Past Exam Questions Mod 5

Question 1

what are the 4 primary areas of preclinical testing

Answer 1

1. efficacy testing
2. ADME
3. toxicology
4. pharmaceutics

Question 2

what are the 4 primary outcome measures for in vivo efficacy testing?

Answer 2

?

Question 3

Describe 3 properties of a drug that can be determined with greater certainty in whole animals compared to in vitro or in silico methods

Answer 3

1. Pharmacokinetics
   - whole animals provide comprehensive insights into the drug ADME
2. Toxicity + safety
   - whole animals reveal acute + chronic toxicity side effects + dose-response relationships
3. Efficacy
   - whole animals allow for the assessment of drug efficacy in complex disease models + physiological + behavioural contexts

Question 4

What are the key study design features of an acute toxicity study and what information is an acute toxicity study aiming to determine?

Answer 4

DESIGN
1. at least 2 species (both sexes)
2. usually 2 routes of administration
- intended route in humans
- intravenous (if feasible)
3. emphasis on signs of toxicity + mode of death rather than LD50 value
4. 3-5 rodents per sex per dose, fewer for non-rodent studies

AIM
- observations for gross signs of toxicity
- changes in behaviour
- changes in fur, skin/mucous membranes
- tremors, convulsions, salivation, diarrhoea, lethargy, sleep, coma

Question 5

What is the primary aim of pharmaceutics testing in preclinical drug development? List 4 types of testing studies used in pharmaceutics testing and characterisation

Answer 5

AIM
to determine if the drug candidates have suitable physical, chemical + biological properties to become a medicine for human use

1. physiochemical profiling + characterisation
2. preliminary formulation development suitable for efficacy and toxicology studies
3. dissolution testing - standard paddle apparatus
4. stability testing - controlled temperature and humidity for extended periods
   [5]. assessment of particle size and any modifications

Question 6

In order to register a new drug in a major market such as the USA, a pharmaceutical company must submit a New Drug Application (NDA). Describe what data and information about a new drug are required for completing an NDA application?

Answer 6

…

Question 7

What are THREE (3) primary aims of Preclinical Drug Development?

Answer 7

• Assess potential therapeutic effects of drug candidate in relevant organisms
• Gather sufficient preclinical data on the drug to evaluate safety of drug candidate for human use
• To determine if drug candidate has potential to ever be developed as a pharmaceutical for human use

Question 8

List FOUR (4) uses of Acute Toxicity Studies in the Preclinical Drug Development program in
terms of what the results from these studies identify and inform.

Answer 8

• Informs likely effects of acute over dosage in humans
• Identifies potential target organs for toxicity, and
• Identify parameters for monitoring in future clinical evaluation
• Useful for the design of repeat-dose toxicity studies (eg selection of
  doses)

Question 9

Describe what a Central Nervous System Multi-parameter Optimisation (CNS MPO) score
represents. List THREE benefits of using a CNS MPO-based approach for the development of
drugs for neurological diseases.

Question 10

What is the purpose of Genotoxicity Testing in Preclinical Drug Development? List a simple
Genotoxic Testing Schedule (Study Design) that would be suitable for small molecule drugs.
If your compound has a positive signal in one of the genotoxicity tests, how would you proceed
with your development plan?

Question 11

Preclinical testing in rodents is typically used for most new drugs or pharmaceuticals. What are some of the risks of relying solely on data from rodent studies for your preclinical drug development program? List THREE (3) alternatives to rodent testing with advantages and limitations of each