Any new drug or pharmaceutical that enters the market is a product of a long and rigorous development, testing, and approval process. Most people are familiar with the idea of clinical trials, where new drugs are tested in humans to collect data on drug safety and efficacy. However, there is a long and bumpy road from identifying a compound with the development potential to producing a drug suitable for clinical trials.

In Vitro Pharmacology in Drug Discovery

Before drug development comes drug discovery, the process by which new candidate drugs are identified. Modern science helps researchers to understand how disease and infections are controlled at the molecular and physiological levels and to use that knowledge to create compounds that will be effective against the chosen targets (e.g., certain disease or infection).

The purpose of drug discovery is to identify a drug candidate: a molecule that targets the chosen disease selectively and effectively, and has favorable medicine-like properties. To find such a drug candidate, pharmaceutical researchers screen large libraries of chemicals for molecules with the necessary properties. Usually, a pool of potentially useful compounds (“hits”) is identified and narrowed down to identify more promising compounds (“leads”).

The next stage is called lead optimization, where the most promising molecules undergo further screening. At this stage, in vitro pharmacology assays are used to extensively optimize the biological activity and properties of the leads. In vitro pharmacology at the lead optimization stage of drug discovery generates high-quality data in a precise and timely manner, allowing researchers to identify the best compound for their chosen purpose. That compound will be the drug candidate that will go on to pre-clinical trials.

In Vitro Pharmacology in Pre-Clinical Trials

When a drug candidate enters the pre-clinical trials phase, researchers already know it is effective against a certain disease or infection. However, there is not yet enough information about this chemical’s safety, toxicity, pharmacokinetics, and metabolism in humans. At the pre-clinical trial stage, all these parameters must be assessed, and the dose for the first use in a human clinical trial must be determined. On average, only one in 5,000 compounds that enter pre-clinical trials becomes an approved drug.

Certain tests at the pre-clinical trial stage are required by drug licensing authorities. For instance, the U.S. Food and Drug Administration requires that before a drug is tested on humans, the manufacturer submits a body of pre-clinical data on safety, typically obtained through in vitro and in vivo studies.

Indeed, safety pharmacology is a crucial stage of the pre-clinical development process. Its purpose is to assess any potential undesirable effects of the drug on the body’s major systems. Although in the past, the majority of safety testing of pharmaceuticals was conducted on animals, today, safety tests are increasingly made using in vitro models that involve isolated cell lines and tissues.

At the pre-clinical trial stage, in vitro pharmacology can be used to:

• obtain high-quality data on the safety and toxicity of your drug candidate;
• identify potential adverse effects early in the drug development process;
• profile compounds to guide pre-clinical in vivo safety and toxicity studies;
• assess the potency and efficacy of your drug candidate against the targeted disease;
• gather data on pharmacokinetics and pharmacodynamics;
• study the drug candidate’s mechanism of action in more depth; and
• evaluate the activity of biosimilar compounds.

In Vitro Pharmacology and Animal Testing

The mention of animal testing alongside in vitro pharmacology raises the question: can in vitro models fully replace animal testing in drug development? Unlike in the cosmetics industry, where non-animal alternatives are sufficient for safety and efficacy testing, the pharmaceutical field has more rigorous demands. As a result, animal testing is still used to investigate repeat dose toxicity, carcinogenicity, and certain other drug properties. However, the ongoing pursuit of better animal welfare keeps driving improvement of in vitro technologies, and a future without animal testing is a real possibility.