Drug Development Flashcards
what is an IND? what does it contain?
Investigative New Drug application –> request FDA authorization to test drugs in humans and ship drug
what is an NDA? what does it contain?
New Drug Application –> seek FDA approval and drug label
what is a drug? (4)
- recognized in official compendium
- diagnoses/cures/mitigates/ treats/prevents disease
- affects structure or function of body
- any component of the above
what can a new drug be? (5)
- blockbuster, patented, first in class
- better efficacy than old drug
- better efficiency than old drug
- new use for old drug
- unapproved but known chemical
what part of the drug label is based on chemistry manufacturing and controls?
description of drug and formulation
what part of the drug label is based on pharmacology?
- clinical pharmacology
- indication and usage
- dosage and administration
what part of the drug label is based on clinical toxicity and safety? (6)
- contraindications
- warnings
- precautions
- adverse reactions
- abuse and dependence
- overdose
4 requirements for FDA approval
- drug is safe and effective
- manufacturing, processing, packaging are adequate and reliable
- labeling claims not false or misleading
- patent life
what happens if a drug is only intended for investigational use?
NDA is overlooked
why is IND LEGALLY required?
so investigational drugs can be shipped
why is IND PRACTICALLY required?
to inform of clinical trials and so FDA can assess safety
In IND, 2 ways to show it is safe to test in humans
- duration of drug exposure in humans is less than duration of drug exposure in animals
- max dose in humans is less than NOAEL in animals
3 exceptions for IND
- academic research
- drug already approved, studying changes in labeling
- bioavailability/bioequivalence studies
3 components of IND
- Non-clinical (basic exposure data)
- CMC (proper identification, quality, production)
- Clinical protocol (specify how to ensure patient safety)
IND Process
- FDA reviews IND
- no response = continue to trials
- response = clinical hold
3 reasons for clinical hold
- deficient or info doesn’t support clinical study
- risk
- unqualified investigators
3 IND Phases
- PHASE 1 –> clinical pharmacology
- PHASE 2 –> controlled studies
- PHASE 3 –> confirmatory studies
what happens in phase 1?
first time in humans
assess risk
- PK
- metabolic activity
- side effects
what happens in phase 2?
proof of concept –> in subjects with disease
determine:
- safety + efficacy for disease
- pharmacologic effect
- dose response
what happens in phase 3?
PIVOTAL –> FDA focuses here with pre-determined end point
determine:
- risk benefit
- special issues like drug-drug interactions
diff btwn IND and NDA
NDA is culmination of studies under IND, facilitation review and approval process
for dry eye drug, what did they do before IND?
- Pharmacology studies for efficacy in vitro / in vivo
- Preclinical studies for safety in vitro / in vivo
7 reasons why a drug is viable for IND
- unmet medical need
- preclinical pharmacology data
- preliminary chemistry
- clinical protocol
- economically valuable –> patents
- suitable drug form
- hired CROs
what does FDA require in relation to signs and symptoms?
FDA must see improvement in pre-specified signs and symptoms in 2 clinical studies
