Drug development is a challenging, long, expensive, and risky process. However, it is crucial to bring new medicines to the market and, in many cases, cover the unmet needs of patients. During drug development and drug marketing, the benefits should always exceed the risks, as wrong decisions can affect the health and life of patients and be very costly for the sponsor.

All drugs, biologics and small molecules approved in the European Union and the United States must demonstrate that they are safe and work for their intended indication. Non-clinical testing is an inseparable element of drug development with the main goal of ensuring that the drug candidate is safe for studies with human subjects. Non-clinical testing provides toxicity, pharmacokinetics (PK), and dosing data to support the first human study. Non-clinical biologics programs often differ from small molecules programs because of the nature of the therapeutic protein, species specificity, and immunogenicity. Developing information on drug use in paediatric populations is especially essential because it supports increasing access to age-appropriate medicines for children. This article discusses the most important aspects of non-clinical studies and provides main guidelines useful in non-clinical development.

Additionally, it highlights the importance of developing the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), which provides global guidances crucial in drug development. The ICH guidelines aim to present the highestlevel of scientific and regulatory recommendations. There are also regional guidelines, like those provided by the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA), which refine the ICH ones by adding important details that have to be taken into account as well.

This article provides a structured, practical overview of the non-clinical studies required in drug development to apply for marketing authorisation. It presents principles and references to useful guidances not only to outline why, when, and how specific studies are planned and carried out but also highlights the key differences and similarities between small molecules and biopharmaceuticals. Furthermore, it serves as a vital resource for professionals navigating the complexities of regulatory approval for various types of medicines.