Introduction to drug development-life cycle of a drug

Question 1

Drug development in the 1800s:

Answer 1

Cleopatra used to test poisons on condemned prisoners

• drug development and discovery started to follow scientific techniques in the late 1800s
• More drugs were discovered, tested and synthesized in large scale in manufacturing plants (from 1900s)

Question 2

Common drugs still used today discovered in the 1800s:

Answer 2

1- Digitalis- foxglove extract for treatment of cardiac problems

2- Quinine- from the bark of cinchona tree for treatment of malaria

3- Aspirin- from the bark of willow tree extract for treatment of fever

Question 3

Describe the stages of the drug discovery pipeline (6):

Answer 3

1. (UMN) Identification of Unmet Medical Needs
   - therapeutic areas that are required for new drug development
   - market analysis
   - input from KOLs (key opinion leaders)
   - practitioners
2. Target identification
   - drug target: causes of the disease- the biological molecules (e.g DNA, proteins) that is associated with the disease
   - Many new scientific approaches are now used to determine the targets
   - biotechnology e.g DNA, RNA, protein techniques and cell cultures
3. Target validation
   - demonstrate the functional role of the target in a disease process
   - in vivo (animal study- pharmacology)
   - in vitro (molecular study-biotechnology)
4. Hit identification
   -Hit: the chemicals that have bioactivity against a drug target in HTS.
   -High-Throughput Screening (HTS)
   a drug discovery process that allows automated testing of large numbers of chemical for a specific biological target
5. Lead generation
   leads are selected from hits
   Lead: a chemical compound that shows promise as a treatment for a disease and may lead to the development of a new drug
   -Evaluate the activity of the compound and action pathway (study of drug pharmacology)
   -structure activity relationship (SAR)
   -Activity and selectivity
   -toxicity potential
6. Lead Optimization (finishing touches)
   - optimize the compound that demonstrate the potential to be transformed into a new drug
   - Modify the chemical structure of a lead compound
   - improving effectiveness
   - diminishing toxicity
   - increasing the organism’s absorption

Question 4

Describe the stages of the drug development pipeline (7):

Answer 4

1. Preclinical Development (Preclinical study)
   - confirm efficacy of the drug
   - ensure safety of the drug
   - information about drug formulation and manufacture protocols

Follow regulation guideline of Good Laboratory Practice (GLP)
Preclinical study
-safety of drug/toxicity tests
-determine the potential risk a lead compound poses to human
-tissue culture
-animal studies
-drug formulation

2. IND filling (investigational new drug)
   - Summit IND to regulation authorities, make sure make sure people will not be exposed to unreasonable risks in clinical trials
   - submitted to Health Sciences Authority (HSA) for approval in Singapore.
3. Phase I Clinical Trial
   - 10-100 healthy human volunteers
   - determine drug safety and safe dose range
   - PK and PD analyses
4. Phase II Clinical Trial
   - 50-500 healthy human volunteers at 3-4 centres
   - Establishment of efficacy
   - drug’s safety and side effects
   - optimal dose and strength
5. Phase III Clinical Trial
   - few hundred-thousand patients
   - confirmatory trials-efficacy and safety
   - identify any long term effects
   - drug-drug interaction
6. New Drug Application Filing
   - submit NDA to HSA for approval in Singapore
   - scientific evidence to demonstrate the safety and efficacy of the drug
7. Phase IV Clinical Trial
   - post marketing surveillance
   - identify undetected adverse effects
   - long term morbidity and mortality profile
   - drug-drug interaction
   - drug-disease interaction

Question 5

Preclinical study, What is Pharmacodynamics?

Answer 5

What drug does to the body,

• study of the biochemical and physiological effects of drugs and the mechanisms of drug action
• the relationship between drug concentration and efficacy of the drug

Question 6

What does ADME mean in Pharmacokinetics?

Answer 6

What body does to the drug,
Absorption 
Distribution 
Metabolism 
Excretion

Question 7

What is Clinical Trials?

Answer 7

A designed human study to determine if the candidate drug is safe for people and effective in treating a disease