Exam 2: Drug Discovery and the Approval Process Flashcards
What is the pharmacognosy or “Eco-mining” approach to how new chemical entities are made?
Looks at medicinal drugs obtained from plants or other natural sources
What is the incrementally modified drug approach to how new chemical entities are made?
Chemical alteration of a known molecule to change its activity
What is the molecular modeling approach to how new chemical entities are made?
Scientists make a stereotypic 3D image of the receptor and the custom build a molecule to react with that receptor
How long is the preclinical phase of human drug development NME?
4.3 years
How long are clinical trials and FDA approval in human drug development NME?
7.5 years
What is the total amount of time for human drug development NME?
11.8 years
What is the total cost of human drug development in the preclinical phase NME?
335 million dollars
What is the total cost of human drug development in the clinical trials and FDA approval phase NME?
467 million dollars
What is the total cost of human drug development in NME?
802 million dollars
What is the cost of veterinary drug development?
Estimates vary, but range from $1.5 to $50 million
What is the time for veterinary drug development?
8-15 years
Why are there lower costs on veterinary drugs?
The product may be a currently approved human drug that is being extended for use in animals, so the development costs have already been covered
How long does a patent last on a drug?
A patent normally lasts for 20 years, but it may begin at any time before, during, or after approval by FDA
What is exclusivity?
Attaches upon approval of a drug product if the statutory requirements are met
Prevents a generic drug from being approved in specific instances
What are examples of when exclusivity may be granted?
Human orphan drug exclusivity- 7 years
New chemical entity exclusivity- 5 years
Generating antibiotic incentives now (GAIN) exclusivity- 5 years added
New clinical investigation exclusivity-3 years
Human pediatric exclusivity
Patent challenge- 180 days for first generic product
How is a withdrawal time determined for a drug that is to be used in a food animal with NOEL?
Genetic toxicity studies
90-day feeding studies in rodents and other mammals
Teratology study in rats
Antimicrobial resistance studies
Chronic toxicity and/or carcinogenicity studies in rodents
How is a withdrawal time determined for a drug that is to be used in a food animal with Allowable Daily Intake (ADI)?
ADI = NOEL/Safety factor
How is a withdrawal time determined for a drug that is to be used in a food animal with safety factors?
Variability between humans = 10X
Interspecies extrapolation = 10-100X
Subchronic (intermittent exposure) extrapolation = 10X
Total possible = 10-10,000X
How is a withdrawal time determined for a drug that is to be used in a food animal with tolerance?
Safe concentration = ADI x 60 kg/ consumption factor
Hot and cold studies look at parent and metabolites
Look at target tissue (the edible tissue from which residues deplete most
slowly)- usually liver or kidney.
How is a withdrawal time determined for a drug that is to be used in a food animal with marker residue?
Monitors depletion of total residues in a tissue
Can be either the parent drug or a metabolite
What activities typically occur during the preclinical stage of drug development?
Synthesis and purification Develop stability and analytical techniques including assay in fluids and tissues Marketing review Scale-up Early pharmacokinetics stiudies Proof of safety Proof of efficacy Management decides "go or no-go"
What is scale-up?
Create a pilot plant to produce a few hundred grams for testing
What happens during proof of safety?
Lab animal acute toxicity studies Range finding (LD50, LD1) Genetic toxicity testing ---Treat all products as carcinogens until proven otherwise Eye irritation studies if a cosmetic
What happens during proof of efficacy?
In-vitro models
In-vivo disease models
What is an INAD?
Investigational New Animal Drug Application
Allows legal Interstate shipment of nonapproved drugs
FDA does not “approve” INAD
Applies to new formulation
What is a NADA?
New animal drug application
Approval by the FDA
Includes ID of sponsor and drug, labeling, manufacturing methods,
samples, safety and efficacy evidence, etc.
Most submission are now performed electronically
What is an ANADA?
Abbreviate New Animal Drug Application
Approved generic drugs- copy an already approved new animal drug
What multiples of dose are typically studied in a target animal margin of safety study?
1x, 3x, and 5x dose
What is meant by the term “pioneer” drug product?
The pioneer drug product is the approved brand name animal drug
What is the intent of a phase 1 clinical trial?
1°: kinetics and set dose
2°: safety
3°: efficacy
What is the intent of a phase 2 clinical trial?
1°: efficacy
2°: safety
3°: kinetics
What is the intent of a phase 3 clinical trial?
Verify effectiveness
Monitor adverse reactions from long-term use
What is the intent of Phase 4 testing and/or post-marketing surveillance?
Required for some drugs to look for long-term side-effects or public health consequences
What is a positive control versus a negative control as it relates to a drug clinical trial?
Positive control is the test drug and is usually used
Negative control is the placebo and is used if the disease is mild
Compare and contrast a single-masked to a double-masked study.
Single masked: Patient doesn’t know treatment, clinician does
Double masked: Neither patient nor clinician know the treatment identity
What must happen for any drug that is marketed?
Each formulation by each company must be individually approved, including the pioneer and each version of all generic products
