Drug Discovery and Development

The discovery and development of new medicines is a long and complex process. The development of one new medicine takes about 10–15 years from the time it is discovered to when it is available for treating patients. The average cost of research and development for a single successful drug is estimated to be $800 million to $1 billion. For every 5,000–10,000 compounds that enter the research and development (R&D) pipeline, ultimately only one receives approval.

Figure 1. Drug discovery and Development pipeline. (Pharma, 2007)

The overall process to develop a new drug can be divided into a discovery phase and development phase:

I. The discovery process includes all early research to identify a new drug candidate and testing it in the laboratory. This process takes approximately 3–6 years and by the end, researchers hope to have a promising candidate drug to test in people.

II. The development process involves a series of clinical trials, each with its own specific goals and requirements. A candidate drug must prove to be safe and effective before it can be approved. This process takes an average of 6–7 years.

In the Discovery process, first a target related to a specific disease needs to be identified. The next step is hit identification, where compounds are identified from molecular libraries. Structure–activity and in silico studies in combination with cellular functional tests are used in an iterative cycle to improve the functional properties of newly synthesized drug candidates. Subsequently, in vivo studies such as pharmacokinetic investigations and toxicity tests are performed in animal models.

In the Development phase, the drug candidate which has now successfully passed preclinical tests, can be administered to patients in clinical trials. This step is marked by three phases that the potential drug must undergo sequentially. Phase I, drug safety testing with a small number of human subjects; Phase II, drug efficacy testing with a small number of people affected by the targeted disease; and Phase III, efficacy studies with a larger number of patients.

Figure 2. Summary of the overall Drug discovery and Development process. (Pharma, 2007)

Research is mostly focused on the Discovery phase in order to identify a promising compound for development. This phase can be broadly divided into major stages:

1. Pre-discovery: Choose and understand the disease
2. Target Identification: Choose a molecule to target with a drug
3. Find a “Lead Compound”: Find a promising molecule that could become a drug
4. Lead Optimization: Alter the structure of lead candidates to improve properties. (Structure-Activity relationships, improve target interactions and pharmacokinetic properties)
5. Preclinical Testing: Laboratory and animal testing to determine if the drug is safe enough for human testing.

Many computational tools are now available and can be used to aid in the drug discovery process, particularly in the rational design of new drugs. Important computer-aided-drug design strategies are summarized in figure 3.

Figure 3. Computer-aided drug design. Adapted from Molecules. 2019 May; 24(9): 1693.

Finally, advances in understanding human biology and disease open up new possibilities for breakthrough medicines. These possibilities will grow as our scientific knowledge expands and becomes increasingly complex.

H. C. S. Chan, H. Shan, T. Dahoun, H. Vogel, and S. Yuan, “Advancing Drug Discovery via Artificial Intelligence,” Trends Pharmacol. Sci., vol. 40, no. 8, pp. 592–604, Aug. 2019.

“Drug Discovery and Development, Understanding de R&D Process” Pharmaceutical Research and Manufacturers of America, 2007, innovation.org.

M. Aminpour, C. Montemagno, and J. A. Tuszynski, “An Overview of Molecular Modeling for Drug Discovery with Specific Illustrative Examples of Applications,” Molecules, vol. 24, no. 9, p. 1693, Apr. 2019