Drug Development

Question 1

what is an IND? what does it contain?

Answer 1

Investigative New Drug application –> request FDA authorization to test drugs in humans and ship drug

Question 2

what is an NDA? what does it contain?

Answer 2

New Drug Application –> seek FDA approval and drug label

Question 3

what is a drug? (4)

Answer 3

1. recognized in official compendium
2. diagnoses/cures/mitigates/ treats/prevents disease
3. affects structure or function of body
4. any component of the above

Question 4

what can a new drug be? (5)

Answer 4

1. blockbuster, patented, first in class
2. better efficacy than old drug
3. better efficiency than old drug
4. new use for old drug
5. unapproved but known chemical

Question 5

what part of the drug label is based on chemistry manufacturing and controls?

Answer 5

description of drug and formulation

Question 6

what part of the drug label is based on pharmacology?

Answer 6

1. clinical pharmacology
2. indication and usage
3. dosage and administration

Question 7

what part of the drug label is based on clinical toxicity and safety? (6)

Answer 7

1. contraindications
2. warnings
3. precautions
4. adverse reactions
5. abuse and dependence
6. overdose

Question 8

4 requirements for FDA approval

Answer 8

1. drug is safe and effective
2. manufacturing, processing, packaging are adequate and reliable
3. labeling claims not false or misleading
4. patent life

Question 9

what happens if a drug is only intended for investigational use?

Answer 9

NDA is overlooked

Question 10

why is IND LEGALLY required?

Answer 10

so investigational drugs can be shipped

Question 11

why is IND PRACTICALLY required?

Answer 11

to inform of clinical trials and so FDA can assess safety

Question 12

In IND, 2 ways to show it is safe to test in humans

Answer 12

1. duration of drug exposure in humans is less than duration of drug exposure in animals
2. max dose in humans is less than NOAEL in animals

Question 13

3 exceptions for IND

Answer 13

1. academic research
2. drug already approved, studying changes in labeling
3. bioavailability/bioequivalence studies

Question 14

3 components of IND

Answer 14

1. Non-clinical (basic exposure data)
2. CMC (proper identification, quality, production)
3. Clinical protocol (specify how to ensure patient safety)

Question 15

IND Process

Answer 15

1. FDA reviews IND
2. no response = continue to trials
3. response = clinical hold

Question 16

3 reasons for clinical hold

Answer 16

1. deficient or info doesn’t support clinical study
2. risk
3. unqualified investigators

Question 17

3 IND Phases

Answer 17

1. PHASE 1 –> clinical pharmacology
2. PHASE 2 –> controlled studies
3. PHASE 3 –> confirmatory studies

Question 18

what happens in phase 1?

Answer 18

first time in humans

assess risk
- PK
- metabolic activity
- side effects

Question 19

what happens in phase 2?

Answer 19

proof of concept –> in subjects with disease

determine:
- safety + efficacy for disease
- pharmacologic effect
- dose response

Question 20

what happens in phase 3?

Answer 20

PIVOTAL –> FDA focuses here with pre-determined end point

determine:
- risk benefit
- special issues like drug-drug interactions

Question 21

diff btwn IND and NDA

Answer 21

NDA is culmination of studies under IND, facilitation review and approval process

Question 22

for dry eye drug, what did they do before IND?

Answer 22

1. Pharmacology studies for efficacy in vitro / in vivo
2. Preclinical studies for safety in vitro / in vivo

Question 23

7 reasons why a drug is viable for IND

Answer 23

1. unmet medical need
2. preclinical pharmacology data
3. preliminary chemistry
4. clinical protocol
5. economically valuable –> patents
6. suitable drug form
7. hired CROs

Question 24

what does FDA require in relation to signs and symptoms?

Answer 24

FDA must see improvement in pre-specified signs and symptoms in 2 clinical studies