Resolving the fate and studying the impact of pharmaceutical wastes on the environment and local community of a pharmaceutical manufacturing hub

In order to treat current bacterial infections worldwide a large quantity of pharmaceutically active ingredients (APIs) are manufactured globally each day. This process started in the UK in the 1940s and 50s following the invention of chemical purification of penicillin during World War II. Clearly a great deal of development, innovation and improved efficacy in the range of APIs has occurred since then. One of the major issues has been the time it takes to develop a new drug, the cost of all the tests needed for testing the efficacy and toxicity of any new drug against existing compounds. If this is too long and expensive no new drugs will get developed as patent life time is limited to around 20 years. Much of this time is taken up with clinical trials so once a drug is off-patent it is worth less and must be produced where employment and other costs are low. This provides a dilemma for those in need of antimicrobial agents as much of the production has moved to lower and middle income countries where costs are lower but this comes as the expense of reduced care about waste management to cut production costs. This now has been the trend during the last twenty-five years with small and medium sized pharmaceutical plants being built in Central America (principally Puerto Rico), Eastern Europe (Croatia), India and China. Out of all these India has emerged as the fastest growing, most successful pharmaceutical producer in the world. Unhappily the cost has been environmental pollution arising from small scale manufacturing developing in industrialised areas already badly polluted. However, there is a recent trend for major pharmaceutical hubs to maximise efficiency and establish suitable, local supplies of resources. Such hubs are newly emerging and there is still time to monitor their impact and most importantly regulate their activities to stop waste antibiotics entering both aquatic and terrestrial habitats and spreading resistant bacteria and damaging human health. We have assembled scientists in India and the UK to work on this globally important issue and study one such pharmaceutical hub and test in real time how pollution impacts both the human community and the resistant status of bacteria around them. In the long term we all have the same goal: to produce drugs efficiently, cleanly and with responsibility for the careful disposal of APIs without pollution. The academic teams will work together to develop chemical, microbial and public health technologies to produce a framework to evaluate impact. In turn these methods and approaches, when supported by appropriately analysed data and models, will establish in theory the best way to mitigate environmental impacts without making production economically non-viable. Antibiotic production is a vitally important industry and deserves to be served by state-of-the-art science to help solve the modern-day global needs of medicine with the market demand for cheap drugs. This dilemma can be addressed by medical anthropology combined with analytical technology and this is precisely what we will do in our team of experts doing battle with the problems of "cheap drugs for bad bugs". We could equally quote "cheap drugs for bad health" as it is the local communities and workforce who are most exposed to enable consumers globally to benefit. This means that we must produce coherent evidence that current practices are impacting human and environmental health and this is not a trivial task but is well served by establishing multidisciplinary teams of international academic experts. Our aims are clear and this is our focus for our India-UK ResPharm team to resolve the dilemmas discussed in producing cheap antimicrobials.

Our proposed study aims to quantify and establish pharmaceutical ingredients (APIs) in production in a specific pharmaceutical hub in India for human and veterinary treatment of bacterial infections. In relation to these APIs we will study the fate of antimicrobial resistance its spread, evolution, persistence in both human and environmental microbiomes. This challenges the neglected area of global pharmaceutical waste disposal, exemplified by the pharmaceutical manufacturing hubs emerging in India. This study offers a particularly rich context as we are able to observe both local environment and local communities and compare with a similar area unaffected by pharmaceutical waste production. Our study design takes longitudinal and interconnected world approaches, producing additional dimensions of datasets on antibiotic resistance gene (ARG) dissemination in sewage/sludge and aquatic systems (river/canal/sea planktonic water and sediment) samples and clinical specimens from temporal and a more inclusive (employees, local exposure and confounding issues such as self-medication) perspectives. The findings will inform policy-makers, implementers, and industry experts and managers to understand impacts of inappropriate waste disposal.
Through continued and purposeful engagement with Indian and global stakeholders such as EMA, WHO, Bio-Pharma UNGA roadmaps on AMR, global ERA and estimates of degradation, the AMR Industry Alliance, we will ensure effective impact on future policy and practice. This project intends to achieve the following benefits:
(a) Better understanding of how ABA and API pollute and degrade with impacts on ARG in the environment of manufacturing hub
(b) Understanding the spread, evolution, persistence, and fate of ARG in the environment in relation to impact of pharmaceutical waste
(c) The wider transferable lessons for national and international stakeholders for future waste disposal
The expected impacts will be measured through the following method (beneficiaries, activities) to achieve the above benefits:
1) Policy-makers and bio-pharma alliances, WHO, EU and EMA. Targeted meetings with (and/or regular updates to) the representatives of health and environment authorities in India to show how ABAs and APIs can spread ARGs. This new knowledge will include how long ABAs/APIs persists in the environment after the emission, and how state-of-the-art molecular, statistical, and modelling methodologies can support analysis of health and environmental risks and decision-making. This will inform potential interventions related to drug manufacturing practices, hygiene practices, wastewater management, infrastructure development, and sewage/ sludge ARG surveillance. These authorities include: a) the Indian Ministry of Health, local industries, national AMR surveillance (CSE). Impacts will be measured through simple phone interview(s)/e-mail to policy-makers about the degree of policy and regulatory recommendations drawn on the project are considered for agenda setting by them, the frequency of dialogue, and actual determination of relevant environmental standards and acceptance of appropriate and timely approach to the detection of environmental ARG in the manufacturing context (e.g. focused sewage ARG surveillance, etc), and improvement in waste treatment efficiency.
2) Health and environmental protection agencies in India and England (e.g. Public Health England). We will report resistance genes identified in the environmental samples in India and the impacts on the human faecal resistome. Impacts will be measured by recording how many times health and environmental protection agencies have responded to our updates, acted upon mitigation strategies (e.g. early warning about the health risks of human activities in the affected areas, including use of water supplies from the river), and how successfully health risks are controlled.
3) Broader community. Recording how many times the project webpage was accessed.