In-Depth Notes on Drug Discovery and Development

Overview of Drug Discovery

  • Total drugs available: Over 5000 drugs in Canada.
  • World prescription market: Exceeds $600 billion annually.

Drug Development Timeline

  • Duration: 8 to 12 years for a new drug to reach the market.
    • Discovery Phase: 1 to 3 years to identify a drug candidate.
    • Development Phase: 1 to 2 years for safety testing and securing an Investigational New Drug (IND) status.
    • Clinical Trials Phase: 1 to 5 years for safety and efficacy testing in humans.

Financial Aspects of Drug Development

  • Cost to market a drug: Approximately $1 billion.
  • New drug approvals: About 30 new prescription drugs each year with over 10,000 compounds tested for each successful product.

Sources for Drug Candidates

  • Natural Products: Historically, many drugs are derived from natural sources but can often be toxic.
    • Example: Taxol (anticancer drug) required sustainable sourcing practices for its production.
  • Rational Design: Involves the design of molecules to target specific biological pathways, such as the process used to develop AIDS antiviral drugs.

High Throughput Screening (HTS)

  • Definition: A method for conducting a large number of tests rapidly to find lead compounds.
  • Optimization: The lead compound is gradually enhanced to improve its efficacy and safety.

Safety Testing Phases

  • Animal Testing: 60,000,000 animals are used annually in research, including:
    • 30 million rodents
    • 200,000 dogs
    • 50,000 primates
  • Ethical Concerns: Animal rights movements challenge the necessity and ethics of testing on animals.
  • Historical Tragedies: Instances like the Sulfanilamide tragedy emphasize the importance of proper testing protocols.

Clinical Trial Phases

  1. Phase I Trials: Focus on safety in approximately 100 healthy volunteers.
  2. Phase II Trials: Evaluate safety and efficacy in 100-300 patients.
  3. Phase III Trials: Investigate rare side effects in thousands of patients.
  • Methodologies: Double-blind study designs are used to minimize bias.

Regulatory Considerations

  • Nuremberg Code: Ensures informed consent, prior animal studies, and emphasizes benefits outweighing risks in human testing.

Patenting and Market Exclusivity

  • Patent Protection: Lasts 20 years from the time of first substance creation, typically allowing 8-12 years of market exclusivity post-approval.
  • Generic Drugs: Available once patents expire, offering cost-effective alternatives that must be equivalent in efficacy and dosage.
  • Marketing Costs: R&D represents approximately 16% while marketing constitutes around 23% of overall drug development costs.

Branding and Marketing Strategies

  • Different Names: Drugs have various identifiers:
    • Generic Name: Identifies drug substance, regulated by the FDA.
    • Brand Name: Protected by copyright, specific to the company.
  • Marketing Focus: Targeted primarily at doctors, with significant spending on promotion to improve awareness and prescriptions.

Different Biological Activities of Drugs

  • Molecular Chirality: "Handedness" of molecules affects their biological activity, impacting efficacy and side effects.
    • Example: Esomeprazole (S-enantiomer of omeprazole) shows different pharmacodynamics compared to omeprazole.

Conclusion

  • Emphasizing the importance of drug safety, ethical practices in testing, financial implications, and the roles of patents and generics in the pharmaceutical industry.