What is a Drug (Exam 1)

what is the objective of phase III trials?

objective is to determine if the drug is better than the current standard of care (why have a drug that works but isn't any better than the current treatment - this could include less side effects as well)

The generic name is assigned, in the United States, by an......(what is it)

official body—the United States Adopted Names (USAN) Council.

where can you buy placebo pills?

olbecalp

how long does oral drug delivery take to distribute through the body? why? how does this effect the half-life?

oral takes longer to get into the system but the effects last longer than do intravenous. it stays longer because the gut is absorbing it

if during phase III, the investigational new drug appears to be effective, will the patients continue to receive treatment or must is cease?

patients will continue to be treated after the trials conclusion and before the drugs market approval

how many people are usually enrolled in a phase I study?

ranging b/t 5 & 100

what does drug formulation refer to? what kind of substances can be added?

refers to the different chemical substances, including the active drug, that are combined to produce a final medicinal product substances added may include: stabilizing agents bulking agents solubilizing agents

how a drug is labelled requires what? all the information provided is......

requires a contract between the company and the FDA, and all the information is a legal document

drug approval requires what? what is the next step?

research and development, clinical trials and once this is done they have a regulatory review to determine who can take the drugs (pregnant women for example)

what occurs during phase II?

researchers compare the drugs efficacy in the testing group to a control group of subjects who receive either a placebo or SOC treatment

3 BIGGIES FOR SAFETY of the Drug INCLUDE

respiration, neurological and cardiac effects

how frequent are drugs with a short half-life administered? what about a long half-life?

short - admin freq long - admin less freq

what are the different statistical designs used during phase I trials? describe them....

single ascending doses (SAD) and multiple ascending doses (MAD) SAD - small groups of subjects are given a SINGLE dose of drug. if no adverse effects are observed, a NEW GROUP of subjects are given a higher dose, and so on, until the max tolerable dose is determined MAD - means that small groups of subjects are given MULTIPLE LOW DOSES of the drug, with subsequent dose escalation for further groups based on safety

what is tested during phase II? how is this done?

this is the phase where efficacy is first measured researchers assess drug efficacy by monitoring established indicators of disease progression

what can be said about the process of producing a biologic?

this process is very complex and even if you do a mass spec, it is hard to interpret and is difficult to define the particular molecule as equivalent

how is a drug typically manufactured? how does this mean that it is made?

through chemical synthesis, which means that it is made by combining specific chemical ingredients in an ordered process

what is the purpose of phase IV? how is this done? what is this process also known as?

to catch an unexpected adverse reactions of an approved drug the FDA relies on patients, physicians, and drug companies to report these incidents pharmacovigilance

what is the overall purpose of phase I studies? how is this done? what else is also important to make sure is occurring regarding the drug being in the body?

to determine the dosage needed phase I is to determine a dose appropriate for use you start with a certain dosage, increase gradually, and once side effects are seen, you stop administration also, there are formulas that are used to extrapolate the dosage in rodents and what the dosage should be for humans dosage is based on circumference you take excretions as well to determine if the drug is being excreted

what kind of data does preclinical testing provide? what does the data collected include? before advancing to clinical testing, what does the FDA require?

toxicity studies in cultured cells and animals genetic toxicity - any harm to the fetus?

do phase I trials ever enroll patients?

yes, sometimes for oncology drugs that are too toxic to give to healthy individuals or to patients with a serious disease for which there is no available treatment

how long is the exclusivity period for biologic drugs? why so long?

12 years longer period is in recognition of the significantly greater manufacturing costs associated with biologics

why are biologics biosimilar and not equivalent?

because it is impossible to demonstrate that a large molecule drug produced by a company other than the innovator company is identical to the original product

what occurs due to generics being produced (more than one generic as well)?

because of the increased competition, the price of generic drugs is significantly reduced

what does phase III test? what is the tested population number?

continues to test efficacy and safety, but in a MUCH LARGER group of patients. a test group of 300 - 5000 patients

and IND application must include what?

- results of animal studies showing drug pharmacology and toxicology - manufacturing information to show that the drug can be mass-produced consistently - and detailed clinical protocols describing how the clinical trials will be preformed, specifying the physicians who will oversee the trails and verifying that they will follow informed consent procedures

how long it takes for a drug candidate to become eligible for testing in human patients depends on many factors, including what?

- the complexity of the disease - the chemical characteristics of the drug candidate (simple properties like drug solubility in water can affect the ability to develop them) - and the amount of resources in both dollars and manpower that the company invests (these are the reasons drug development takes a while)

a successful drug development process starts with what? proceeds with what? ends with what?

- the identification of potential new drugs in the lab - proceeds to testing those compounds in animals and then humans - ends with FDA approval for marketing

how long is the exclusivity period for small molecule drugs?

5 years with a 6 month extension for products developed for pediatric use

how is a biologic manufactured? EX

A biologic is manufactured in a living system such as a microorganism, or plant or animal cells (e.g. recombinant DNA technology).

can a drug manufacturer ever change the manufacturing process? if so, what is required on the drug level?

A drug manufacturer can change the manufacturing process extensively and analyze the finished product to establish that it is the same as before the manufacturing change.

What is a generic chemical drug? what must it have? as what? what must the generic form be to the 1st drug form? what does this mean?

A generic drug must have the same : active ingredient, strength, dosage form, and route of administration as the reference (patented) drug It must be "bioequivalent." This means that generic drugs are the same chemically as their innovator counterparts and that they act the same way in the body.

when determining how a drug is formulated, what all do you need to know?

Active ingredient (the drug itself) What dosage of active ingredient? Are fillers or excipients added? What is the format for the drug? Pill, capsule, delayed release form, liquid, etc.

who must establish procedures which assure the drug is manufactured in a way that is consistent and consistently meets specifications? who approves this?

Company must establish procedures which assure the drug is manufactured in a way to consistently meet specifications. FDA then approves these procedures.

The Controlled Substances Act of 1970 has control over what? what was established by this? what were defined due to this?

Control over the coding of drugs and the enforcement of these codes given to the Food and Drug Administration (FDA) and the Drug Enforcement Agency (DEA) 5 different classifications of controlled substances were established Regulations regarding the prescription, distribution, storage, and use of these drugs was defined

Good manufacturing Practices (GMP) were implemented by the FDA to ensure that

Drug Products are manufactured in an appropriate and safe way

what do all drugs generally have? what can be done to finished drugs? why is this done?

Drugs generally have well-defined chemical structures, and a finished drug can usually be analyzed to determine all its various components (makes sure all atoms are in the right place).

Information contained on the external label of a drug vial or container is regulated by the..... Information contained on the external label of a drug vial or container is..... this is also true for what else?

FDA legally binding Same for the more extensive information contained in the package insert.

a drug can have different effectiveness, even if it is the same drug due to what?

HOW IT IS ADMINISTERED (EVEN IF THE SAME DRUG)

FDA Approval or Licensing (what are the different types?)

IND = Investigational New Drug NDA = New Drug Application (drugs) BLA = Biologics Licensing Application (biologics) ANDA=Abbreviated New Drug Application (generics) PMA = Pre-market approval (devices) NADA = New Animal Drug Application

after RND and cell culture from rodents, you can apply for an..... what can you do next if this is approved?

IND and then once approved, you can stick it in people IND = Investigational New Drug

why would a drug company have a brand name different than the generic?

MARKETING, (people would rather by tylenol rather than the generic because the name brand is "better", even though the generic has to meet the same quality standards as the trade name drugs)

how long can the discovery phase of drug development last?

b/t 2 years to more than a decade

what is the Definition of a "legal" drug? can these ever be dangerous or misused? EX.

Natural or synthetic substance which (when taken into a living body) affects its functioning or structure, and is used in the diagnosis, mitagation, treatment, or prevention of a disease or relief of discomfort. A legal or medicinal drug (such as amphetamines), however, can be harmful and addictive if misused.

what is the size and complexity of most biologics? what does this mean regarding the products and the process?

Most biologics are very large, complex molecules or mixtures of molecules. Therefore, for biologics, "the product is the process." Manufacturers that the manufacturing process remains substantially the same over time.

what do you get after you get an IND? what happens after this is approved?

NDA = New Drug Application (drugs) you can sell it to the public

is the term generic used when referring to copies of biologic drugs? what term is used then?

NO biosimilar

how is a drug regulated or controlled?

The Controlled Substances Act of 1970

How are drugs administered?

There are mainly 4 methods: oral administration, injection, suppositories, and inhalation.

what does the term generic refer to?

a small molecule drug that is an EXACT MOLECULAR COPY of an innovator drug MOLECULAR EQUIVALENCE

when is an ANDA filed? why would you file this? how long is the exclusivity period for an ANDA, if accepted?

after the patent protection and exclusivity periods have expired for the brand name drug this application is filled when wanting to manufacture a generic 180 days

who is administered the drug in phase II?

all participants are PATIENTS

what is a SOC treatment?

an approved treatment commonly used for the same indication

what is the next step after promising preclinical results are obtained?

application for an investigational new drug (IND)

where must the patients be during phase III trials?

at different geographic locations

the first differentiation of what a drug is is whether it is........

biological or chemical in nature

Overview of Drug Development/Approval Process (pic) as well as explanation. why are these steps taken and what is the purpose of each? explain

chemical drug synthesized, the FDA mandates a lot of testing must be done before it goes into people (in vitro and cell culture), then you use a rodent model and then an animal that isn't a rodent (animal studies done because the FDA dictates it, you are looking for ethnicity and also looking at how the drugs are excreted through the body (in vivo study), then you have to convince the FDA you can make this drug at 3 chemical plants throughout the world so you have to have you step by step process, SOP (diff geological locations can produce the same equivalent drug), then you submit for an IND, once approved, you can inject the drug into humans starting with phase I, then II, then III. if all ethnicity studies come out as expected, the FDA will approve the NDA application and you can sell the new drug.

what does IND status allow drugs to begin?

clinical testing

the safety of a drug is determined by what?

clinical trials

Because of the complexity of biologics, the only way to establish whether there are differences that affect the safety and effectiveness of the follow-on product is to..... FDA has stated that it has not determined how_____________________ can be established for complex proteins.

conduct clinical trials. inter-changeability

what events create regulations and laws, or the need for them?

crisis

different types of delivery require what?

different formulations of the drug

how many names do drugs have an what are they?

drugs basically have 3 names, their chemical name, their generic name, as well as the trade name

when do drug companies typically apply for patents?

during the early phases of DRUG DISCOVERY

The federal food, drug, and cosmetic (FD&C) act in 1938 was passed to...... due to what event?

ensure drug safety in the aftermath of the death of more than 100 patients from a poorly manufactured sulfanilamide drug the act also contains guidelines pertaining to drug effectiveness as well

what are active ingredients and fillers in a drug called? what determines what fillers are used?

excipients (what is inside the pill), and depending on the format (pill, capsule) depends on what fillers there are.

A Drug is adulterated if it is..... when can it be considered this, even if it meets what other standards?

found not to be manufactured according to cGMP's A drug can meet its specifications, contain no detectable impurities, be both safe and effective and still be considered adulterated if the manufacturing was not in compliance with cGMP's.

how does a drug get its generic name?

generic name came to be through a committee that gets together to determine the name of the drug, or the group of drugs with certain prefixes.

the outer label of a drug provides what?

gives you the trade name, the generic name, the dosage, the class, the use and for what patients, lot numbers, who makes the drug, any warnings

the path to drug approval is regulated and overseen by......

governmental agencies

after you determine an active pharmaceutical ingredient and it works, what occurs next in the drug formation industry?

how it needs to be delivered is determined (is it toxic and when should the active ingredient need to actually be released), the life of the drug in vivo as well as on the shelf (stabilizer in the drug itself to make sure it stays on the shelf for longer)

it is impossible to determine the identity of 2 biologicals created by 2 companies, so how do you determine biologic equivalence? what is approved at what level to determine equivalence?

if they are biologically similar, and the product is compared by the process not the molecule itself. the process is what is approved at the level of the FDA

legal drugs can be used how as well?

illegally

what are examples of why we would need different release forms?

immediate (broken arm) delayed (chronic pain that requires constant injections or attention)

what did the orphan drug act provide? what did it introduce?

incentives for researchers to develop drugs fro treating rare disease - those affecting fewer than 200,000 people introduced tax breaks and an extra 2 years of market exclusivity, making orphan drug research a more attractive investment

how does a drug being difficult to excrete do?

increases the half-life of the drug and the risk of toxicity as well

what was one of the 1st biologics ever made? how was it made?

insulin through recombinant DNA in a bacterium

how fast are drugs that are administered intravenously distributed through the body? how does this effect the half-life?

intravenous is distributed through the body very rapidly and if you need something immediately, you wont really worry about half-life

when a drug contains an ose, what does this mean?

it has a sugar ose = sugar

what is the hydrophobicity of steroids?

they are very hrdophobic

The chemical name is based on the

molecular structure of the drug

how many individuals are tested in phase II trials?

more participants than phase I, typically ranging b/t 50 - 1000 possibly including more than 1000 (depending on the size of the patient pop for which the sponsor is seeking approval)

phase II is usually the first time you are looking at what? with the exception of who?

phase II is usually the first time you are looking at ethicatcy (with the exception of cancer patients)

considering the company gets it IND, phase I looks good and tolerable dose is defined, as well as dose for efficacy, you then enter

phase III

what occurs even after a drug is approved?

post-marketing safety monitoring continues in phase IV

what is the drug development process?

preclinical = R and D

what is considered the last phase of drug discovery? who is this governed by? what is required by the drug companies during this phase?

preclinical development and safety testing in animals governed by the GLP companies required to test a drug candidate in a least 2 animal species, and record data on toxicology, pharmacokinetics, and pharmacodynamics

what are orphan drugs? what is the exclusivity period for these drugs?

products developed to treat a patient pop of less than 200,000 7 years

what are 2 important components of the drug formation process? examples of why these are important aspects....

solubility and permeability solubility - the drug getting into the system before it goes fully through the gut permeability - drug for depression being able to cross the blood brain barrier

what is a biologic? what is it made from? what is the output of this process regarding quantity?

some kind of molecule, mostly a protein but can be RNA, DNA, etc, but it is made from a living system that produces the particular protein, DNA, RNA etc. you get these large proteins to be made in large vast, purified in large quantities.

if the drug meets the expected clinical endpoints during phase III, the sponsoring company will do what? how long does approval usually take? what happens after the application is reviewed?

submit a new drug application (NDA) for small molecule drugs, or a biologic licensing application (BLA) for biologics the FDA will take b/t 10 months and 2 years to review the data the agency will either grant approval, deny approval, or request additional studies

clinical trials are used to test what?

test safety and efficacy

pharmacodynamics describe what.....

the DRUG does in the body i.e. how increasing conc. of the drug influence potential toxicity

the 3 phases of clinical trials are guided by......

the GCP

The brand name is developed by....... what does it identify?

the company requesting approval for the drug identifies it as the exclusive property of that company.

what is an example of phase IV pulling a drug?

the diabetes drug troglitazone, caused acute liver failure in some patients. similarly, a cholesterol lowering statin called cerivastatin, caused at least 52 deaths from kidney failure

what does the suffix define most of the time?

the drug class

patent protection in the market is very dependent on what? what then becomes critical to drug companies?

the duration of the clinical trials expedition of clinical trials is critical

what does the FDA granting a period of exclusivity mean?

the holder of an approved new drug application receives limited protection from new competition in the marketplace for the innovation represented by its approved drug product

What did the Biologics Price Competition and Innovation Act create?

the legal authority for the FDA to approve biosimilar drugs

what can you do with the lot number?

the lot number you can go to the paperwork, the day the drug was made, who made it at each step - need this documentation and it is required at all steps

what does phase I test? what occurs during this trial? what do researchers establish because of this?

the safety of the drug in a SMALL number of HEALTHY VOLUNTEERS volunteers recieve escalating doses of the drug until any side effects start to appear at which point the escalation is stopped researchers establish the maximum tolerated dose (MTD) for a drug, which becomes the benchmark for the rest of the trials

FDA's determinations on drug approval depend on what? Regulatory review of the data is a multidisciplinary approach which includes what information? FDA's assessment on the validity/reliability of the data is often based on what? what does this include?

the submission of reliable data from clinical trials Clinical, pharmacology/toxicology, clinical pharmacology, drug quality (chemistry), and statistics inspections at the time of marketing application submission - Clinical investigators - Sponsors - Contract Research Organizations (CROs)

what is half-life?

the time is takes for half the drug to be gone from the body by some mechanism (metabolism, etc)

what does bioavailability refer to?

the total amount that reach the target tissue and the time taken to get there after administration

how is the trade name of a drug determined?

the trade name is determined by the company that discovered the drug (why there is a trademark symbol beside the name)

Phase I studies are almost never conducted on who, with the exception of who? who is usually administered the drugs? how many individuals does phase I testing include?

these studies are almost never done in patients with the exception of cancer patients, volunteers are usually who they are administered to --> there are usually a relatively small number of individuals

how are phase II and phase III trials set up?

usually randomized, double-blinded studies

what do pharmacokinetics (PK) measure?

what the BODY does to a drug i.e. how the drug is absorbed, distributed, broken down, and excreted

what does the efficacy of a drug mean?

whether the drug cures or lessens the effects of the disease does the drug act as it is intended to act in a patient population?

how many groups are being tested in phase II? why and what will they receive? why is the placebo not always a viable option for some patients when testing drug effectiveness?

you always have at least 2 groups because a control one group will get the drug and the other will get either a placebo or SOC (standard of care) for cancer, it is considered not human to give a placebo, which is why the SOC is compared to the experimental drug

why do we do testing for new drugs on animal models? what models do you use?

you use a rodent model and then an animal that isn't a rodent (animal studies done because the FDA dictates it, you are looking for ethnicity and also looking at how the drugs are excreted through the body (in vivo study),