IND Studies Flashcards
What does and IND Seek
Seeks permission to perform clinical trials
Application must justify safety and quality
Must adhere to 21 CFR 312
What is the rugulation for and IND (cfr number)
21 CFR 312
Whap applicaiton is 21 CFR 312
Application to FDA to seek permission to test a new drug or biologic in man
Claimed Investigational Exemption for a New Drug
Usually begins in Phase 1
When is an IND needed
You study a NEW drug or biologic in the US
You want to market a new indication or different route of administration for an approved drug
When is an IND not needed
Your study uses an approved dose for an approved indication
Must not put patients at new risk
Must not support a new labeling or advertising claim
You are conducting bioavailability or bioequivalence for generic applications
List the drug development process
- Basic Research
Peer review
Not refulated - Preclinical Development
IND submitted after Preclincial developent - Early Clinical Development phase 1 and 2a
- Late Clinical Developmetn
Phase 2b and Phase 3 - NDA submission
6 if approved phase 4 post marekting trails
GLP, GMP AND GCP start at early clinical develoment
What are the 3 main parts to an IND
- Quality, purity, consistency, identity
- Pharamacology and Toxicology
- Phase 1, 2 and 3
what does pharmacology answer
What does this drug do to my cells?
What does this drug do to my organ systems?
Choosing animal models
Reasonably, animal models should replicate specific aspects of human pathology, rather than reproduce the whole spectrum of clinical manifestations of a disease
Strategy and research here is important to assure that the models are accepted by regulatory reviewers
What does Pharmacokinetics answer
How fast is this absorbed?
How fast do I break it down?
How fast do I get rid of it?
What does toxicolocy answer
Predicts potential toxic effects in mam
Acute Toxicity Testing
Typically carried out in two species, one rodent and one nonrodent
Biologics may need to be carried out in primates
You will need enough animals to have a control group and additional groups to test an escalating dosage range
Not generally sufficient for NDA but might be sufficient for early IND
Minimal Acute Toxicity Test
Usually 4-5 groups, 5 animals per dosage level for each sex, followed for 14 days
LD50 is no longer the gold standard, but animals followed until significant toxicity is observed
Outcome measures: animal behavior, weight, gross necropsy
Usual regulatory limit is 1.5 g/kg
Fixed Dose Toxicity Test
5 groups, 5 animals per dosage level for each sex, followed for 14 days
Fixed dose levels: 5,50,500,2000 mg
Outcome measures: animal shows clear signs of toxicity
Chronic Toxicity Studies
One rodent, one nonrodent species
Animals should be very similar, standard weights
Drug given over more than 90 days
Dosing
High Dose: changes growth or leads to pathology (10X that for humans)
Low Dose: 2X expected clinical dose
Medium Dose: intermediate between other two
NOEL stand for
No observalbe effect level
NOAEL
No observable adverse effect level
LOEL
Lowest observed effect level
MTD
Maximum tolerated dose
LD 50
Lethal does for 50% of animals
Long-term toxicity studies have durations that depend on plan for use in humans
6 months for most biotechnology-derived pharmaceuticals
9 months studies for most drugs given chronically
Two weeks adequate for acute or short-tem or single use products
Immunotoxicology studies needed
for most biologics
