Pharmacology Lecture 1: FDA & Drug Development

What is the purpose of the FDA?

Ensure drug safety

What are the six centers of the FDA?

1. Drug evaluation

2. Biologics evaluation

3. Food safety

4. Devices

5. Veterinary medicine

6. Toxicology

What was established by the Federal Pure Food and Drug Act of 1906?

Standards of drug purity

What was missing from the Federal Pure Food and Drug Act of 1906?

Drug safety

What was established from the 1938 amendment of the Federal Pure Food and Drug Act to ensure drug safety?

FDA

What new requirement was made from the 1938 amendment?

Drug safety testing

What was prohibited from the 1938 amendment?

Misbranded drugs

What was the purpose of the Durham-Humphrey Amendment of 1952?

Distinguish between prescription and OTC drugs

What was established by the Controlled Substances Act of 1970?

Schedules of drugs

Who are the schedules of drugs from the Controlled Substances Act of 1970 regulated by?

DEA

Which drug schedule has high potential of abuse and is not accepted for medical use?

Schedule I

What requirement was made by the Poison Prevention Act of 1970?

Child-resistant containers

What was the purpose of the Hatch-Waxman Act of 1984?

Approve generics without additional preclinical/clinical testing after exclusivity expires

What is the data needed to be submitted for generics after expiry?

Bio-availability

What is bio-availability data submitted as for generics?

ANDA

What was established by the FDA Modernization Act of 1997?

Priority review system

What was the purpose of the Drug Safety Oversight Board?

Monitor post marketing pharmaceutical use

What are the five steps of drug development?

1. Synthesis of new chemical

2. Safety evaluation (animals/humans)

3. Effectiveness evaluation (humans)

4. Review of application

5. Post-marketing surveillance

What report is made during post-marketing surveillance?

All adverse effects

When does Phase 1 of clinical testing begin?

After IND approval

What test subjects are used in Phase 1 of clinical testing?

Healthy males

What two things are established in Phase 1 of clinical testing?

1. Effects of predetermined dose

2. Dose when toxicity appears

About how many subjects are used for testing in Phase 1 of clinical testing?

20 - 80

What is the purpose of Phase 2 of clinical testing?

Determine effectiveness of drug

How are drugs distributed in Phase 2 of clinical testing?

Double blind with placebo control

What design is ideal for Phase 2 of clinical testing?

Cross over design

What test subjects are used in Phases 2 - 3 of clinical testing?

People with target disease

What must be established for Phase 3 of clinical testing to begin?

Effective dose range

What is the purpose of Phase 3 of clinical testing?

Verify efficacy

When does Phase 4 of clinical testing begin?

After FDA approval

Who can use the drug during Phase 4 of clinical testing?

Public

What is the study of adverse effects of drugs/chemicals on living things called?

Toxicology

What is Effective Dose (ED50)?

Dose causing specific effect in 50% of mice

What is Lethal Dose (LD50)?

Dose that kills 50% of mice

How can you calculate Therapeutic index (TI) or Margin of Safety?

LD50 / ED50

Is a larger Therapeutic index (TI) more or less safe?

More

Does a larger Therapeutic index (TI) have a larger or narrower margin of safety?

Larger

What two things are determined in Short-Term Toxicity Testing?

1. Lethal Dose

2. Margin of safety

What is an acceptable margin of safety?

2000+

What is evaluated in long-term toxicity testing?

Blood chemistries

What does teratogenic mean?

Monster

What event caused the need for teratogenic studies?

Thalidomide tragedy

What is evaluated in teratogenic studies?

Birth defects

What does IND stand for?

Investigational New Drug application

What are the five requirements needed before submitted an IND?

1. Good margin of safety

2. No long term toxicity

3. No cancer

4. No reproductive effects

5. No birth defects

How long does it take for an IND to be approved?

30 days

What are the six components of IND?

1. Animal study data

2. Human test protocols

3. Chemical structure

4. Drug synthesis

5. Dose form

6. Packaging

How many years of animal and human testing must be done for an NDA?

8 years

How long does a NDA review take?

8 months - 1 year

How long does exclusivity start from phase I of clinical testing after an NDA?

17 years