5. Drug Development Flashcards
A. Preclinical Investigation
Current initial exploration of the potential pharmacological action(s) of a new molecule often begins with studies in ____ and/or ____ affinities in isolated tissue(s); this is in ____ testing.
If the in vitro results indicate potential pharmacological activity, further research on this new molecule is performed on various animal models (in ____) of the target disease.
Toxicological studies in ____ are also started.
• When drug company creates a molecule and registers it > they have \_\_\_\_ years of patent life from that point • May ahveeneough data > IND > submit to FDA to start clinical trial ○ FDA says yes, no or needs more data
cell cultures binding affinities vitro vivo animals 17
B. Request for Investigational New Drug (IND) Approval
When a pharmaceutical company believes its preclinical investigation shows that a good degree of pharmacological activity exists–and toxicity is low–an ____ is submitted to the FDA for approval to begin clinical trials.
After a review, the FDA may either approve the IND or instruct the company to conduct further testing.
If the IND is approved, clinical testing can begin.
IND
C. Clinical Trials
There are many requirements for the performance of a good clinical trial including:
- Careful Planning
Necessary in order to obtain maximum amount of
useful ____ with minimum ____ to patients.
A protocol can not be ____ while the study is in progress unless a very ____ condition develops.
If, for example, a researcher forgot to include taking a ____ to evaluate changes in a particular enzyme, and the testing of some patients has already been completed, the investigation has to be revised and started again. Data from the completed patients will be ____.
data harm altered dangerous blood sample unusable
- Control Groups
Wherever possible, a ____ group must be included in the study. The placebo medication must be very similar – or identical to– the active drug with respect to ____, taste and ____.
In many cases, the control group receives an older, established ____ for comparison.• Control groups, and if possible a placebo, cant do a placebo for new anti-epilectic drug
○ Has to be an identical outward product
If blue placebo - its relaxing; but if red - it’s the opposite
placebo
color
smell
drug
- Double Blind Format
Wherever possible, neither the ____ nor the ____ should know what the patient is receiving; this serves to eliminate bias in both patient and physician.
Having the patient unaware of what drug is being administered does not mean that patients should also be unaware that they are involved in a drug test!
In the USA, it is unacceptable to involve a patient in a clinical trial without informing the patient. A ____ is prepared which lists potential ____s; this must be signed by the ____ and should also be signed by a ____ and by the ____.
• Double blind format ○ Neither the patient nor who is running the study knows whats in the pill ○ The patient still knows they're in a s tudy - must sign a consent form (ESSENTIAL) § Must be written at \_\_\_\_ grade level- so patients know whats happening to them
patient doctor consent form ADR patient witness doctor 6/7
- Randomization
Before the first patient is enrolled, a table of random numbers is employed; this process will allow creation of a ____ list of the sequence of drug and placebo administration (e.g., pt #1 gets a placebo, pts #2 & #3 receive the drug, etc).
Obviously, this randomization serves to eliminate ____ in regard to which patient gets the ‘real’
drug and who gets the placebo
• Randomiztion Don’t want any bias
pre-determined
bias
BIOLOGICS
FDA: ____
The BLA is a request for permission to introduce, or deliver for introduction, a ____ product into interstate commerce.
A BLA is submitted by any legal person or entity who is engaged in manufacture or an applicant for a license who takes responsibility for compliance with product and establishment standards.
therapeutic biologics applications (BLA)
biologic
Therapeutic biological products now under CDER review authority
include:
• ____ for in-vivo use
• Cytokines, growth factors, enzymes, immunomodulators; and thrombolytics
• Proteins intended for therapeutic use that are extracted from ____ or microorganisms, including ____ versions of these products (except ____)
• Other non-____ therapeutic immunotherapies
monoclonal animals recombinant clotting factors vaccine
Some drugs: classified as ____ for purposes of FDA review.
Many have active moieties not approved by FDA previously, either
as a single ingredient drug or as part of a ____ product.
Frequently provide important new therapies for pts.
Some are ID’ed as NMEs for administrative purposes but may contain active moieties closely related to active moieties in previously____ products.
For example, CDER classifies biological products as NMEs for
purposes of FDA review, regardless of whether the Agency previously has approved a related active moiety in a different
product.
new molecular entities (NMEs)
combinatino
FDA-approved
Off-label use
Use of a marketed product in this manner when the intent is the “practice of medicine” does not require submission of an ____, Investigational Device Exemption (IDE) or review by an Institutional Review Board (IRB). However, the ____ at which the product will be used may, under its own authority, require IRB review or other institutional oversight.
• If using a durg off label, can you use a durg off label > if drug is contraindicated, no, but if approved for use 1 and 2 > \_\_\_\_ (alzheimers) > small study where give patients who were on narcotics to decrease narcotic use bc they get good pain relief
IND
institution
FDA Orphan Drug Act
• #1 goal of drug company> make money • Terible disease but not a lot of patients; if <200k patients, if you decide to develop ad rug fro this condition you get \_\_\_\_ ○ Great coneciton bt \_\_\_\_ and \_\_\_\_
tax credits
government
private industry
C. Clinical Trials (continued) 5. Official Phases
Phase 1
First time that ____ receive investigational drug. In most cases, subjects are ____ young (usually 18 to 25 years old) volunteers.
____ number of subjects (» 2O-8O).
This non-\_\_\_\_ phase is designed to collect \_\_\_\_ data which include: Ø \_\_\_\_ Ø biotransformation - T1⁄2ß of \_\_\_\_ - \_\_\_\_(and their T1⁄2ßs) Ø elimination
Phase 1 is ____ if new drug is the first –or among the first–in its class. This testing is ____ if many similar drugs on market.
For highly toxic drugs, e.g., antineoplastic agents, ____ patients are used in Phase 1.
• Phase I - pharmocokinetic > group who is young and healthy > first humasn to get the drug How is it absorbed, what is the biotrasnformatino, estimates on enzymes in vitro, but what is the half in huamsn; only exception in phase I is in cacner drugs where there' run on cancer patients; not a large study
humans healthy limited blinded pharmacokinetic absorption parent drug metabolites
extensive
limited
actual
Phase 2
For most drugs, this is first time that a new drug is given to patients with target ____.
Number of patients ____ but may = 200. Both ____ and ____ must be examined here.
In addition, final ____ form for further clinical trials should be established.
• phase II > patients are actually for the drug > looking at sfaety and efficacy ○ When you see safety, doesn't mean its not toxic, just wanna see how toxic it is
disease variable safety efficacy dosage
Phase 3
Depending upon results obtained in Phase 2, and other considerations, this part of a clinical trial may be either ____ or ____. Dose selection, a critical aspect, in drug development, should be based on the D-R relationship obtained from Phase ____ & ____.
Several hundred to several thousand patients may receive the new drug.
During clinical trials, ____ testing will be continued with particular emphasis on evaluating ____ toxicity, ____, and any adverse effects on ____.
limited extensive 1 2 animal chronic teratogenicity fertility
D. Request for Approval of New Drug Application (NDA)
The pharmaceutical company now submits both clinical and additional preclinical data to FDA to obtain approval to market new drug.
FDA either:
Ø ____ NDA
Ø requires company to conduct additional ____ (preclinical and/or clinical).
If approved, marketing of new drug begins.
approves
testing
