10/19 & 10/20: Bioequivalance

biosimilar

highly similar and with no clinically meaningful differences when compared to the reference product

Problem with off label uses for biosimilars

insurance tends to not cover off label uses, and the FDA can't approve the use of new medications when its still under patent

What makes demonstrating interchangeability difficult

manufacturers must take into account that patients who switched from 1 biosimilar to another might see different results

Determine the release mechanism: croscarmellose, ethylcellulose, microcrystalline cellulose

membrane controlled system

What kind of release mechanism does Klor-Con M10 use

membrane controlled system, starts dissolving within seconds since its not enterically coated or in a wax matrix

What kind of deviance is allowed for excipients of generics

must have identical stands of strength, quality, purity and identity, can differ in colors, flavors, and preservatives

Where do you find information on FDA therapeutic equivalence

orange book

What are the alternative to bioequivalence testing

pharmacodynamic testing and in vitro testing

What tests are used to determine bioavailability

plasma concentration, Tmax, AUC

can a bio similar be interchanged, or does it need to be prescribed every time

prescribed every time

What are the main differences between brand and generic drugs

price, insurance coverage, inactive ingredients, appearance

What database is used for finding biosimilars

purple book

What can be different between generics and brand names

shape, scoring, release mech, packaging, excipients, expiration date, and labeling(within certain limits)

What is the problem with using pharmacodynamic testing

some medications don't enter the blood stream

Who determines if something can be equivalent

state board

how is the orange book results demonstrated

table format

When are biosimilars prescribed for patients

tend to be used for those who had previously used the reference product (experienced) or those who haven't(naive) works for either

Reference product

the drug with original FDA approval, prescribed by provider

If you search a brand name drug in the orange book, what will you not find

the generics

Reference listed drug

the standard against which all generic drug products are compared

What can be altered as we look at the labels for the biosimilars

the testing conducted, difference in medicinal use, different labels

How is bio similar naming effective

used to track and remediate adverse effects, prevents inadvertent substitution, and allows for accurate product indentification

Determine the release mechanism: magnesium stearate, hydrogenated alcohol, PEG

wax matrix ER release form

What sort of things play into interpatient variability

weight, age, sex, race

What is the orange book website

www.fda.gov/cder/ob

Do two drugs being condsidered as generics need the same salt form? solution? ROA

yes to all three

What is the four criteria that must be hit for something to be considered a true generic

1. approved as safe and effective 2. pharmaceutically equivalent 3. bioequivalent 4. Adequately labeled 5. Follows GMP regulations

What is used to measure bioequivalence

Cmax, Tmax, AUC

What kind of release mechanism is used for Klor-Con

ER version that is contained in a wax matrix

What kind of generics are allowed to skip human trials due to unethical designations

IV solutions, its assumed that so long everything is the same there is no reason to undergo painful testing

Bioequivalence

The absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.

TE codes

Therapeutic equivalency

Bioequivalence criteria

Two drug products are deemed bioequivalent if the 90% confidence intervals of the geometric mean of the (generic/innovator) test ratio (Cmax or AUC) fall within the bioequivalence limits of 80-125%

Types of studies used for determining biosimilars

analytical studies, animal studies, clinical pharmacology studies, and additional clinical studies, can do pharmacokinetic studies

What type of average is used for the bioequivalence criteria

arithmetic mean, gets rid of outsliers

How can the purple book be searched

brand name or proper name

Can the RLD be brand or generic

brand only

What class of BCS drugs can be approved through in vitro testing alone in order to minimize the necessity for human testing

class 1

"A" rated drugs

considered therapeutically equivalent and may be interchanged

What does it mean to be pharmaceutically equivalent

contains identical amounts of the same active ingredient and in the identical dosage form and ROA

biosimilars (have/do not have) clinically meaningful differences from existing FDA approved biologics

do not have

What does it mean to be bioequivalent

does not present a known or potential bioequivalence problem or its meets an acceptable in vitro standard or if it does present such a known or potential problem, it is shown to meet appropriate stands

Can the RS be brand or generic

either

interchangeable product

highly similar with no clinically meaningful difference then compared to the reference product, the application includes additional data and information about the impact of switching or alternating between the product and reference product

Pharmaceutical equivalents must deliver (different/identical) amounts of the active ingredient over (different/identical) dosing period and they have (different/identical) inactive ingredients

identical, identical, different

"B" rated drugs

inadequate evidence of bioequivalence and should not be interchanged

How are biosimilars named

it takes the core name and then follows it with 4 RANDOM letters

How do bioequivalence criteria differ for drugs with Narrow TI

its much more strict since there is less room for error

What do biosimilars have in common with the reference product

living source, ROA, strength, dose, treatment benefits, potential side effects as reference product

Are generics always approved for the same use as brand name

no

Do generic products tend to be run in populations with the disease state

no

If a patient switches from one bio similar to another, should they be experiencing cross antigenicity

no

Do interchangeable products need prescriber approval to be changed

no, it goes through rigorous testing to prove similarity

Do generics need to go through all of the physical and biological trials that brand name medications need to go through to be approved for market

no, its assumed that if they are equivalent that they would do the same thing

Is it possible to have an AB2 or AB3 without AB1

no, its likely that the AB1 is no longer on the market

do large molecules have generics

no, they have biosimilars

What are the sources of variation in BE testing

normal vs. disease state interpatient variability content uniformity of dosage form release and subsequent absorption of drug and dosage form correlation of dissolution rate to absorption rate variability in experimental measurement for data

AP

parental equivalent

the way the purple book demonstrates its results stresses what main idea

that its more important to read the labels before determining anything since there are very few interchangeables

In addition to establishing biosimilarity, the manufacturer must demonstrate what to prove that it can be interchangeable

that switching between two products would not increase safety risk or decrease effectiveness

The reference product is similar to what

the RS or RLD of SMDs

How are biosimilars evaluated and approved by the FDA

the abbreviated pathway involves an extensive structural and functional comparison of the bio similar and reference product, all biologics are evaluated for their variations and how they are being controlled, FDA monitors all safety and effectiveness

Searching by what metric will bring up both the brand and generics in terms of equivalents

the active ingredient

Reference standard

the comparative product for TE testing

bioavailability

the rate and extend to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of drug action

What does an AB1 designation mean

there are multiple manufacturers of a certain dose, ROA, and MOA that are not all equivalent, the numbers help determine which ones are equivalent, AB1s are equivalent to each other, same all AB2s but AB1s are not equal to AB2

While there is a lot variability, most generic drugs when tested against the bioequivalence of the brand name tend to be what

they cluster close to 100%, there are not many outliers on the far end of the acceptable ranges

how is the purple book results demonstrated

tile formation

AT

topical equivalent