Drugs

Product-Specific Guidances for Generic Drug Development

To successfully develop and manufacture a generic drug product, an applicant should consider that their product is expected to be:  pharmaceutically equivalent to its reference listed drug (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, consequently,  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.

According to 21 CFR 320.24, different types of evidence may be used to establish bioequivalence for pharmaceutically equivalent drug products, including in vivo or in vitro testing, or both.  The selection of the method used to demonstrate bioequivalence depends upon the purpose of the study, the analytical methods available, and the nature of the drug product.  Under this regulation, applicants must conduct bioequivalence testing using the most accurate, sensitive, and reproducible approach available among those set forth in 21 CFR 320.24.  As the initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance: Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).

To further facilitate generic drug product availability and to assist the generic pharmaceutical industry with identifying the most appropriate methodology for developing drugs and generating evidence needed to support ANDA approval, 
FDA publishes product-specific guidances describing the Agency’s current thinking and expectations on how to develop generic drug products therapeutically equivalent to specific reference listed drugs. 

FDA publishes these product-specific guidances to foster drug product development, and ANDA submission and approval, ultimately providing increased access to safe, affordable generic drugs.

These guidances are published in an incremental manner and listed below in alphabetical order according to the active ingredient’s name.  The most recently published guidances (new and revised) are listed below.

Additionally, as part of FDA’s commitments under the Generic Drug User Fee Amendments Reauthorization of 2017 (GDUFA II), FDA will publish guidances for reference listed drugs that are (1) new chemical entities and (2) approved on or after October 1, 2017, at least 2 years prior to the earliest lawful ANDA filing date.1 This goal does not include complex products as defined in the GDUFA II Commitment Letter.  FDA will strive to issue guidance for a complex product as soon as scientific recommendations are available.

In addition to the provided information, sponsors and investigators of any IND-exempt pharmacokinetic (PK) studies, pharmacodynamic (PD) studies, or bioequivalence (BE) and/or bioavailability (BA) studies involving human subjects in support of an ANDA should refer to the current RLD labeling, including BOXED WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS sections.  This information should be considered during study design and conduct; including attention to appropriate subject screening and selection, inclusion and exclusion criteria, and appropriate clinical safety monitoring.

Some of the product-specific guidances include discussion regarding data formats.  Please note that under section 745A(a) of the Federal Food, Drug, and Cosmetic Act, separate Agency-wide guidances specify the electronic formats, subject matter, and scope of applicability for certain submissions, including submissions to ANDAs.  As these are finalized guidances and subject to described timetables for implementation, these guidances are binding and the electronic format(s) specified must be used for submissions to ANDAs.  Questions and general information regarding the preparation of submissions in electronic format may be directed to CDER at esub@fda.hhs.gov. Questions regarding submission of datasets to CDER may be sent to edata@fda.hhs.gov.

The Agency is seeking feedback and considers comments to the docket on these guidances.  The comments should be submitted to the Dockets Management Staff (DMS) under Docket FDA-2007-D-0369-0015.  For electronic comments, refer to the regulations.gov website OR mail your written comments to DDM (HFA-305), FDA, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.  Please contact the Regulations.gov Help Desk at 1-877-378-5457 (toll free) for assistance regarding submissions.   

For additional information on development of generic drug products, please refer to FDA’s webpage on biopharmaceutics guidances.
 
1GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2018-2022 (GDUFA II Commitment Letter) available at https://www.fda.gov/downloads/forindustry/userfees/genericdruguserfees/ucm525234.pdf

Total number of currently published Product Specific Guidances: 1,682 

Product-Specific Guidances Arranged by Active Ingredient

A B C D E F G H I  J K L M N O P Q R S T U V  W  X  Y Z

Newly Added Guidances Published since February 1, 2019 (22 New; 52 Revisions) updated  2/22/2019

Active Ingredient
(link to Specific Guidance)
TypeRoute of AdministrationDosage FormRLD Application Number
(link to Orange Book)
Date Recommended
 
Acalabrutinib  (PDF - 30KB)DraftOralCapsule2102592/2019
Acetaminophen; Caffeine; Dihydrocodeine bitartrate (PDF - 45KB)DraftOralCapsule2047852/2019

Angiotensin II acetate (PDF - 40KB)

DraftIntravenousSolution2093602/2019

Bexarotene (PDF - 56KB)

DraftTopicalGel0210562/2019

Bosentan (PDF - 40KB)

DraftOralTablet, for suspension2092792/2019

Bromocriptine mesylate (PDF - 46KB)

DraftOralTablet208662/2019
Chlorothiazide (PDF - 43KB)DraftOralSuspension0118702/2019

Daptomycin (PDF - 48KB)

DraftIV InfusionPowder2099492/2019

Dexamethasone(PDF - 43KB)

DraftOralConcentrate (Solution)0882522/2019

Dihydroergotamine mesylate (PDF - 62KB)

DraftNasalSpray metered0201482/2019

Diltiazem hydrochloride(PDF - 28KB)

DraftOralCapsule, Extended Release0194712/2019

Doxycycline calcium (PDF - 49KB)

DraftOralSuspension0504802/2019

Doxylamine succinate; Pyridoxine hydrochloride (PDF - 27KB)

DraftOralTablet, Extended Release2096612/2019
Fish oil; Medium chain triglycerides; Olive oil; Soybean oil (PDF - 53KB)DraftIntravenousEmulsion2076482/2019

Isocarboxazid (PDF - 59KB)

DraftOralTablet0119612/2019

Ivacaftor; Tezacaftor (PDF - 38KB)

DraftOralTablet2104912/2019
Ribociclib succinate; Letrozole (PDF - 107KB)DraftOralTablet2099352/2019

Loratadine; Pseudoephedrine sulfate (PDF - 52KB)

DraftOralTablet, Extended Release0204702/2019

Methsuximide (PDF - 51KB)

DraftOralCapsule0105962/2019

Ozenoxacin (PDF - 121KB)

DraftTopicalCream2089452/2019

Paroxetine mesylate (PDF - 48KB)

DraftOralTablet0212992/2019
Succimer (PDF - 47KB)DraftOralCapsule0199982/2019

Newly Revised Guidances Published since February 1, 2019

Active Ingredient
(link to Specific Guidance)
TypeRoute of AdministrationDosage FormRLD Application Number
(link to Orange Book)
Date Recommended
 
Acetaminophen; Butalbital (PDF-17 KB) RevisedDraftOralTablet899872/2019
Aripiprazole (PDF - 138 KB) RevisedDraftOralTablet214362/2019
Azelastine hydrochloride; Fluticasone propionate (PDF - 78KB) RevisedDraftNasalSpray, metered2022362/2019
Betamethasone dipropionate; Clotrimazole (PDF - 38KB) RevisedDraftTopicalCream188272/2019
Betamethasone dipropionate; Clotrimazole (PDF - 41KB) RevisedDraftTopicalLotion200102/2019
Betamethasone dipropionate; Calcipotriene Hydrate (PDF - 244KB) RevisedDraftTopicalOintment218522/2019
Betamethasone dipropionate; Calcipotriene Hydrate (PDF - 261KB) RevisedDraftTopicalSuspension221852/2019
Butenafine hydrochloride (PDF - 167KB) RevisedDraftTopicalCream205242/2019
Butenafine hydrochloride (PDF - 168KB) RevisedDraftTopicalCream213072/2019
Butoconazole nitrate (PDF - 168 KB) RevisedDraftVaginalCream2009232/2019
Butoconazole nitrate (PDF - 179 KB) RevisedDraftVaginalCream204212/2019
Calcipotriene (PDF - 277KB) RevisedDraftTopicalAerosol, Foam225632/2019
Calcipotriene (PDF - 295KB) RevisedDraftTopicalCream205542/2019
Calcipotriene (PDF - 54KB) RevisedDraftTopicalOintment0202732/2019

Ceritinib (PDF - 38KB) Revised

DraftOralCapsule2057552/2019
Ciclopirox (PDF - 37KB) RevisedDraftTopicalSuspension198242/2019
Ciclopirox (PDF - 107KB) RevisedDraftTopicalCream187482/2019
Ciclopirox (PDF - 80KB) RevisedDraftTopicalGel205192/2019
Clotrimazole (PDF - 164KB) RevisedDraftTopicalSolution0181812/2019
Clotrimazole (PDF - 76KB) RevisedDraftTopicalCream726402/2019
Clotrimazole (PDF - 78KB) RevisedDraftVaginalCream180522/2019
Clotrimazole (PDF - 78KB) RevisedDraftVaginalCream205742/2019
Clotrimazole (PDF - 82KB) RevisedDraftVaginalTablet177172/2019
Clotrimazole (PDF - 81KB) RevisedDraftVaginalTablet205252/2019

Crisaborole (PDF -41KB) Revised

DraftTopicalOintment2076952/2019
Dexamethasone; Tobramycin (PDF-49KB) RevisedDraftOphthalmicSuspension508182/2019
Dexamethasone;Tobramycin (PDF - 35 KB) Revised DraftOphthalmicSuspension505922/2019
Diclofenac sodium (PDF - 172KB) RevisedDraftTopicalGel210052/2019
Econazole nitrate (PDF - 78KB) RevisedDraftTopicalCream0187512/2019
Fluorouracil (PDF - 176KB) RevisedDraftTopicalCream169882/2019
Fluorouracil (PDF - 168KB) RevisedDraftTopicalCream209852/2019
Fluorouracil (PDF - 41KB) RevisedDraftTopicalCream168312/2019

Fluticasone propionate (PDF - 197KB) Revised

DraftNasalSpray, metered0201212/2019
Haloperidol (PDF - 15KB) RevisedDraftOralTablet

015921

2/2019
Imiquimod (PDF - 164KB) RevisedDraftTopicalCream (2.5%)224832/2019
Imiquimod (PDF - 171KB) RevisedDraftTopicalCream (3.75%)224832/2019
Imiquimod (PDF - 163KB) RevisedDraftTopicalCream207232/2019

Ingenol mebutate (PDF - 124KB) Revised

DraftTopicalGel (0.05%)2028332/2019

Ingenol mebutate (PDF - 121KB) Revised

DraftTopicalGel (0.015%)2028332/2019

Ivacaftor; Lumacaftor (PDF - 41KB) Revised

DraftOralTablet2060382/2019
Ketoconazole (PDF - 73KB) RevisedDraftTopicalCream0190842/2019
Miconazole (PDF - 63KB) RevisedDraftBuccalTablet224042/2019

Mometasone furoate monohydrate (PDF - 113KB) Revised

DraftNasalSpray, Metered0207622/2019
Oxiconazole nitrate (PDF - 61KB) RevisedDraftTopicalCream198282/2019
Oxiconazole nitrate (PDF - 65KB)DraftTopicalLotion202092/2019
Tazarotene 0.1% (PDF - 240KB) RevisedDraftTopicalCream211842/2019
Tazarotene 0.05% (PDF - 251 KB) RevisedDraftTopicalGel206002/2019
Tazarotene 0.05% (PDF - 224KB) RevisedDraftTopicalCream211842/2019
Terbinafine hydrochloride (PDF - 163KB) RevisedDraftTopicalCream209802/2019
Treprostinil diolamine (PDF - 41KB) RevisedDraftOralTablet, Extended Release203496 2/2019
Tretinoin (PDF - 117KB) RevisedDraftTopicalCream900982/2019

Triamcinolone acetonide (PDF - 170KB) Revised

DraftNasalSpray, metered0204682/2019
 
 

 

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