Discovery

Discovery begins with target identification. Choosing a biochemical mechanism involved in a disease condition. Drug candidates are tested for their interaction with the drug target. Thousands of molecules for each potential drug candidate are subjected to a rigorous screening process which can include radioligand binding assays and/or functional binding assays as well as other screening methods. Once scientists confirm interaction with the drug target. After careful review, one or more lead compounds are chosen.

Characterization

When the candidate molecule shows promise as a therapeutic, it must be fully characterized. The compound will undergo a multitude of assays to determine preferred conditions for maintaining function, toxicity, bioactivity, and bioavailability. Early stage pharmacology studies help to characterize the underlying mechanism of action of the compound. Assays may include but not limited to, in vitro receptor distribution, ex vivo receptor occupancy, radiolabeling compound with either 3H, 14C or 125I, in vivo receptor occupancy.

Formulation, Delivery, Packaging Development

Researchers must devise a formulation that ensures the proper drug delivery parameters. It is critical to begin looking ahead to clinical trials at this phase of the drug development process. Drug formulation and delivery may be refined continuously until, and even after, the drug’s final approval. Researchers determine the drug’s stability—in the formulation itself, and for all the parameters involved with storage and shipment, such as heat, light, and time. A simple stability test can be utilized for this process. The formulation must remain potent and sterile and it must also remain safe (nontoxic).

Pharmacokinetics & Drug Disposition

Pharmacokinetic (PK) and ADME (Absorption/Distribution/Metabolism/Excretion) studies provide useful feedback for formulation scientists. PK studies yield parameters such as AUC (area under the curve), Cmax (maximum concentration of the drug in blood), and TMAX (time at which CMAX is reached). The data from animal PK studies is then compared to data from early stage clinical trials to check the predictive power of animal models.

Preclinical Toxicology Testing & IND Application

Pre-clinical testing analyzes the bioactivity, safety, and efficacy of the formulated drug product. This testing is critical to a drug’s eventual success and is scrutinized by many regulatory commissions. During the pre-clinical stage of the development process, plans for clinical trials and an Investigative New Drug (IND) application are prepared. Studies taking place during the pre-clinical stage should be designed to support the clinical studies that will follow.