The US Food and Drug Administration (FDA) has released 37 new bioequivalence (BE) standards intended to facilitate the development of abbreviated new drug applications (ANDAs) that best meet FDA's expectations for evidence.
Bioequivalence refers to the "absence of a significant difference" between the bioavailability—specifically the extent and rate of absorption—of two (supposed) pharmaceutical drug equivalents over the course of a period of time, at the same dose and under the same conditions. "The generic version must deliver the same amount of active ingredients into a patient's bloodstream in the same amount of time as the pioneer drug," FDA explains on its website.
Drugs that are deemed to be bioequivalent are, for regulatory purposes, essentially the same.
But in practical terms, generic drug companies are often most concerned with two things:
- how to prove that two drugs are bioequivalent
- how to show bioequivalency in a way that will be acceptable to FDA
In order to facilitate that process, FDA regularly publishes what it calls "bioequivalence recommendations for specific products," which contains more than 1,000 recommendations.
These recommendations most often contain the recommended number of bioequivalence studies that must be conducted in order to obtain approval, as well as the general designs of the study, acceptable parameters of bioequivalency, and any other considerations sponsors must keep in mind.
On 22 July 2014, FDA released 37 new BE standards, including ones for generic versions of Janssen's Invokana, Pfizer's Xalkori, Biogen Idec's Tecfidera, and AstraZeneca's Nexium 24HR.
- Alogliptin benzoate
- Alogliptin benzoate; Metformin hydrochloride (HCl)
- Alogliptin benzoate; Pioglitazone HCl
- Amoxicillin (multiple reference listed drugs)
- Atenolol; Chlorthalidone
- Carbinoxamine maleate
- Colestipol HCl
- Daunorubicin citrate
- Diflorasone diacetate
- Dimethyl fumarate
- Diphenhydramine HCl
- Doxycycline (multiple reference listed drugs)
- Doxylamine succinate; Pyridoxine HCl
- Esomeprazole strontium
- Ethinyl estradiol; Levonorgestrel and Ethinyl estradiol
- Ethinyl estradiol; Norethindrone acetate
- Fosfomycin tromethamine
- Gentamicin sulfate
- Hydromorphone HCl
- Lanreotide acetate
- Linagliptin; Metformin HCl
- Menthol; Methyl salicylate
- Metformin HCl; Sitagliptin phosphate
- Paroxetine mesylate
- Promethazine (multiple reference listed drugs and strengths)
- Propranolol HCl
- Ropinirole HCl
- Sucralfate (multiple reference listed drugs and dosage forms)
Those guidances are still in draft form. FDA also said it had revised 12 other BE guidances.
- Dronedarone HCl
- Duloxetine HCl
- Esomeprazole magnesium
- Hydrochlorothiazide; Moexipril HCl
- Imatinib mesylate
- Mesalamine (multiple reference listed drugs)
- Nilotinib HCl monohydrate
- Pentosan polysulfate sodium
The documents are set to be posted on FDA's website on 23 July 2014, and will be available here.
Federal Register Notice