3 - Stages of Drug Development

• process of bringing a novel drug from “bench to bedside”

  Drug development
• Stages of Drug Development

  • Early Drug Discovery
  • Preclinical Research
  • Investigational New Drug Application
  • Clinical Research
  • Regulatory Review, Approval, and Post- Marketing Surveillance Survey
• • performed in laboratories in vitro using animal
  • potential druggable targets are identified, and discovering potential compounds that can elicit the desired biological effect on those targets

  Early Drug Discovery
• identifying which part of the disease process can potentially be interfered by a potential drug compound

  target identification
• a biological target is “druggable” if its activity can be altered by a therapeutic agent.
• a compound that interacts with the target of interest

  hit
• drug targets can be discovered through: published research, databases, target deconvolution, target discovery
• hits can be discovered through: high-throughput screening, phenotypic screening, virtual screening, fragment-based screening, or structure-based design
• in phenotypic screening, the approach is based on determining if a compound exerts a desired effect through change in phenotype
• refines several of the most promising “hits” to create more potent and selective candidates with “optimized” pharmacokinetic properties

  Early Drug Discovery: Hit-to-Lead and Lead Optimization
• original hits have very low affinity and are optimized by several orders of magnitude
• identifies which high-quality leads will proceed

  as clinical candidate

  Candidate Selection
• clinical candidates should: 1) bind selectively to targets, 2) elicit the desired functional response when interacting with the target molecule, and 3) must have adequate bioavailability and biodistribution to elicit the desired response
• tests a candidates efficacy and safety before it is tested to target species / humans

  Preclinical Research
• in vitro or in vivo models are used to provide evidence of the candidate’s biological effect
• required before submitting an IND (investigational new drug), which is required to proceed to clinical development

  a.What does the drug to the body?

  b. What does the body do to the drug?

  c. It is potent, but is it safe?
• 3 Types of Investigational New Drug Application (IND)

  1. Investigator
  2. Emergency use
  3. Treatment
• Investigator: submitted by physician responsible for investigating, manages the dispensing and administration of drug (requested for the study of an unapproved drug, approved drug for use in an unlicensed indication, or drug used to a different patient population)
• Emergency use: authorizes the use of a drug in an emergency situation, and is used for patients who do not meet existing clinical study criteria, or in situations where an approved clinical protocol does not exist
• Treatment: submitted to gain access to an experimental drug that has shown promise in clinical trials for treating a serious or life-threatening condition
• IND can be categorized are “commercial” or “research”
• IND sponsor is required to wait 30 days before starting clinical trials
• clinical trials designed to answer specific questions related to the IND
• Clinical Research: Phase I

  • 20-100 participants, either healthy or diagnosed with the specific disease condition
  • phase lasts several months
  • Primary purpose: To determine safety, and to gather information on dosage,
  • phase I studies also guide how best to administer the drug to limit toxicity and enhance therapeutic effect
• Clinical Research: Phase II

  • several hundred participants, should be diagnosed with the specific disease condition the drug aims to treat
  • phase lasts several months to two years
  • Primary purpose: To acquire additional safety data – to determine efficacy and adverse effects
• Clinical Research: Phase III

  • 300 – 3000 participants, should be diagnosed with the specific disease condition the drug aims to treat
  • phase lasts 1 – 4 years
  • Primary purpose: To determine the drug’s efficacy and to monitor adverse reactions due to the increased number of participants during Phase III, long-term or rarer side effects that may have gone undetected in Phase I and Phase II are usually detected
  • the greatest proportion of safety information is collected during Phase III
• New Drug Application: needed for marketing authorization, provides the regulator with enough information to determine if:

  a.The drug is safe and effective as a treatment for the condition it has been developed for

  b. The drug’s therapeutic benefits outweigh the risks

  c. The drug’s labeling is fit-for-purpose and whether all required details are included

  d. The methods used to manufacture the drug and measures to ensure the drug's quality are satisfactory
• submitted for therapeutic biological products such as monoclonal antibodies, cytokines, growth factors, enzymes, immunomudulators, proteins, and non-vaccine therapeutic immunotherapies

  Biologics License Application
• Product Launch: carried out after relevant activities, which include:

  a.Manufacturing scale-up and serialization

  b. Printing of final product label information, packaging and artwork

  c. Product storage, shipping and distribution arrangements

  d. Production staff and quality team availability
• monitoring of a drug after it has received approval and has reached the market

  Post-Marketing Safety Surveillance
• Phase IV: several thousand participants diagnosed with the disease the drug is approved for use

  • the purpose of is to obtain additional information about the long-term risks and benefits of taking a drug now that it is being more widely used.
  • the “real-world” data can also help determine if there is scope to develop the drug further.