Antibiotics reach patients at the end of a manufacturing chain that produces its own waste. In some places where antibiotics are made, waste and wastewater contain high concentrations of active pharmaceutical ingredients (APIs). When those compounds enter waterways or soils, bacteria encounter antibiotics released during production, independent of the medicines’ use by patients. That exposure raises a question for antimicrobial resistance (AMR) efforts: can the production of antibiotics create conditions that favor resistance to them?
Research near manufacturing sites gives a qualified answer: yes, it can. Investigators have measured antimicrobial contamination and resistance in environments affected by production waste. At one wastewater treatment plant, researchers found that a resistant bacterium became more abundant as wastewater moved through treatment. These findings establish a reason to examine what leaves production sites and how well controls address the risk, although they cannot establish manufacturing’s share of global AMR or trace a particular patient’s infection to a particular discharge.
What Leaves an Antibiotic Manufacturing Site?
The issue extends across the production chain. Antibiotic active ingredients are made, incorporated into finished products, and packaged through processes that can generate liquid and solid waste. The World Health Organization’s (WHO’s) guidance addresses these stages, from active ingredient production through formulation and primary packaging. It sets out targets intended to reduce the risk of resistance emergence and spread, as well as harm to aquatic life.1,2
This broad scope matters when several facilities contribute to one antibiotic. A company that sells the finished medicine may rely on other manufacturers to produce its active ingredient or formulate the product. Examining the final facility alone would leave earlier production stages outside the assessment. The WHO therefore identifies manufacturers, regulators, antibiotic purchasers, auditors, and waste-management services among the audiences for its guidance.
The available research offers evidence of contamination, but not a complete inventory of manufacturing emissions. In a systematic review, researchers at the Chinese Center for Disease Control and Prevention assembled published measurements of antibiotics and resistance genes in wastewater and solid waste associated with pharmaceutical production.3 They also identified a shortage of publicly available data about manufacturing processes and waste. That gap makes it difficult to judge how consistently controls are applied across production sites or to compare releases across the wider industry.
What Studies Near Production Sites Show
An investigation in Hyderabad, India, sampled water in and around a major bulk-drug production area, including locations near manufacturing facilities and sewage treatment plants, the Musi River, and nearby communities. The researchers detected antimicrobials at all 28 sampling sites and found resistant Gram-negative bacteria in more than 95% of their samples. They described the contamination as apparently associated with the selection and dissemination of resistant pathogens. The study measured contamination and resistance in the same environments; it could not identify a facility as the source of a particular resistant infection.4
Another study examined effluents from an azithromycin-synthesis facility and a veterinary-drug formulation facility, along with sediments at their discharge sites and upstream and downstream. Sediments exposed to the discharges contained a greater proportion of resistant bacteria than upstream sediments. The researchers also measured increases in the relative abundance of resistance genes and genetic elements associated with their movement. In laboratory experiments, resistance carried by material recovered from exposed sediments transferred to a recipient Escherichia coli strain. These results provide evidence of changes in the receiving environments at the sites studied.5
The upstream comparisons show differences associated with the discharges. They do not by themselves reveal what happened to resistance after it left the sampling area. The WHO’s explanation of its manufacturing guidance emphasizes concern about the emergence of new resistance and says manufacturing emissions are unlikely to contribute significantly to transmission of resistance already widespread in society.5,6
When Treatment Changes the Wastewater
Removing antibiotic residues is one aim of wastewater treatment. A study of a full-scale plant serving a manufacturer of primarily beta-lactam antibiotics shows why conventional measures of chemical removal may not tell the entire story. Researchers examined bacterial communities and resistance genes across 11 treatment units.7 The plant substantially reduced chemical oxygen demand and biochemical oxygen demand, meeting the local discharge limits the researchers reported for those measures. Yet beta-lactam residues persisted, and some exceeded the predicted no-effect concentration thresholds used in the study. Antibiotic-resistant Aeromonas veronii also became more abundant as wastewater moved from influent to effluent, while some resistance genes persisted through treatment.
The researchers attributed the enrichment of A. veronii probably to prolonged beta-lactam selection pressure and the organism’s adaptation to aquatic environments. Their findings concern one plant. What makes the result consequential is the difference between the measures: satisfactory performance against conventional chemical indicators did not mean the absence of antibiotic residues or enrichment of a resistant organism.
The investigators also compared their wastewater-derived A. veronii with publicly available genomes. In that analysis, its closest evolutionary relative was an isolate from the stool of a patient with diarrhea in the same province. The comparison did not establish that the plant was the source of the patient’s isolate. The authors called for further epidemiological work to determine whether a transmission pathway exists.
For facilities assessing their wastewater, the study makes a case for looking beyond conventional chemical indicators and antibiotic concentrations. Measurements of resistant organisms and resistance genes can reveal changes as water passes through treatment. The study does not specify how often this happens at other plants, but it identifies a question that chemical measurements alone cannot answer.
From Concern to Discharge Targets
The WHO published guidance on wastewater and solid waste management for antibiotic manufacturing in 2024.1,2 It provides targets addressing resistance-related human health risks and risks to aquatic life. WHO describes the guidance as an independent scientific basis that regulators and other decision-makers can use when incorporating targets into binding requirements. Publication of the guidance did not itself create one legal discharge limit that applies in every manufacturing country.
The AMR Industry Alliance’s Antibiotic Manufacturing Standard supplies another framework. It requires manufacturers to have an environmental management system and meet predicted no-effect concentration targets for antibiotics. A predicted no-effect concentration is a risk-assessment target: a concentration intended to be low enough to avoid a specified adverse effect. It gives manufacturers a basis for assessing emissions, rather than a guarantee that every possible resistance risk has disappeared. The Alliance updated its standard in 2025 to align more closely with WHO guidance, including provisions on waste management, active ingredient discharge limits, and transparency about suppliers.8,9
Applying a target requires evidence about performance. The relevant production sites and waste streams must be identified, and controls must be assessed and maintained. The BSI Kitemark for Minimized Risk of AMR provides independent assessment against the Alliance’s standard.10 BSI describes an initial document review and on-site assessment that can validate adherence to concentration targets through approaches including mass balance or sampling and analysis. Certification is followed by annual surveillance and periodic recertification.
WHO’s guidance, the Alliance’s standard, and BSI certification have different roles. The guidance supplies independently developed targets and risk-management recommendations. The standard states requirements a manufacturer can adopt, and certification assesses conformity with those requirements. Regulators can draw on guidance when developing enforceable rules. Keeping those roles clear makes it easier to ask what a manufacturer is required to do, who verifies it, and what evidence is available to others.
When Purchasing Standards Reach the Factory
The National Health Service (NHS) antimicrobial products subscription model offers a concrete example of a purchaser requiring evidence about manufacturing.11 Under the model, the NHS pays a fixed annual fee for access to selected antibiotics, rather than paying according to the volume used. Companies bidding for contracts under this program need the BSI Kitemark for Minimized Risk of AMR. This environmental requirement applies to the defined subscription program, not every antibiotic purchase by the NHS.
BSI says certification must cover all manufacturing sites involved in producing the relevant antibiotic. That includes active ingredient facilities, finished-product facilities, and sites operated by contract manufacturers. The requirement reaches beyond the company submitting a bid to the production steps on which its medicine depends. It gives the purchaser a way to ask whether controls have been assessed throughout that chain, rather than relying on a statement about the final product’s manufacturing site alone.
The route to certification allows for implementation over time. According to BSI’s description of the NHS tender process, an applicant can provide evidence of certification or submit a delivery plan acceptable to the NHS before a contract is awarded. BSI says certification must then be achieved within 12 months of the contract’s start. Its assessments and continuing surveillance provide a means of checking specified controls as production continues.
The NHS example gives practical force to the WHO’s inclusion of antibiotic purchasers among the audiences for its guidance. A purchaser can make independently assessed manufacturing performance part of a supply decision, while manufacturers must account for the facilities that contribute to their product. The example also illustrates why implementation needs careful design: the WHO calls for stepwise improvement that protects antibiotic supply and affordable access alongside stronger environmental controls.
Making Performance Visible
Manufacturers can identify where antibiotic residues enter waste streams, assess those streams against relevant targets, and verify controls across the production sites involved. The treatment-plant study adds a reason to consider resistant bacteria and resistance genes alongside chemical pollutants when evaluating wastewater. Independent assessment offers one way to check whether specified controls are in place and maintained.
Regulators and purchasers have different means of acting on that evidence. Regulators can use the WHO’s guidance as a basis for requirements, inspections, and monitoring. Purchasers can specify what evidence suppliers must provide, as the NHS subscription model demonstrates. Both approaches depend on information about actual production sites and waste-management practices. The WHO calls for audits and public transparency, while the systematic review of manufacturing waste identifies limited data availability as a barrier to evaluating mitigation.
The evidence does not yield a global percentage of AMR attributable to manufacturing, and the studies considered here do not establish a path from a particular discharge to a particular patient’s infection. Manufacturers, regulators, and purchasers can still act on the risks the evidence does identify. Discharge measurements, coverage of each production site, and independent verification would give them a firmer basis for judging whether antibiotic manufacturing is controlling its contribution to environmental resistance risk.
