AMR occurs worldwide, and can affect humans, animals or plants. When an antimicrobial is overused or misused, some microbes will eventually adapt and become resistant, making that specific antimicrobial ineffective against subsequent infections caused by those microbes. The result is that another antimicrobial must then be used, which, if overused or misused, may result in further resistance, leading to fewer or no options for treating that infection. It is a vicious cycle.

Within AMR, resistance of bacteria to antibiotics is particularly problematic. Since the 1930s, the introduction of new antibiotics has been followed by the emergence of resistance, usually within a decade, but since the 1980s, resistance is emerging faster, usually within three years, and all antibiotics now face some level of resistance that can vary from rare to common [1]. Unfortunately, the pipeline of new antibiotics is drying out. Between 2017 and 2021, there were only 12 new antibiotics introduced to the market [2] .

That is why the World Health Organization is considering AMR as one of the most urgent health threats and development challenges, posing a threat to global health, food security, and achieving the 2030 Sustainable Development Goals. AMR puts a strain on health systems and limits treatment options, leading to prolonged illnesses, loss of trust in healthcare and increased healthcare costs. Additionally, AMR is a challenge for food security, as it can spread through the food chain, impacting animal, plant and human health and causing economic losses in the agricultural sector. Furthermore, AMR has wider societal impacts, including economically, as it drives up the costs of care and affects productivity of patients/caregivers through prolonged hospital stays. It threatens our environment, including water supplies, and leads to prolonged loss of income, medical debt, poverty, family loss, and grief.

The 2030 Agenda for Sustainable Development offers a framework to ensure healthy lives, and recall commitments to fight malaria, HIV/AIDS, tuberculosis, hepatitis, the Ebola virus disease, neglected tropical diseases and other communicable diseases and epidemics [3]. Antimicrobial resistance challenges the sustainability and effectiveness of the public health response to these and other diseases as well as gains in health and development and the attainment of the 2030 Agenda [4] [5] [6]. In 2019, 4.95 million deaths were associated with drug-resistant bacterial infections, including 1.27 million deaths directly attributable to bacterial antimicrobial resistance, 20 per cent of whom were children under five [7], and that without a stronger response there will be an estimated average loss of life expectancy of 1.8 years globally by 2035 [8] .

It is worth noting that lack of access to appropriate, safe, effective and affordable antimicrobials and diagnostic tools, particularly in developing countries, is responsible for more deaths than antimicrobial resistance. In the South-East Asia Region (SEAR), four million people died in 2019 due to sepsis as an immediate or intermediate cause of death. Of these deaths attributed to sepsis, between 0.39 and 1.41 million people died because of bacterial AMR [9]. Countries and societies should promote careful balance for affordable access to antimicrobials when needed while implementing measures to avoid their irresponsible use[10].

[1] Pay L. (2008). Antibiotic Research and Development. Cambridge HealthTech Institute, Needham, MA, USA.

[2] WHO (2022, June 22). Lack of innovation set to undermine antibiotic performance and health gains. <https://www.who.int/news/item/22-06-2022-22-06-2022-lack-of-innovation-set-to-undermine-antibiotic-performance-and-health-gains>

[3] Transforming our World: The 2030 Agenda for Sustainable Development. United Nations. 2015. Available at: https:// sdgs.un.org/sites/default/files/publications/21252030 %20Agenda%20for%20Sustainable%20Development% 20web.pdf. Accessed November 07, 2024

[4] Antimicrobial resistance and the United Nations Sustainable Development Cooperation Framework: guidance for United Nations country teams. World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO) and World Organisation for Animal Health (OIE), 2021. Available at: https://www.who.int/publications/i/item/ 9789240036024.

[5] Antimicrobial resistance and the United Nations Sustainable Development Cooperation Framework: guidance for United Nations country teams. World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO) and World Organisation for Animal Health (OIE), 2021. Available at: https://www.who.int/publications/i/item/ 9789240036024.

[6] Bhattacharya, Riya, et al. Impact of antimicrobial resistance on sustainable development goals and the integrated strategies for meeting environmental and socio-economic targets. Environmental Progress and Sustainable Energy 43.1 (2024): e14320

[7] Antimicrobial resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet 2022; 399(10325): 629-55

[8] Global Leaders group on antimicrobial resistance. Towards specific commitments and action in the response to antimicrobial resistance. March 2024. Available at: GLG report: Towards specific commitments and action in the response to antimicrobial resistance (amrleaders.org).

[9] AMR, IHME. Antimicrobial resistance. Seattle, USA: Research and analysis; 2019. Available at: https://www. healthdata.org/antimicrobial-resistance. Accessed September 04, 2024

[10] Zayed, B., Haputhanthri, T., Rijal, S., & Singh A. (2024). A policy response to antimicrobial resistance in the South-East Asian Countries: Implications for Sri Lanka’s Health Policy Reforms. Ceylon Medical Journal, 69, Special Issue 1, si 03

In September 2024, the second High-Level Meeting on Antimicrobial Resistance (AMR) was organized during the UN General Assembly high-level week. Its political declaration:

• Committed to ‘Ensure equitable and timely access to and greater supply of antimicrobials, vaccines and diagnostics in developing countries, especially in low- and middle-income countries’
• Called to take steps to increase global access to and appropriate use of antimicrobials in settings with the highest unmet need, including by aligning regional and subregional medicine registration and reforming regulatory and policy pathways, as necessary, to accelerate authorization of safe and effective products, especially for new antimicrobials
• Noted as drivers of antimicrobial resistance the ‘lack of regulation of over-the-counter use of antimicrobials; over-prescription by health care workers; lack of evidence-based standard treatment and prophylaxis guidelines; poor treatment adherence; inappropriate use of antibiotics, including during seasonal viral outbreaks; substandard and falsified antimicrobial medicines, which require surveillance and legal enforcement by national regulatory authorities; lack of adequate infrastructure, surveillance and monitoring systems, and affordable and effective diagnostic tests, including rapid and point-of-care tests; and lack of availability of and access to essential and quality-assured antimicrobials’.

The 19th International Conference of Drug Regulatory Authorities (ICDRA) was held in New Delhi, India from 14 to 18 October 2024. The event was hosted by Central Drugs Standard Control Organization (CDSCO) of India in collaboration with the World Health Organization (WHO).

One of the session theme was dedicated to the Regulators’ Role in Containing Antimicrobial Resistance (AMR).

The following recommendations were adopted during ICDRA:

Recommendations to Member States

1. Strengthen national regulatory frameworks, facilitate global scientific research and alignment on new and preserve existing antimicrobials for human and veterinary use.
2. Expand networking and partnerships with stakeholders, including patients and Animal owners organizations under the “One Health” approach.
3. Scale up awareness of AMR among the general public and human and animal health professionals.
4. Enhance information and data sharing to promote Antimicrobial Stewardship and improve access to safe, effective, and quality Antimicrobials.

Recommendations to WHO

1. In collaboration with other members of the “Quadripartite” group (FAO, WOAH, and UNEP) WHO should strengthen its technical support and guidance to member states in implementing the call for action of the 1st Global Joint Summit and the Political Declaration of the United Nations General Assembly High-Level session on AMR.
2. Consider environmental aspects when addressing the specificities of the use of antibiotics for human use.

National regulatory authorities (NRAs) play a pivotal role in combating antimicrobial resistance (AMR) by ensuring the safe, effective, and judicious use of antimicrobials. Common responsibilities span from regulating antimicrobial production and distribution to participating in policies that encourage responsible use and stewardship:

1. Regulating Antimicrobial: NRAs are responsible for the timely approval of antimicrobial drugs that are safe, effective, and meet quality standards, including through providing validated product information. Through market control and surveillance, NRAs prevent circulation of substandard or falsified medicines, helping curbing resistance due to ineffective treatments. NRAs also regulate advertisement to the public and healthcare professionals.
2. Enforcing Prescription and Dispensing Policies: Through strict regulations on the sale and dispensing of antimicrobials, NRAs can prevent over-the-counter sales and ensure antimicrobials are prescribed only when medically necessary, limiting misuse, which is a major driver of AMR.
3. Participation in antimicrobial Stewardship Programs: NRAs often collaborate with healthcare institutions to implement stewardship programs that promote the responsible use of antimicrobials. These programs provide guidelines for appropriate dosing, duration, and choice of antimicrobial therapy.
4. Pharmacovigilance and Surveillance: NRAs conduct pharmacovigilance to monitor adverse drug reactions. They also often support surveillance systems that track resistance patterns, helping inform public health responses and adjustments to treatment guidelines.
5. Public Awareness and Education: NRAs often play a role in educating healthcare providers, veterinarians, and the public on the risks of AMR and the importance of responsible antimicrobial use. This includes promoting campaigns and initiatives to raise awareness about AMR.
6. Collaborating with International and Regional Bodies: NRAs work with global organizations like WHO, the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (WOAH), and United Nations Environment Programme (UNEP) to align national policies with international guidelines and standards. This cooperation helps to harmonize regulations, facilitate safe trade, and address AMR as a global health challenge.
7. Supporting Research and Innovation: Some NRAs also support research into new antimicrobials, diagnostic tools, and vaccines. By fostering innovation, they contribute to expanding treatment options and alternative therapies, which can help reduce dependence on existing antimicrobials.

NRAs exist within an ecosystem of stakeholder organisations acting collaboratively to ensure multi-sectoral responses to public health challenges arising from AMR.

A survey was conducted to identify the situation in the different SEARN members, the role and practices of NRAs in the region with respect to shortages, the connection with other organisations, and their challenges.

Highlights:

• Roles: Beyond their usual regulatory functions, NRAs are mostly involved in:
  • monitoring uses of antimicrobials, conducting or participating in public awareness and education, and regulating veterinary antimicrobials.
  • A majority also reported a role monitoring the use of antimicrobials, and well as monitoring or addressing shortages.
  • Most NRAs were not involved in antimicrobial stewardship programs or in contributing to clinical guidelines.
  • Responsibilities in these activities were shared with Ministries of Health, Hospitals, and other actors such as Ministries of agriculture, or learned societies and healthcare professional associations.
• A prescription was legally required in all responding countries
  • in a about half some antibiotics are limited to hospitals/reference centers.
  • All SEARN members restrict prescription of antibiotics to some defined healthcare professionals, generally supported by clinical guidelines.
  • In most SEARN members, the dispensing was limited to pharmacies, and adherence to good practices is supported by general rules, such as records/archiving.
  • In most countries, there are legals penalties for non-compliance with the regulation of antimicrobials.
• Marketing authorizations:
  • Half of SEARN members considered novel antimicrobial as a priority product eligible for facilitated approval pathway, although none introduced waiver or reduced fee schemes for these.
  • None of SEARN members developed standard wording to address AMR in SmPC or packaging. One did in package inset/PIL, and 2 reported a specific logo on the packaging of antimicrobials.
• Market control and surveillance: Antimicrobials were prioritized in all but one NRAs’ sampling plans and advertisement is generally controlled.
• Licensing establishments and regulatory inspections:
  • Most SEARN members indicated that compliance with regulation of antimicrobials was a criteria for licensing retail stores and considered during inspections
  • Disposals of unused/expired antimicrobials and management of production waste are considered in most countries during their inspections
  • This is reflected in the QMS of a majority of SEARN members (e.g. SOP, templates, checklists, etc)
• Laboratory testing
  • Most of SEARN members indicated that their NQCL has a capacity to test for identity and quantity of antimicrobials
  • Testing priorities are mostly driven by information from market control and surveillance, sometimes also from use and AMR data
  • The number of samples tested and the proportions of out of specification results varied greatly between countries
• Despite these results indicating that elements are in place to regulate antimicrobials, SEARN members highlighted multiple challenges in regulating antimicrobials:
  • The most quoted challenges were related to enforcement of legal provisions, insufficient competency of pharmacists or retail store owners, insufficient information about antimicrobial use, and insufficient HR in the NRA
  • About half of SEARN members also reported insufficient legal provisions, political support, absence or insufficiently dissuasive penalties/sanctions, regulating product information requirements, and financial resources
  • Most did not identify competency of NRA staff as a challenge
• When asked what SEARN could do, most requested
  • training of staff in different regulatory functions,
  • advocacy to the government,
  • recommendation on how to effectively address AMR through regulation,
  • examples of product information and check list/template for considering AMR during
  • Some members were also kin for examples of legal provisions

During its July 2025 meeting, the Assembly recommended WHO and partners to support countries to ensure equitable access to antimicrobials, and appropriate use though:

• effective One Health coordination
• strengthening regulation of veterinary antimicrobials
• effective implementation of antimicrobial guidelines
• collecting more information about prescription patterns of antimicrobials
• developing antibiotic treatment guidelines
• conducting communication campaigns to the general public and healthcare professionals
• conducting effective antimicrobial stewardship programme
• training officers in charge of collecting information on antimicrobial use
• developing IT tools to support national antimicrobial use and access metrics collection and experience sharing
• standardizing antimicrobial use and access data collection
• facilitating experience sharing between countries