Are We Throwing Away Medicines Too Early?

Abstract

Recent research has highlighted the healthcare sector as a significant contributor to the climate crisis. According to data from a 2019 study, the sector accounted for 4.4% of global net carbon emissions in the U.K. Furthermore, the study found that medications accounted for 25% of NHS carbon emissions, highlighting the substantial environmental impact of the pharmaceutical industry. (1) Medicine’s contribution to carbon emissions mainly arises from its production and transport (scope 3), as brilliantly illustrated in the article “The long journey of a benzodiazepine”. (2) In addition to their contribution to carbon emissions, the role of pharmaceuticals as micropollutants is of global concern. (3) For example, The Global Monitoring of Pharmaceuticals Project examined 258 rivers in 104 countries and found that concentrations of at least one active substance at 25.7% of sampling points were above concentrations considered safe for aquatic organisms or capable of selecting for antimicrobial resistance. (4) Regulatory authorities require comprehensive stability data for marketing approval of medicines. The expiry date, which in the United States only became mandatory for pharmaceutical companies in 1979, (5) is typically between 1 and 5 years and is usually set conservatively. Short shelf lives of medicines are also a challenge for managers of hospitals, nursing homes, and national strategic stockpiles, who have to dispose of large quantities of outdated medicines each year. (6) According to one report, hospitals alone discard more than $800 million in drugs annually in the United States. (7) The improper disposal of medicines via landfill sites or in wastewater has been linked to the contamination of ecosystems and the development of antimicrobial resistance, which is one of the top global public health and development threats according to the World Health Organization. (8) Similarly, the incineration of drug waste has been associated with harmful air pollution and increased carbon emissions. (9) In addition, there is a significant number of medicines that go unused because of their expiration date. For obvious reasons, this problem is particularly severe in resource-limited countries. (10) Zilker et al. systematically reviewed available data of the stability of finished pharmaceutical products and drug substances beyond their labeled expiry dates. They found some extreme examples, like an ampule of metamizole that was at least 53 years old, which contained 99.7% of the claimed concentration of the active ingredient, and a 72-year-old ampule! containing sodium salicylate combined with caffeine, without any noticeable degradation. They concluded that for a large proportion of medicines, it seemed reasonable to extend the expiration date well beyond five years. (11) A study showing the results of the U.S. Department of Defense/Food and Drug Administration Shelf life Extension Program (SLEP) concluded that 88% of the medicines studied (unopened in their original container) were extended at least one year beyond their original expiry date, for an average extension of 66 months. (12) More recently, the stability of an expired acetaminophen suspension (three decades from the manufacturing date) has also been proven. (13) Some authors have estimated that each dollar spent on SLEP to demonstrate longer than labeled drug stability resulted in $13–94 saved on reacquisition costs. (14) Some authors have discussed the use of expired (nonretested) medicines when no suitable alternatives exist. (15) To date, the only evidence of damage caused by an expired medicinal product was Fanconi syndrome caused by degradation products of tetracycline (such as epi-anhydrotetracycline or anhydrotetracycline). (16) However, those cases occurred decades ago with a formulation that is no longer available. This debate is particularly timely in the case of antibiotics, in the context of recurrent drug shortages. (17) Obviously, certain aspects related to dosage form, storage conditions (heat and humidity), lot, excipients, etc., may have an impact on the quality of the product. (12) For example, the presence of starch in formulations of hydrochlorothiazide can alter the dissolution time, affecting bioavailability. Moreover, API–excipient interactions may lead to the browning of tablets (e.g., vigabatrin-microcrystalline cellulose). (18) Another property of many active pharmaceutical ingredients that is unknown by the majority of healthcare workers is their persistence in different environmental matrices. In fact, around half of available active pharmaceutical ingredients (APIs) are considered “persistent” or “very persistent” according to standardized criteria. (19) There are striking examples, like the benzodiazepine oxazepam, which has persisted unaltered in Swedish lake sediments for three decades, (20) or the barbiturate pentobarbital, which has been associated with accidental secondary poisoning events involving animal carcasses buried for years. (21) Of course, the environmental impact of medicines goes beyond the API itself, as illustrated by the propellants used in metered dose inhalers that can persist in the atmosphere for long periods of time. (22) Although pharmaceutical excipients can make up the predominate weight of finished pharmaceutical formulations, there are few studies on their ecotoxicity and environmental fate. (23) A study of 35 excipients used in galenic production at a Swiss pharmaceutical company suggested no environmental risk. (24) However, a more recent work, which tested the biodegradability of 14 cellulose-based pharmaceutical excipients using OECD 301 standard methods, found that none met the criteria for “readily biodegradable” classification, and potential inhibitory effects on inoculum respiration were identified for 10 compounds. (25) Other excipients of environmental concern commonly used in the pharmaceutical sector are dyes. (26) In short, we are throwing away medicines that have been conserved in our pharmacy shelves under controlled temperature and humidity conditions, in their original packages, because they have “expired”, but some APIs in those same medicines, when excreted by patients, are able to persist in the environment for decades!, causing environmental damage. Paradoxically, part of those “expired” antibiotics can contribute to antimicrobial resistance. For example, drug products containing ciprofloxacin, a highly persistent antibiotic, could remain stable for more than 11 years past their initial expiry dates. (12) Automated dispensing systems in three intensive care units at a French hospital facilitated inventory tracking and, in combination with staff training, expiration date monitoring, and stock rotation, were found to eliminate waste of expired medications, saving €14 772/year. (27) Some authors have even suggested that the extraction, purification, and repackaging of expired antibiotics may represent a revolution, creating an opportunity for new “recycling” companies that may be different from traditional pharmaceutical companies. (17) Regardless, measures to combat the unnecessary discarding of medicines should carefully consider potential trade-offs, as discussed in a recent interesting article. (28) Expiration dates have been exceeded in exceptional cases like antivirals for the flu and SARS-CoV-2 pandemics. (29−31) There is also evidence of long-term stability of potassium iodine, a drug that is stockpiled for radiation emergencies. (32) The Critical Medicines Alliance from the European Commission’s Health Emergency Preparedness and Response Authority (HERA) is now identifying the best measures to address and avoid shortages of critical medicines. (33) In summary, we believe that mandatory testing of all pharmaceutical products during longer periods and the publication of the actual shelf life according to scientific knowledge might be considered by the regulatory authorities, in line with the proposed measures by the European Union Strategic Approach to Pharmaceuticals in the Environment and the Standing Committee of European Doctors (CPME). (34,35) Replacing the expiry dates by retesting dates (manufacturers might be required to set a preliminary expiration date and then update it after long-term testing) would be a step forward in tackling the environmental consequences of pharmaceuticals and contribute to more sustainable and ethical healthcare worldwide. Paraphrasing experts from the Mayo Clinic, (17) “Extending Shelf Life Just Makes Sense”. Blanca de la Nogal-Fernández is a hospital pharmacist at the Hospital del Bierzo in Ponferrada, Spain. She specialises in oncology, medication safety, and geriatrics. She holds a postgraduate degree in pharmaceuticals in the environment from the University of the Basque Country (UPV/EHU). His research focuses on sustainable pharmacy and rational use of medicines. Sandra Lantaron-Santamaria is in her final year of pharmacy studies at the University of the Basque Country. She is currently doing her supervised internship in the pharmacy service of the Psychiatric Hospital of Alava, Mental Health Network of Alava, of the Basque public health system-Osakidetza. Matias Cuenca Castillo, originally from Ecuador, is currently studying for a Master’s degree in environmental agrobiology and a postgraduate degree in pharmaceuticals in the environment at the University of the Basque Country (UPV/EHU). In 2023, he earned his undergraduate degree in biotechnology, followed by a Master’s degree in the same field in 2024. His academic work focuses on the identification and quantification of emerging environmental pollutants. He has also worked as a teaching assistant in biology. Finally, he is passionate about both science and literature. Vladimir Akhrimenko is a Ph.D. student in the Doctoral Programme in Drug Research and Evaluation Application of Pharmaceutical Technologies to the Development of Advanced Therapies at the Department of Pharmacy and Food Sciences, University of the Basque Country (UPV/EHU). In 2024, he successfully completed his undergraduate degree in pharmacy at the University of the Basque Country. His current research focuses on the monitoring of pharmaceutical compounds in different environmental matrices, including coastal waters, surface waters, and wild animals. Gorka Orive holds a Ph.D. and is a professor of pharmacy at the University of the Basque Country. He is the author of more than 400 scientific articles (H index = 93), has amassed 30 300 scientific citations, has attended 350 conferences, and has supervised 18 doctoral theses. He has received more than €1.5 million in public–private research funding and is the principal investigator of numerous scientific projects. According to Stanford University’s 2021 ranking, he is number one in Spain and 30th in the world among the most influential pharmaceutical scientists of the 21st century. He is also an entrepreneur, having founded Geroa Diagnostics, responsible for the development of the first diagnostic biomarker for Alzheimer’s disease based on patient saliva. He is co-founder of Cybosense, a biotechnology company specializing in regenerative medicine and cybernetics. He received an honorary doctorate from the University of Buenos Aires in 2022. Unax Lertxundi is a hospital pharmacy specialist working as the Chief Pharmacist in the Araba Mental Health Network, Osakidetza, the public Basque Health System. He also belongs to the Bioaraba Health Research Institute and holds a Board Certification in Psychiatric Pharmacy. His research focuses on sustainable pharmacy and the safe use of medicines, especially in addressing drug pollution issues from a healthcare perspective. He is one the promoters of the Basque Sustainable Pharmacy initiative and one of the organizers of the postgraduate program of pharmaceuticals in the environment of the University of the Basque Country. This article references 35 other publications. This article has not yet been cited by other publications.