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

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

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.

Planned Impact

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.
 
Description The comparative analysis of two sites one of which is a pharmaceutical manufacturing hub and the other a farming community provided a clear contrast in the burden of antimicrobial resistance genes (ARGs) in the environment with these genes being enriched in the pharmaceutical hub. The environmental reservoirs of ARGs is a worrying development and we assessed the source of such genes, we found significant indications of human faecal pollution at the manufacturing hub in addition to antibiotic contamination of the environment. Antibiotics are excreted by humans and there were indications that the infection burden and thus antibiotic consumption was greater in the hub community compared to the farming community. There were also irregularities in manufacturing practices due to COVID stoppages and changes in production of various drugs, this information was collected during community interactions at both sites in order to understand local activities, infection control at local clinics and prescription audits.
Exploitation Route Preliminary results so far but changes in waste disposal practices are essential.
Sectors Chemicals

Environment

Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology

URL http://respharm.net
 
Description Discussion of need for monitoring AMR to protect public health with The Rt Hon Sir Jeremy Wright KC MP
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Description PCT Sub-Project Early Careers Pump Priming Initiative - Enabling Citizen Scientists to Monitor Antimicrobial Resistance in Water Environments
Amount £5,350 (GBP)
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 03/2023 
End 09/2023
 
Description PCT Sub-Project Early Careers Pump Priming Initiative - PFAS co-selection of AMR in the environment
Amount £9,495 (GBP)
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 03/2023 
End 09/2023
 
Description Pump Priming Fund - Constructed Wetlands and AMR evolution
Amount £5,450 (GBP)
Organisation University of Warwick 
Sector Academic/University
Country United Kingdom
Start 11/2022 
End 04/2023
 
Description Rivers as a resource for all (Citizen Science: "know your river") - Research England Enhancing Research Culture Fund
Amount £49,225 (GBP)
Organisation University of Warwick 
Sector Academic/University
Country United Kingdom
Start 02/2022 
End 07/2022
 
Description Sustainable Cities GRP Small Grant Scheme - Anthropogenic pollution bioremediation and AMR in constructed wetland
Amount £2,500 (GBP)
Organisation University of Warwick 
Sector Academic/University
Country United Kingdom
Start 03/2023 
End 06/2023
 
Description 10th IWA Microbial Ecology and Water Engineering Specialist Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of research outputs on river pollution linked to AMR and antibiotic release and bioremediation strategies using sustainable solutions at international conference.
Year(s) Of Engagement Activity 2023
 
Description 29th Molecular Microbial Ecology Group Meeting (MMEG) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation of research outputs on river pollution linked to AMR, antibiotic release and bioremediation strategies using sustainable solutions at international conference. Network opportunities and discussion of future collaborations.
Year(s) Of Engagement Activity 2023
 
Description BSAC Antibiotic Resistance and Mechanisms Workshop for Researchers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Poster presentation (Investigating the effect of pharmaceutical manufacturing waste on the environmental and human resistome in India) on the latest project outcomes. The presentation raised interest and discussion with experts of the field on the waste management of antibiotic production and its impact on human and environment health.
Year(s) Of Engagement Activity 2023
URL https://bsac.org.uk/arm-workshop-for-researchers-2023-posters/
 
Description BSAC Antibiotic resistance and mechanisms (arm) workshop for researchers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation of the poster "Rivers as a resource for all - A Citizen Science project: "Know your river"" to experts of the sector resulting in discussion of citizen science approaches in active research to engage with the public and enhance public awareness on environmental and health issues such as AMR and river pollution.
Year(s) Of Engagement Activity 2022
 
Description Citizen Science: Know Your River - social media 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The citizen science project "Know Your River" was set to promote public engagement in active research activity related to environmental pollution and AMR. The social media accounts linked to the project allowed to reach a wide audience and promote interest and participation in the project.
Year(s) Of Engagement Activity 2022
 
Description Citizen Science: Know Your River - stakeholders meetings 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Third sector organisations
Results and Impact As part of the outcomes of the Know Your River project we were invited to several meetings with third party organisations, business and the general public to discuss further collaborations initiatives.
Year(s) Of Engagement Activity 2022
 
Description Citizen Science: Know Your River - website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The citizen science project "Know Your River" was set to promote public engagement in active research activity related to environmental pollution and AMR. The website allowed to reach a wide audiences and promote interest and participation in the project. It is also used as a platform to provide information on the topic and further readings to the interested audience. Citizen were actively involved in the project by replying to an anonymous survey and/or collecting river water samples to analyse. The website was used to share the results of their efforts with the wider public.
Year(s) Of Engagement Activity 2022
URL https://warwick.ac.uk/fac/sci/lifesci/outreach/know_your_river/
 
Description Conference: Engineering and Science for Deeply Uncertain Times - invited oral presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of the outcomes of integrated projects on river pollution, AMR and effects on human health. The talk has promoted interest in the research and discussion on future sustainability.
Year(s) Of Engagement Activity 2023
 
Description EDAR6 international conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of the poster "Investigating the effect of pharmaceutical manufacturing waste on the environmental and human resistome in India" to experts of the sector resulting in valuable discussion of the problem of AMR transmission through the the environment and the role of manufacturing pollution in the dissemination of AMR.
Year(s) Of Engagement Activity 2022
 
Description India-UK Tackling AMR in the Environment from Antimicrobial Manufacturing Waste (AMR-India) Whole programme meeting and Stakeholders engagement 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Remote participation and presentation of projects research outputs and further discussions with experts of the field. Discussion of further steps for the project and integration with other projects in the programme.
Year(s) Of Engagement Activity 2023
URL https://indiaukamrenvironment.org/upcoming-events/
 
Description Innovations against AMR - World AMR Awareness Week 2023 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact As part of the World Antimicrobial Resistance Awareness Week (WAAW) 2023, in collaborations with industrial partners we organised a conference open to academic researchers, industries, charities and policy makers to bring together experts of the field and provide a platform to establish links across academia and industries, showcase innovations and communicate them to wider audiences. There were network opportunities for postgraduate students to showcase their research and interact with expert from different areas.

Research outputs were also presented to the audience (lecture) and further interest was discussed with local water industry representatives.
Year(s) Of Engagement Activity 2023
URL https://warwick.ac.uk/fac/sci/lifesci/news/amr_conference_2023/
 
Description Innovations against AMR: World Antimicrobial Awareness Week - Poster presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact As part of the World Antimicrobial Awareness Week, the outcomes of the citizen science project Know Your River were presented to the public. Businesses and third sector organisations representative were engaged to discuss potential future collaborations.
Year(s) Of Engagement Activity 2022
 
Description Invited seminar at an international institute in Switzerland 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of the outcomes of integrated projects on river pollution, AMR and effects on human health. The talk has promoted interest in the research and further international collaborations were discussed.
Year(s) Of Engagement Activity 2023
 
Description Lecture given on water utility companies in UK polluting rivers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lecture presented at 6th International Symposium on the Environmental Dimension of antibiotic resistance, 22-27th September 2022 Gothenburg Sweden entitled "The Impact Of Lethal And Sub-lethal Selective Effect Of Antibiotics In The Environment ". There were many questions and discussion about pathogens and antibiotic resistance in the environment.
Year(s) Of Engagement Activity 2022
 
Description Lecture given on water utility companies in UK polluting rivers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lecture presented at the13th International Meeting on Microbial Epidemiological Markers organised by ESCMID. The talk was entitled "The riverine resistome - what should we be monitoring?" There were many questions and discussion about pathogens and antibiotic resistance in the environment.
Year(s) Of Engagement Activity 2022
 
Description Microbiology today - Knocking out AMR (October 2023 issue) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Piece titled "The Importance of One Health to Tackle the Antimicrobial Resistance Crisis" emphasising the role of the natural environment in the One Health Approach to tackle AMR and the importance of public engagement and citizen science to help mitigate the AMR crisis. The journal is distributed as printed copy to members of the Microbiology Society and is also available online for the general public.
Year(s) Of Engagement Activity 2023
 
Description Online workshop for local science and public sector workers in Islamabad regarding diagnostics of pathogens and what is qPCR 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact We produced a video and also provided online zoom workshop session describing qPCR and providing technical as well as general information for diagnosis of pathogens in various scenarios.
Year(s) Of Engagement Activity 2021
 
Description Poster presentation at 'Innovations against AMR' - World AMR Awareness Week 2023 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact I presented our research at this workshop as part of the World Antimicrobial Resistance Awareness Week (WAAW) 2023. It was a conference open to academic researchers, industries, charities and policy makers and provided an opportunity to share and discuss our research methodology and findings with academics and those from industry, including water companies.
Year(s) Of Engagement Activity 2023
URL https://warwick.ac.uk/fac/sci/lifesci/news/amr_conference_2023/
 
Description Poster presentation at Molecular Ecology Microbiology Meeting December 2023 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of a poster at this conference allowed discussion of the research with other academics and people from industry. There was considerable interest in the methodologies and findings. New connections with colleagues were forged and new ideas for moving the project forward were sparked.
Year(s) Of Engagement Activity 2023
URL https://appliedmicrobiology.org/ems-event-calendar/past-events/mmeg-molecular-microbial-ecology-grou...
 
Description Presentation of research output and engagement with Local MP 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact Presentation of research output and discussion with Local Member of Parliament regarding potential policy changes, interaction with water industry sector and future steps of research. The meeting provided an opportunity to showcase research and established new connections.
Year(s) Of Engagement Activity 2023
 
Description ResPharm workshop: Tackling AMR in the environment 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited oral presentation at the project workshop in India. The presentation resulted in further discussion and sharing of research practices. Training was provided for junior researchers.
Year(s) Of Engagement Activity 2022
 
Description Training workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact A training workshop was conduction in April 2022 at PGIMER Chandigarh India to establish and provide molecular techniques for the characterisation of pathogens using nanopore MinION portable sequencing devices. Both practical aspects of preparing DNA, flow cells and environmental samples were demonstrated together with desk based bioinformatic analysis of sequence output from the MinION plus also sequencing of 16S rRNA gene using MinION with amplicons generated by PCR.
Year(s) Of Engagement Activity 2022
 
Description Website for use by general public 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Website designed to inform the general public about our project work related to the disposal of industrial waste produced during the manufacture of antibiotics in India.
Year(s) Of Engagement Activity 2022
URL http://www.respharm.net
 
Description Workshop for assisting in production of online geostatistical mapping 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A workshop was organised online and Dr Emma Travis presented guidance and an overview of a diversity of methods to evaluate best ways of collecting and displaying information gathered about antibiotic resistance across space and time. Recorded and available via YouTube.
Year(s) Of Engagement Activity 2022
URL https://www.youtube.com/channel/UCPRSE-3KaIBGBJJMFwkC7fA