Manufacturers of antibiotics are dumping waste into waterways that is driving antimicrobial resistance (AMR), warns the first-ever guidance from the World Health Organization (WHO) on waste water management and AMR.

Antibiotic pollution is “largely unregulated” and a “neglected” issue,  according to the WHO guidance, which explains how to mitigate liquid and solid waste during the formulation of active pharmaceutical ingredients (APIs). 

High levels of antibiotics in waterways downstream from factories have been “widely documented,” according to the guide, which notes that the highest concentrations of antibiotics in the environment come from manufacturing plants.

Resistant pathogens can be traced back to discharge from pharmaceutical manufacturing plants, hospitals, farms, or sewage systems. Even properly functioning wastewater treatment systems may not fully remove resistant pathogens and their genes, a Centers for Disease Control and Prevention (CDC) fact sheet notes. 

“Pharmaceutical waste from antibiotic manufacturing can facilitate the emergence of new drug-resistant bacteria, which can spread globally and threaten our health. Controlling pollution from antibiotic production contributes to keeping these life-saving medicines effective for everyone,” said Dr Yukiko Nakatani, WHO Assistant Director-General for AMR said in a recent press release. 

Manufacturing steps

The guidance, which covers each manufacturing step from the formation of APIs to the finished product, provides a framework for policymakers, antibiotic procurers, investors, wastewater management, industry, and other stakeholders to set targets for pollution mitigation.

It sets targets based on predicted no-effect concentrations (PNECs) for antibiotic resistance and for ecological effects (PNECeco). Two further levels “enable progressive improvement to methods that provide a greater degree of certainty that discharges are not leading to harmful effects.” It also includes best practices for risk management, public transparency, and how to progressively implement these policies. 

Given the urgency and danger AMR poses, several organizations – including the WHO Executive Board, G7 health ministers and the UN Evironmental Program (UNEP) – have called for the creation of guidelines to regulate antibiotic manufacturing..

AMR claimed 1.27 million lives in 2019, surpassing deaths from HIV and malaria. Deaths are projected to reach 10 million annually by 2050. Despite AMR’s burden on public health, the issue remains underfunded, with little innovation and talent to produce new lines of antibiotics. 

Once antibiotic residues enter the environment, especially aquatic ecosystems, they exert pressure on bacteria -both pathogenic and non-pathogenic – to adapt and become resistant. Yet quality assurance criteria “typically do not address” antibiotic pollution, says the guidance. 

The WHO’s awareness campaign earlier this year highlighted patient stories and experiences with AMR. 

Reducing unnecessary risk

Globally, there is a lack of accessible information on the environmental damage caused by manufacturing of medicines, and the potential risks of AMR. Although research is still ongoing on the extent of manufacturing pollution and the rise of resistant pathogens, the experts behind the guidance operate under the assumption that progress can be made to limit the risk.

“The guidance provides an independent and impartial scientific basis for regulators, procurers, inspectors, and industry themselves to include robust antibiotic pollution control in their standards,” said Dr Maria Neira, WHO Director of the Department of Environment, Climate Change and Health, in a press release.

“Critically, the strong focus on transparency will equip buyers, investors and the general public to make decisions that account for manufacturers’ efforts to control antibiotic pollution.” 

Hopes for political commitment

The guidance comes just a few weeks before diplomats descend on New York City for the United Nations General Assembly High Level Meeting on AMR on 26 September. The last HLM on this issue was eight years ago.

Experts, like Wellcome Trust’s Jeremy Knox, head of infectious disease policy, expressed hopes that the HLM will spur “some commitments which are steps in the right direction,” in earlier Health Policy Watch coverage. 

Advocating more stringent regulation may close loopholes that allow antibiotic pollution to end up in the environment in the first place.

“The role of the environment in the development, transmission and spread of antimicrobial resistance needs careful consideration since evidence is mounting,” said UNEP’s Jacqueline Alvarez. 

“There is a widespread agreement that action on the environment must become more prominent as a solution.”

Image Credits: Janusz Walczak, FAO.