APIs in water: why the pharma industry must act now

Once discharged through wastewater, APIs can remain biologically active, affecting aquatic ecosystems and adding pressure to already vulnerable water bodies. Global monitoring has also shown that pharmaceutical pollution is not a localised issue, with APIs detected in water sources across many countries. Addressing this challenge requires action across the pharmaceutical lifecycle, including prevention and control at source, responsible use and disposal, monitoring and advanced wastewater treatment. This article focuses on the engineering decisions manufacturers can make around source characterisation, treatment selection and implementation.

In the context of the EU, industrial water treatment requirements fall under the Industrial Emissions Directive (IED) and are guided by Best Available Techniques Reference Documents (BREFs), of which neither has any specified limits for APIs yet. While the OFC (Organic Fine Chemicals) BREF has no Best Available Technology Conclusions (BAT) and associated emission limits published, it does list some BAT reference data that includes advanced treatment/API removal.

In addition to EU regulation, industries could also have local permit requirements concerning pharmaceutical residues, APIs, or AMR-related substances. And while the official requirements for industrial treatment of micropollutants and APIs are limited, another EU Directive will start to play a role for pharma manufacturers: the revised Urban Wastewater Treatment Directive.

Antibiotic APIs require particular attention because antibiotic pollution from manufacturing wastewater can contribute to the selection and spread of antimicrobial resistance (AMR). Monitoring and controlling these emissions at source therefore supports both environmental protection and the continued effectiveness of antibiotics.

The EU’s Urban Wastewater Treatment Directive (UWWTD) has shaped how Europe collects, treats, and discharges urban wastewater since it was first adopted in 1991. Its purpose has remained clear: to protect human health and the environment from the impacts of untreated or insufficiently treated wastewater.

But the pressures on Europe’s water systems have changed significantly over the past three decades. New pollutants, climate-related stress, resource constraints, and growing expectations for environmental protection are now reshaping what effective wastewater treatment needs to deliver. The revised Directive, in force from 1 January 2025, responds to this shift by setting a more ambitious framework for urban wastewater management across Europe.

This makes the new Directive more than a regulatory update. It is intended as a key driver for how utilities and industries, including pharmaceutical manufacturers, should prepare for the next generation of wastewater treatment - including the removal of micropollutants such as active pharmaceutical ingredients.

The UWWTD introduces a 'polluter pays' principle through Extended Producer Responsibility (EPR). Under the Directive, Member States must establish EPR schemes for listed products by 31 December 2028, and pharmaceutical and cosmetics producers will be expected to cover at least 80% of the full costs of quaternary treatment and associated micropollutant monitoring, subject to the Directive's scope, exemptions and national implementation.

Because of its significant financial implications, the polluter pays principle has been met with legal challenges and industry pushback in several parts of Europe. Overall, the regulatory landscape remains a dynamic playing field. One open question is how Producer Responsibility Organisations will be set up to implement EPR in individual member states and whether this will be coordinated across Europe or handled differently from country to country.

Beyond the polluter pays principle, the revised UWWTD may also have more indirect implications for pharmaceutical manufacturers. One of the key factors here is how industrial wastewater is discharged. For manufacturers connected to a municipal wastewater system, their utilities may decide to introduce stricter requirements for the concentrations of APIs permitted in industrial discharges. For sites that discharge directly to receiving waters, environmental authorities may instead choose to incorporate API-related considerations into environmental permits and discharge requirements, using UWWTD as a guide.

Although pharmaceutical manufacturing contributes only a relatively small share of the total pharmaceutical residues entering the aquatic environment, these developments mean that manufacturers may still face increasing pressure to reduce emissions at source. As a result, pharmaceutical companies may need to invest in on-site treatment upgrades even where the UWWTD does not directly regulate industrial wastewater treatment. In many cases, this also makes technical and economic sense, as treating concentrated industrial wastewater is often more effective than removing the same compounds after they have been diluted within the municipal wastewater system.

For pharmaceutical manufacturers, this creates a complex and evolving regulatory landscape. While uncertainty remains around the implementation of the polluter pays principle and related Extended Producer Responsibility schemes, expectations around the management of API emissions continue to grow. At the same time, manufacturers may face indirect pressure through stricter discharge requirements and environmental permits aimed at reducing pharmaceutical residues at source.

Waiting for complete regulatory certainty before acting is therefore unlikely to be the best strategy when it comes to APIs. It takes time to develop and implement an advanced treatment system optimised for a specific site.

How can pharmaceutical manufacturers assess API emissions and environmental risk?

API treatment in some form or another will be the reality for pharma manufacturers in the future, whether it is for pre-treatment prior to discharge to a municipal plant or treatment before discharging directly into the environment. The current organic COD (chemical oxygen demand) removal known from the IED will not be sufficient in the future. The greatest successes will come down to preparing early and ensuring a proper data foundation to understand the exact need of the individual production site.

For companies that are not yet actively addressing API removal, the first thing to do is to gather data to understand what they are actually discharging and to what extent the discharge poses a threat to the environment. A key consideration is whether the concentration discharged to the environment exceeds the Predicted No Effect Concentration (PNEC), meaning the concentration below which no environmental impact is expected. The objective is to ensure that the actual environmental concentration remains lower than the PNEC.

Once that understanding is in place, companies can determine what action is needed to remove APIs from the water. This often requires laboratory studies, bench-scale testing or pilot trials to identify the right technology for the specific wastewater stream. In some cases, data may show that additional treatment is not required because concentrations are already below levels of concern. In other cases, the assessment may point to a need for advanced treatment to reduce environmental risk.

Some pharmaceutical companies are already acting proactively by establishing internal discharge limits, investing in treatment technologies before regulations require it, and applying those standards globally rather than only in Europe. The proactive companies we now see establishing internal discharge limits are typically those who already monitor their data and have the first two or three treatment steps in place.

Most pharmaceutical manufacturers are already familiar with the core stages of wastewater treatment. Preliminary and primary treatment removes solids, grit, oils, and other physical material, while secondary biological treatment reduces much of the organic load. In many systems, tertiary treatment is then used to remove remaining nutrients, fine particles, and pathogens before discharge or reuse.

What is changing under the revised UWWTD is the increased focus on removal of micropollutants such as APIs. Conventional wastewater treatment stages can reduce some pharmaceutical residues, but it does not fully remove every API. Removal efficiency varies according to the compound, wastewater matrix and treatment process, and APIs may remain present at low concentrations while retaining biological activity in the receiving water environment.

This is why quaternary treatment will increasingly play such an important role. As an advanced treatment step, it is designed to target micropollutants that pass through the earlier stages of treatment.

While established technologies such as ozonation and activated carbon are increasingly used to remove pharmaceutical residues from wastewater, selecting the right solution is rarely straightforward. Treatment performance depends on various factors such as wastewater composition, site constraints, operational requirements and the specific compounds present in the discharge. Because pharmaceutical wastewater streams can vary significantly between facilities, much more than urban wastewater streams, treatment solutions are rarely one-size-fits-all.

As a result, technology selection should be based on a site-specific assessment rather than a standardised approach. Pilot testing and multi-criteria evaluations can help organisations identify the most effective and efficient treatment strategy for their individual circumstances. Collecting representative data, evaluating environmental impacts and validating treatment technologies can therefore take years. The earlier companies begin collecting data and assessing their options, the better positioned they will be to respond as expectations and regulations continue to evolve.

For one pharmaceutical manufacturer, the question was not whether wastewater treatment would become more demanding, but how best to prepare for it. At their site, wastewater is currently treated on-site using conventional technologies before the treated effluent is discharged to a local river. Within the context of the revised UWWTD, the local authorities have indicated that stricter limits on micropollutants and solvents will be implemented in the future , and the manufacturer needed to understand which advanced treatment options could provide both reliable performance and a cost-effective path towards future compliance.

To support the client, Ramboll conducted a feasibility study assessing a broad range of commercially available and emerging technologies for the removal of active pharmaceutical ingredients. The study focused on identifying a robust treatment concept capable of addressing a wide range of APIs and achieving more than 80% removal, while also reflecting the specific conditions and requirements of the site.

In close collaboration with the client, Ramboll developed a longlist of relevant technologies, narrowed these down through a site-specific screening process, and then carried out a detailed multi-criteria analysis of the shortlisted options. For this location, advanced oxidation combined with biological filtration was identified as the most favourable treatment solution.

This project is a strong example of how pharmaceutical manufacturers can move from regulatory uncertainty to practical decision-making – by assessing available technologies early, understanding site-specific constraints, and identifying treatment concepts that are both technically robust and commercially realistic.

The future regulatory framework for pharmaceutical residues in wastewater is still evolving, and the impact will vary between sites and geographies. However, the direction of travel is clear. Expectations from regulators, authorities, and society are increasingly focused on reducing the environmental impact of pharmaceutical residues in water bodies. Organisations that begin building knowledge and understanding their environmental impact today will be better equipped to navigate future requirements and identify the most effective path forward for each site.

For pharmaceutical manufacturers, acting early supports three practical outcomes: stronger regulatory readiness, better-informed investment decisions, and lower environmental risks. The organisations making the greatest progress are not necessarily those investing first in advanced treatment technologies. They are the ones investing first in understanding their wastewater and the environmental impact of their discharges.