Lecture 1 Flashcards
A chemical substance that affects living organisms and is used by clinicians to prevent, diagnose, treat, or relieve symptoms of a disease or abnormal condition.
Drug
The ideal drug is a hypothetical concept that encapsulates the desired qualities of a medication. While no drug can perfectly meet all these criteria, these properties serve as a benchmark for drug development and evaluation.
Ideal Properties of Drugs
- Efficacy and Potency
- Safety and Selectivity
- Pharmacokinetics
- Stability and Compatibility
- Cost-Effectiveness
- Convenience
Refers to blood entry in Pharmacokinetics
Absorption
Refers to drug processing mainly by the liver
Metabolism
Refers to elimination through the kidneys, lungs or biliary exretion
Excretion
The ideal drug would be highly effective, safe, selective, and convenient, while also being affordable and easy to administer. While this is an ambitious goal, drug development efforts strive to create medications that come as close as possible to these ideals.
Out of every 10,000-15,000 new compounds identified during discovery,
FIVE are considered safe for testing in human volunteers. Only ONE of these compounds is typically APPROVED as a marketed drug.
How many years will it take for drug discovery and pre-clinical trial?
3-6 years
How long will it take for clinical trials (phase I to III)
6-7 years
How long does FDA Review, Manufacturing, and Phase IV Post-Approval take?
0.5 to 2 years
biological processes underlying a disease to identify potential targets, such as proteins or enzymes
Disease Understanding
targets are validated to ensure that interfering with them will likely have a therapeutic effect
Target Validation
Millions of compounds are screened to identify those that interact with the target
Screening
The most promising compounds (hits) are further refined to improve their potency, selectivity, and pharmacokinetic properties.
Hit-to-Lead Optimization
It is a critical phase in the process of developing a new drug. It involves extensive testing and evaluation of the compound to ensure its safety and efficacy before it can be tested in humans.
Pre-Clinical Research
“In living”
Experiments are performed on living organisms, such as animals or humans.
Examples: Testing a new drug on rats to assess its efficacy and safety.
In Vivo
“In glass”
Experiments are performed outside of a living organism, often in a laboratory setting, using artificial conditions.
Examples: Culturing cells in a petri dish to study their behavior.
In Vitro Testing
In Vivo Testing
Toxicity studies
Pharmacologic studies
In Vitro Testing Studies
Cell-Based Assays
Biochemical Assays
The application for clinical testing in humans, which is submitted to the FDA.
Investigational New Drug (IND) Application
Identifies unexpected side effects or adverse events that may not have been detected in clinical trials.
Post-Market Surveillance
Ensures that the drug’s labeling accurately reflects its benefits and risks.
Labeling Updates
Explores the drug’s effectiveness in different patient populations or for new indications.
Efficacy Assessment
Compares the drug’s effectiveness to other available treatments.
Comparative Effectiveness Research
Evaluates the drug’s long-term safety profile, especially for drugs used for chronic conditions.
Long-Term Safety Assessment
Most drug candidates fail during development due to safety, efficacy, or regulatory issues.
High Failure Rates
The process is expensive and time-consuming, often taking over a decade to complete.
Cost and Time
Protecting intellectual property is
crucial to recoup investments and maintain market exclusivity.
Intellectual Property
Navigating complex regulatory
requirements can be challenging.
Regulatory Hurdles
Typical duration of drug discovery
10-15 years
Average Cost for Drug Development
$1 Billion +
It is the ability of the drug to exhibit its maximum effect
Efficacy
It refers to the concentration or strength of the drug that produces an effect
Potency
It refers to the drug having a specific target or site of action
Selective
The ability of the drug to be stable in different environments (longer shel life)
Stability
Drugs should be compatible with other substances
Compatibility
Drivers of Drug Development
Unmet Medical Needs
Market Potential
Scientific Advancements
Competitive Landscape
Intellectual Property
It is an In Vivo test performed to test if the lead compound is harmful (increasing dose of lead compound is administered to subjects
Toxicity Studies
It is an In Vivo test testing for the therapeutic effect of the product.
Pharmacologic Studies
It is an In Vitro test used to test certain compounds in artificial environments
Cell-Based Assays
It is an In Vitro test that uses enzymes/proteins to evaluate
Biochemical Assays
IND Application must include:
- Animal Pharmacology and toxicity data
- Data from any prior human research
- Clinical Protocols for proposed human studies
- Principal Investigators Information
Manufacturing Information
Purpose of Phase I Clinical Trials
Safety, Tolerability, Pharmacokinetics
Purpose of Phase II Clinical Trials
Efficacy, Safety, Optimal Dosage
Purpose of Phase III Clinical Trials
Efficacy, Safety in a large population
NDA data for evaluation:
- Proposed Labeling
- Safety Updates
- Drug Abuse Information
- Patent Information
- Data from studies conducted outside US
- Institutional Review Board compliance information
- Directions for use
- Potential Interactions with other medications
Content of IND
Pre clinical data and clinical trial protocols
Content of NDA
Pre clinical and Clinical data
Manufacturing information
Labeling
Key Challenges in Drug Discovery
High Failure Rates
Cost and Time
Intellectual Property
Regulatory Hurdles
This includes the prevalence of the disease, the target patient population, and the potential pricing and reimbursement landscape.
Market Potential
New discoveries about disease mechanisms or the identification of promising drug targets, can provide a strong rationale for drug development.
Scientific Advancements
The availability of existing treatments and the potential for new competitors, is assessed to determine the potential for a new drug to gain market share.
Competitive Landscape
Number of Volunteers in Phase I Clinical Trial
20 to 100
Number of Volunteers in Phase II Clinical Trial
100 to 500
Number of Volunteers in Phase III Clinical Trial
1,000 to 5,000
Drug Development Process:
Drug Discovery
Pre-Clinical Research
Clinical Trials
Post-approval Monitoring
Examples of animals used in In Vivo Testing
Mice
Rats
Rabbits
