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The overuse and misuse of antimicrobials in humans is a core driver of antimicrobial resistance (AMR)¹. It has become increasingly clear that this overuse and misuse is global. And that access to antibiotics – without access to quality healthcare, diagnostics, stewardship and regulatory control – can result in negative health outcomes^2,3. Carefully designed interventions to optimize use are needed to build sustainable access and prevent an increased burden of AMR, worse patient outcomes and unnecessary out-of-pocket spending.

Governance, legislation and regulation, as well as the enforcement of rules and standards, play a key role in providing stronger control over healthcare and the production, sales and use of pharmaceuticals, including antibiotics. The World Health Organization (WHO), together with the Food and Agriculture Organization (FAO) and the World Organisation for Animal Health (OIE), recently published an overview and analysis of existing international instruments that set norms and standards related to the use of antimicrobials across the human, animal and plant sectors, and their release into the environment⁴.

Antimicrobials: A fragile market with limited regulatory control

The WHO estimates that more than half of all medicines are inappropriately prescribed, dispensed, or sold⁵. For antibiotics, this trend could be much higher⁶. Simultaneously, sustainable access to quality antibiotics remains a problem in many areas of the world and leaves people either untreated or treated with suboptimal antibiotics⁷. A lack of international regulation, control and enforcement on pharmaceutical sales and use influences the quality and sustainable availability of antibiotics, including shortages and supply chain interruptions⁸. Between 72,000 and 169,000 deaths due to pneumonia in children under the age of five are estimated to be caused by substandard and falsified antibiotics, adding up to between 5-12% of total deaths⁹.

Regulation on the use and sales of antimicrobials can come in many shapes on different levels: internationally, regionally or nationally. This can provide guidance and standards on how to ensure the quality and efficacy of antimicrobials.

Regulation would be able to counter this currently volatile market by ensuring quality and availability as well as by ensuring the production, sale and prescription of antibiotics for optimal use. New regulation of antimicrobial use, therefore, is increasingly being developed on a national level. Greece, for instance, banned over-the-counter sales of antibiotics last summer¹⁰. India has taken legislative action on irrational fixed-dose combinations¹¹. Sweden and the U.K. are carrying out pilot alternative reimbursement models for antibiotics spurring R&D and access¹². These are recent successful examples but globally, plenty of regulatory opportunities remain both nationally and internationally.

Opportunities in international regulation and standards for healthcare

The report recently published by the WHO, FAO and OIE named ‘International instruments on the use of antimicrobials across the human, animal and plant sectors’ found that there are many international standards for the production, sale and use of antimicrobials in healthcare, especially regarding Good Manufacturing Practices (GMP) and quality control. The report, however, found that there is currently no overarching international instrument for AMR. This means that global standards for the use of antimicrobials in healthcare are dispersed.

Identified gaps are mainly related to the marketing, sales and use of antibiotics. The main gaps are:

1. Additional and updated treatment guidelines to guide the prescribing of antimicrobials by healthcare workers
2. Basic standards of clinical best practice with regards to managing AMR for healthcare professionals
3. Standards on advertising, marketing and sales of antimicrobials
4. Control over substandard and falsified antimicrobials or irrational fixed-dose combinations
5. Environmental standards, including the correct disposal of antimicrobials

As a first step in responding to the first gap, the WHO is publishing a handbook for the use of essential antibiotics in the community (forthcoming Q3-Q4 2021). Optimizing international and national guidelines will likely have a major impact on antimicrobial prescription practice in the community. The WHO, FAO and OIE will also pilot a new programme over 2021 and 2022 for the assessment of national AMR-relevant regulation, funded by the AMR Multi-Partner Trust Fund. Another major opportunity for new international standards for drug resistance may lie in the recent global call for a pandemic preparedness treaty¹³.

Calls, commitments and opportunities for further regulation and enforcement

Many major reports on AMR such as the AMR Review¹⁴, the Global Action Plan¹⁵, and the Report of the Inter-Agency Coordination Group on AMR¹⁶ call for the legislation and regulation of the sale, use and the production of antimicrobials. The pharmaceutical industry group ‘AMR Alliance’ has also committed to working with policymakers for ‘an economic and regulatory environment that enables the sustainable supply of quality-assured antibiotics¹⁷.’

Governance, legislation and regulation, as well as the enforcement of rules and standards play a key role in providing stronger control over healthcare and the production, sales and use of pharmaceuticals, including antibiotics.

Regulation on the use and sales of antimicrobials can come in many shapes on different levels: internationally, regionally or nationally. This can provide guidance and standards on how to ensure the quality and efficacy of antimicrobials. It can also provide guidance on when and where to use them, who is allowed to prescribe and dispense them, what information should be provided to the user, and how to safely dispose of antimicrobials. Cooperation in the development of international norms and standards can improve efficiency in the global implementation of standards.

Many regulatory opportunities remain for preserving antibiotics as a public good for ourselves and future generations.

References

1. Holmes AH, Moore LSP, Sundsfjord A, Steinbakk M, Regmi S, Karkey A, et al. (2016) Understanding the mechanisms and drivers of antimicrobial resistance. The Lancet. 387(10014): 176–187.
2. Sulis G, Gandra S. (2021) Access to antibiotics: not a problem in some LMICs. The Lancet Global Health. 9(5) E561-E562.
3. Do NTT, Vu HTL, Nguyen CTK, Punpuing S, Khan WA, Gyapong M, et al. (2021) Community-based antibiotic access and use in six low-income and middle-income countries: a mixed-method approach. The Lancet Global Health. 9(5)E610-E619.
4. World Health Organization, Food and Agriculture Organization of the United Nations, World Organisation for Animal Health. (2020) International instruments on the use of antimicrobials across the human, animal and plant sectors. 
5. World Health Organization. (2004) The World Medicines Situation. 
6. Chang Y, Chusri S, Sangthong R, McNeil E, Hu J, Du W, et al. (2019) Clinical pattern of antibiotic overuse and misuse in primary healthcare hospitals in the southwest of China. PloS one. 14(6): e0214779. 
7. Daulaire N, Bang A, Tomson G, Kalyango JN, Cars O. (2015) Universal Access to Effective Antibiotics is Essential for Tackling Antibiotic Resistance. The Journal of law, medicine & ethics: a journal of the American Society of Law, Medicine & Ethics. 43 Suppl 3: 17–21. 
8. Access to Medicine Foundation (2018) Shortages, stockouts and scarcity: The issues facing the security of antibiotic supply and the role for pharmaceutical companies. 
9. World Health Organization (2017) A study on the public health and socioeconomic impact of substandard and falsified medical products. 
10. Ekathimerini. (2020) Law bans sale of antibiotics without prescription.
11. Miranda MRH, Dubey A, Ravi GS, Charyulu RN. (2019) Fixed-dose combinations banned in India: is it the right decision? An eye-opening review. Expert opinion on drug safety. 18(10): 977–985. 
12. Gotham D, Moja L, van der Heijden M, Paulin S, Smith I, Beyer P. (2021) Reimbursement models to tackle market failures for antimicrobials: Approaches taken in France, Germany, Sweden, the United Kingdom, and the United States. Health policy 125(3): 296–306. 
13. World Health Organization. (2021) Global leaders unite in urgent call for international pandemic treaty.  
14. Review on Antimicrobial Resistance (2016) Tackling drug-resistant infections globally: final report and recommendations. 
15. World Health Organization. (2015) Global action plan on antimicrobial resistance. 
16. Interagency Coordination Group on Antimicrobial Resistance. (2019) No Time to Wait: Securing the future from drug-resistant infections. Report to the Secretary-General of the United Nations. Final report. 
17. AMR Industry Alliance (2020) 2020 Progress Report.