Chapter 9 - Bioequivalence

Question 1

define bioequivalence

Answer 1

the equivalence of bioavailability of 2 (or more) products or 2 or more dosage forms of the same drug

Question 2

true or false

the same drug in 2 different dosage forms can be bioequivalent

Answer 2

true

Question 3

what are the 3 parameters of bioavailability that are evaluated for bioequivalence

Answer 3

cmax
tmax
AUC

Question 4

3 reasons that bioequivalence is important

Answer 4

generic substitution

subbing products that are the same drug, but different manufacturers

substituting a dosage form with another of the same drug

Question 5

4 terms for bioequivalence

Answer 5

pharmaceutical equivalents
pharmaceutical alternatives

biological equivalents (bioequivalents)

therapeutic equivalents

Question 6

true or false

when 2 products are bioequivalent, it has been determined that they have the same concentration at the receptor site

Answer 6

FALSE - we’re not able to measure concentration at the receptor site yet.

we can only see if the plasma profiles are similar

Question 7

5 parameters that determine if 2 things are pharmaceutical equivalents

Answer 7

-same API
-same strength
-same concentration
-same dosage form
-same route administration

Question 8

true or false

sodium ibuprofen and ibuprofen are the same API

Answer 8

not technically – they are not pharmaceutical equivalents. they are the same therapeutic moeity – so pharm alternatives

Question 9

true or false

in order to be considered pharmaceutical equivalents, the 2 products need to have the same excipients

Answer 9

FALSE - can be different excipients - we dont care

as long as same:

API
strength
concentration
dosage form
route of administration

Question 10

bioequivalents are _______ that have comparable bioavailability

Answer 10

pharmaceutical equivalents

Question 11

2 values that need to be considered for salt forms of drugs

Answer 11

s and f values

Question 12

true or false

extended release vs immediate release of the same drug are pharmacuetical equivalents

Answer 12

FALSE - pharmaceutical alternatives

Question 13

define therapeutic equivalents

Answer 13

pharmaceutical equivalents that can be expected to have the same clinical effect
(when administered to patients in the conditions specified in the labeling)

“same clinical effect” means same conc at receptor site, however, we do not have the technology to do this yet. the best we have rn is BIOEQUIVALENTS

Question 14

True or false

therapeutic equivalents must meet all 5 requirements of pharmaceutical equivalents + more

Answer 14

true

Question 15

true or false

therapeutic equivalents cannot be different strengths

Answer 15

TRUE - must be the same strength. must meet all requirements of pharmacueitcal equivalents + more

Question 16

true or false

all bioequivalents must contain the same inert ingredients

Answer 16

FALSE - can be different

Question 17

1 of the main issues that causes bioinequivalence

Answer 17

dissolution rate variations due to different excipients

Question 18

true or false

dissolution rate does not have a major effect on the plasma profile

Answer 18

FALSE - it does

Question 19

for which drugs do we not really care about performing bioequivalence studies and why

Answer 19

OTC drugs and those with wide TI — dont really care about small variations if the therapeutic window is large

Question 20

bioavailability studies are usually limited to….

Answer 20

important, life-saving, and potent drugs

too expensive

Question 21

according to ______, the medically significant cases of bioinequivalence are mainly due to what 4 issues?

Answer 21

USP

-particle size of the API
-excess mg stearate as lubricant
-polymer used in coating
-not enough disintegrant

Question 22

3 scenarios in which a drug is a candidate for an expensive bioequivalence study

Answer 22

-all drugs with a low (narrow) therapeutic index

-all drugs with low solubility (less than 0.3%) at the site of administration or the site of absorption

-all dosage forms which release their drug slowly

Question 23

1 of the 3 candidates for undergoing a bioequivalence study is for the drug to have a low solubility either at the site of administration or the site of absorption

detail what “low solubility” means

Answer 23

less than 0.3%

Question 24

true or false

the FDA requires that the inert ingredients in generic drugs be the same as the brand drug

Answer 24

FALSE - can vary

Question 25

true or false generic drugs can have different labeling instructions than their brand name products

Answer 25

FALSE - must be the same

Question 26

true or false generics MUST be identical to the brand in all of these: strength dosage form route of administration

Answer 26

true

Question 27

true or false generics can have different indications than their brand name

Answer 27

FALSE - must have both the same indications AND precautions

Question 28

true or false the FDA is not as strict on their "good manufacturing practice" regulations for generic products as they are for brand

Answer 28

FALSE - the same strict regulations appply

Question 29

briefly break down the coding system for therapeutic equivalence

Answer 29

categories A and B there is a 2nd letter - a P or a T - to indicate parenteral or topical category A - products that DO NOT pose bioavailability problems category B - products that DO pose serious bioavailability problems

Question 30

what is category "AB"

Answer 30

products whose bioavailability problems have been resolved ie -- controlled release products need to do an in vitro/in vivo correlation bioequivalence study category B is switched to "AB" if passed

Question 31

true or false products in category A are bioequivalent and may be substituted with other category A products

Answer 31

true

Question 32

true or false products listed in category AB may be substituted with products in category A

Answer 32

FALSE - can only be substituted with AB products

Question 33

a panel of ____ or more subjects is used for a bioequivalence study

Answer 33

24

Question 34

true or false usually patients with disease states are selected for bioequivalence studies

Answer 34

FALSE - usually healthy subjects don't want disease state bc can change the plasma profile

Question 35

true or false the 24 or more subjects used in a bioequivalnce study should be of varying age and gender to ensure that the product works the same in everyone

Answer 35

FALSE should be similar age and weight, prefer same gender too ALLL subjects evaluated by physician to assure they're suitable to participate

Question 36

name and explain the type of study that is typically used for bioequivalence studies

Answer 36

double blind crossover study 2 groups. each group receives both products, BUT at different times blood samples collected, and drug concentration determined washout period between the 2 treatments to make sure that the first drug is completely eliminated before the 2nd drug is given "double blind" means that neither the researcher nor the subject know the treatment that they are gettting

Question 37

what is an advantage of using a crossover study, in which each patient actually receives BOTH drugs

Answer 37

variations in absorption and other factors between individuals are virtually eliminated

Question 38

who analyzes the data generated from a bioequivalence study

Answer 38

by an impartial researcher or agency to avoid bias

Question 39

in a bioequivalence study, what parameters are compared to determine biooequivalnce

Answer 39

cmax tmax AUC

Question 40

true or false the results of bioequivalence studies are evaluated using geometry

Answer 40

FALSE - suitable statistical methods test (T) is compared to the reference (R) Student's T test

Question 41

the ratio of T/R should be ____________ to be considered bioequivalent

Answer 41

between 0.8-1.2 20% confidence interval

Question 42

why dont we want the sibjects to have any variations?

Answer 42

we want the difference to come purely from the drug and not from any other factors

Question 43

how did we determine that we must use at least 24 subjects for bioequivalence studies

Answer 43

the 80/20 rule

Question 44

explain the 80/20 rule

Answer 44

80% chance of seeing a 20% difference between the products if products have similar bioavailability under 80/20 rule, they're considered bioequivalent

Question 45

what was the predecossr to the 80/20 rule

Answer 45

the 75/25 rule now we use 80/20 bc 75% was too low and 25% was too high

Question 46

some academicians want to see the ____ rule why is the industry pushing back?

Answer 46

90/10 would make more expensive -- want to keep 80/20