Improving drug safety testing approaches

Hannah Coghlan is a third year PhD student based in the Department of Pharmacology and Therapeutics. In 2023, she undertook a Professional Internship for PhD Students with the National Centre for the 3Rs in work that could reshape the 3Rs principle.

Taking Research Interests Out of the Lab

Hannah Coghlan's PhD research focuses on the mechanisms employed by cells, particularly those in the liver, to protect themselves from damage caused by drugs and their intermediates. Her work aims to improve the understanding of how differences in these mechanisms between humans and the animals used in drug research might impact the results of drug safety testing. The ultimate goal of her research is to enhance the selection process and reduce the use of animals during drug development.

This research has the potential to contribute to the 3Rs principle—an initiative that seeks to replace, reduce, and refine the number and methods of animal use in research. In April 2023, at the British Toxicology Society annual conference, Hannah discussed this principle with representatives from the National Centre for the 3Rs (NC3Rs), an organisation that collaborates with the scientific community to promote these ethical research practices. As a result of these discussions, she was given the opportunity to complete an internship within the NC3Rs Toxicology and Regulatory Sciences team. Their work involves conducting research projects to identify new areas where the 3Rs could be implemented.

The Use of Animals in Developing Biosimilars

When a drug is being developed, companies must demonstrate that it is both effective and safe. In some cases, this can be achieved through experiments in cells (in vitro research), while in others, the best or only way to ensure a drug’s effectiveness and safety is through studies involving animals (in vivo research).

Biosimilars are copy-cat versions of existing biological medicines that can be produced once the patent for the original biological medicine expires. While it might be assumed that these biosimilars would be equally effective and safe as their original counterparts, biological medicines have complex structures that can be influenced by various uncontrollable factors. As a result, the exact structure, effectiveness, and safety of a biosimilar cannot always be guaranteed to be identical to the original medicine. Consequently, companies developing biosimilars are required to conduct experiments directly comparing the biosimilar and the original medicine to establish their similarity.

The Problem and the Project

Medicine regulators do not always agree on whether animal studies are necessary to demonstrate a new medicine’s effectiveness or safety. Due to this uncertainty, drug developers often conduct animal studies even when they might not be required, in an effort to meet regulatory expectations across different regions. Some regulators have recently updated their guidelines to indicate that animal studies are not always necessary to demonstrate the similarity between a biosimilar and the original medicine. However, these guidelines remain inconsistent worldwide, and since the updates are relatively recent, their impact has not been easy to measure.

Hannah's project aimed to help NC3Rs gain a better understanding of how and why developers use animal testing in the development of biosimilars. During her three-month internship, she spent time analysing data from drug approval documents issued by regulatory agencies to identify trends in animal use and highlight specific concerns that NC3Rs could address in a more targeted manner moving forward.

By utilising publicly available data from drug developers and regulators, Hannah was able to identify notable and, in some cases, concerning trends in the use of animal testing for biosimilars. She also presented the results of this project at the British Toxicology Society annual conference in April 2024.