Paul Kau Member Name
Director/Senior Environmental Scientist
Dheeraj Chaudhary Member Name
Almost a century ago, Sir Alexander Fleming discovered penicillin, which was embraced as a veritable miracle, saving countless lives. Nowadays, however, antibiotics are often misused or overused, and antibiotic-related pharmaceutical pollution is threatening ecosystems and human health around the world. This is not a surprise, as Fleming had warned of the dangers of antibiotic resistance:
“The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted.” – Alexander Fleming (discovered penicillin)
The development of antimicrobial resistance (AMR) and the increase of superbugs can be linked to the discharge of pharmaceuticals into the environment (PiE). Global pharmaceutical companies and their supply chains are facing increasing pressure from consumers, investors, and regulators to act. However, many wastewater treatment plants are unable to effectively remove various active pharmaceutical ingredients (APIs), including antibiotics. With these chemicals being released into waterbodies and aquatic systems, AMR is inevitable.
Pharmaceutical pollution is exacerbated by production in countries with less developed and/or loosely enforced regulatory frameworks, where wastewater may sometimes be discharged without treatment. The industry is making efforts to foster sustainable pharmaceutical production, establishing industry coalitions such as the AMR Industry Alliance and the Pharmaceutical Supply Chain Initiative (PSCI) to provide platforms for sharing resources and industry performance standards. PSCI has also recently launched a supplier community platform to help suppliers share responsible best practices. However, these initiatives are largely voluntary and will require wider participation and adoption within the industry to make a difference.
So, how does one start an EHS (supply chain) audit program?
If you do not already have a robust mechanism for assessing supply chain risks, consider the PSCI Audit Program Guidance, which sets out the procedures and requirements for a credible and transparent audit approach for the pharmaceutical supply chain. This program focuses on five key areas of responsible business practices: management systems; ethics; human rights and labour; environment; and health and safety. Although the audit questionnaire is designed for the broader pharmaceutical industry, users can customise the questions to their specific needs (e.g. more specifics on wastewater management strategies, or refinement of risk category definitions).
Audit programs will typically include many facilities in different countries and, consequently, many different auditors. In theory, all auditors should assess and weigh the risk of observations consistently; however, this is not always easy to achieve in practice. The auditing team should have clear, standardised definitions of risk categories and those definitions should be periodically reviewed to capture and share new observations.
Following the audit, it can sometimes be challenging to reach agreement on the Corrective Action Plan, as the company and supplier may take different views on the costs and benefits of specific actions (or even the relevance of the observation itself). In such cases, the corrective actions may need to be broken into staged sub-actions to enable progress.
Once you have established a robust audit program, it can serve as the benchmark on which to improve environmental performance.
What about the control of PiE and AMR?
The PSCI Audit Program assesses management of PiE at an elevated level only (although its website provides a number of helpful resources on PiE and AMR). Local environmental laws and regulatory frameworks for waste and wastewater are generally not specifically regulated for APIs from antibiotic manufacturing (especially in emerging markets). As PiE may be a notable contributor to development of AMR, pharmaceutical companies should look to their antibiotic suppliers and encourage responsible practices across global supply chains.
There are typically no regulatory limits on the discharge of APIs in wastewater effluent, but a risk-based approach can be effective. Effluents with high levels of antibiotics can harm the environment, but low levels of antibiotics may also be damaging if the concentration is too low to kill exposed bacteria but high enough to exert selection pressure for resistance. So where does the threshold lie?
It can be complicated and costly to determine predicted no-effect concentrations (PNECs) for ecotoxicological and/or antibiotic resistance concentrations as the basis for risk-based targets. While the PNECs published by the AMR Industry Alliance provide good guidance on the target values, it may still be difficult and/or costly for facilities to source laboratories to test for antibiotics, especially in a large supply chain involving many APIs. An initial approach could be to prioritise the risks via a desktop screening PiE impact assessment program, and selectively target facilities with antibiotics that have high environmental hazard or endocrine activity, high solubility, high unaccountable losses, high degree of wet cleaning and/or discharge to sensitive aquatic systems.
Once the high-risk antibiotics at the selected facilities have been identified, their corresponding predicted environmental concentrations (PECs) will need to be determined. This value should consider how much antibiotic is lost in production, removed through wastewater treatment, and ultimately diluted in the receiving waters. The PEC and AMR Industry Alliance PNEC values can then be compared as a relatively simple and cost-effective indicator of a potential PiE concern.
Could Zero Liquid Discharge provide a solution?
A potential mitigation measure for a high-risk PiE facility is the implementation of a zero liquid discharge (ZLD) practice. This is particularly attractive where water is scarce, wastewater discharge is expensive, or where the technology is required to satisfy regulatory requirements. ZLD is an expanded treatment process in which wastewater is purified and recycled, leaving little to no effluent. Although the treatment requirements will vary, ZLD often includes reverse osmosis, ultrafiltration, evaporation and various other membrane technologies.
ZLD is a fast-growing alternative to traditional primary (physico-chemical) and secondary (biological-activated sludge) technologies and can effectively reduce AMR risks, but it is not without challenges.
When considering ZLD, you must assess whether there is an energy source that permits cost-efficient operations as ZLD can be very energy intensive. The added energy requirements could also affect your carbon emission reduction goals – so could you use waste heat from another process, or use a renewable generation source such as solar or wind?
Capital costs and operation and maintenance costs are likely to be higher for ZLD than for traditional technology options. Greater skilled labour will also be required as ZLD are complicated systems to operate and maintain.
Large quantities of sludge (both hazardous and other solid waste) are generated from ZLD, so management options for hazardous wastes will be required. Last but not least, be wary of how ‘purified water’ from ZLD is used. In some jurisdictions, such water can be discharged back into the environment (e.g. as gardening water) without monitoring requirements for chemicals such as APIs.
Where to from here?
The pharmaceutical industry must be more proactive in developing an integrated, comprehensive, and effective approach to combating AMR. Reliance on regulatory drivers is unlikely to protect against AMR, as regulation is inadequate in many jurisdictions. Instead, the industry should maintain long-term global collaboration platforms, enabling sharing of collective experiences and leading practices.
The battle against superbugs is not easily won, but a pharmaceutical community that works collaboratively and diligently to implement industry best practices will be step in the right direction – a step towards a sustainable healthcare system for present and future generations.