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Flashcards in Mid-term Exam Deck (79):

Approx. how many individuals were employed in the biopharmaceutical industry in the U.S. in 2014?

Around 854,000


How much revenue did the biopharmaceutical industry pull in in 2014?

Around $558 billion


What is a drug?

A substance recognized by a pharamacopoeia or formulary.

A substance intended to be used for the diagnosis, cure, mitigation, treatment, or prevention of a disease.

A substance other than food intended to affect the structure or function of any part of the body.

A substance intended to be used as a component of a medicine, but not as a device or a component, part, or accessory of a device.


What are the 5 stages of drug research and development?

Basic research, discovery, pre-clinical, clinical, and FDA review and approval.


Which application must be submitted to begin pre-clinical trails?

IND (Investigational new drug)


Describe the three phases of clinical trials.

Phase I: Test for safety and dose ranges in a small number of healthy humans.

Phase II: Test for efficacy in a few dozen to hundreds of people who the drug is intended to treat.

Phase III: Test for efficacy in hundreds or thousands of individuals which the drug is intended to treat.


Which applications can be submitted in the FDA review and approval phase of research and development?

NDA (new drug application) or BLA (biological license application)


What happens after a drug has been approved by the FDA?

The drug may then begin to be manufactured and post-market clinical trials must be done.


What is observed in the discovery process of drug development?

The process of the disease as well as the chemicals which modify the targets.


What are the subjects of pre-clinical research?

In vitro, in vivo, and animal toxicity and dosing studies, as well as pharmacokinetic studies.


What is 21 CFR Part 11?

The part of title 21 in the code of federal regulations which allows for the creation of the FDA


Define safety, efficacy, and effectiveness.

Safety determines the highest possible dose level which can deliver the desired clinical benefit and takes into account any potential adverse side effects.

Efficacy determines whether a drug has a positive clinical effect compared to placebo studies. Efficacy is determined under ideal (controlled) settings.

Effectiveness describes a drugs ability to be used under real-world conditions such as in cases of co-morbidity, interacting drugs, or conditions which may not be as strictly controlled as a laboratory.


Describe the 5 phases of clinical trials.

Phase 0: First-in-man low-dose trials of between 10 and 15 individuals to test that the drug is effective towards the targets, though it is not expected to show clinical benefit or adverse effects. This phase may be conducted while waiting for IND review with prior approval.

Phase I: Initial safety evaluations in 20-80 healthy volunteers. Single, single-ascending, and multiple ascending doses. Dose escalation ends when unacceptable adverse side-effects occur. Usually conducted with Phase 0 trials.

Phase II: Begin to explore efficacy. Trials done in 100-300 individuals with targeted medical condition. Multiple dose trials often against placebo. Observes clinical effects and reveals any adverse side-effects.

Phase III: Final confirmation of safety and efficacy. Done in 1000-3000 individuals with targeted illness. Multiple dose trials with ascending doses. Confirms clinical efficacy, and evaluates safety of side-effects.

Phase IV: Trials done after approval by the FDA. Number of subjects depends on previous trial endpoints. Doses vary. May be used to determine alternate uses for the drug. Further confirms clinical efficacy.


What is an MSR activator and which illness is it used to treat?

An Msr activator is used to reduce oxidative damage due to age by attacking methionine sulfate reductase.


Sancillo & Co. is known for research into what chemical?

Omega fatty acid for the treatment of such diseases as sickle cell and short-bowel syndrome.


Define API

Active pharmaceutical ingredient


Define GMP

Good manufacturing practices (all aspects of companies including labs)


Define cGMP

Current good manufacturing practices (current practicing requirements beyond those listed in GMP)


Define GLP

Good laboratory practices (primarily focuses on testing of animals).


Define GCP

Good clinical practices


Define QA

Quality Assurance (system which ensures that the drug product is made to the same standards each and every time it is made)


Define QC

Quality Control (mostly refers to the laboratory level of quality)


Define CFR

Code of Federal Registry (Laws)


21 CFR 211 defines what?

GMPs for drugs


21 CFR 111 defines what?

GMPs for supplements


21 CFR 110 defines what?

GMPs for human food


Define CRO

Contact research organization


Define CMO

Contract Manufacturing Organization


Define 3PL

3rd party logistics company


Define USP

United States Pharmacopeia (private company which sets the standards for drug manufacturing in the united states)


Define IP

Intellectual Property (Patents and trade secrets)


What is an FD483

A list of objectionable observations made during a regulatory investigation.


Define PAI

An FDA investigation of a pharma company or contractor prior to the approval of a drug or device.


Define BA/BE study

Bioavailability and bioequivalence clinical trial used by generic drug companies to gain approval.


Define CDER

Center for Drug Evaluation and Research of FDA


Define CBER

Center for Biologics Evaluation and Research of FDA


Define IND

Investigational new drug application


Define NDA

New drug application


Define NCE

New chemical entity


Define ANDA

Abbreviated new drug application (for generic companies)


Define SOP

Standard operating procedures


Define NF

National Formulary


What are the 5 drug schedules and give an example of each.

Schedule 1: High abuse rate with no known medical use. Cannabis and heroine.

Schedule 2: High abuse with known medical use. Ritalin, methadone, oxycodone.

Schedule 3: General potential for abuse. Low dose hydrocodone (Vicodin), testosterone and other anabolic steroids.

Schedule 4: Lower abuse potential. Diazepam (Valium)

Schedule 5: Low abuse rate and limited quantities of narcotics. Low dose codein products.


The national formulary contains information regarding the standards for what kind of materials.

Excipient materials


Around how long does it take for a drug to reach the market once the initial phases have begun?

Between 15 and 20 years.


What are the 4 attributes of the Lipinsky Rule of 5's?

1. No more than 5 hydrogen bond donors
2. No more than 10 hydrogen bond acceptors
3. A molecular mass less than 500 Daltons
4. An octanol-water partition coefficient logP of no greater than 5.


What do in vitro tox studies intend to figure out?

Cytotoxicity, protein binding, CYP inhibition/induction, Membrane permeability, metabolic stability, interspecies comparison, and ADME.


Define bioassay.

A live system such as a culture, organ, or whole organism which can be used to measure drug effects.


What is Cmax?

The maximum serum concentration within a test subject.


What is Tmax?

The time at which Cmax is observed.


What is AUC?

Area under curve (reflective of total drug experience)


In acute toxicology studies, what does LD_50 stand for?

The dosage of drug required to kill 50 percent of test animals.


What is the goal of chronic toxicity studies?

Determination of the NOAEL (no observed adverse effect level), MTD (maximum tolerated dose), the MOS (margin of safety), and the shape of the dose-response curve.


What is MABEL?

Minimal anticipated biological effect levels


What is HED and how is it calculated? How is HED used to calculate ADI?

HED (human equivalent dose) is the NOAEL determined from animal toxicity studies converted to be acceptable for human intake. It is calculated by dividing the initial NOAEL by 10. The HED can be divided by 10 do give the ADI (acceptable daily intake).


Through which organization is animal treatment in laboratories managed?

IACUC (Institutional Animal Care and Use Committee)


What dictates the tests required for each dosage form?

The united states pharmacopeia.


Define specificity

The ability to identifiy analyte even in the presence of such expected components such as impurities and matrices.


What is precision?

The degree of agreement among all test results.


What is accuracy?

Closeness of test results to a "true" theoretical value.


What is range?

The upper and lower limit of analyte which has shown acceptable levels of precision, accuracy, and linearity.


Define robustness?

The measure of a procedure's capacity to remain unaffected by small deviations in the procedural parameters listed in the test method.


What is detection limit?

The lowest level of analyte able to be detected, but not necessarily quantified under the stated experimental conditions.


What is quantitation limit?

The lowest level of analyte which can be determined with the desired precision and accuracy under the stated experimental conditions.


What are the 4 categories of tests?

Category 1: Analytical procedure for a major component of the drug substance.

Category 2: Analytical procedures for impurities in bulk drug products or any degradation compounds in finished drugs.

Category 3: Analytical procedures for determining performance characteristics.

Category 4: Identification tests


When is a drug considered adulterated?

When the facilities or controls, manufacture, processing, packaging, or storage of a drug do not comply with good manufacturing practices.


What is a batch?

A specific quantity of drug which is completely uniform in content and is manufactured in the same way with the same conditions.


What is a lot?

The portion of a batch produced at the same exact time.


In what case would you use a softgel capsule?

For delivering liquid lipophilic actives.


Once a drug has been developed what is normally used to help ensure its preservation?



How long does it take the FDA to review INDs?

30 days


What are the 4 types of DMFs?

Type II: Drug substance, drug products and any intermediates involved in their manufacture.

Type III: Pharmaceutical packaging.

Type IV: Excipients

Type V: Other


Is it ever required to file a DMF?



What is a QTPP?

Quality target product profile. A summary of characteristics of a drug which are used to ensure quality, safety, and efficacy of the drug.


What are CQAs?

Critical Quality Attributes. Any physical, chemical, biological, or microbiological property of an output material which ensures drug quality.


What are CMAs?

Critical material attributes. Any physical, chemical, biological, or microbiological property of an input material which ensures drug quality.


What are CPPs?

Critical process parameters. Input processing parameters which can affect CQAs on variation.


What is bracketing?

The design of a stability schedule such that only the extreme of certain design factors are tested at all time points.


What is matrixing?

The design of a stability schedule such that a selected subset of the total number of possible samples for all possible for all factor combinations are tested at the same time point.