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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance:  Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).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 Division of Dockets Management (DDM) under Docket FDA-2007-D-0369-0015.  For electronic comments, refer to the website http://www.regulations.gov 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
 

 

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 since October 1, 2018 (2 New; 23 Revisions) updated  10/9/2018

Active Ingredient
(link to Specific Guidance)
Type Route of Administration Dosage Form RLD Application Number
(link to Orange Book)
Date Recommended
 

Capsaicin (PDF - 187KB)

 Draft Topical

Patch

022395 10/2018

Estradiol; Norethindrone acetate (PDF - 299KB)

 Draft Transdermal

Film, Extended Release

020870 10/2018

Newly Revised Guidances since October 1, 2018

Active Ingredient
(link to Specific Guidance)
Type Route of Administration Dosage Form RLD Application Number
(link to Orange Book)
Date Recommended
 

Buprenorphine (PDF - 161KB) Revised

Draft Transdermal Film, Extended Release

21306

10/2018
Clonidine (PDF - 126KB)  Revised Draft Transdermal Film, Extended Relese 18891 10/2018
Diclofenac Epolamine (PDF - 595KB)  Revised  Draft Topical Patch 21234  10/2018
Estradiol (PDF - 146KB) Revised Draft Transdermal Film, Extended Release 19081 10/2018
Estradiol (PDF - 148KB) Revised Draft Transdermal Film, Extended Release

20375

21674

10/2018
Estradiol (PDF - 137KB) Revised Draft Transdermal Film, Extended Release 20538 10/2018

Estradiol (PDF - 155KB) Revised

Draft Transdermal Film, Extended Release 203752 10/2018
Ethinyl Estradiol; Norelgestromin (PDF - 142KB) Revised Draft Transdermal Film, Extended Release 21180 10/2018

Fentanyl (PDF - 105KB)  Revised

 

Draft Transdermal Film, Extended Release 19813 10/2018
Granisetron (PDF - 424KB) Revised Draft Transdermal Film, Extended Release 22198 10/2018
Lidocaine (PDF - 147KB)  Revised Draft Topical Patch 020612 10/2018

Menthol; Methyl Salicylate (PDF -158KB) Revised 

Draft Topical Patch 22029 10/2018

Methylphenidate (PDF - 266KB)  Revised

Draft Transdermal Film, Extended Release 21514 10/2018

Nicotine (PDF - 153KB)  Revised

Draft Transdermal Film, Extended Release 20076

 

20165

10/2018
Nitroglycerin (PDF - 154KB) Revised  Draft Transdermal Film, Extended Release 20145 10/2018
Nitroglycerin (PDF - 158KB)  Revised Draft Transdermal Film, Extended Release 20144 10/2018
Oxybutynin (PDF - 125KB) Revised Draft Transdermal Film, Extended Release 21351 10/2018

Oxybutynin (PDF - 179KB)  Revised

Draft Transdermal Film, Extended Release 202211 10/2018
Rivastigmine (PDF - 156KB) Revised Draft Transdermal Film, Extended Release 22083 10/2018
Rotigotine (PDF - 143KB)  Revised  Draft  Transdermal Film, Extended Release 21829 10/2018
Scopolamine (PDF - 270KB) Revised
Draft Transdermal Film, Extended Release 17874 10/2018
Selegiline (PDF - 288KB) Revised Draft Transdermal Film, Extended Release 21336 10/2018
Testosterone (PDF - 172KB)  Revised Draft Transdermal Film, Extended Release 020489 10/2018

Newly Added Guidances since September 1, 2018 (42 New; 12 Revisions) updated  9/13/2018

Active Ingredient
(link to Specific Guidance)
Type Route of Administration Dosage Form RLD Application Number
(link to Orange Book)
Date Recommended
 

Abemaciclib (PDF - 41KB) 

 Draft Oral

Tablet

208716 9/2018

Albuterol sulfate (PDF - 117KB) 

 Draft  Inhalation

Powder, metered

205636 9/2018

 Allopurinol; Lesinurad (PDF - 41KB)

 Draft Oral Tablet 209203 9/2018

 Amantadine HCl (PDF - 40KB)

Draft Oral Capsule, Extended Release 208944 9/2018

 Amphetamine Aspartate; Amphetamine Sulfate; Dextroamphetamine Saccharate; Dextroamphetamine Sulfate (PDF - 56KB)

Draft Oral Capsule, Extended Release 022063 9/2018

Azelaic acid (PDF - 96KB)

 Draft Topical  Foam, Aerosol 207071 9/2018

Benznidazole (PDF - 44KB)  

Draft Oral Tablet 209570 9/2018

Brigatinib (PDF - 41KB)

Draft Oral Tablet 208772 9/2018

 Brimonidine tartrate; Timolol maleate (PDF - 41KB) 

Draft Ophthalmic Solution/drops 021398 9/2018

 Chlorzoxazone (PDF - 41KB)

Draft Oral Tablet 011529 9/2018

 Ciprofloxacin HCl (PDF - 101KB)

Draft Ophthalmic Ointment 020369 9/2018

Dapagliflozin propanediol; Saxagliptin HCl (PDF - 42KB)

Draft Oral Tablet 209091 9/2018

 Delafloxacin meglumine (PDF - 40KB)

Draft Oral Tablet 208610 9/2018

 Desonide (PDF - 39KB)

Draft

Topical

Gel

021844

9/2018

 Deutetrabenazine (PDF - 60KB)

Draft Oral Tablet 208082 9/2018

 Diazepam (PDF - 61KB)

Draft Oral Tablet 013263 9/2018

 Efinaconazole (PDF - 44KB) 

Draft Topical Solution 203567 9/2018

Enasidenib mesylate (PDF - 54KB)

Draft Oral Tablet 209606 9/2018

Glecaprevir; Pibrentasvir (PDF - 41KB)

Draft Oral Tablet 209394 9/2018

Ibuprofen; Pseudoephedrine HCl (PDF - 39KB)

Draft Oral Tablet 019771 9/2018

 Ivermectin (PDF - 103KB)

Draft Topical Lotion 202736 9/2018

Lamotrigine (PDF - 54KB)

Draft Oral Tablet, Disintegrating 022251 9/2018

 Luliconazole (PDF - 107KB)

Draft Topical Cream

204153

9/2018

 Midostaurin (PDF - 42KB)

Draft Oral Capsule

207997

9/2018

 Miltefosine (PDF - 62KB)

Draft Oral Capsule 204684 9/2018

 Morphine sulfate (PDF - 63KB)

Draft Oral Capsule 208603 9/2018

 Neratinib maleate (PDF - 41KB)

Draft Oral Tablet 208051 9/2018

 Olaparib (PDF - 43KB)

Draft Oral Tablet 208558 9/2018

 Olive Oil; Soybean Oil (PDF - 42KB)

Draft Injection Injectable 204508 9/2018

 Oxycodone HCl (PDF - 61KB)

Draft Oral Tablet 209777 9/2018

 Penciclovir (PDF - 49KB)

Draft Topical Cream 020629 9/2018

 Perflutren (PDF - 45KB)

Draft Intravenous Injectable 021064 9/2018

 Pilocarpine HCl (PDF - 41KB)

Draft Ophthalmic Solution 200890 9/2018

 Pitavastatin magnesium (PDF - 40KB)

Draft Oral Tablet 208379 9/2018

 Pitavastatin sodium (PDF - 39KB)

Draft Oral Tablet 209875 9/2018

 Pregabalin (PDF - 42KB)

Draft Oral Tablet, Extended Release 209501 9/2018

 Secnidazole (PDF - 41KB)

Draft Oral Granules 209363 9/2018

 Sofosbuvir; Velpatasvir; Voxilaprevir (PDF - 53KB)

Draft Oral Tablet 209195 9/2018

 Spironolactone (PDF - 39KB)

Draft Oral Suspension 209478 9/2018

 Sulfur hexafluoride lipid-type A microsphere (PDF - 45KB)

Draft Intravenous Suspension 203684 9/2018

 Talc (PDF - 38KB)

Draft Intrapleural Aerosol 020587 9/2018

Tavaborole (PDF - 44KB)

Draft Topical Solution 204427 9/2018
 

Newly Revised Guidances since September 1, 2018

Active Ingredient
(link to Specific Guidance)
Type Route of Administration Dosage Form RLD Application Number
(link to Orange Book)
Date Recommended
 
Acetazolamide (PDF - 17 KB)Revised Draft Oral Tablet 008943 9/2018
Chlorpromazine Hydrochloride (PDF - 45KB) Revised  Draft  Oral Tablet

084112

084114

 9/2018
Doxorubicin Hydrochloride (PDF-66KB)Revised Draft Injection Injectable, Liposomal 50718 9/2018

Morphine sulfate (PDF - 43KB)Revised

Draft Oral Tablet, Extended Release 206544 9/2018

Nicotine Polacrilex (PDF - 25KB) Revised

Draft Buccal Chewing Gum 20066

18612

9/2018
Nicotine Polacrilex (PDF - 35KB) Revised Draft Oral Troche/lozenge 22360 9/2018

Nicotine Polacrilex (PDF - 41KB)Revised

Draft Oral Troche/lozenge 21330 9/2018
Nisoldipine (PDF - 38KB)
Revised
Draft Oral Tablet, Extended Release 20356 9/2018

Oxycodone (PDF - 54KB)  Revised

Draft Oral Capsule, Extended Release 208090 9/2018
Raltegravir Potassium (PDF - 28KB) Revised Draft Oral Tablet 22145 9/2018
Tacrolimus (PDF - 80KB) Revised Draft Topical Ointment 0.1% 50777 9/2018
Tacrolimus (PDF - 77KB) Revised Draft Topical Ointment 0.03% 50777 9/2018

 

 

 

 
 

 

Resources

Page Last Updated: 10/09/2018
Note: If you need help accessing information in different file formats, see Instructions for Downloading Viewers and Players.
Language Assistance Available: Español | 繁體中文 | Tiếng Việt | 한국어 | Tagalog | Русский | العربية | Kreyòl Ayisyen | Français | Polski | Português | Italiano | Deutsch | 日本語 | فارسی | English