FDA releases 52 new and revised bioequivalence guidelines for generics Posted 03/11/2017

As part of its ongoing efforts to provide product-specific guidance for generics makers the US Food and Drug Administration (FDA) has again released several new and revised bioequivalence documents. The agency announced on 18 October 2017 that it had released 33 new draft guidance documents and 19 revisions to guidance documents on bioequivalence requirements for the development of generics containing 47 different active ingredients.

The new draft bioequivalence guidance documents cover generics of Mylan’s anti-allergic reaction injection EpiPen (epinephrine), Novartis’ cancer treatment Afinitor (everolimus) and AstraZeneca’s cancer treatment Lynparza (olaparib), among others, see Table 1.

Revised bioequivalence guidance documents include those for generics of Eli Lilly’s erectile dysfunction drug Cialis (tadalafil), non-steroid anti-inflammatory drugs (NSAIDs) bromfenac and diclofenac, glaucoma treatment brimonidine and antibiotics ciprofloxacin and ofloxacin, as well as various HIV treatments, among others, see Table 2.

FDA bioequivalence requirements demand that the generic drug performs in the same way in the body and has the same active ingredient(s), strength, dosage form and route of administration as the brand-name reference drug.

Table 1: FDA new draft bioequivalence guidance documents

Active ingredient

Route of administration

Dosage form

Link

Azelastine hydrochloride

Nasal

Spray, Metered

Click here

Azithromycin

Oral

Suspension

Click here

Barium sulfate

Oral

Paste

Click here

Betamethasone dipropionate

Topical

Lotion

Click here

Budesonide

Rectal

Aerosol Foam

Click here

Canagliflozin; Metformin HCl

Oral

Tablet ER

Click here

Dantrolene sodium

Intravenous

Suspension

Click here

Dapsone

Topical

Gel

Click here

Deflazacort

Oral

Suspension

Click here

Deflazacort

Oral

Tablet

Click here

Docosanol

Topical

Cream

Click here

Empagliflozin; Metformin HCl

Oral

Tablet ER

Click here

Epinephrine

Intramuscular/ subcutaneous

Injectable

Click here

Erythromycin

Topical

Gel

Click here

Everolimus

Oral

Tablet for suspension

Click here

Fluorometholone

Ophthlamic

Drops, Suspension

Click here

Fluticasone propionate

Inhalation

Powder

Click here

Hydrocortisone acetate

Rectal

Aerosol, metered

Click here

Ivermectin

Topical

Cream

Click here

Levorphanol tartrate

Oral

Tablet

Click here

Lisdexamfetamine dimesylate

Oral

Tablet, chewable

Click here

Methylphenidate HCl

Oral

Tablet ER

Click here

Mometasone furoate

Inhalation

Powder

Click here

Nitisinone

Oral

Capsule

Click here

Olaparib

Oral

Capsule

Click here

Osimertinib mesylate

Oral

Tablet

Click here

Permethrin

Topical

Cream

Click here

Pirfenidone

Oral

Tablet

Click here

Salmeterol xinafoate

Inhalation

Powder

Click here

Telotristat etiprate

Oral

Tablet

Click here

Terbutaline sulfate

Oral

Tablet

Click here

Tiotropium bromide

Inhalation

Powder

Click here

ER: extended release; FDA: US Food and Drug Administration; HCI: hydrochloride.

Table 2: FDA revised draft bioequivalence guidance documents

Active ingredient

Route of administration

Dosage form

Link

Brimonidine tartrate

Ophthalmic

Solution/ drops 0.2%

Click here

Brimonidine tartrate

Ophthalmic

Solution/ drops 0.1%

Click here

Bromfenac sodium

Ophthalmic

Solution/ drops

Click here

Ciprofloxacin HCl

Ophthalmic

Solution/ drops

Click here

Cobicistat/ elvitegravir/ emtricitabine/ tenofovir alafenamide fumarate

Oral

Tablet

Click here

Dapsone

Topical

Gel, 5%

Click here

Diclofenac sodium

Ophthalmic

Solution/ drops

Click here

Emtricitabine/ rilpivirine hydrochloride/ tenofovir alafenamide fumarate

Oral

Tablet

Click here

Emtricitabine/ tenofovir alafenamide fumarate

Oral

Tablet

Click here

Esomeprazole magnesium

Oral

Tablet DR

Click here

Lisdexamfetamine dimesylate

Oral

Capsule

Click here

Mesalamine

Oral

Tablet DR

Click here

Mycophenolate mofetil

Oral

Suspension

Click here

Ofloxacin

Ophthalmic

Solution/ drops

Click here

Olopatadine HCl

Ophthalmic

Solution/ drops 0.2%

Click here

Olopatadine HCl

Ophthalmic

Solution/ drops 0.1%

Click here

Ropinirole HCl

Oral

Tablet ER

Click here

Sucralfate

Oral

Suspension

Click here

Tadalafil

Oral

Tablet

Click here

DR: delayed release; ER: extended release; FDA: US Food and Drug Administration; HCI: hydrochloride.

The draft guidance documents recommend what in vivo and in vitro studies generics companies should carry out in order to demonstrate bioequivalence. The number of studies, the population to be studied, blood sampling timepoints and analytes to be measured in blood samples are also detailed in the draft guidance documents. Some of the documents also provide discussion on data formats.

FDA also has an overarching guidance document on bioequivalence recommendations for specific products [1], as well as a dissolution methods database.

Comments on the draft guidance documents can be posted to the Division of Dockets Management (DDM) under Docket FDA-2007-D-0369-0015. This can be done via the website www.regulations.gov or written comments can be mailed to DDM (HFA-305), FDA, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, USA.

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Reference
1. GaBI Online - Generics and Biosimilars Initiative. US guidelines for generics [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Nov 3]. Available from: www.gabionline.net/Guidelines/US-guidelines-for-generics

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Source: US FDA

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