Steps in Drug Discovery & Development

Drug discovery is the process by which new medications are discovered.

STEPS IN DRUG DISCOVERY AND DEVELOPMENT

Step 1: Discovery and Development

Discovery

Typically, researchers discover new drugs through:

  • New insights into a disease process that allow researchers to design a product to stop or reverse the effects of the disease.
  • Many tests of molecular compounds to find possible beneficial effects against any of a large number of diseases.
  • Existing treatments that have unanticipated effects.
  • New technologies, such as those that provide new ways to target medical products to specific sites within the body or to manipulate genetic material.

At this stage in the process, thousands of compounds may be potential candidates for development as a medical treatment. After early testing, however, only a small number of compounds look promising and call for further study.

Development

Once researchers identify a promising compound for development, they conduct experiments to gather information on:

  • How it is absorbed, distributed, metabolized, and excreted.
  • Its potential benefits and mechanisms of action.
  • The best dosage.
  • The best way to give the drug (such as by mouth or injection).
  • Side effects or adverse events that can often be referred to as toxicity.
  • How it affects different groups of people (such as by gender, race, or ethnicity) differently.
  • How it interacts with other drugs and treatments.
  • Its effectiveness as compared with similar drugs.

Step 2: Preclinical Research

Before testing a drug in people, researchers must find out whether it has the potential to cause serious harm, also called toxicity. The two types of preclinical research are:

  • In Vitro
  • In Vivo

FDA requires researchers to use good laboratory practices (GLP), defined in medical product development regulations, for preclinical laboratory studies. The regulations set the minimum basic requirements for:

  • study conduct
  • personnel
  • facilities
  • equipment
  • written protocols
  • operating procedures
  • study reports
  • and a system of quality assurance oversight for each study to help assure the safety of FDA-regulated product

Usually, preclinical studies are not very large. However, these studies must provide detailed information on dosing and toxicity levels. After preclinical testing, researchers review their findings and decide whether the drug should be tested in people.

Step 3: Clinical Research

Designing Clinical Trials

Researchers design clinical trials to answer specific research questions related to a medical product. These trials follow a specific study plan, called a protocol that is developed by the researcher or manufacturer. Before a clinical trial begins, researchers review prior information about the drug to develop research questions and objectives. Then, they decide:

  • Who qualifies to participate (selection criteria)
  • How many people will be part of the study
  • How long the study will last
  • Whether there will be a control group and other ways to limit research bias
  • How the drug will be given to patients and at what dosage
  • What assessments will be conducted, when, and what data will be collected
  • How the data will be reviewed and analyzed

Clinical trials follow a typical series from early, small-scale, Phase 1 studies to late-stage, large scale, Phase 3 studies.

The Investigational New Drug Process

Drug developers, or sponsors, must submit an Investigational New Drug (IND) application to FDA before beginning clinical research.

In the IND application, developers must include:

  • Animal study data and toxicity (side effects that cause great harm) data
  • Manufacturing information
  • Clinical protocols (study plans) for studies to be conducted
  • Data from any prior human research
  • Information about the investigator

Clinical trials include Phase 1, 2, 3, 4.

Step 4: FDA Drug Review

Once FDA receives an NDA, the review team decides if it is complete. If it is not complete, the review team can refuse to file the NDA. If it is complete, the review team has 6 to 10 months to make a decision on whether to approve the drug. The process includes the following:

  • Each member of the review team conducts a full review of his or her section of the application. For example, the medical officer and the statistician review clinical data, while a pharmacologist reviews the data from animal studies. Within each technical discipline represented on the team, there is also a supervisory review.
  • FDA inspectors travel to clinical study sites to conduct a routine inspection. The Agency looks for evidence of fabrication, manipulation, or withholding of data.
  • The project manager assembles all individual reviews and other documents, such as the inspection report, into an “action package.” This document becomes the record for FDA review. The review team issues a recommendation, and a senior FDA official makes a decision.

Step 5: FDA Post-Market Drug Safety Monitoring

Even though clinical trials provide important information on a drug’s efficacy and safety, it is impossible to have complete information about the safety of a drug at the time of approval. Despite the rigorous steps in the process of drug development, limitations exist. Therefore, the true picture of a product’s safety actually evolves over the months and even years that make up a product’s lifetime in the marketplace. FDA reviews reports of problems with prescription and over-the-counter drugs and can decide to add cautions to the dosage or usage information, as well as other measures for more serious issues.

DNA microarrays in drug discovery and development

DNA microarrays can be used to measure the expression patterns of thousands of genes in parallel, generating clues to gene function that can help to identify appropriate targets for therapeutic intervention. They can also be used to monitor changes in gene expression in response to drug treatments. Here, we discuss the different ways in which microarray analysis is likely to affect drug discovery.

Drug targeting and retrometabolic drug design approaches

Traditional methods for drug design have relied on optimization of drug activity with little regard for drug safety. Such manipulation often produces highly potent derivatives with equally elevated toxicities giving rise to no or disadvantageous changes in the therapeutic index of the derivatives. Inclusion of metabolic and toxicological concerns in the drug design process is embodied in the retrometabolic approach.