Drug development remains a difficult and costly process, as it requires a long and complicated set of steps including an initial discovery followed by preclinical validation, IND filing, and NDA/BLA review. Cures or better therapies are often the result of creative collaborations between various experts from different industries.
The Center for Therapeutic Innovation team’s expertise includes pre-clinical development of pharmaceuticals and biotechnology products, pre-IND (Investigational New Drug) requirements from FDA, IND filing and documentation review, drug safety assessments as required by ICH E2A/E6 protocols, FDA and other regulatory submissions for Phase III clinical trials, post-marketing surveillance studies, and regulatory conferences. The Center for Therapeutic Innovation has a unique and valuable combination of expertise in pharmaceutical product development and post-marketing surveillance of new drugs.
The discovery and development of a new drug are challenging, expensive and often lengthy affairs. This introductory review looks at key preclinical stages of the drug discovery process, from initial target identification and validation through to assay development, high throughput screening and hit identification. From there we will follow a hit to its lead optimization, with a brief look at the market factors needed to get a candidate drug to market. The pharmacological approach to drug discovery is the study of drugs that combat disease. This course will look at key stages in the discovery process, from initial target identification and validation through to hit selection, lead optimization and clinical development. Assays are developed and screened using high-throughput screening (HTS) technologies.
Like all scientific study, the field of pharmacology follows a process. We will look at each stage in order, starting with the initial identification of a target molecule and our investigation of how it might be interacted with by a potential new drug. From there we will move on to the selection of assay candidates and then on to high throughput screening, where we isolate the most promising compounds. Later, through lead optimization, we make these compounds even better than before. Finally, only one candidate will remain and this will be ready for clinical trials.
Due to the delicate nature of pharmacological investigations, aqueous solubility and water-soluble derivatives are preferred. In addition, highly polar functional groups can cause solubility issues for certain target molecules. The pharmaceutical scientist should be aware of these issues when considering the selection of assays for in vitro (and to a lesser extent in vivo) drug discovery evaluation.
The bioavailability of a drug is the extent and rate at which the active moiety (drug) enters systemic circulation, where it can have its pharmacological effects. It is largely determined by the properties of the dosage form, which depend partly on its design and manufacture. Bioavailability is one of the most important considerations in the evaluation of a drug dosage form. It is used to describe the rate and extent to which a drug reaches the systemic circulation (systemic bioavailability) or only part of the dosage (absorption) reaches the systemic circulation. For example, in oral administration it refers to how quickly and completely drugs can be absorbed, and their concentrations reached in blood plasma. The factors affecting bioavailability may be intrinsic (pharmaceutical formulation and process-related factors) or extrinsic (diet, disease state, and genetics).