Transcript DRUG PRODUCT DEVELOPMENT

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
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NEW DRUG
Doesn’t have to be a new chemical entity:
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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
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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
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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
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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
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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
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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
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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
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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
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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
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1 to 4
years
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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)
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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
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