Drug Research and Development Overview

Mission of Novartis

• Focus on helping patients overcome diseases and improve quality of life.
• Aim to ensure innovative medicines are effective, safe, and available quickly.

Drug Development Process

Initial Steps

• Target Discovery:
  • Identify proteins in the body tied to diseases.
  • Confirm their relevance and role in disease.
  • Focus on understanding cellular protein networks and pathways.

Drug Discovery Techniques

• Use high-throughput screening and computer-based design to find compounds that bind to targets.
• Refine promising compounds to improve safety and effectiveness.
• Average time to bring a drug to market: 14 years, average cost: $2 billion.

Pre-Clinical Stage

• Conduct further experiments on drug candidates for safety and pharmacokinetics.
• Importance of animal studies for understanding complex disease mechanisms.
• Commitment to refining, reducing, and replacing animal use while upholding animal welfare standards.

Clinical Trial Phases

Overview of Clinical Trials

• Conducted in multiple phases to evaluate safety and effectiveness.

Phase 1

• Tested on healthy volunteers (20-100 individuals).
• Focus on safety and pharmacokinetics.

Phase 2

• Tested on 100-250 patients with the disease.
• Evaluate efficacy, determine optimal dose, and monitor side effects.

Phase 3

• Larger group (1,000-3,000+ patients).
• Confirm effectiveness, monitor side effects, and compare to existing treatments.

Phase 4

• Post-marketing surveillance to gather additional safety and efficacy data.

Registration Process

• All new drugs must be registered with health authorities.
• Data compiled into a registration dossier which includes efficacy and safety data.
• Dossier customized for different regions and countries.

Drug Safety Monitoring

• Mandatory post-authorization safety updates and annual reports maintained as long as the drug is on the market.

Overview of Drug Discovery Steps (Derek Lowe)

1. Disease Pathology: Determine therapeutic area and target disease.
2. Target Identification: Specify precise process to target.
3. Assay Development: Decide on type of assay to run.
4. Hit to Lead: Select the most promising hits from screening.
5. Lead Optimization: Improve properties like potency and pharmacokinetics.
6. Pre-Clinical Development: Address scale-up questions and toxicity testing.
7. Clinical Trials: Begin clinical testing with human subjects.

In Vitro and Animal Testing

• In Vitro Studies: Initial chemical entity testing; identifies potential lead compounds.
• Animal Testing: Pre-clinical studies to assess efficacy, toxicity, and pharmacokinetics.
  • Types of toxicity: acute, subacute, chronic.
  • Reproductive Toxicity: Studies effects on fertility and teratogenicity.
  • Mutagenicity Tests: Use of the Ames test for screening.

FDA Pregnancy Drug Categories

• Category A: Safe in all trimesters.
• Category B: Safe based on animal studies; not tested in humans.
• Category C: Unsafe; benefits may outweigh risks.
• Category D: Known risks; may be used in life-threatening situations.
• Category X: Contraindicated in pregnancy.

Orphan Drugs

• Target rare diseases affecting fewer than 200,000 people.
• Development often neglected due to low profit potential.

Conclusion

• Importance of thorough research and testing in drug development.
• Encouragement to study ahead for upcoming topics.