Understand The R&D Process

Discovery of Therapeutic Approach

The search for a therapy, whether a drug, biologic, or medical device, begins when a disease or clinical condition does not have an effective treatment currently available. Finding a therapeutic approach relies on research that provides an understanding of the disease process. Although not as costly as preclinical studies and clinical trials, this stage is considered a high risk financially because it may take many years and capital to find a target and subsequently a candidate therapy that will make it through all the clinical trials and be approved for market. This stage also has the greatest potential for failures and often requires researchers to go back to either identifying a new target or candidate therapy. 

  • Identifying a target: Using knowledge about the disease, researchers develop a hypothesis that inhibiting or activating a specific target involved in the disease process will be able to change the course of the disease in a positive way. There is no set way to find a potential target beyond an educated guess. 
    • A target can be a gene, RNA, protein, biological pathway, physiological response, virus, or bacteria. 
    • A target must have the potential to be affected by a therapy in a measurable way. For example, the interaction between a target and a drug or biologic must cause a biological response that can be measured both in a test tube or cell culture (in vitro) and in a living organism (in vivo). A target medical device interaction must also be measurable. 
    • A target goes through multiple levels of validation to make sure that, if it is affected in the hypothesized way, the result will indeed be therapeutic. 
  • Determining therapy type: After identifying a target, researchers will need to determine the type of therapy that will be able to affect the target. The term “therapy”, as used in NCATS Toolkit, includes:
    • Drugs and medications: Conventionally, drugs are synthesized pharmaceutical molecules or compounds intended to treat or cure a disease. However since the FDA includes biologics in their definition of drugs, a more accurate term for this type of therapy is small molecule drug.
      • Small molecule drugs are currently still the most common therapy that is developed. 
      • Examples include: acetaminophen, ibuprofen, metformin, gabapentin, and amoxicillin. 
    • Biologics: Also called biopharmaceuticals, biologics are derived from biological sources. 
      • Biologics include a wide range of therapies such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. 
      • Most biologics developed as a therapy are complex mixtures that are not easily identified or characterized. 
      • Examples include: insulin, Botox (onabotulinumtoxina), Humira (adalimumab), and Rituxan (rituximab).
    • Medical devices: In contrast to drugs and biologics, many complex devices involve a number of components that, together, form a system. 
      • Medical devices may be intended to diagnose, cure, treat, or mitigate disease. 
      • The definition of medical device is wide, and examples can range from adhesive bandages and tongue depressors to implanted cardiac and neurological devices, stair-walking wheelchairs, robotic surgical systems, and magnetic resonance imaging (MRI) devices.
  • Finding a potential therapy: In the best-case scenario, when focused on drug or biologic development, several potential therapies are identified that have the desired effect. Further testing and screening then narrows the field to several lead candidates for intensive testing before industry or researchers proceed to preclinical studies. 
    • Typically, researchers discover new drugs that can affect a validated disease target through: 
      • Screening many molecular compounds and biologics to find ones that have the potential produce the desired effect when interacting with the target.
        • Prior to screening, researchers develop biological assays (bioassays) that can measure compound-target interactions.
        • When possible the bioassay is adapted to high throughput screening (HTS). 
          • HTS automates and miniaturizes the bioassay using robotics, data processing, and sensitive detectors. 
          • HTS can quickly perform millions of assays to determine the therapeutic-like properties of large libraries of compounds.
        • NCATS Toolkit provides more information and resources to learn more about bioassays in Discovery: Understand Discovery Research Tools.
      • Designing a therapy to create the desired effect. 
      • Repurposing existing treatments that have unanticipated effects and are found to affect the target “accidentally.”
      • Using new technologies, such as those that provide new ways to target therapies to specific sites within the body or to manipulate genetic material.
    • Lead therapies are tested further to ensure their effect is reproducible in other assays or in vitro systems. Identified therapies are also compared to determine which may work best. Further considerations include:
      • Absorption, distribution, metabolism, and excretion properties. In other words, how a body processes the therapy (pharmacokinetics).
      • Impact on other functions within the body (pharmacodynamics).
      • Potential toxicity or side effects.
      • Dose-response curves.
      • Method of administration, for example, whether it is taken in pill form, injected, or inhaled and whether this administration will work for the patient population.
      • Interactions with other drugs and treatments, especially those used by the patient population.
      • Differing effects on different groups of people, such as by age, gender, race, or ethnicity.
      • Ability to be produced and manufactured.
  • NCATS Toolkit provides more information on the Discovery stage of therapy development including key areas your group can support the process. Key areas include:
    • Collecting patient data.
    • Facilitating scientific collaboration. 
    • Funding research.


Preparation for Clinical Trials
Developing Products for Rare Diseases & Conditions U. S. Food and Drug Administration (FDA) (link)
Tips to Learn More
How Does FDA Approve a Drug U. S. Food and Drug Administration (FDA) (link)
The Drug Development Process U. S. Food and Drug Administration (FDA) (link)
The Device Development Process U. S. Food and Drug Administration (FDA) (link)
CDER Learn Training and Education U. S. Food and Drug Administration (FDA) (link)
Drug Approval: Bringing a New Drug to the Market U. S. Food and Drug Administration (FDA) (link)
European Patients' Academy European Patients' Academy on Therapeutic Innovation (link)