The World Health Organisation (WHO) has released new guidance on what it calls an “important but neglected challenge” in efforts to tackle antimicrobial resistance (AMR), providing targets aimed at limiting the emergence and spread of AMR from antibiotic manufacturing plants – a documented source of antibiotic pollution but which remain largely unregulated.
Developed in collaboration with international experts, the document also includes risk management plans to help antibiotic manufacturers ensure they meet the established targets, engage with independent auditors, and are transparent.
CIDRAP reports that the guidance tackles the growing concern that the unregulated release of antibiotic residues from manufacturing sites into local waterways is promoting the development of resistant pathogens and helping undermine the effectiveness of antibiotics globally.
“Pharmaceutical waste from antibiotic manufacturing can trigger the emergence of new drug-resistant bacteria, which can spread globally,” said Yukiko Nakatani, MD, PhD, the WHO’s interim assistant director-general for AMR.
Limiting residues
The aim of the guidance, which covers all steps from the manufacturing of active pharmaceutical ingredients (APIs) to formulation into finished products, is to establish a framework for applying targets for managing both liquid and solid wastes from the manufacturers.
The targets, expressed as PNECs (predicted no-effect concentrations), are for concentrations of antibiotics that are not likely to select for resistance (PNECres) or disturb the ecosystem (PNECeco).
Targets are needed because liquid effluent and solid waste from antibiotic manufacturing sites, as well as the downstream water bodies that receive that effluent and waste, can contain very high concentrations of antibiotic residues, even higher than those found in wastewater containing excreta from people and animals being treated with antibiotics.
The concern is that those residues interact with bacteria in the environment and create selection pressure for the development of resistance. While resistance may develop first in non-pathogenic bacteria, it could spread to pathogenic bacteria through the transfer of AMR genes.
Although it’s unclear how much this pollution contributes to the emergence and spread of resistant pathogens that threaten human and animal health, the WHO and the experts who contributed to the guidance believe that setting PNEC targets for antibiotic manufacturing can help reduce unnecessary risk.
The guidance is not the first attempt to regulate pollution from antibiotic manufacturing.
In 2022, the AMR Industry Alliance and the British Standards Institute (BSI) collaborated on a voluntary standard that requires antibiotic manufacturers to have an effective environmental management and wastewater treatment system that minimises API discharges in wastewater.
In 2023, the groups created a verification scheme, managed by BSI, that provides certification for manufacturing sites that meet the standard.
Steve Brooks of the AMR Industry Alliance, who also provided input on the report, said the targets in the WHO guidance are similar to those created by the Alliance. And while there are some differences, he believes the groups can work together to promote responsible antibiotic manufacturing.
Although the guidance isn’t binding, it is hoped that national or regional regulatory bodies, wastewater management services, antibiotic procurers, and third-party auditors will adopt the targets and create mechanisms that either require or motivate antibiotic manufacturers to meet them.
antibiotic guidance
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Global analysis ties pollution to antibiotic resistance