Drug Approval and Development

Describe the processes by which new drugs are approved for research and clinical use in Australia, and to outline the phases of human drug trials (Phase I-IV)

Drug Approval

The Therapeutic Goods Administration (TGA) approves medicine for both research and clinical use in Australia.

Research

Drug trials are approved for research purposes under two schemes:

1. Clinical Trials Exemption
   Drugs must be evaluated by an expert committee to evaluate all aspects of pharmacology, toxicology, mutagenicity, teratogenicity, organ dysfunction, and other side-effects.
2. Clinical Trials Notification
   A drug which has been approved in another nation with similarly stringent requirements (New Zealand, Netherlands, UK, Sweden, US) may be used in a trial with oversight by a local ethics committee.

Clinical Use

The TGA classifies medicines into:

• Registered Medicines
  Assessed by the TGA for quality, safety, and efficacy.
  • All prescription (high-risk) medicines. Assessed on:
    • Quality
      • Composition of drug substance
      • Batch consistency
      • Stability data
      • Sterility data (if applicable)
      • Impurities
    • Non-clinical
      • Pharmacology data
      • Toxicology data
    • Clinical
      • Efficacy: results of clinical trials
  • Most OTC (low-risk) medicines
  • Some complementary medicines
• Listed Medicines
  Assessed by the TGA for quality, safety, but not efficacy.
  • Some OTC medicines
  • Most complementary medicines

Phases of Drug Development

• "Phase 0"
  • Pre-clinical R&D
  • In vitro and animal testing
• Phase I
  • First administration in humans
  • Basic pharmacokinetic and toxicology data
  • 20 - 100 human subjects
• Phase II
  • Administration to select patient groups
  • Aim to establish dose-response curve
  • Evidence of efficacy
• Phase III
  • Full-scale evaluation of benefits, potential risks and costs analysis
  • 2000-3000 patients, usually treated in groups of several hundred for relatively short durations (3-6 months), regardless of the length of time the drug will be used in practice³
  • May not reveal uncommon or long-term risks
• Phase IV
  • Post-marketing surveillance

References

1. PS Myles, T Gin. Statistical methods for anaesthesia and intensive care. 1st ed. Oxford: Butterworth-Heinemann, 2001.
2. Medicines and TGA classifications. Therapeutic Goods Administration. Available at: https://www.tga.gov.au/medicines-and-tga-classifications
3. Chris Anderson. Pharmaceutical Aspects and Drug Development. ICU Primary Prep.