Regulations fall within the jurisdiction of the individual states.
Pharmaceutical equivalence: same active ingredient, same dosage form, same route of administration, identical in dosage strength or concentration, may contain different excipients
Therapeutic equivalence: pharmaceutical equivalence and bioequivalent
Bioequivalence | ADME
A = absorption
D = distribution
M = metabolism
E = elimination
The manufacturer must submit graphs to the FDA illustrating the two products containing the same drug have similar blood concentration vs. time curves, including:
Time to peak
Peak concentrations
Area under the curve (AUC)
References
Approved Drug Products with Therapeutic Equivalence Evaluations aka The Orange Book
The Electronic Orange Book (internet version)
United States Pharmacopeia Dispensing Information (USP/DI) Volume III plus supplements
Facts and Comparisons, Inc Approved Bioequivalence Codes
FDA’s Internet Website http://www.fda.gov
Drugs marketed before 1938 are not required to be in The Orange Book.
A Rated
Bioequivalent to the innovator’s drug product
Therapeutically equivalent to the brand name or reference product
A-rated products may be substituted for one another.
B Rated
NOT bioequivalent to the innovator’s drug product
B-rated products may not be substituted for one another.
Generally, a tablet cannot be substituted for a capsule, an ointment for a cream. Most sustained-release or controlled-release are not interchangeable.
AB Rated
Previously not considered to be bioequivalent and now organized into bioequivalence groups (AB1, AB2, AB3, etc)
Must have the same number or lack of number to be bioequivalent
Cannot substitute an AB1 product for a product designated as AB2
The Federal government has not passed regulations limiting the substitution of these products although a few states have.
Examples:
Carbamazepine
Digoxin
Levothyroxine
Lithium
Phenytoin
Theophylline
Valproic acid
Warfarin
