Katrina’s Blog™

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on the science and technology of drugs and medical devices, including discovery, development, manufacturing, and regulation.

Making a New Medicine Part 1: Discovery and Development

July 1, 2024
| Medical Products, Product Development

The discovery and development of a new medicine is a complex and lengthy process. Many founders begin searching for a new therapy without understanding these details. In my experience, most of the public views drug development as “the news reports that scientists show it works in a mouse, so my doctor will be able to write a prescription next week.” In an educational effort for summer break, I offer this four-part series describing the different stages of drug development, which are applicable in all regulatory jurisdictions.

A picture of various medicine bottles meant to represent the creating of a new medicine.

The process of finding a new medicine starts with discovery research. The aim of these studies is to clearly identify the hypothetical mechanisms for the target disease state, develop relevant mechanistic models for testing potential therapeutics, and find active drugs (either chemical or biological) in the model. This is the most challenging part of pharmaceutical research. The proposed mechanism for drug action must be understood well enough to create a model system that demonstrates a direct connection between the presence of a drug and a relevant change in the system. This system change is often referred to as the target, and increased confidence in a target is established when multiple model systems (for example, published studies supporting the mechanism, cell lines expressing a receptor, animal models, or measurable genetic variants) support the mechanism. Once a target has been defined, active drugs must be found by various screening methods (sampling in an existing compound library, computer modeling of the molecular target, or brute force measurements of many compound structures), which frequently evaluate thousands of individual compounds before finding a ‘hit’ which shows the desired activity in the target. Many programs fail to find a hit with sufficient activity for development and unique enough to permit filing a patent even after screening thousands of compounds. When a hit is found, analog compounds are created and screened to find a lead compound and at least one backup acceptable for preclinical development. Compounds are also frequently screened in parallel for properties that are known to make them easier to develop as a medicine. These are often referred to as ‘druggable’ properties. The entire process can take years and occurs before the clock starts on patent exclusivity for a medicine.

A picture of Artery Biology Blood.
Image from Vector8DIY on Pixabay.

The preclinical research phase begins once our project team finds a lead candidate molecule (and hopefully a backup) and legal is drawing up a patent that will cover this family of compounds. Once the patent is approved, the race will be on to achieve regulatory approval within the patent’s 20-year exclusivity window. The lead candidate will typically start preclinical studies as soon as the target activity has been confirmed. These studies include additional testing for druggable properties (solubility, metabolic turnover rates from in vitro model systems, and interactions with other potential target systems that could create safety or efficacy issues). In vitro and in vivo studies to understand the Absorption, Distribution, Metabolism, and Elimination (ADME) and toxicology properties are also performed. Analytical methods for measuring the compound and its degradation or metabolic products are developed and validated. Additional work is done to scale up the production of the lead compound and refine the process to produce bulk drug substance batches for use in clinical studies. The project team organizes their data to prepare a regulatory document known as the Investigational New Drug (IND) application. The format and content of the IND are specified by the regulatory agency and include the preclinical data supporting the mechanism and proposed treatment approach, as well as the plans for human studies to demonstrate the safety and efficacy in human clinical use. Regulatory approval of the IND is required before clinical trials can start.

A picture of a model kidney.
Photo by Robina Weermeijer on Unsplash

Learn More

Readers interested in more details on discovery research will find this 2011 review article published by Hughes et al. in the British Journal of Pharmacology, which presents an accessible explanation of the drug discovery process. [1] More details on preclinical development may be found in this 2009 article by Steinmetz and Speck, which focuses on therapies in neurodegenerative diseases. [2]

Part 2 of this series provides an overview of the clinical trial process and a closer look at the first two trial phases.

As always, contact me any time if you have questions.


[1] Hughes, J. P., Rees, S., Kalindjian, S. B., & Philpott, K. L. (2011). Principles of early drug discovery. British journal of pharmacology162(6), 1239–1249. https://doi.org/10.1111/j.1476-5381.2010.01127.x

[2] Steinmetz, K. L., & Spack, E. G. (2009). The basics of preclinical drug development for neurodegenerative disease indications. BMC Neurology, 9(1), S2. doi:10.1186/1471-2377-9-S1-S2 


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