Skip to content

Drug development

Following the drug discovery phase, the most promising lead compounds progress through the drug development pipeline. This process involves a series of stages designed to assess potential drug candidates' safety, efficacy, and manufacturability. The drug development process is heavily regulated by agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to ensure that only safe and effective medicines reach the market.

Preclinical Studies

Preclinical studies are conducted to evaluate the safety and efficacy of lead compounds in non-human models. These studies involve both in vitro (cell-based) and in vivo (animal) experiments to assess the pharmacokinetic and pharmacodynamic properties of the compounds, as well as their potential toxicity.

The main objectives of preclinical studies are to:

  • Determine the compounds' absorption, distribution, metabolism, and excretion (ADME) properties.
  • Establish the safety profile and identify potential adverse effects.
  • Provide evidence of the compound's efficacy in relevant disease or condition animal models.
  • Determine the optimal dose and route of administration for further studies.

Investigational New Drug (IND) Application

Before a potential drug candidate can be tested in humans, the sponsor (usually a pharmaceutical company) must file an Investigational New Drug (IND) application with the regulatory agency. The IND application includes data from the preclinical studies and detailed protocols for the proposed clinical trials.

Clinical Trials

Once the IND application is approved, the drug candidate enters the clinical trial stage. Clinical trials are conducted in three main phases.

  • Phase 1 These trials involve a small group of healthy volunteers (20-100) and are designed to assess the drug candidate's safety, tolerability, and pharmacokinetics. The main objective is to determine the maximum tolerated dose (MTD) and identify any potential side effects.
  • Phase 2 These trials involve a larger group of patients (100-500) with the disease or condition the drug intends to treat. The main objectives are to evaluate the drug candidate's safety and efficacy and to determine the optimal dose for Phase 3 trials.
  • Phase 3 These trials involve a large group of patients (1,000-5,000) and are designed to provide definitive evidence of the drug's safety and efficacy. The drug candidate is typically compared to a placebo or the current standard of care treatment. Successful completion of Phase 3 trials is required for regulatory approval.

New Drug Application and Regulatory Approval

Following the successful completion of clinical trials, the sponsor submits a New Drug Application (NDA) to the regulatory agency. The NDA includes all data from the preclinical and clinical studies and information on the manufacturing process and proposed labeling for the drug.

The regulatory agency reviews the NDA to determine whether the drug's benefits outweigh its risks. If the drug is approved, the sponsor can begin manufacturing and marketing the drug.

Post-Market Surveillance

After the drug is marketed, the sponsor must conduct post-market surveillance to monitor the drug's safety and efficacy in the larger patient population. This stage involves collecting and analyzing data on adverse events and other safety concerns, as well as conducting additional studies to evaluate the drug's long-term effects further.

Throughout the drug development process, computational methods can play a crucial role in guiding decision-making and optimizing the chances of success. In the following sections, we will explore how computer-aided drug design (CADD) techniques can be applied at various stages of drug development.

  1. Chapter 4 of Rosa, J. M. C. (2023). Pharmaceutical chemistry: Drug design and action. Walter de Gruyter GmbH & Co KG. ↩

  2. Chapter 4 of Kumar, T. D. A. (2022). Drug design: A conceptual overview. CRC Press. DOI: 10.1201/9781003298755 ↩

  3. Chapter 1 of Strømgaard, K., Krogsgaard-Larsen, P., Madsen, U. (2017). Textbook of drug design and discovery. CRC Press. ↩