S1B5 - Drug Developmend and Approval Flashcards
(34 cards)
Assays can be developed to screen for molecules that activate or inhibit a molecular target. What is the name for the compounds that are discovered this way?
Lead compounds can be discovered in a variety of screening assays.
Derivatives of a lead compound are synthesized to search for a compound with the required properties of a drug. Which step in pre-clinical drug development is this?
Medicinal Chemistry
- Derivatives of a lead compound are synthesized to search for a compound with the required properties of a drug.
- Drug properties
- Affinity (lower (Memantine) or higher), activity, or more selectivity
- stability in vivo and bioavailability - adsorption, distribution, metabolism, excretion (ADME)
- toxicity and adverse effects
What does GLP stand for in the context of drug development?
GLP; Pre-clinical research must meet good laboratory practice standards (GLP).
- Set of rules that dictate study design, facilities, and personnel to proper documentation of data.
Is pre-clinical drug testing done in vitro or in vivo?
Pre-clinical testing
-
In vitro testing;
- The pharmacological profile of the compound can be determined using in vitro assays. The goal of these experiments is to determine the potency and selectivity of the compound.
- Cell culture assays (activity, selectivity, toxicity)
- Tissue slices grown in culture (activity, selectivity, toxicity)
What does IND stand for in the context of drug development?
Investigational New Drug Application (IND)
- If pre-clinical testing, both in vitro and in animals, justifies human testing, an Investigational New Drug Application (IND) is filed
- The application also includes plans for human testing. A review by a panel organized by the FDA determines if it is reasonably safe to move forward with human testing.
- Clinical trials require review and approval of an IND. Also, approval of the Institutional Review Board (IRB) is required.
What does IRB stand for in the context of drug development?
Institutional Review Board (IRB)
-
Protection of human research subjects
- Informed patient consent!
- fully informed of their risks and have given informed consent.
- informed that they have alternatives
- promptly report adverse events
- placebo vs drug
- new drug vs standard of care
- comprised of scientists and non-scientists that oversees the clinical trials.
- Reviews and approves the clinical trial protocols.
- The protocols describe the patient population, the criteria for patient inclusion or exclusion, the schedule of tests and procedures, the medications and dosages to be studied, the length of the study, measurable outcomes, and the study’s objectives.
What is a randomized control trial?
Randomized Control trial is a research study in which participants are randomly allocated into an experimental group or a control group and followed over time for the variables/outcomes of interest.
What is the formal step for submitting a drug for approval for marketing in the United States, and who do you sent it to?
A New Drug Application (NDA) is the formal step for submitting a drug to the FDA for approval for marketing in the United States.
Describe the 5 schedules of drugs with abuse potential.
- Schedule I; no accepted medical use and a high potential for abuse. Heroin, marijuana (cannabis)
- Schedule II; high potential for abuse, severe psychological or physical dependence. cocaine, methamphetamine, methadone, oxycodone, methylphenidate
- Schedule III; moderate to low potential for physical and psychological dependence. Combination products with low amounts of
- Schedule IV; a low potential for abuse and low risk of dependence. Xanax, Ambien
- Schedule V; lower potential for abuse than Schedule IV and consist of preparations containing limited quantities of certain narcotics. Antidiarrheal, antitussive, and analgesic purposes.
What does REMS stand for in the context of drug development?
Risk Evaluation & Mitigation Strategies (REMS)
- Another tool the FDA uses to increase drug safety are Risk Evaluation and Mitigation Strategies (REMS).
What is orphan drug status in the context of drug development?
Orphan Drug Status
- An orphan drug is developed specifically to treat a rare medical condition (an orphan disease). Orphan drugs status can provide longer patent exclusivity, tax incentives. and financial incentives
- orphan status if a drug is intended to treat a disease affecting less than 200,000 American citizens
- seven-year market exclusivity
- tax credits on development costs
- fast-track approvals of drugs indicated for rare diseases
What are the three typical steps in pre-clinical drug development?
Typical steps in pre-clinical development
- Lead compound discovery
- Medicinal chemistry
- Pre-clinical testing
- In vitro studies
What are the major drug properties that drug developers are looking for in the medicinal chemistry step of pre-clinical development?
Drug properties
- Affinity (lower (Memantine) or higher), activity, or more selectivity
- stability in vivo and bioavailability - adsorption, distribution, metabolism, excretion (ADME)
- toxicity and adverse effects
What does GCP stand for in the context of drug development?
GCP; Clinical trial research must meet good clinical practice (GCP) standards.
- Set of rules that dictate key aspects of clinical trials from study design, facilities, and personnel to proper documentation of data.
What does IACUC stand for in the context of drug development?
IACUC
-
Institutional animal care and use committee
- Approves protocols for care and use of vertebrate animals in research
- Animal care
- Minimize stress and pain
- Minimize animal numbers, but ensure that experiments are adequately powered.
What two important things does animal studies address in drug development?
Animal studies address safety and efficacy
- Experiments in animal models are used to address
- efficacy of a drug candidate and other issues
- pharmacokinetic properties
- adverse effects and toxicity
What is the purpose of phase IV clinical trials?
Phase IV trials detect long-term adverse effects associated with widespread use and can result in a drug being withdrawn from the market. In other words, phase IV trials ask the question “can the drug stay?”
What is the study design of phase III clinical trials?
Phase III clinical trials involve a large number of patients with the disease to be treated (approximately 1,000 - 3,000 subjects) who are randomly assigned to one of two groups:
- The treatment being investigated or
- The best treatment currently available (or placebo)
What is the purpose of phase II clinical trials?
Phase II trials determine appropriate dosing, efficacy, and adverse effects. In other words, phase II trials ask the question “does the drug work?”
What is a clinical trial? What is the purpose of clinical trials?
Clinical trials are experimental studies with human participants. The purpose of these studies is to compare the therapeutic benefits of two or more treatments (or to compare a treatment with a placebo).
For a new medication, during which phase of clinical trials is efficacy first determined?
A) Phase IV
B) Phase II
C) Phase III
D) Phase 0
E) Phase I
Phase II
Answer Explanation
During Phase 0, a single, subtherapeutic dose is given. The goal is to obtain preliminary pharmacokinetic and pharmacodynamic data.
Phase I trials determine safety, pharmacokinetics, and pharmacodynamics.
Phase II trials identify/prove efficacy and adverse effects.
Phase III trials compare the treatment to the existing gold standard. This differs from Phase II in that Phase II merely seeks to show that the drug works for the proposed indication.
Phase IV consists of post-marketing surveillance.
What is a typical study sample in phase II of a clinical trial?
Phase II trials involve a small number of patients (generally fewer than 100) that have the disease to be treated.
What is the purpose of phase III clinical trials?
Phase III trials compare the treatment being investigated to the current “gold standard” treatment. In other words, phase III trials ask the question “is the drug as good or better?”
What is a typical study sample in phase I of a clinical trial?
In phase I trials a small number of healthy subjects (between 20 and 80 subjects) receive a single dose of the treatment of interest.
