1. CHEE 440 1 DRUG PRODUCT DEVELOPMENT u Drug ä agent intended for use in the diagnosis, mitigation, treatment, cure, or prevention of disease in man or animals u New Drug ä defined in section C.0 1A.001(2) of Food and Drug Regulations (HPFB) ä any agent that has not been generally recognized as safe and effective under the conditions recommended

2. CHEE 440 2 NEW DRUG u doesn’t have to be a new chemical entity ä formulated differently / new dosage form ä manufactured differently ä combination of 2 or more drugs ä new use for an old drug ä new dosage schedule ä new route of administration

3. CHEE 440 3 GOAL DRUG u desired features ä produce desired effect ä administered by desirable route ä minimum dosing and dosing frequency ä optimal onset and duration of activity ä efficient and complete elimination ä easily produced at low cost ä pharmaceutically elegant ä physically and chemically stable

4. CHEE 440 4 PRECLINICAL STUDIES u chemical and physical properties u biological properties ä pharmacology ä ADME ä toxicology u Preformulation ä dosage form needs to be sterilizable, prepared in a reproducible fashion, stable, free of impurities

5. CHEE 440 5 IND SUBMISSION u Investigational New Drug u required before testing in humans u in Canada, filed with Health Products and Food Branch ä 60 day waiting period u in USA, filed with Food and Drug Administration ä 30 day waiting period

6. CHEE 440 6 IND Contents u manufacturer/sponsor name u proprietary name and chemical name of drug u dosage form (route of administration, ingredients, manufacture procedure, packaging, purity, labelling) u data from preclinical animal trials u relationship between preclinical and clinical trials u protocol of clinical trials u names and credentials of all persons involved in all trials u locations of laboratories used u info an any other clinical trials done in other countries

7. CHEE 440 7 CLINICAL TRIALS PHASE 1 ä concerned with tolerability and safety of the drug ä generally involves 20-100 carefully chosen healthy volunteers ä initial dose is quite low, if well tolerated, progressively larger doses given until evidence of drug action observed ä determine the metabolism and pharmacological action of drug in humans

8. CHEE 440 8 CLINICAL TRIALS PHASE 2 ä purpose is to determine efficacy of drug (dosage) and to detect side effects not noted in healthy volunteers ä patients suffering from disease are treated in limited numbers (up to several hundred) under close observation

9. CHEE 440 9 CLINICAL TRIALS PHASE 3 ä deals with safety and efficacy of drug ä several hundred to a thousand patients ä private practitioners of varying background and experience brought in by the more experienced clinicians ä practitioners report to principal investigator who relays the info and his evaluation to HPFB or FDA

10. CHEE 440 10 PHASE SUMMARY

11. CHEE 440 11 NEW DRUG SUBMISSION u NDS in Canada, ND Application in US u contents ä all the preclinical and clinical data »includes pharmacokinetics and bioavailability, discussion of risk and benefits, complete proposed product labeling u HPFB and FDA rule on acceptability (2-4 years)

12. CHEE 440 12 POST-MARKETING u 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 u PHASE 4