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New Drug Development and Approval

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Chapter 2

Chapter 2

Published in: Health & Medicine, Business
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  • Here is what we are trying to achieve (refer to slide).
    Note that you can comment on:
    We conduct basic animal health research in RY, but our animal health care products are marketed by Merial, a joint venture between Merck and Rhone- Poulenc (note that RP is now known as Aventis (RP merged with Hoechst).
    Outcomes research is when we attempt to prove that our compounds not only cause important chemical effects in the body (such as reduced blood pressure or reduced cholesterol), but that these effects lead to reduced morbidity and mortality over time. The Zocor 4S study is an example.
    The research budget for MRL is $2.4 billion this year.
  • Here is what we are trying to achieve (refer to slide).
    Note that you can comment on:
    We conduct basic animal health research in RY, but our animal health care products are marketed by Merial, a joint venture between Merck and Rhone- Poulenc (note that RP is now known as Aventis (RP merged with Hoechst).
    Outcomes research is when we attempt to prove that our compounds not only cause important chemical effects in the body (such as reduced blood pressure or reduced cholesterol), but that these effects lead to reduced morbidity and mortality over time. The Zocor 4S study is an example.
    The research budget for MRL is $2.4 billion this year.
  • Transcript

    • 1. New Drug Development and Approval Process
    • 2. Stages of Drug Development and Review • Sponsors–companies, research institutions, and other organizations develop a new drug. • Pre-clinical testing and Proposal for human testing.
    • 3. • Schedule of tests and procedures, • Medications and dosages to be studied • Length of the study • Study’s objectives, and other details INTERNATIONAL REVIEW BOARD
    • 4. Phase 1 studies are usually conducted in healthy volunteers. Determine what the drug’s most frequent side effects are and, often, how the drug is metabolized and excreted. The number of subjects typically ranges from 20 to 80. Stages of Drug Development and Review
    • 5. • Phase 2 emphasis is on effectiveness. • This phase aims to obtain preliminary data on whether the drug works in people who have a certain disease or condition. Stages of Drug Development and Review
    • 6. • For controlled trials, patients receiving the drug are compared with similar patients receiving a different treatment–usually an inactive substance (placebo), or a different drug. • Safety continues to be evaluated, and short-term side effects are studied. • Typically, the number of subjects in Phase 2 studies ranges from a few dozen to about 300. Stages of Drug Development and Review
    • 7. • Phase 3 studies begin if evidence of effectiveness is shown in Phase 2. • These studies gather more information about safety and effectiveness, studying different populations and different dosages and using the drug in combination with other drugs. • The number of subjects usually ranges from several hundred to about 3,000 people. Stages of Drug Development and Review
    • 8. • Post-market requirement and commitment studies must be done after FDA has approved the drug for marketing. • Additional information about a product’s safety, efficacy, or optimal use. Stages of Drug Development and Review
    • 9. • New Drug Application (NDA)–This is the formal step a drug sponsor takes to ask that the FDA consider approving a new drug for marketing in the United States. • An NDA includes all animal and human data and analyses of the data, as well as information about how the drug behaves in the body and how it is manufactured Stages of Drug Development and Review
    • 10. Drug Candidate safety testing Animal Studies - relevant species - transgenic KO/KI mice - conditional KOs - agonists/antagonists - antibodies - antisense - RNAi Studies of Disease Mechanisms Human Studies Phases I,II, III Target -receptor; -ion channel; -transporter; -enzyme; - signalling molecule Lead Search -Develop assays (use of automation) -Chemical diversity -Highly iterative processMolecular Studies The Drug Discovery Process Lead optimization -selectivity -efficacy in animal models -tolerability: AEs mechanism- based or structure-based? -pharmacokinetics -highly iterative process Drug Approval and Registration Target selection & validation Discovery Development
    • 11. Target Selection & Validation • Define the unmet medical need (disease) • Understand the molecular mechanism of the disease • Identify a therapeutic target in that pathway (e.g gene, key enzyme, receptor, ion-channel, nuclear receptor) • Demonstrate that target is relevant to disease mechanism using genetics, animal models, lead compounds, antibodies, RNAi, etc.
    • 12. Discovery • Develop an assay to evaluate activity of compounds on the target - in vitro (e.g. enzyme assay) - in vivo (animal model or pharmacodynamic assay) • Identify a lead compound – screen collection of compounds (“compound library”) – compound from published literature – screen Natural Products – structure-based design (“rational drug design”) • Optimize to give a “proof-of-concept” molecule—one that shows efficacy in an animal disease model • Optimize to give drug-like properties—pharmacokinetics, metabolism, off-target activities •
    • 13. Development Pharmaceutical R&D Formulation Clinical Investigator & patient Clinical Pharmacology Clinical Research Statistics & Epidemiology Data Coordination Research Information Systems Information Services Regulatory Affairs Project Planning & Management Marketing Process R&D Chem Eng. R&D Manufacturing Bio Process R&D Safety Assessment Toxicology Drug Metabolism (ADME) Pharmacology Pre-Clinical Clinical
    • 14. Clinical Trials Product Profile Marketing SOIProduct Profile Marketing SOI Information Learned 1. Absorption and metabolism 2. Effects on organs and tissue 3. Side effects as dosage is increased Information Learned 1. Effectiveness in treating disease 2. Short-term side effects in health -impaired patients 3. Dose range Information Learned 1. Benefit/risk relationship of drug 2. Less common and longer term side effects 3. Labeling information Compassionate Use Phase II Several hundred health-impaired patients Treatment Group Control Group Phase III Hundreds or thousands of health- impaired patients Investigational New Drug application IND Phase I 20 - 100 healthy volunteers take drug for about one month Remote data entry
    • 15. Clinical Trials Continued APPROVAL PROCESS (Ex. FDA) Reviews, comments, and discussions Drug Co./Regulatory liaison activities APPROVAL Submit to Regulatory Agencies Advisory Committee Regulatory Review Team New Drug Application (NDA) Worldwide Marketing Authorization (WMA) in other countries
    • 16. Drug Discovery—Convergence of Disciplines Patent Law Combinatorial Chemistry Synthetic Chemistry Physical Chemistry Physiology Biochemistr y DMP K Enzymology Immunolog y Pharmacology Information Technology Modelling Physiolog y Safety Assessment Metabolism Pharmacology Pathology Behavior Novel Molecule Intellectual Property Structural Activity Pharmacokinet ic Properties In Vivo activity Safety Design Pharmaco - dynamics Physiology Physiology Physiology
    • 17. Sources of New Drugs Plant Materials 1. Reserpine ( Tranquilizer and a hypotensive agent) 2. Periwinkle (anti-tumor) Vincristine Vinblastine 3. Pacific yew tree (ovarian cancer) Paclitaxel
    • 18. Sources of New Drugs 2. Semi-synthetic drugs Ex Dioscorrea (Mexican yams) Cortisone and Estrogen 3. Animals Hormonal substances Ex Thyroid extract (Insulin, Pituitary hormone) Urine of pregnant mares (estrogen) Biologicals (serum, antitoxins, vaccines)
    • 19. Sources of New Drugs4. Genetic Engineering Recombinant DNA production (produce any protein) --“Gene Splicing” lower organisms to make protein -- human growth hormone, human insulin, hepatitis B vaccine Epoetin Alpha, and interferon Monoclonal antibody production --dx home pregnancy products -- combat disease such as LE, juvenile onset diabetes, MG
    • 20. Sources of New Drugs 5.Human Gene Therapy used to prevent, treat, cure, diagnose, or mitigate human diseases caused by genetic disorders. ADA (adenosene deaminase deficiency) Sicke cell anemia Malignant melanoma Renal cell cancer Heart disease
    • 21. GOAL DRUG Produced the specified desired effect Administered at the most desired route Have optimal onset and duration of activity Exhibits no side effect Eliminated from the body completely
    • 22. http://www.slideshare.net/rahul_pharma/drug-discovery- and-development-10698574

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