Drug+Discovery+Testing+and+Approval+for+Fundamentals

Drug Discovery, Testing, and Approval

Drug Sources

  • Animals, Vegetables, Minerals, and Humans

    • Animals

      • Hog Pancreas: Basis for insulin for diabetes.

      • Sheep and Cattle Adrenal Glands: Source of adrenaline for allergic reactions.

      • Horse Urine: Source of estrogen drugs for menopause symptoms.

      • Snake Venom: South American viper venom, a drug for high blood pressure.

      • Leech Saliva: Prevents blood clotting during surgeries.

      • Israeli Scorpion Venom: Potential detection of brain cancer cells (in development).

    • Plants

      • Foxglove: Source of Digitalis, used for heart failure and irregular rhythms.

      • Opium Poppy: Provides codeine and morphine; related to illegal heroin.

      • Potato: Powder may clot blood instantly, reducing blood transfusions (in development).

      • Molds: Produce antibiotics like penicillins and erythromycins.

      • Pharmaceutical Plants: Future potential for plants as factories to produce human proteins.

    • Minerals

      • Lithium: Used for manic depression; also in glass and battery manufacturing.

      • Magnesium: Relieves constipation and heartburn.

      • Kaolin: Used for diarrhea remedies; also in china production.

      • Calcium: For indigestion relief and osteoporosis prevention.

    • Humans

      • Blood: Factor VIII extracted for treating hemophilia.

      • Urine: Follicle stimulating hormone (FSH) extracted to enhance ovulation.

The Human Genome Project

  • Definition: Complete set of instructions for making and maintaining a human.

  • Uses:

    • Genetic Testing: Predicting single gene mutation diseases (e.g., Lou Gehrig's Disease).

    • Drug Tolerance: Understanding genetic factors in medication response to prevent issues.

    • Disease Treatment: Gene therapy to replace defective genes.

Current and Future Drug Sources

  • Big Pharma's Role: Historical perspectives on drug discovery processes, current trends, and future expectations.

  • Biologics: Focus on drugs like trastuzumab (Herceptin®).

    • From Rx to Generic: Process exemplified by omeprazole (Prilosec®).

  • Regulatory Pathways:

    • IND: Investigational New Drug.

    • NDA: New Drug Application.

    • BLA: Biological License Application.

The Pharmaceutical Business Today

  • Sales and Profits: >$600 billion gross sales worldwide, with high margins supporting research.

  • Market Composition: Dominated by a few large companies, many small companies.

  • Development Costs: Estimated $700 million to $2 billion to bring a drug to market; only one-third cover costs.

  • Blockbuster Drugs: ~40 drugs exceed $1 billion in annual sales.

Pharmacogenomics/Pharmacogenetics Promise

  • Overview: Genetic markers for personalized medicine.

  • Priories: Knowing which medication suits an individual can greatly improve treatment outcomes and minimize side effects.

Applied Pharmacogenetics

  • Disorders and Corresponding Drugs:

    • Pain: Codeine; effectiveness related to the P450 CYP2D6 enzyme.

    • Breast Cancer: Trastuzumab effective with EGF receptor overexpression.

Special Populations in Drug Testing

  • Geriatric Care: Polypharmacy and its implications.

  • Pregnancy: Important category, dynamic labeling requirements regarding drug safety for pregnant women.

FDA Regulations and Drug Approval Process

  1. FDA Mission: Ensure safety, efficacy of drugs and protect public health.

  2. Approval Process:

    • Effective, nontoxic, and tested across populations (children, elderly).

    • Trials Required:

      • Preclinical studies in animal models.

      • Phase I: Safety and pharmacokinetic data in healthy volunteers.

      • Phase II: Assess efficacy and safety in a small patient group.

      • Phase III: Larger, diverse population studies to confirm drug value.

    • Post-marketing: Monitor long-term effects and efficacy.

Recent Legislative Updates

  • FDA Modernization Act 2.0: Significantly revising drug testing requirements to potentially eliminate animal testing.

Drug Manufacturing and Approval Stages

  • Stages:

    • In vitro Studies: Preliminary testing of drug effects.

    • Clinical Testing: Phase I, II, and III trials.

    • NDA Submission and Review:

      • Includes safety, pharmacokinetics, and efficacy studies.

    • Post-marketing Surveillance: Analyzing ongoing patient data after drug launch.

Pharmacovigilance and Drug Safety Reporting

  • Adverse Drug Events: Approximately 100,000 deaths annually due to such events.

  • Reporting Systems: MedWatch multi-faceted approach for monitoring drug safety.

Risk Management in Drug Therapy

  • FDA Evaluations: Balancing patient benefits and risks individually.

    • Box Warnings: Alerts for drugs carrying significant risks.

Other Regulatory Frameworks

  • Orphan Drug Act: Supports development of drugs for rare diseases.

  • Clinical Trials Information: Platforms like ClinicalTrials.gov to gather data on ongoing studies.

Repurposing Drugs**

  • Opportunity to use existing drugs for new indications.

Dietary Supplement Regulations**

  • DSHEA of 1994: Establishes guidelines and safety frameworks for dietary supplements.

  • Nutraceutical Differences: Lower regulatory scrutiny compared to pharmaceuticals.