Drug toxicity and Drug Development

Question 1

Identify the 3 levels of risk-benefit analysis that occur related to drug therapy?

Answer 1

FDA: evaluates benefits/risks for the population (Accessibility)

Provider: evaluates benefits/risks for a patient (Applicability)

Patient: evaluates benefits/risk in terms of personal values (Acceptability)

Question 2

State the 3 elements of information needed for an application of an Investigational New Drug (IND) with the FDA.

Answer 2

1. Animal pharmacology and toxicology (largest part of IND)
2. Manufacturing information
3. Clinical protocol and investigator information

Question 3

What is the difference between the no observable adverse effect level and minimal anticipated biological effect level for determining the first dose in man for an investigational drug?

Answer 3

No observable adverse effect level: determined through toxicology and is the highest dose that fails to provoke any observable adverse effects in the organism.

Minimal anticipated biological effect level: determined based on pharmacology and is the lowest dose that causes a biological effect on the organism.

Question 4

What are the primary reasons adverse drug events are not detected until the drug is approved and marketed for a period of time?

Answer 4

1. The incidence of the adverse effect can be rare compared to clinical trial numbers.
2. It takes long term studies to distinguish and adverse effect compared to a common effect

Question 5

How do you determine if preclinical toxicology studies are needed for an excipient to be included in a dosage form?

Answer 5

If the excipients are not found on the GRAS list, they will need to conduct preclinical toxicology studies for the excipient.

Question 6

What are the 5 categories of preclinical toxicology studies typically completed in the development of a new drug?

Answer 6

Acute Studies: Effect of a dose in at least 2 species.

Repeated Dose Studies: Length depends on anticipated therapy in at least 2 species.

Genetic Toxicity: Determine likelihood that compound is mutagenic or carcinogenic.

Reproductive Toxicology: Needs depend on target population in multiple species.

Carcinogenicity: Only for compounds used in chronic or recurring conditions.