Chapter 9 - Bioequivalence Flashcards
define bioequivalence
the equivalence of bioavailability of 2 (or more) products or 2 or more dosage forms of the same drug
true or false
the same drug in 2 different dosage forms can be bioequivalent
true
what are the 3 parameters of bioavailability that are evaluated for bioequivalence
cmax
tmax
AUC
3 reasons that bioequivalence is important
generic substitution
subbing products that are the same drug, but different manufacturers
substituting a dosage form with another of the same drug
4 terms for bioequivalence
pharmaceutical equivalents
pharmaceutical alternatives
biological equivalents (bioequivalents)
therapeutic equivalents
true or false
when 2 products are bioequivalent, it has been determined that they have the same concentration at the receptor site
FALSE - we’re not able to measure concentration at the receptor site yet.
we can only see if the plasma profiles are similar
5 parameters that determine if 2 things are pharmaceutical equivalents
-same API
-same strength
-same concentration
-same dosage form
-same route administration
true or false
sodium ibuprofen and ibuprofen are the same API
not technically – they are not pharmaceutical equivalents. they are the same therapeutic moeity – so pharm alternatives
true or false
in order to be considered pharmaceutical equivalents, the 2 products need to have the same excipients
FALSE - can be different excipients - we dont care
as long as same:
API
strength
concentration
dosage form
route of administration
bioequivalents are _______ that have comparable bioavailability
pharmaceutical equivalents
2 values that need to be considered for salt forms of drugs
s and f values
true or false
extended release vs immediate release of the same drug are pharmacuetical equivalents
FALSE - pharmaceutical alternatives
define therapeutic equivalents
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
True or false
therapeutic equivalents must meet all 5 requirements of pharmaceutical equivalents + more
true
true or false
therapeutic equivalents cannot be different strengths
TRUE - must be the same strength. must meet all requirements of pharmacueitcal equivalents + more
true or false
all bioequivalents must contain the same inert ingredients
FALSE - can be different
1 of the main issues that causes bioinequivalence
dissolution rate variations due to different excipients
true or false
dissolution rate does not have a major effect on the plasma profile
FALSE - it does
for which drugs do we not really care about performing bioequivalence studies and why
OTC drugs and those with wide TI — dont really care about small variations if the therapeutic window is large
bioavailability studies are usually limited to….
important, life-saving, and potent drugs
too expensive
according to ______, the medically significant cases of bioinequivalence are mainly due to what 4 issues?
USP
-particle size of the API
-excess mg stearate as lubricant
-polymer used in coating
-not enough disintegrant
3 scenarios in which a drug is a candidate for an expensive bioequivalence study
-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
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
less than 0.3%
true or false
the FDA requires that the inert ingredients in generic drugs be the same as the brand drug
FALSE - can vary
true or false
generic drugs can have different labeling instructions than their brand name products
FALSE - must be the same
true or false
generics MUST be identical to the brand in all of these:
strength
dosage form
route of administration
true
true or false
generics can have different indications than their brand name
FALSE - must have both the same indications AND precautions
true or false
the FDA is not as strict on their “good manufacturing practice” regulations for generic products as they are for brand
FALSE - the same strict regulations appply
briefly break down the coding system for therapeutic equivalence
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
what is category “AB”
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
true or false
products in category A are bioequivalent and may be substituted with other category A products
true
true or false
products listed in category AB may be substituted with products in category A
FALSE - can only be substituted with AB products
a panel of ____ or more subjects is used for a bioequivalence study
24
true or false
usually patients with disease states are selected for bioequivalence studies
FALSE - usually healthy subjects
don’t want disease state bc can change the plasma profile
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
FALSE
should be similar age and weight, prefer same gender too
ALLL subjects evaluated by physician to assure they’re suitable to participate
name and explain the type of study that is typically used for bioequivalence studies
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
what is an advantage of using a crossover study, in which each patient actually receives BOTH drugs
variations in absorption and other factors between individuals are virtually eliminated
who analyzes the data generated from a bioequivalence study
by an impartial researcher or agency to avoid bias
in a bioequivalence study, what parameters are compared to determine biooequivalnce
cmax
tmax
AUC
true or false
the results of bioequivalence studies are evaluated using geometry
FALSE - suitable statistical methods
test (T) is compared to the reference (R)
Student’s T test
the ratio of T/R should be ____________ to be considered bioequivalent
between 0.8-1.2
20% confidence interval
why dont we want the sibjects to have any variations?
we want the difference to come purely from the drug and not from any other factors
how did we determine that we must use at least 24 subjects for bioequivalence studies
the 80/20 rule
explain the 80/20 rule
80% chance of seeing a 20% difference between the products
if products have similar bioavailability under 80/20 rule, they’re considered bioequivalent
what was the predecossr to the 80/20 rule
the 75/25 rule
now we use 80/20 bc 75% was too low and 25% was too high
some academicians want to see the ____ rule
why is the industry pushing back?
90/10
would make more expensive – want to keep 80/20
