Drug Development Process and Product Stability

These flashcards cover key concepts related to the drug development process, drug stability, and kinetics discussed in the lecture.

What are the five stages of drug development as discussed in the lecture?

1. Drug discovery and development 2. Preclinical research 3. Clinical research (Phases 1, 2, and 3) 4. FDA review and new drug application (NDA) 5. Post-marketing safety studies.

This is the first step in the drug development process and is the process by which new drugs are discovered

Drug discovery and development

What does drug discovery include?

Repurposing an existing drug, Producing variants of an existing drug, Identifying a new therapeutic target that acts on a specific disease pathway

What is the order of a new target being identified?

Target identification and validation → Assay development and screening → High throughput screening → Hit to lead selection → Lead optimization

the compound is tested to determine its safety and efficacy before human testing, involves in vitro studies or in vivo studies in non-human model

Preclinical research

What does the FDA require in preclinical research?

Good Laboratory Practices

What is the goal of preclinical testing?

file for the Investigational New Drug (IND) application with the FDA to allow for subsequent testing in humans

Once an IND application is approved, clinical trials can begin

Clinical Research

What is the main purpose of Phase 1 clinical trials?

To establish the safety and dosing regimen of the drug candidate

What is the main purpose of Phase 2 clinical trials?

Side-effects and efficacy. However, due to a small sample size, these studies do not give a definitive indication of efficacy or a beneficial effect. The data produced provide the basis for deciding to move forward to phase 3. Data generated from this phase cannot be used to make clinical decision

What is the main purpose of Phase 3 clinical trials?

To confirm the efficacy demonstrated in the phase 2 studies but more importantly to provide comprehensive safety data that may have been undetected in the shorter and smaller phase 2 studies.

What is included in the New Drug Application (NDA) submitted to the FDA?

An extensive document that includes all drug information generated from preclinical and clinical research to demonstrate safety and efficacy.

After a successful phase 3 study, the sponsor (agency paying for the clinical trials) submits an NDA to the FDA

FDA review and new drug application (NDA)

What is phase 4 of drug development?

Confirm safety in larger population after long-termtreatment and to confirm clinical efficacy in a larger population.

What is the purpose of the accelerated approval program by the FDA?

To provide earlier approval of certain drugs for serious health conditions and unmet medical needs based on a surrogate endpoint.

A marker, such as a laboratory measurement or physical sign, thought to predict clinical benefit but not itself a measure of clinical benefit.

Surrogate endpoint

Is confirmatory trials required after market approval?

Yes

What does 'half-life' (t50%) mean in pharmacology?

The time it takes for the concentration of a drug in the body to be reduced by half.

t50

half-life

t90

self-life

As a constant, where the rate of reaction is independent of the concentration of the drug.

Zero-Order Reactions

most widely seen driving force for diffusion

Concentration gradient

the process of movement of molecules from a high concentration to a low concentration without expending energy

Passive diffusion

Osmotic drug release relies on osmotic pressure as a driving force to control the release of drugs

Pressure

type of diffusion that involves the movement of solvent from low to high concentration of the solute across a semipermeable membrane to achieve equilibrium

Osmosis

based on this principle of osmosis to create pressure for controlled drug release

Osmotic drug release

What makes up osmotic drug release system?

drug (agent), an osmotic layer (with high solute concentration), and a semipermeable membrane

How does an osmotic drug release system work?

It utilizes osmotic pressure to control the release of drugs by moving water across a semipermeable membrane, generating pressure to release the drug.

a process in which pressure (such as centrifugal force, vacuum, blood pressure) along with a concentration gradient results in the separation of molecules based on size across a semipermeable membrane

Ultrafiltration

used in patients with end-stage renal disease to remove accumulated waste products and water, while maintaining the composition of blood electrolytes, larger proteins, and other high-molecular-weight molecules in the blood circulation

Hemodialysis

Define 'first-order reaction' in terms of drug degradation.

A reaction where the rate of decrease in drug amount is proportional to the amount of drug present.

What is electrophoresis and its purpose?

A technique that separates large molecules (e.g., proteins, DNA) based on size and charge using electric current.

a technique that utilizes electrical current as a driving force to separate large molecules (e.g., proteins, DNA, RNA) on a gel based on the molecular size and charge of the molecule

Electrophoresis

What is the driving force for electrophoresis?

electric current