ECOPHARMACOVIGILANCE
Revolutionising drug safety for a sustainable future
Payal P Gajbhiye, Senior Drug Safety Physician, Parexel
Ecopharmacovigilance (EPV) is an emerging field that monitors and addresses the environmental impact of pharmaceuticals. It involves detecting, evaluating, and preventing adverse effects on ecosystems and wildlife. EPV strategies include eco-friendly drug design, green chemistry, biodegradable products, and improved waste management. The goal is to balance medical advancements with environmental preservation, recognising the interconnectedness of human health and ecosystem vitality.
A new era in pharmaceuticals is dawning, focusing on sustainability and environmental responsibility. This emerging field, called EcoPharmacoVigilance (EPV), combines traditional pharmacovigilance with environmental awareness.
Environmental contamination by pharmaceuticals has both direct and indirect impacts, potentially compromising human health and well-being. EPV serves as a valuable tool for detecting, evaluating, understanding, and addressing the negative environmental effects of pharmaceuticals, thereby helping to control pharmaceutical pollution. This narrative review examines the long-term effects of pharmaceutical contaminants on flora and fauna, with a particular focus on the possible implications for human health. It also investigates the origins and pathways of environmental pharmaceutical contamination, as well as EPV methodologies and their potential contribution to achieving lasting solutions.
Understanding EPV
EPV is the ongoing monitoring of pharmaceuticals' environmental effects. It involves detecting, evaluating, understanding, and preventing adverse impacts on ecosystems and wildlife. EPV expands human-centric pharmacovigilance to include the entire biosphere, acknowledging that drug residues often remain in the environment long after use.
EPV emerged in the early 2000s, driven by increasing evidence of pharmaceuticals in the environment and their potential impact on non-target species. This marked a crucial shift in environmental science and pharmacy, emphasizing the need for a holistic approach to pharmaceutical management that includes environmental protection.
Routes of medication infiltration in ecological systems
The consumption of medications in both human and animal populations is increasing rapidly. It's estimated that 100,000 tons of antimicrobials are used annually, with over 30 billion doses of NSAIDs consumed yearly in the US alone. Drugs enter the environment through various routes. Consumed drugs are excreted as metabolites or unchanged, often in water-soluble forms that end up in sewage systems. Pharmaceutical companies contribute to environmental contamination due to outdated processes, despite sewage treatment efforts. Some drugs, like cocaine, oral contraceptives, and carbamazepine, are not fully eliminated by treatment processes and enter water systems. Numerous drugs, including antibacterials, hormones, and pain relievers, have been detected in rivers and water bodies. This environmental contamination is a cause for concern. For example, a report published in the Washington Times found that wastewater from Indian drug factories contained antibiotic levels sufficient to treat a city of 90,000 people daily. Irrigation with contaminated sewage can also introduce drugs into the food chain and improper disposal of leftover medicines significantly contributes to environmental contamination. Drug residuals from formulations for instance, fentanyl transdermal patches can retain 28-84 per cent of the loaded drug after use. The presence of these pharmaceuticals in the environment, even in small amounts, leads to their unintended re-entry into human systems through drinking water and the food chain, creating an alarming situation.
Blurb: Ecopharmacovigilance (EPV) emerges as a crucial tool, offering a route towards a more sustainable and adaptable global health system. By embracing EPV principles, we can work towards balancing the benefits of medical advancements with the imperative of preserving our planet's ecosystems.
Examining the ecological impact of drug pollution
Environmental exposure to pharmaceuticals affects humans and animals in a variety of ways. Low-dose exposure through drinking water may contribute to microbial resistance. This issue is compounded by pharmaceutical companies' reduced focus on developing new antimicrobials. While the effects of low-dose exposure are not fully understood, certain groups like pregnant women, children, the elderly, and those with renal or hepatic issues may be at higher risk due to altered pharmacokinetic. Even in micro-doses, some drugs may exhibit synergistic effects or cause nocebo effects. Type B adverse reactions are also possible at these concentrations. In the Indian subcontinent, vultures experienced kidney failure and population decline due to indirect exposure to diclofenac used in livestock treatment. Traces of oral contraceptives in water have been linked to decreased frog populations. Ivermectin, an anthelmintic used in veterinary practice, adversely affects organisms like dung beetles when excreted through animal feces. Presence of sex hormones in aquatic environments has led to the feminisation of male fish. Some researchers have attempted to correlate the significant decline in human sperm count over the past 50 years with environmental pharmaceutical exposure.
Many individuals are unknowingly exposed to a variety of drugs through environmental sources. The environmental threats arise not only from the active pharmaceutical ingredients but also the excipients used in drug formulations. These consequences highlight the complex and far-reaching impacts of pharmaceutical pollution on ecosystems and human health.
Objective of EPV
The main purpose of EPV is to protect environmental health by minimising ecological exposure and harm throughout a pharmaceutical's lifecycle. This mainly involves tracking pharmaceutical compounds in environmental matrices and evaluating their risks and developing methods to reduce pharmaceuticals' environmental footprint, from green chemistry to improved waste management.
EPV evaluation methods
The primary method for assessing a drug's environmental risk is the Predicted Environmental Concentration to Predicted No-Effect Concentration (PEC:PNEC) ratio, a commonly used risk quotient.
Key components of PEC:PNEC:
1.Predicted Environmental Concentration (PEC):
• Estimates the maximum expected drug concentration in the environment
• Based on physicochemical properties and annual usage volume
• Includes patient use and excretion into wastewater systems
2. Predicted No-Effect Concentration (PNEC):
• Derived from ecotoxicological tests on three trophic levels:
a) Algae
b) Daphnids
c) Fish
The calculation includes an assessment factor to account for interspecies toxicity differences and uncertainty in quantitative structure-activity relationship predictions
Risk Assessment Process:
1. If PEC:PNEC < 1:
• Drug is considered to have negligible environmental risk
• No further information required
2. If PEC:PNEC > 1:
• Additional testing is typically needed to refine PEC or PNEC
• If refinement fails to bring the ratio below 1, the drug becomes a candidate for further EPV risk management
This method provides a standardised approach to evaluate and quantify the potential environmental impact of pharmaceuticals, helping to identify drugs that may require additional scrutiny or risk management strategies.
7 Key EPV strategies
EPV employs various approaches to mitigate the environmental impact of pharmaceuticals which includes
1. Eco-friendly drug design
2. "Green chemistry" in pharmaceutical development
3. Creation of biodegradable products
4. Reduction of manufacturing emissions
5. Education on rational drug use
6. Improved prescribing practices
7. Proper management of unused medications
The "GREENER" concept for developing environmentally friendly pharmaceuticals includes good practice for patients, reduced off-target effects and high specificity, exposure reduction via less emissions, no persistent, bioaccumulative, and toxic (PBT) () properties, effect reduction (avoiding undesirable moieties) and risk and hazard mitigation.
Novel EPV approaches also involve Environmental monitoring for pharmaceutical contamination and The CHEM21 project, funded by the European Union (EU) and industry, has introduced innovative, eco-friendly manufacturing processes.
Research Initiatives include biological monitoring across species by means of Measuring, predicting, and identifying effects of pharmaceutical pollutants. European Commission is currently evaluating pharmaceutical impact on environment and public health. It is imperative to have collaborative research between industry, academia, and government.
The key Industry Actions that are taken in this direction includes Implementation of Environmental Risk Management Plans (ERMPs) by some EU pharmaceutical companies such as AstraZeneca. These plans include information on physicochemistry, human metabolism, pharmacokinetics, preclinical toxicology, and environmental data of the active pharmaceutical ingredient and Continuous updates are made based on newly identified or emerging environmental risks.
Academic research is progressing at a rapid pace. The Society of Environmental Toxicology and Chemistry identified top 20 questions related to pharmaceuticals in the environment and has highlighted areas for future research.
These strategies aim to comprehensively address the environmental impact of pharmaceuticals through innovative design, manufacturing, monitoring, and research initiatives.
Remedial measures for pharmaceutical environmental impact
While pharmaceuticals are essential in modern life, it's crucial to maintain ecological balance. Proposed solutions to protect our planet include:
1. Improving sewage treatment plants
2. Educating the public on responsible drug use
3. Developing biodegradable products
4. Establishing local regulations for household medicine disposal
5. Raising awareness about pharmaceutical pollution risks
Biopharmaceuticals could be an alternative, but more research is needed before widespread adoption. Environmental safety should be mandatory in drug development, including comprehensive environmental impact studies. In the EU, Environmental Risk Assessment (ERA) is required for market authorisation. ERA considers factors like drug dose, characteristics, metabolism, biodegradation, environmental concentration, and ecotoxicity.
Regulatory actions across the globe
• The U.K. has implemented strict regulations
• The U.S. Senate has passed legislation to monitor drugs in the environment
India:
• Efforts are underway to establish environmental protection systems
• The Jatayu Conservation Breeding Centre aims to save endangered vulture species
• Despite higher contamination levels, India is working to improve its environmental safeguards
Key Challenges:
• Predicting chronic hazards from acute toxicity studies
• Lack of uniform national guidelines for leftover medicine disposal
Recommendations:
1. Collaboration between regulatory and scientific communities
2. Mandatory drug take-back service guidelines for end-users
3. Strict legislation and widespread implementation of existing laws
Proactive measures are essential to address pharmaceutical pollution, rather than reacting only after alarming incidents occur. A comprehensive approach involving regulation, education, and innovation is necessary to preserve our environment while maintaining access to essential medications.
Conclusion
The intricate relationships between human health, environmental sustainability, and ecosystem vitality highlight the necessity for a comprehensive and unified strategy. The World Health Organization's "One Health" approach acknowledges the interdependence of human health, animal welfare, and environmental conditions.
To achieve a future where pharmaceutical progress and environmental conservation coexist in harmony, we must:
1. Enhance scientific knowledge
2. Adopt cutting-edge manufacturing techniques
3. Promote worldwide cooperation among:
- Regulatory authorities
- Pharmaceutical industries
- Research institutions
Ecopharmacovigilance (EPV) emerges as a crucial tool in this pursuit, offering a route towards a more sustainable and adaptable global health system. By embracing EPV principles, we can work towards balancing the benefits of medical advancements with the imperative of preserving our planet's ecosystems. This integrated approach recognises that human health cannot be isolated from the health of our environment and other species. It emphasizes the need for a paradigm shift in how we develop, produce, and manage pharmaceuticals, considering their full lifecycle impact on the broader ecosystem.
Ultimately, this holistic perspective aims to create a future where medical progress and environmental stewardship are not competing interests, but mutually reinforcing goals in the quest for global well-being.
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Author Bio
Dr. Payal Gajbhiye is a distinguished Senior Drug Safety Physician at Parexel, bringing over a decade of unparalleled expertise to the forefront of pharmaceutical safety. With more than 12 years of handson experience spanning pharmacovigilance, clinical trials, and clinical practice, Dr. Gajbhiye stands as a beacon of knowledge and innovation in the field. She serves on the editorial board of the esteemed Journal of Pharmacovigilance and Drug Safety (JPADR), where her insights shape the discourse on critical safety issues in the pharmaceutical industry. Her commitment to advancing the field is evident in her active participation in various professional groups. Her passion for nurturing talent has led her to become a sought-after mentor, dedicated to shaping the next generation of professionals in the pharmaceutical and healthcare sectors.
