Drug Discovery and Development Overview

Drug Discovery

• Drugs are extracted from various sources, including plants, mammals (hormones and microorganisms), and semisynthetic/synthetic compounds.
• Plant poisons, like morphine from opium poppies and digitalis from foxgloves, are sources.
• Inorganic chemicals, such as potassium, sodium, chloride, and calcium, are also used.
• Biologics, including insulin, estrogen hormones, epinephrine, and diphtheria antitoxin, are used.
• Drugs from the sea, like algae, invertebrates, and sponges, are also a source.

Drug Research & Development Team

• A team of scientists from diverse disciplines, such as pharmaceutical chemistry, pharmaceutics, clinical toxicology, clinical pharmacology, biopharmaceutics, and clinical pharmacokinetics, work together.

FDA Drug Approval Process

• Drug Discovery and Development: Takes 2-10 years.
• Pre-clinical Research and Development: Includes initial substance synthesis, lab studies, and Institutional Review Board (IRB) meetings. Takes 3-6 years.
• Clinical Trials:
  • Consists of Phase 1, 2, and 3 clinical trials.
  • Phase 1: Healthy volunteers (20-80). Focuses on safety.
  • Phase 2: Patients with target disease. Few dozens to few hundreds of patients. Focuses on effectiveness and short-term side effects.
  • Phase 3: Larger scale trials. Hundreds to thousands of patients. More populations, different dosages, and combinations. Focuses on safety, effectiveness, and combination therapies.
• FDA Drug Application
  • IND (Investigational New Drug): submitted after pre-clinical trials. Includes clinical protocol (IRB Approved). Introductory and investigative plan. Chemistry, Manufacturing, and Control (CMC) information. Animal pharmacology and toxicology studies data.
  • NDA (New Drug Application): submitted after clinical trials. Includes animal and human data, data analysis, drug behaviour, and manufacturing details.
• FDA Review:
  • FDA has 30 days to review IND. If no response within 30 days, sponsor can begin clinical trials.
  • FDA reviews NDA, reviews for 60 days, may refuse incomplete application.
  • FDA decides whether it is safe for human testing.
  • May issue a clinical hold (when risk to subjects identified).
• FDA Approval and Manufacturing:
• Post-Market Surveillance: Takes 8-9 months, FDA reviews the NDA, reviews for 60 days, may refuse incomplete application
  • FDA performs facility inspections.
  • FDA reviews drug labels for appropriate information.
  • FDA approves, or issues complete response letter.
  • Post-market surveillance begins.
  • Drug sponsors must submit periodic safety updates to the FDA.

Drug Manufacturing

• Once FDA approves NDA, companies can market and produce the drug.
• Newly Approved Drug (Patent Drug): Extremely novel product developed by the company holding patent for 20 years to market.
• Generic Drug: Identical copy (ingredients, formulation, strength), manufactured by companies other than the innovator.
• Non-Prescription Drug: FDA applies same standards to non-prescription drugs.

Future of Drug Discovery

• Human Genome Project: Changed drug discovery and development methods dramatically. Aims to decipher the human genome and identify and characterize genes.
• Surrogate Markers: Laboratory measurements or physical signs that predict long-term treatment results.
• Metabolomics: Study of small molecules (metabolites).
• New Methods of Drug Discovery:
  • Rational drug design: Using known small molecules with tailored properties to target known biomolecules (proteins or nucleic acids).
  • Powerful computers: Computer simulations to aid in solving complex chemistry problems.
  • Computational chemistry: Theoretical chemical methods to calculate molecular interactions and properties using efficient computer programs.
  • X-ray crystallography: Determining atomic and molecular structures of crystals.
  • Nuclear magnetic resonance (NMR) spectroscopy: Characterization technique for determining molecular structure at atomic level.
  • 3-Dimensional Structure-Activity Relationship (SAR): Correlations between chemical structure, biological function, and target activity using diverse molecular structures.

Time and Cost of Drug Development

• Developing a new pharmaceutical drug usually takes 8-15 years (some take longer, some faster).
• Clinical and preclinical contract studies, like toxicology studies and analytical sample costs, drive up development costs.

Timeline of Drug Development

• Key milestones and estimated timelines for drug discovery and development (Target Selection, Discovery and Screening, Lead Selection, Lead Optimization, etc.)