Lecture 8: Regulatory Issues in Health Care

Question 1

What are the steps for the Drug Development Process?

Answer 1

1. Pre-clinical research (animals only, no humans)
2. Investigational New Drug Application Filed (IND)
3. Clinical research or “Drug Trials” (Phase I, II, & III)
4. New Drug Application Filed (NDA)
5. Post marketing Surveillance (Phase IV)

Question 2

What are the 2 criteria that needs to be met that justifies commercial development in pre-clinical testing?

Answer 2

1. Need to determine if the drug is reasonably safe for testing in humans
2. The compound needs to exhibit pharmacological activity (need to make sure it works)

That justifies commerical dvelopment

Question 3

When drug looks safe in animal models then what is the next step in the drug development process?

Answer 3

Investigational New Drug (IND) (because we want to test in humans)
*FDA has 30 days to respond

Question 4

What are the 3 broad areas the IND application must contain information about?

Answer 4

1. Animal pharmacology and toxicology studies: testing whether the product is reasonably safe for initial testing in humans (may include any experience with the drug in humans in other countries)
2. Manufacturing information: can we make enough of it? Can we adequatel produce and supply consistent amounts and batches of the drug for testing?
3. Clinical Protocols and Investigator Information-test whether initial phase trials will expose subjects to unnecessary risks and ensure the clinical investigators oversees the trials are qualified

Question 5

Describe phase 1 of clinical trials

Answer 5

• Focus is on SAFETY in humans
• 100 **healthy subjects **or less
• Look at PK and safe dosing range
• 1-3 years

Question 6

What does it mean when IND is approved by FDA?

Answer 6

You can start phase 1 of clinical trials

Question 7

Describe phase 2 of clinical trials

Answer 7

• Assessment of Safety and Efficacy
• 100-500 patients
• 1-3 years
• placebo vs. drug vs. standard of care drug for disease

Question 8

Describe Phase 3 of clinical trials

Answer 8

• Generate statistically significant data about the Safety, Efficacy, and the overal benefit-risk relationship of drug
• 1000-5000 patients may be enrolled
• *Testing to ensure the drug company is working to guarantee high quality production of the drug for use in the trials as well as planning for full scale production of the medicine
• • essential in determining if the drug is safe and effective
• Last 1-4 years
• *most expensive and longest clinical trial
• *labeling instructions

Question 9

What phase of clinical trial is the longest and most expensive?

Answer 9

Phase 3

Question 10

Once phase 3 clinical trials have concluded what does the drug company need to submit before prescribing?

Answer 10

New Drug Application (NDA)
* FDA can request additional studies or information

Question 11

How many years does FDA have to make their decision on NDA?

Answer 11

1-3 years

Question 12

What has to be approved before drugs can go to market?

Answer 12

New Drug Application
*Advisory committee makes recommendation from FDA

Question 13

Describe Phase 4 of clinical trials

Answer 13

1. Post marketing Surveillance
2. “Unofficial stage”
3. studies done and information collected AFTER drug is already on the market
4. Real World Evidence
5. ***HELPS identify rare side effects that don’t show up on the clincial trial

Question 14

How many years does it take to create a brand name drug?

Answer 14

15-20 years

Question 15

What does the FDA need to approve for generic drugs? What is that document called?

Answer 15

Abbreviated New Drug Application (ANDA)

Question 16

What is the only thing the generics have to prove?

Answer 16

Bioequivalence (same rate and extent of absorption as the brand name product)
*smaller group of subjects, cost 1-5million, 1-3 years

Question 17

What is the biggest concern with biosimilars?

Answer 17

immunogenecity and “exact copy”
(is my biosimilar going to cause an allergic reaction?)
**remember biosimilars are used for complex biotech drugs and endogenous human chemicals and proteins

Question 18

what is bioequivalence?

Answer 18

same rate and extent of absorption as the brand name product

Question 19

1906 Pure Food and Drug Act

Answer 19

Prohibited the interstate commerce of adulterated (not pure) food and drugs

Question 20

1911 Shirley Admendments

Answer 20

Prohibited false and misleading claims for drug products

Question 21

1938 Federal Food, Drug and Cosmetic Act

Answer 21

Scientific proof of safety before a drug could be marketed (1st time drug had to prove it worked)
**safety!

Question 22

1962 Harris-Kefauver Amendments

Answer 22

Scientific proof of efficacy (effectiveness)

Question 22

1951 Durham-Humphrey Amendment

Answer 22

Created two classes of products **prescription **and over-the-counter. Created “Legend Drugs”

Question 23

1983 Orphan Drug Act

Answer 23

Gave economic and tax incentives for pharmaceutical manufacturers to develop drugs for **rare disease **

Question 24

1984 Drug Price Competition and Patent Restoration Act

Answer 24

Created the ANDA for generic drugs (prove bioequivalence) and restored some of patent life for the time a drug sat at the FDA waiting approval