New Drug Development and Approval Process-outline

New Drug Development and Approval Process-outline - PHCY...

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Unformatted text preview: PHCY 6100 Lecture Outline New Drug Development and Approval Process 1. Discovery of a new drug a. Randomly b. Many years of tireless pursuit c. through targeted screening d. molecular modification or mechanism‐based drug design) 2. Sources of new drugs a. Botanical i. plant extractives or folklore remedies ii. Taxol® = Paclitaxel obtained from the Pacific yew tree; used to treat ovarian cancer b. Animal i. hormones, serum, vaccines, culture of tissue c. Chemical i. synthetic molecules ii. semi‐synthetic molecules d. Genetic engineering (Biotechnology) i. Recombinant DNA (rDNA) ii. Humulin® = human Insulin iii. Humatrope®; Protropin ® = human growth hormone iv. Intron® = r Interferon alfa‐2b (Leukemia, Melanoma, Lymphoma, chronic hepatitis B and C) e. Monoclonal antibody (MoAb) therapy i. Xolair ® = omalizumab [asthma] ii. Humira ® = adalimumab [rheumatoid arthritis] iii. Orthoclone OKT3 ® = moromonab‐CD3 [organ transplant rejection] f. Gene therapy: immunodeficiency disorders i. Somatic cells: end‐stage differentiated cells ii. Stem cells: self‐renewing cells 3. Definitions a. Goal drug: the ideal drug, not attainable. b. Lead compound i. Prototype compound with a fundamental desired pharmacologic/biologic activity ii. Can be modified to improve desired features iii. Ex: original penicillin + semi‐synthetic penicillins; benzodiazepine structure + antianxiety drugs (chlordiazepoxide= Librium®). c. Prodrug i. Inactive substance requiring metabolic transformation to become pharmacologically active. ii. Designed for solubility, absorption, biostability, prolonged release. Teixeira 1 PHCY 6100 Lecture Outline 4. New drug by FDA’s definition a. Any new chemical entity b. New use for an established drug c. New dosage schedule or regimen d. New route of administration e. New dosage form f. Change in drug product’s formulation or method of manufacture = alteration of safety and/or therapeutic efficacy g. Combination of old drugs or changes in the proportions of each drug in an established product 5. Drug Nomenclature a. Empirical formula i. # of atoms and their relationships ii. Ex: C14H19Cl2NO2 = Chlorambucil (chemotherapy agent for Leukemia) b. Systematic name i. relative location of ea. Atom ii. Ex: (4‐[bis(2‐chloroethyl)amino]‐4‐[p‐[bis(2‐chloroethyl)amino]phenyl]‐butyric acid. c. Nonproprietary name (generic name) i. given by USAN Council ( U.S. Adopted Names) specifically for ea. Compound ii. Ex: CL 11,111, Chlorambucil d. Proprietary, Trademark or Brand name i. patented name given to manufacturers ii. Ex: Leukeran® e. NDC = National Drug Code i. number assigned permanently to a drug product by the FDA. ii. Ex: NDC 0081‐5421‐12 4 first numbers indicate the manufacturer = Labeler Code 4 or 3 numbers indicate the drug formulation = Product Code 3 or 2 numbers indicate the package size and type = Package Code 6. New Drug Approval Process (FDA) a. Biologic characterization of drug (Pharmacology, Metabolism, Toxicology b. Formulation studies (dosage form design) c. INDA (Review and approval by FDA to test in human subjects): Phases I, II, III clinical trials d. NDA (Review of clinical trials by Advisory Committee of FDA): pre‐approval for marketing e. Post‐marketing surveillance‐ MedWatch (Inspection and review by FDA): Phase IV 7. Time‐line 8. Drug Development a. Complex b. Time‐consuming Teixeira 2 PHCY 6100 Lecture Outline c. Work done in diverse fields d. Disease process research e. Money 9. Basic Research a. Screen large number of compounds (1/2000) b. Add compounds to cell cultures, cellular substances c. Analyze structure if desirable effect is shown 10. Animal Studies a. Short term b. Toxic side effects c. Safe dosage range d. If too toxic abandoned 11. Drug Approval Process a. Risk versus benefit b. Animal data to check toxicity c. Phase I clinical trials d. Phase II clinical trials e. Phase III clinical trials f. Review by FDA advisory committee g. Inspection and review by FDA 12. IND‐ Investigational Exemption for a New Drug a. Permission to test on humans b. FDA has 30 days to evaluate data c. Sponsor proposes protocol 13. Requirements for IND a. Sound, statistical methods b. Designs that yield valid comparisons c. Qualified researchers d. Suitable basis for choosing test subjects e. Safeguards to protect patients 14. Protocol‐ “Plan of Study” a. Kinds of patients b. Conditions and parameters to be measured c. How data will be reported 15. Clinical Investigator a. Statement of education b. Scientific training c. Experience d. Signed statement that trial will be conducted ethically 16. Subjects a. Randomized to prevent experimenter’s bias b. Signed informed consent simple words i. native language ii. purpose and duration of study Teixeira 3 PHCY 6100 Lecture Outline iii. risks and discomforts iv. alternative procedures v. benefits 17. IRB‐Institutional Review Board (Ethics Committee) a. Responsible to review and monitor biomedical research b. Hospitals, Universities, other c. Members: doctors, scientists; ethnically diverse d. Non‐government and non‐regulatory 18. Criteria‐ Approving Research a. Risks to subjects are minimized b. Risks are reasonable in relationship to benefits c. Selection of subjects is equitable d. Informed consent is documented e. All data monitored 19. Relationships‐ IRB, Clinical Investigator, and Sponsor 20. Foreign Studies‐ May Be Used If... a. Well‐designed b. Well‐conducted c. Qualified investigators d. Ethical principles applied 21. Clinical Trials a. Randomized b. Controlled i. Age ii. Gender iii. Disease state iv. Double‐blind, placebo‐controlled 22. Phase I Clinical Trials a. Up to100 patients b. How drug is absorbed, processed and excreted c. Effects on organs and tissues d. Initial observation of side effects e. How much drug should be received f. How often the drug should be received g. Safety precautions h. 13‐14/ 20 drugs pass to phase II 23. Phase II Clinical Trials a. Up to several hundred people with the disease b. Determine drug effectiveness in treating the illness c. Clearer picture of side effects and risks 24. Phase III Clinical Trials a. Up to several thousand patients b. Long term studies‐ 3‐6 years c. Final safety and effectiveness data Teixeira 4 PHCY 6100 Lecture Outline d. Less common side effects e. Optimum dosage f. 5‐6 out of 20 drugs studied enter phase III 25. Exceptions a. Retrovir i. strong evidence in phase II trials ii. 1 vs. 19 deaths b. Diseases with no known cures 26. NDA‐ New Drug Application a. Composition b. Toxicology c. Behavior in body d. Results of all testing e. Manufacturing process f. Labeling 27. Review of NDA a. FDA i. Inspections ii. Data submitted are adequate iii. Final approval b. Advisory committee i. expertpanel ii. review of data by experts 28. Post‐market surveillance a. Process is not perfect b. Monitoring of unexpected side‐effects c. May change labels, new warnings d. Phase IV clinical trials Teixeira 5 ...
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This note was uploaded on 10/15/2010 for the course PHCY 6100 taught by Professor Teixeira during the Fall '10 term at Wyoming.

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