DRUG PRODUCT DEVELOPMENT Drug agent intended for use in the diagnosis, mitigation, treatment, cure, or prevention of disease in man or animals New Drug defined in section C.0 1A.001(2) of Food and Drug Regulations (HPFB) any agent that has not been generally recognized as safe and effective under the conditions recommended B. Amsden CHEE 440 NEW DRUG Doesn’t have to be a new chemical entity: formulated differently / new dosage form manufactured differently combination of 2 or more drugs new use for an old drug new dosage schedule new route of administration B. Amsden CHEE 440 GOAL DRUG desired features produce desired effect administered by desirable route minimum dosing and dosing frequency optimal onset and duration of activity efficient and complete elimination easily produced at low cost pharmaceutically elegant physically and chemically stable B. Amsden CHEE 440 PRECLINICAL STUDIES Determine chemical and physical properties Determine biological properties: pharmacology ADME toxicology Preformulation dosage form needs to be sterilizable, prepared in a reproducible fashion, stable, free of impurities B. Amsden CHEE 440 IND SUBMISSION • Investigational New Drug • required before testing in humans • in Canada, filed with Health Products and Food Branch 60 day waiting period • in USA, filed with Food and Drug Administration 30 day waiting period B. Amsden CHEE 440 IND Contents • manufacturer/sponsor name • proprietary name and chemical name of drug • dosage form (route of administration, ingredients, manufacture procedure, packaging, purity, labelling) • data from preclinical animal trials • relationship between preclinical and clinical trials • protocol of clinical trials • names and credentials of all persons involved in all trials • locations of laboratories used • info an any other clinical trials done in other countries B. Amsden CHEE 440 CLINICAL TRIALS PHASE 1 concerned with tolerability and safety of the drug generally involves 20-100 carefully chosen healthy volunteers initial dose is quite low, if well tolerated, progressively larger doses given until evidence of drug action observed determine the metabolism and pharmacological action of drug in humans B. Amsden CHEE 440 CLINICAL TRIALS PHASE 2 purpose is to determine efficacy of drug (dosage) and to detect side effects not noted in healthy volunteers patients suffering from disease are treated in limited numbers (up to several hundred) under close observation B. Amsden CHEE 440 CLINICAL TRIALS PHASE 3 deals with safety and efficacy of drug several hundred to a thousand patients private practitioners of varying background and experience brought in by the more experienced clinicians practitioners report to principal investigator who relays the info and his evaluation to HPFB or FDA B. Amsden CHEE 440 PHASE SUMMARY Number of Patients Duration Purpose Phase 1 20 - 100 several months mainly safety Phase 2 up to several months to mainly efficacy hundred 2 years some short term safety Phase 3 200 - 2000 B. Amsden 1 to 4 years CHEE 440 safety and efficacy NEW DRUG SUBMISSION NDS in Canada, ND Application in US contents all the preclinical and clinical data • includes pharmacokinetics and bioavailability, discussion of risk and benefits, complete proposed product labeling HPFB and FDA rule on acceptability (2-4 years) B. Amsden CHEE 440 POST-MARKETING PHASE 4 Systematic and comprehensive monitoring of the patterns of use and beneficial or harmful effects of drug as used in medical practice and by the consumer B. Amsden CHEE 440