FDA Adds 34 New and 33 Revised Bioequivalence Study Recommendations for Generic Drug Developers

The US Food and Drug Administration (FDA) on Tuesday published 67 generic drug-specific recommendations (34 new and 33 revised) describing the agency’s expectations for developing generics that are therapeutically equivalent to reference-listed drugs (RLDs).

The guidance is intended to help the generic pharmaceutical industry identify the most appropriate ways to generate evidence needed to support abbreviated new drug application (ANDA) approval.

This is FDA’s third release of new and revised bioequivalence guidance for generic drug developers in 2016, as the agency previously released 19 new draft guidance documents and 19 revisions in June, as well as 31 draft guidance recommendations in January and revisions for 11 products.

FDA, which is seeking feedback before finalizing the draft bioequivalence (BE) guidance and the 33 revisions, is focusing on the following new products:

• Acetaminophen; Oxycodone hydrochloride, which is a pain reliever also known as Percocet
• Alectinib hydrochloride, which is currently a lung cancer treatment made by Genentech
• Betamethasone dipropionate, which can be used as a skin ointment
• Betamethasone valerate, which is also a topical skin treatment
• Captopril Carbidopa; levodopa, which is used as a Parkinson’s disease treatment
• Cholic acid, which is approved to treat bile acid synthesis disorders
• Clobetasol propionate (multiple reference listed drugs), which is a psoriasis medication
• Cobicistat; Elvitegravir; Emtricitabine; Tenofovir alafenamide fumarate, which is Gilead’s HIV treatment approved by FDA in November 2015
• Crotamiton (multiple reference listed drugs), which can treat scabies or severe itching
• Desonide, which can treat dermatitis and other skin problems
• Dexlansoprazole, which treats heartburn
• Elbasvir; grazoprevir, which is better known as Merck’s hepatitis C treatment Zepatier and first approved in January 2016
• Eltrombopag Olamine, which is indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy
• Esomeprazole magnesium, which is AstraZeneca’s Nexium and used to treat acid reflux
• Fluticasone propionate, which is used to help allergies
• Halobetasol propionate, which is a skin ointment
• Hydrocodone bitartrate (multiple reference listed drugs), which is used as a pain treatment
• Hydrocortisone valerate, which is a cream to treat inflammation
• Ibuprofen
• Iron dextran to treat iron deficiency anemia
• Methylphenidate hydrochloride, which can treat ADHD
• Morphine sulfate, which is a pain treatment
• Olopatadine hydrochloride, which can treat eye itching
• Oxymorphone hydrochloride, which is a pain treatment
• Prochlorperazine to treat nausea or vomiting and anxiety or schizophrenia
• Pyrazinamide, which is a tuberculosis treatment
• Rolapitant hydrochloride, which treats nausea or vomiting associated with chemotherapy
• Triamcinolone acetonide (multiple reference listed drugs), which is a topical corticosteroid
• Umeclidinium bromide, which is for patients with chronic obstructive pulmonary disease 

To successfully develop and manufacture a generic drug, FDA says ANDA applicants should ensure their product is: pharmaceutically equivalent to its RLD (i.e., to have the same active ingredient, dosage form, strength and route of administration under the same conditions of use); bioequivalent to the RLD (i.e., to show no significant difference in the rate and extent of absorption of the active pharmaceutical ingredient);  and therapeutically equivalent (i.e., to be substitutable for the RLD with the expectation that the generic product will have the same safety and efficacy as its reference listed drug).

Product-Specific Recommendations for Generic Drug Development