nation-wide.ConclusionsWhere data are available, weighting survey results by sales volume is a cost-effective way of improving the accuracy of estimates of out-of-specification medicines measured in field surveys.

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Section: Discussionmentioning

confidence: 99%

A randomised survey of the quality of antibiotics and other essential medicines in Indonesia, with volume-adjusted estimates of the prevalence of substandard medicines

Pisani,

Rahmawati,

Mulatsari

et al. 2023

Preprint

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“…Self-prescription and self-medication are contributing to SF marketing and use. 4 This along with static antibiotic pipeline (inadequate production of novel antibiotics) to tackle resistant microbes will increase global health threats from infectious diseases. 5 In addition to its adverse health effects, the marketing and use of SF medicines are associated with societal economic costs.…”

Section: Introductionmentioning

confidence: 99%

Improving access to medicines to reduce marketing and use of substandard and falsified medicines in Africa: Scoping review

Sorato,

Davari,

Kebriaeezadeh

2024

The Journal of Medicine Access

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Background: Both constrained access to essential medicines and combatting marketing of substandard and falsified (SF) medicines are unmet health sector goals in Africa. Objective: To answer the question of how improved access can reduce the continuous surge of SF medicines in Africa. Design: We conducted a scoping review based on standard protocol. Methods: We searched articles published in the English language from PubMed/Medline, Cochrane Library, Embase, Scopus, Web of Science, and Google Scholar by using a systematic search query. Results: Seventy-one articles were included in this review. Access to quality essential medicines is still a major problem in developing countries in Africa and will continue as a threat for the next decade of health care. Ensuring access to quality medicines and preventing SF medicines in Africa need a systematic approach to address their underlying causes. Failure to ensure access to medicines is the major reason for the availability of SF medicines. Improving access to quality medicines can reduce SF medicine marketing and use. Manipulating the entire supply chain for efficiency, avoiding trade agreements that could reduce access, using compulsory licensing provisions, and pharmaceutical price control, providing incentives for drug development, and promoting rational use of medicines can improve access. Conclusion: Ensuring access to medicines and preventing SF medicine marketing cannot be achieved in the planned period in developing countries in Africa unless a comprehensive strategy is used. Improving access to quality medicines can reduce SF medicine marketing and use, that is, ensuring access through uninterrupted supply, improved efficiency, enhanced local production, preventing SF medicine entry, improved medication use system, and improved affordability. Therefore, it is essential to improve supply chain capability, address challenges of the supply chain, improve leadership and governance, establish country-specific anti-counterfeiting and anti-substandardization committees, and collaborate with all relevant stakeholders.

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“…2 Furthermore, underdosed anti-infectives can contribute to the emergence of antimicrobial resistance. 3 …”

Section: Introductionmentioning

confidence: 99%

Quality of Essential Medicines from Different Sources in Enugu and Anambra, Nigeria

Gabel,

Lächele,

Sander

et al. 2024

The American Journal of Tropical Medicine and Hygiene

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This study investigated the quality of 13 essential medicines in the states of Enugu and Anambra, Nigeria. A total of 260 samples were purchased from licensed pharmaceutical manufacturers and wholesalers and from vendors in pharmaceutical markets with unclear licensing status. Samples were analyzed for identity, content, and dissolution according to the United States Pharmacopeia (USP) 42 monographs. Forty-five samples of this study could be examined for authenticity with the Mobile Authentication Service scheme of the Nigerian National Agency for Food and Drug Administration and Control. Out of all samples, 25.4% did not comply with the USP 42 specifications. Strikingly, 21 out of 22 dexamethasone tablet samples (95%) were out of specification (OOS). Nine out of 19 glibenclamide samples (47%) failed dissolution testing, and 7 out of 17 cotrimoxazole samples (41%) failed assay testing. Medicines against noncommunicable diseases showed a slightly higher percentage of OOS samples than anti-infectives (21.2% versus 17.6%). The rates of OOS samples were similar in medicines stated to be produced in Nigeria, India, and China but were very different between individual manufacturers from each of these countries of origin. Therefore, prequalification of products, manufacturers, and suppliers are very important for quality assurance in medicine procurement. Unexpectedly, the total proportions of OOS samples were similar from licensed vendors (25.2%) and from markets (25.5%). Four samples (1.5%), all collected in markets, were clearly falsified and did not contain the declared active pharmaceutical ingredients. The proportion of falsified medicines was found to be lower than frequently reported in the media for Nigeria.

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The uncertain role of substandard and falsified medicines in the emergence and spread of antimicrobial resistance

Cited by 9 publications

References 72 publications

A randomised survey of the quality of antibiotics and other essential medicines in Indonesia, with volume-adjusted estimates of the prevalence of substandard medicines

A randomised survey of the quality of antibiotics and other essential medicines in Indonesia, with volume-adjusted estimates of the prevalence of substandard medicines

Improving access to medicines to reduce marketing and use of substandard and falsified medicines in Africa: Scoping review

Quality of Essential Medicines from Different Sources in Enugu and Anambra, Nigeria

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