Cutting off antibiotic resistance at the source – change how we produce generic drugs

By Alexis Gkantiragas.

Reports have suggested that more people would die from antibiotic-resistant infections than cancer by the year 2050 – a staggering 10 million per year (1). While this figure has been subject to some debate (2) already, 33 thousand deaths annually in Europe have been attributed to antibiotic resistant infections (3). Currently, most drugs that are produced are made in factories in India and China which are not subject to any regulations concerning their handling of waste generated from the manufacturing process. As a result, waste is not correctly disposed of, and ends up contaminating the surrounding environment (4).

Antibiotic resistance comes about primarily due to bacteria being exposed to antibiotic. When they grow in an environment exposed to them, they have what is called ‘a selective pressure’ for antibiotic resistance. This means that there is evolutionary pressure on the bacteria to become antibiotic resistant. Any bacteria that can become resistant will divide and replace the bacteria killed by the antibiotic.

For example, if antibiotics are given to patients for infections that they can’t treat – it will lead to an increased risk that their gut bacteria become antibiotic resistant. From there, these bacteria can become dangerous or can even pass on the resistance genes to other, more harmful bacteria. So if you contaminate the environment with antibiotics, the bacteria in the surrounding area will likely all become resistant. This means those resistance genes are more widespread in the environment and can be spread to pathogenic (disease-causing) bacteria.

Once a drug has come off patent, other companies (as opposed to the original manufacturer) can produce the drug. To gain approval to do this, the hopeful generics manufacturer must submit a ‘bioequivalence‘ application to the regulator (5). It proves that the generic compound is the same as the original. If they are equivalent, it will likely be approved, and the drug will be marketed under the generic scientific name.

The proposed change would be relatively minor – alongside the bioequivalence data; the applying entity would need to submit and document a plan to dispose of contaminated waste to the European Medicines Agency (EMA) for any drug to be licensed in the EU. This would likely cause a slight rise in the cost of generic drugs – but would enormously decrease the number of antibiotics contaminating the environment and causing antibiotic resistance.

While it is challenging to quantify the difference this would make, it is worth considering that many other interventions in this area are either expensive or very challenging to implement.

For example, developing entirely new antibiotics and bringing them through the approval process and to market comes with a price tag of around 1 billion USD (6). Similarly, getting doctors not to prescribe antibiotics for the flu is incredibly challenging since there is always a small chance that a bacterial infection may be responsible, and doctors may also be worn down by patients pestering.

For this reason, it appears that including a requirement for proper waste disposal in generic drug manufacture will be an inexpensive, relatively easy to implement and impactful change to current regulations. As a general principle, investing money in the prevention of transmissible diseases saves a great deal of money and lives in the long run.

Alexis is a final year undergraduate biochemistry student at UCL, CEO for the Journal of Young Investigators, research analyst at an early stage biotech company, published writer and scientist and moderately sleep deprived.


(1) O’neill, J., 2016. Review on antimicrobial resistance: tackling a crisis for the health and wealth of nations. 2014. HM Government: London.

(2) de Kraker, M.E., Stewardson, A.J. and Harbarth, S., 2016. Will 10 million people die a year due to antimicrobial resistance by 2050?. PLoS medicine13(11).

(3) Cassini, A., Högberg, L.D., Plachouras, D., Quattrocchi, A., Hoxha, A., Simonsen, G.S., Colomb-Cotinat, M., Kretzschmar, M.E., Devleesschauwer, B., Cecchini, M. and Ouakrim, D.A., 2019. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. The Lancet Infectious Diseases19(1), pp.56-66.

(4) Rehman, M.S.U., Rashid, N., Ashfaq, M., Saif, A., Ahmad, N. and Han, J.I., 2015. Global risk of pharmaceutical contamination from highly populated developing countries. Chemosphere138, pp.1045-1055.

(5) Kanfer, I. and Shargel, L. eds., 2016. Generic drug product development: international regulatory requirements for bioequivalence. CRC Press.

(6) Wouters, O.J., McKee, M. and Luyten, J., 2020. Estimated research and development investment needed to bring a new medicine to market, 2009-2018. Jama323(9), pp.844-853.