Drug Development And Approval Process Flashcards
Which organization approves drugs?
The FDA
What subsects of the FDA are involved in drug approval?
The Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), and the Center for Devices and Radiological Health (CDRH)
What is a drug?
A substance that exerts an action on the body by chemical action or metabolism and is used in the diagnosis, cure, mitigation, treatment, or prevention of disease
What is a new drug referred to as?
Not generally recognized as safe and effective (GRASE)
What is the first stage of new drug development and approval?
Drug discovery and development
What does cGMP stand for?
Current good manufacturing practices
What does GLP stand for?
Good Laboratory Practices
Describe compound-centered drug discovery
Producing compounds that will work with biological receptors. Typically mimicked compounds that are endogenous or in nature
What is lead optimization?
Find the right match between the target and chemical compound. Maintain the desired properties while reducing any deficiencies. The right match is called a lead compound
What is the second stage of new drug development and approval?
Pre-clinical research and development
What happens during preclinical testing?
-Pharmacodynamic, pharmacokinetic, and toxicology testing
-therapeutic effects and safety tested in animals
-takes 1-3 years
-No prior approval is needed to begin
What is the 3rd stage of the new drug development and approval process?
Clinical trial
What does a company have to submit between the pre-clinical and clinical trial phases?
A Investigational New Drug application
What are drugs studied in a clinical trial called?
Investigational drugs
Why do clinical trials have phases?
To establish the efficacy and safety, to protect the human test subjects, and to ensure the integrity and usefulness of the clinical study data
Before proceeding with a clinical study, what do you have to do?
Submit a investigational new drug application and have no objection by FDA and have the IRB approve it
What does the IRB look at before approving a clinical study?
The protection of human test studies and informed consent documents
What is the gold standard of clinical trial design?
Double blind randomized controlled trial
What sample size should you use?
A sample size that is sufficient to reveal a conclusion statistically
What is a superiority design?
Shows that a treatment is better than a placebo
What is a non inferiority design?
You are making sure that the new drug is not worse than the standard
What is equivalence design?
You are determining whether one intervention is the same in effectiveness as another
Describe phase 1 of a clinical trial
-healthy volunteers
-establish pharmacokinetic profile, safety, and dosage (in a fast track study, people with the diagnosis are allowed to be included)
-study size is small, and generally the study goes for 1 year or less
Describe the phase II of a clinical trial
-establish the pharmacokinetic profile, safety, and efficacy with a bigger study size
- uses people with the disease
-2 parts: A and B. A=pilot study. B=single or double blinded control study
-Medium size (100s)
-lasts weeks to months
Describe phase 3 of a clinical trial
The final stage before drug approval
-PK profile, safety, efficacy, final formulation, indications, labeling, marketing claims, product stability, packaging, storage conditions established
-double blind with a large study size
What is submitted after the clinical trial?
A new drug application
What does the FDA reviewer of the NDA look for
Whether the drug is safe and effective and benefits>risks, if the package insert is appropriate, and whether the quality control methods are appropriate
What are the 3 options that the FDA reviewer could provide in response to a NDA
Approval letter, approvable letter, or nonapprovable letter
What is the fast track in regards to the new drug application?
-priority and rolling review
-drug fills an unmet medical need or treats a serious disease.
What is accelerated approval in regards to the new drug application?
-Drugs that fill unmet medical need and treats serious disease
-accelerated through approval process
-after marketing trials have to verify clinical benefits
-Reapply after marketing
What is a priority review in regards to the NDA
The FDA will review the NDA within 6 months because the drug is important for serious conditions
What is a breakthrough therapy designation
A expedited process for drugs that treat serious conditions
-based on preliminary clinical evidence that says that it is an improvement on available therapy
-Requested at end of phase 2
Explain postmarketing surveillance
Not usually required, but sometimes for fast-track.
Double blinded with a huge study size over many years (general population)
What is FAERS?
The FDAs Adverse Event Reporting System. It is a database for adverse events and medication errors.
What is the FDA’s sentinel initiative?
A national electronic system to monitor safety of FDA regulated medical products after they reach the market. It complements the adverse event reporting system
What is an orphan drug
-A drug used to treat rare diseases affecting fewer than 200,000 people in the US
-Orphan Drug Act of 1983 gives grants, tax credits, and 7 year market exclusivity
What is an abbreviated new drug application?
An application for generic drugs after the patent is up. It requires demonstration of bio equivalence to the innovator drug and must deliver the same amount of active ingredients in the same time.
What are the principles of OTC status?
safe, easy to use method (usually oral), high benefit to risk ratio, and adequacy of labeling for self-medication
What does GRASE stand for?
Generally Recognized As Safe and Effective
What is a biologic?
A substance derived from living organisms
Which organization deals with biologics licensure?
CBER
What is responsible for devices with therapeutic claims?
CDRH
What are the classes of devices?
I, II, III
All promotional information must be …
Truthful, fairly balanced, and fully disclosed
Does the FDA have the jurisdiction to inspect manufacturer’s premises?
Yes
What can enforcement look like?
A warning letter, seizure, or recall
What are the 3 classes of recall?
Class I: seriously harmful, class II: temporary or medically reversible harm, class III: not likely to cause adverse effects
What is an example of a reason a drug would have a class III recall?
The drug may not be effective even though it is not dangerous
What are some limitations to the drug approval process??
The FDA does not review advertisements, postmarketing surveillance may not be adequate, pressure for speedy approvals may result in compromise to safety or efficacy, sometimes there are conflicts of interest, and the FDA does not compare competing drugs or require tests of clinical efficacy for new devices
