drug discovery and development

Question 1

Describe the stages of development of a new drug

Answer 1

1. basic research
2. pre-clinical research
   → done by contract research organisations
3. clinical research
   
   1. phase 1
   2. phase 2
   3. phase 3 -
4. regulatory review

Question 2

Demonstrate an understanding of the aim of preclinical development

Answer 2

find out:
- exploratory toxicology
- exploratory safety
- regulatory toxicology
- regulatory safety
- toxicokinetics = exposure
- dosage

Question 3

Describe properties that may be taken into account when selecting a “lead molecule” for drug development

Answer 3

• bind selectively to the receptor site on the target
• elicit the desired functional response of the target molecule
• have adequate bioavailability and biodistribution to elicit the desired responses in animals and humans
• must also pass formal toxicity evaluation in animals

Question 4

Describe tests used to explore drug safety during lead selection and the goals of non-clinical safety evaluations

Answer 4

• toxicity
  
  • on/off target = goes where you want it to go
  • reversibility
• toxicokinetics
  
  • relate toxicity to exposure
  • e.g how long to clear, conc
• max non-toxic dose / min affective dose
• dose selection for fist in human
• identification of specific monitoring requirements

Question 5

Describe the different phases of a clinical trial and under what circumstances a drug may be withdrawn

Answer 5

• phase 1
  
  • is it safe?
  • is it tolerated well?
  • what are the pharmacokinetic properties
• phase 2
  
  • proof of concept
  • how much should be given?
  • how well does it work?
• phase 3
  
  • 1000+ patients
  • definitive results
  • multi centre
  • multi national
  • application for marketing
• phase 4
  
  • post marketing surveillance
  • detect rare or long-term adverse effects

Question 6

Demonstrate understanding of the differences between small molecule and biopharmaceuticals, in terms of safety and pre-clinical development and how these apply to immunotherapies being developed for treatment of cancer

Answer 6

biopharmaceuticals
- biologics
- antibody based
- vaccines - HPV, COVID
- RNAi - DMD
- cell-based - CART for children with acute lymphoblastic leukaemia
- gene therapy - e.g factor 9 for haemophilia
e.g
biological molecules
- high MW
- derived from organisms
- complex structure
monoclonal antibodies
- high MW
- derived from organisms
- complex structure

small molecules
- low MW
- chemically synthesised
- defined structure