by In Vitro Screening and Testing
The first major step in evaluating potential drug candidates is conducting in vitro screening and testing. In vitro means “in the glass” and refers to experiments done in a controlled environment outside of a living organism, such as a test tube, culture dish, or microfluidic device. During in vitro screening, thousands of potential drug compounds are rapidly tested against important disease targets like proteins or cellular pathways to see if they have any effect. Hits from the initial screens are then put through more rigorous in vitro testing to characterize how they interact with the target and what effects they have on cells. This testing helps identify the most promising candidates to move forward to the next stages of evaluation.
A key part of in vitro testing involves examining potential Preclinical Assets candidates for toxicity against non-target cells or toxicity pathways. Even though a compound may interact effectively with the intended target, it still needs to be safe and tolerable enough to eventually administer to humans. Toxicity screening helps identify hazardous compounds early so promising alternatives can be advanced instead. Overall, in vitro screening and testing is a crucial initial filtering step to narrow down the enormous number of potential drugs into a more manageable set of candidates worthy of further investigation.
In Vivo Pharmacology Studies
Once top candidates have been identified through in vitro work, the next major step is conducting in vivo pharmacology studies in animal models of disease. Here, potential drug substances are tested within a living organism to examine important characteristics like pharmacokinetics, pharmacodynamics, safety, and initial signals of therapeutic benefit compared to control groups. Pharmacokinetic studies look at how the body affects the potential drug – understanding how it is absorbed, distributed to tissues, metabolized, and eliminated from the body over time. Meanwhile, pharmacodynamic studies investigate how the drug substance affects the body – determining what biological responses and potential therapeutic effects it produces.
For a neurological disease candidate, in vivo studies may involve examining target engagement and disease-relevant outcomes in rodent models. Cancer drug prospects could be tested through implanting human tumor cell lines into mice and monitoring tumor growth inhibition. The goal is to select candidates that have favorable pharmacokinetics for development as drugs, show good distribution to tissues relevant for the disease, and produce meaningful pharmacodynamic responses like target inhibition or improvements in disease-related outcomes without significant adverse effects. Data from in vivo pharmacology helps advance the most promising potential drugs into more advanced development stages.
ADME-Tox Testing and Safety Pharmacology
Another key component of Preclinical Assets evaluation is conducting ADME-tox (absorption, distribution, metabolism, and excretion with toxicity) testing as well as dedicated safety pharmacology studies. ADME studies shed light on crucial drug properties like how well a compound is absorbed when dosed orally, what organs and tissues it accumulates in, what metabolic pathways break it down in the body, and how long it remains before being eliminated in urine or bile/feces. Metabolism profiling also helps identify major metabolites formed which provides insights into potentially active or toxic breakdown products.
Meanwhile, dedicated safety pharmacology studies rigorously profile potential drug impacts on vital organ systems like the heart and arteries (cardiovascular), lungs (respiratory), and brain and central nervous system even at doses much higher than the anticipated therapeutic level. Any undesirable or dangerous effects are characterized. Together, ADME-tox testing and safety pharmacology studies work to uncover liabilities and guide further optimization efforts as well as identify a safe starting dose for initial clinical trials in humans. Unacceptable findings from these stages result in candidates being dropped from consideration as unsafe or unable to ever reach therapeutic levels in patients.
Microdosing and Translational Biomarker Studies
Towards the later end of the preclinical period, exploratory microdosing and biomarker studies may be conducted to support initial clinical trial planning and decision making. Microdosing involves administering very low, subtherapeutic doses of a potential drug substance to humans or animal models while intensively monitoring pharmacokinetics. It aims to get an early read on how a drug candidate behaves in actual patients versus animal models as well as validate animal-to-human translation. Biomarker profiling can also be done by collecting relevant biological samples after microdosing and analyzing them for downstream drug effects like target modulation.
Microdosing and biomarker results provide invaluable insights into selecting the right starting dose and doses to evaluate in First-In-Human clinical trials. They also help verify animal models are reasonably predicting human drug behavior as well as identify optimal biomarker strategies and clinical samples to monitor for initial signs of biological activity and safety in early patients. Data from these final preclinical stages significantly de-risk initial clinical trials by ensuring doses started in humans are physiologically relevant based on actual drug performance in people.
The Preclinical Assets phase involves a rigorous iterative process of evaluating potential new drug candidates through in vitro and in vivo testing before ever reaching humans. It serves as a crucial filtering and optimization stage to select the most promising molecular entities based on factors like desired target engagement, initial efficacy signals, acceptable safety profiles, and drug-like properties suitable for continued development. By systematically advancing candidates through these preclinical assessment steps, risks are minimized in subsequent clinical evaluation while the best shots at a successful new therapy are brought forward. It lays the vital groundwork for determining whether a given drug prospect merits entering human trials.
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1. Source: Coherent Market Insights, Public Source, Desk Research
2. We have leveraged AI tools to mine information and compile it.
Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemical and materials, defense and aerospace, consumer goods, etc.
