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WorksheetsCeutics - Exam 1 - New Drug Dev & Drug Disc Mirza
Total questions: 121
Worksheet time: 2hrs 1mins
What is the definition of "A New Drug" by the FDA's perspective
Any drug that is NOT recognized as being safe and effective in the conditions recommended for its use in the labeling among qualified experts
A new chemical entity
A new formulation or method of manufacture of ‘old drug’
A new combination (including proportions) of two or more old drugs
A new use/route of administration/dosage form for an established drug
When was the Wiley Act passed (first food and drug law)
1900
1906
1938
1945-1965
2000-2003
What was the main source of drugs until the beginning of the 20th century
plants
minerals
animals
microorganisms
genetic engineering
What are some key problems that prevents plants from being the widespread source of new drugs
their purity
their consistency
limited quantities
limited types
What are some examples of minerals as sources of new drugs
salt
iodine
iron
hydrogen
What are some examples of animals as sources of new drugs
insulin
thyroid hormone
fish oil
serotonin in crayfish
What is a significant natural source of drugs that produces many antibacterial drugs
plants
minerals
animals
microorganisms
genetic engineering
What was the first antibiotic discovered?
penicillin
amoxicillin
gentamicin
tobramycin
How are organic synthesis drugs produced
via plants
artificially
via animals
via genetic engineering
What are the different types of organic synthesis
semisynthetic drugs
synthetic drugs
plant-based drugs
mineral-derived drugs
What are some advantages of drugs synthesized in the chemistry laboratory
high purity
less expensive
large scale production within a short amount of time
large scale production within a long amount of time
create more complex drugs
What are some characteristics of genetic engineering as a drug source
its the process of direct manipulation of an organism's genome
alters the cell's ability to produce proteins to add one or more new traits
alters the spiral DNA chain
its the process of indirect manipulation of an organism's genome
What are the key techniques of genetic engineering as a drug source
recombinant DNA (rDNA)
monoclonal antibodies
semisynthetic techniques
synthetic techniques
How are recombinant DNA engineered
selectively hydrolyze a population of DNA molecules
join two different DNA molecules
utilizing nonhuman cells
large scale production within a short time
How does recombinant DNA genetic engineering work
manufactures proteins identical to those produced in humans
manufactures proteins similar to those produced in humans
manufactures proteins identical to those produced in the lab
manufactures proteins similar to those produced in the lab
What are monoclonal antibodies, where are they produced, and what is the major advantage
laboratory-produced copies of a specific protein (antibody)
mAb are produced entirely within the cells of higher animals, including the patient
they can be designed specifically to only target a certain antigen
mAb are produced entirely within the cells of any animal, including the patient
they can be designed specifically to only target all antigens
What are the purposes of drug discovery
to find active ingredients
modify the chemical structures of existing active ingredients of drugs to form the basis of a new agent
to target disease or indication
modify the chemical structures of existing inactive ingredients of drugs to form the basis of a new agent
to find inactive ingredients
What is an ideal goal drug
Can produce the desired effect
Can be administered by the most desirable route (orally) at a minimal dosage and frequency
Shows optimal onset and duration of activity
No side effects
After exerting a necessary effect, it should be eliminated from the body efficiently and without residual effects
What's the first step of creating a goal drug
identify target disease
identify indication
formation of a discovery team
finding a rational design
What are things that need to be taken into consideration when identifying a target disease or indication?
is this drug a priority in the Pharmaceutical Industry; will there be a profit after developing and testing the drug
is the disease widespread
does the disease affect the developed world
are there drugs already on the market; what are the advantages/disadvantages
can others identify a market advantage for a new therapy
What does the discovery project team do
Biology experts share knowledge of target and develop tools for further studies
Chemistry engages to identify lead chemical matter to interact with the desired target (receptor, enzyme, nucleic acid)
ADME experts understand what body does to the drug
Toxicology experts evaluate the safety
Pharmaceutical scientists provide expertise in formulation and drug delivery
What are some common drug targets
lipids
proteins
nucleic acids
carbohydrates
What are agonists
receptor activators
receptor blockers
What are antagonists
receptor activators
receptor blockers
What makes up a Clinical Proof of Concept (POC)
right target
right drug
discovery target
discovery drug
What is the goal of target validation and what should be avoided
evaluate target and confirm its role in the disease state
avoid research paths that lead to dead ends
evaluate target and confirm its role during inactivity
avoid research paths that lead to endless possibilities
When creating a new drug molecule, what is the first thing that is identified
a lead compound
the right drug
indication
goal drug
What is a lead compound
a prototype having desired activity but also undesirable characteristics
a prototype having undesirable characteristics
the right drug for the right target
What are lead compound discovery methods
Drug metabolism studies - metabolites produced are screened for the same or other activities
Clinical observations - new activities found in clinical trials
Rational design- identify biological causes for disease states, use natural ligand or enzyme substrate as the lead
Rational design- a known drug to be used as the lead
High-Throughput Screening (HTS)
What happens during drug metabolism
metabolites are isolated and screened to determine if the observed activity is derived from the drug or the metabolite
metabolites are gathered and screened to determine if the observed activity is derived from the drug or the metabolite
What was Viagra (sildenafil citrate) originally tested as
antihypertensive
antianginal
vasodilator
pulmonary arterial hypertension
What is structure-activity relationship (SAR)
the relationship between the chemical structure of a molecule and its biological activity
the relationship between the chemical structure and the drug excipients
the relationship between the API and excipients
the relationship between excipients and biological activity
What does lead optimization result in
a drug candidate
a lead compound
target identification
formation of a discovery project team
What is a drug candidate
compound worthy of extensive biological, pharmacological, and animal testing
drug metabolites that are isolated and screened for the drug candidate
What is observed during the lead optimization stage of new drug development
activity
potency
side effects
route of administration
What is type of activity is observed during lead optimization
the particular biological effect
the strength of the biological effect
the inhibitory concentration
the effective concentration
What is type of activity is observed during lead optimization
the particular biological effect
the strength of the biological effect
the half maximal inhibitory concentration (IC50)
the half maximal effective concentration (EC50)
What are some things an oral drug must do in the body other than its intended purpose
dissolve, cross membranes, partition into target organ
survive a range of pHs (1.5-8.0)
survive intestinal bacteria and liver metabolism
avoid active transport to bile, excretion by kidneys, and partition into undesired places
be excreted as fast as possible to avoid tissue toxicity
What is a prodrug
A compound that requires metabolic biotransformation after administration to produce the desired pharmacologically active compound
A compound that does not require metabolic biotransformation after administration to produce the desired pharmacologically active compound
A compound that requires metabolic biotransformation after administration to produce the desired pharmacologically inactive compound
A compound that does not require metabolic biotransformation after administration to produce the desired pharmacologically inactive compound
What is a prodrug typically designed to modify
solubility
absorption
biostability
release profile
change the reaction at intended target
What are some issues that can arise when modifying existing drugs
shorter duration
multiple side effects
patent issues
incompatibility with other drugs
unpredictability of excipients
What type of approach is modifying existing drugs known as
"Me-Too"
"Me-Better"
"Me-First"
"Me-Longer"
What is High Throughput Screening (HTS)
An industrialised process which brings together validated, tractable targets and chemical diversity to rapidly identify novel lead compounds for early phase drug discovery
An industrialised process which brings together unvalidated, tractable targets and chemical diversity to slowly identify novel lead compounds for late phase drug discovery
A database of clinicians who have combined together to create a high functioning work environment spanning across many specialties for the highest level of patient care
A consolidation of clinician notes to allow patients to quickly send information to other organizations for rapid health screenings
How many new drug projects originate from a HTS
50-70%
50-90%
40-60%
40-70%
What is needed for HTS to occur
have validated, tractable targets
HTS assay technologies and automation
chemical diversity
a screening to ensure bioavailability
An HTS can
carry out robotically in well-plates on sub-microgram amounts of compound
can assay 100,000 compounds a day
carry out robotically in well-plates on but needs relatively large amounts of compound
can assay 10,000 compounds a day
What are the different drug sources
natural sources
organic synthesis
genetic engineering
High-Throughput Screening
What are some parts of the drug discovery process
drug metabolism studies
clinical observations
rational design
high-throughput screening
genetic engineering
What are the steps in drug development
genomics and proteomics
drug discovery
drug development
clinical use
During genomics and proteomics, what is target identification seeking
the target is expressed
the target is functional
the target is safe
the target is effective
During drug discovery, during compound screening and preclincial testing of the lead compound, what is being researched
relative efficacy of different agents
species variation
biodistribution/pharmacokinetics
toxicity, safety
validate imaging for subsequent clinical use
During drug development, during Phase 1, 2, & 3 clinical trials, what is being observed
efficacy
safety
human pharmacokinetics
dose adjustment
availability
During clinical use and selling of the drug, what is continued to be monitored
efficacy
dose adjustment
presence of target
use of excipients
Each year, about 10,000 compounds are produced and tested for 12-15 years. After this process, how many compounds are approved to become drugs by the FDA
1
10
1,000
5,000
What is the purpose of pre-clinical testing
to assess the potential of lead compounds as safe and effective therapeutic agents
to assess the potential of lead compounds as ineffective therapeutic agents
to ensure the chances of creating the compound into a drug
to ensure there are no other compounds being made for the same purpose
What are the key components of pre-clinical studies
toxicology studies
pharmacokinetic (ADME) studies
material properties studies (pre-formulation)
clinical trial success
What does toxicology deal with
the adverse or undesired effects of drugs
the poisoning of a person from a drug
the study of bad relationships
What are animal toxicity studies performed to establish
substance's potential toxicity (short term/long term use causing acute/chronic effects)
substance's potential for specific organ toxicity
mode/site/degree of toxicity, dose-response over specified time
gender, reproductive, teratogenic toxicities
carcinogenic and genotoxic potential
Which equation about therapeutic index is correct
therapeutic index = safe drug concentration / effective drug concentration
therapeutic index = effective drug concentration / safe drug concentration
What are preformulation studies performed to understand
the physical and chemical properties of a lead compound to enable the most optimal formulation design
the physical and mechanical properties of a lead compound to enable the most optimal formulation design
the physical and chemical properties of a goal drug to enable the most optimal formulation design
the physical and mechanical properties of a goal drug to enable the most optimal formulation design
What are the properties of interest when it comes to preformulation studies
solubility (less than 10 mg/mL is considered poorly soluble)
partition coefficient (preference for lipid vs aqueous environment)
solid-state form, particle size and morphology
stability (retention of API within dosage form)
dissolution rate (rate a drug dissolves)
What is the next step if the pre-clinical studies is successful
FDA approval is needed to initiate testing in humans
FDA approval is needed to being producing drugs for retail
Testing in humans begins (no approval necessary)
Producing drugs begins (no approval necessary)
What drug formulations are typically used for Phase 1 and Phase 2 clinical trials
initial formulation
final formulation
adjusted formulation
different formulation
Who typically formulates the clinical trial drugs
drug manufacturer
compounding pharmacy
retail pharmacy
specialty pharmacy
How must a clinical trial formulation be prepared
under the conditions and procedures set out by the FDA
loosely following FDA guidelines to find differences in drug compounds
under the conditions and procedures set out by the APhA
under the conditions and procedures set out by the manufacturer
What are capsules filled with during Phase 1 clinical trials
API
Excipients
API + Test Excipients
API + Final Excipients
What phase contains the final dosage form that had been selected during the new drug development process and is submitted to the FDA for approval
Phase 1
Phase 2
Phase 3
Production
What processes are occurring during the New Chemical Entity process of new drug development
organic synthesis
molecular modification
isolation from plants
biological characterization
Preformulation and Formulation
What processes occur during the Preclincial Studies stage of new drug development
biological characterization
preformulation and formulation
manufacturing & control
package and label design
molecular modification
What application do you apply for after finding a new chemical entity and performing preclinical studies
IND
NDA
ANDA
BLA
Why does a Investigational New Drug (IND) application need to be filed
for the FDA to allow for a clinical investigation of a new drug
for the FDA to approve the production of a final drug product
for the FDA to begin producing the investigational drug
to document the new drug for a patent
What is the goal of an investigational new drug application
to protect the right and safety of the human subjects
to ensure that the investigational plan is coherent and sound
to gain marketing permission for a new drug product in the US
to create a process to collect data after drugs are on the market
After submitting an IND, what types of review does the active ingredient go through
Pharmacology/toxicology review
Chemistry review
Clinical review
Selling potential review
What are the key elements of the IND application process
sufficient data on safety & efficacy
implication on human pharmacology, results from pre-clinical testing
protocols describing clinical studies in detail
manufacture & analysis of chemical composition
describe the qualification of personnel
What are the possible IND review outcomes
No advice
Partial Clinical Hold
Full Clinical Hold
Continue
Pass
If an IND application comes back with no advice, what does that indicate
the IND sponsor can start the clinical trial
the IND sponsor can have a limited study performed
the IND sponsor cannot begin clinical studies until all issues are resolved
the IND sponsor may not continue at all, the danger is too great
Why would there be a clinical hold on an IND application
unreasonable risk
unqualified risk
misleading/incomplete investigator brochure
insufficient information
no potential profit
If an IND application comes back with a partial clinical hold, what does that indicate
the IND sponsor can start the clinical trial
the IND sponsor can have a limited study performed
the IND sponsor cannot begin clinical studies until all issues are resolved
the IND sponsor may not continue at all, the danger is too great
If an IND application comes back with a full clinical hold, what does that indicate
the IND sponsor can start the clinical trial
the IND sponsor can have a limited study performed
the IND sponsor cannot begin clinical studies until all issues are resolved
the IND sponsor may not continue at all, the danger is too great
Right after an IND application receives a "no advice" response, what happens
preclinical trials can begin
a new chemical entity is created
clinical trials can begin
a new drug application is placed
marketing
Which clinical trial phase focuses on human safety
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase focuses on drug effectiveness
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase focuses on the safety, effectiveness, and dosage of a drug
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase is tested on "tens" of participants
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase is tested on "hundreds" of participants
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase is tested on "thousands" of participants
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase takes up to 2 years to complete
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase takes between 1-4 years to complete
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase takes several months to complete
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase has a 70% success rate
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase has a 45% success rate
Phase 1
Phase 2
Phase 3
Marketing
Which clinical trial phase has a 5-10% success rate
Phase 1
Phase 2
Phase 3
Marketing
What are some characteristics of phase 1 clinical trials
"first time in human" studies
determine pharmacological and metabolic activity and side effects as a function of dose
assess risk/benefits
provide support and information for design of phase 2 studies
begin adding excipients to doses and test its reaction in the body
What are some characteristics of the phase 2 clinical trials
Further evaluate pharmacological effect and test the efficacy of a drug
Further evaluate pharmacological effect and test the potency of a drug
Dose identification & dose response characteristics
Often blinded randomized trials
Often open but randomized trials
What are some characteristics of phase 3 clinical trials?
confirmatory studies
provide additional efficacy and safety information to evaluate the overall benefit-risk relationship of the drug
address special issues (renally/hepatically impaired patients & drug-drug interactions)
blinded randomized trials
continuation of dose identification & dose response
What is the average time it takes the preclinical research and development phase
6.5 years
7 years
1.5 years
15 years
What is the average time it takes the clinical research and development phase
6.5 years
7 years
1.5 years
15 years
What is the average time it takes for the NDA to be approved
6.5 years
7 years
1.5 years
15 years
What is the average time it takes for the drug to go from initial synthesis to approval of NDA
6.5 years
7 years
1.5 years
15 years
After all 3 phases of clinical trials are completed, what application needs to be submitted to move forward in the new drug development
NDA
IND
ANDA
BLA
When can a new drug application (NDA) be filed and what is the goal of an NDA
after 3 phases of clinical investigations show sufficient drug safety and therapeutic effectiveness
after 3 phases of pre-clinical investigations show sufficient drug safety and therapeutic effectiveness
to gain marketing permission for the new drug product in the US
to gain the patent for the new drug product in the US
What are the possible outcomes for an NDA review
Approval Letter
Approvable Letter
Not Approvable Letter
Denial
What does an NDA review approval letter indicate
product ships and becomes public
this could be approved if the specific deficiencies are corrected
FDA can't see how the deficiencies could possibly be corrected
What does an NDA review approvable letter indicate
product ships and becomes public
this could be approved if the specific deficiencies are corrected
FDA can't see how the deficiencies could possibly be corrected
What does an NDA review not approvable letter indicate
product ships and becomes public
this could be approved if the specific deficiencies are corrected
FDA can't see how the deficiencies could possibly be corrected
What is the steps of new drug development
new chemical entity, preclinicial studies, IND, clinical trials, NDA, NDA review, postmarketing
preclinicial studies, new chemical entity, IND, clinical trials, NDA, NDA review, postmarketing
new chemical entity, IND, preclinicial studies, clinical trials, NDA, NDA review, postmarketing
new chemical entity, preclinicial studies, IND, NDA, clinical trials, NDA review, postmarketing
What occurs during phase 4 (postmarketing surveillance)
continued data collection for drugs
adverse drug experiences are reported to the FDA w/in 15 working days of receipt of information
long-term effectiveness, serious & unexpected adverse effects, & drug interactions are monitored
pharmacists must report adverse experiences to FDA's MedWatch program
passively collect data without any true action
What are the different types of new drug applications
IND
NDA
ANDA
BLA
NCE
Which new drug application grants marketing approval of a generic drug product
IND
NDA
ANDA
BLA
NCE
A generic (duplicate) drug product must be comparable to an innovator drug in which aspects
dosage form, strength
intended use
ROA
quality, performance characteristics
color
What must a generic drug going through the ANDA application demonstrate
bioequivalence
higher potency
greater efficacy
decreased toxicity
What phases of clinical trials must a generic drug go through
pre-clinical (animal)
clinical (human)
no clinical trial is required
What are you trying to manufacture/market if you submit a biological license application
blood products
vaccines
toxins
cellular and genetic therapies
intravenous dosage form drugs
Who handles BLAs and why
Center for Biologics Evaluation and Research (CBER)
The approval process is regulated by specific FDA requirements
Center for Biologics Effectiveness and Research (CBER)
The FDA needs to document the biologic without an extra approval process
What is Orphan Drug Development
a drug development process for a rare disease
a drug development process for those in the foster care system
a single drug produced where no generic will be allowed
During orphan drug development, the same law applies to which process
IND
NDA
BLA
NCE
How many clinical trials are needed during orphan drug development (with exceptions for serious conditions where no other therapy is available)
1
2
3
4
During orphan drug development, one trial must have
a clinical end point
a minimal amount of excipients
a stronger API than others on the market
a marketing campaign to increase potential earnings
What are some benefits in developing an orphan drug
7 yr marketing exclusivity
tax credit
research grant
waiver of application fees
gaining profits from the majority of the population switching to this drug
Which of the following applications needs to be filed and approved with the FDA prior to the clinical trial of a new small molecule drug
NDA
IND
ANDA
BLA
Which of the following is the most common source of the modern small molecule drugs
genetic engineering
plants
animals
organic synthesis
