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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance:  Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).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 November 1, 2018 (22 New; 41 Revisions) updated  11/28/2018

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

Amphetamine (PDF - 55KB)

 Draft Oral

Suspension, Extended Release

204325 11/2018

Atropine sulfate; Diphenoxylate HCl (PDF - 40KB)

 Draft Oral

Tablet

012462 11/2018

Dichlorphenamide (PDF - 42KB)

 Draft Oral

Tablet

011366 11/2018

Doxepin hydrochloride (PDF - 52KB)

 Draft Topical

Cream

020126 11/2018

Ertugliflozin; Metformin HCl (PDF - 42KB)

 Draft Oral

Tablet

209806 11/2018

Ertugliflozin; Sitagliptin phosphate (PDF - 42KB)

 Draft Oral

Tablet

209805 11/2018

Ertugliflozin (PDF - 40KB)

 Draft Oral

Tablet

209803 11/2018

Estradiol (PDF - 36KB)

 Draft Transdermal

Gel

022038 11/2018

Latanoprostene bunod (PDF - 41KB)

 Draft Ophthalmic

Solution/drops

207795 11/2018

Letermovir (PDF - 40KB)

 Draft IV (infusion)

Solution

209940 11/2018

Letermovir (PDF - 40KB)

 Draft Oral

Tablet

209939 11/2018

Levothyroxine sodium (PDF - 49KB)

 Draft Oral

Capsule

021924 11/2018

Lifitegrast (PDF -41KB)

 Draft Ophthalmic

Solution/drops

208073 11/2018

Macimorelin acetate (PDF -36KB)

 Draft Oral

Solution

205598 11/2018

Metoprolol succinate (PDF - 45KB)

 Draft Oral

Capsule, Extended Release

210428 10/2018

Netarsudil dimesylate (PDF -41KB)

 Draft Ophthalmic

Solution/drops

208254 11/2018

Nitazoxanide (PDF -100KB)

 Draft Oral

Suspension

021498 11/2018

Penicillamine(PDF - 40KB)

 Draft Oral

Tablet

19854 11/2018

Plecanatide (PDF - 114KB)

 Draft Oral

Tablet

208745 11/2018

Reserpine (PDF - 42KB)

 Draft Oral

Tablet

009838 11/2018

Ribociclib succinate (PDF - 40KB)

 Draft Oral

Tablet

209092 11/2018

Thiothixene (PDF - 41KB

 Draft Oral

Capsule

016584 11/2018

Newly Revised Guidances since November 1, 2018

Active Ingredient
(link to Specific Guidance)
Type Route of Administration Dosage Form RLD Application Number
(link to Orange Book)
Date Recommended
 
Acetaminophen; Butalbital; Caffeine (PDF-17 KB) Revised Draft Oral Capsule

89007 

40885

11/2018
Acetaminophen; Butalbital; Caffeine (PDF-17 KB) Revised Draft Oral Tablet

40511

11/2018
Acetaminophen; Oxycodone Hydrochloride (PDF - 17 KB) Revised Draft Oral Tablet

40330

 

11/2018

 

Adapalene(PDF - 88 KB) Revised Draft Topical Cream 20748 11/2018
Adapalene (PDF - 88 KB) Revised Draft Topical Gel 20380 11/2018
Adapalene (PDF - 88 KB) Revised Draft Topical Gel 21753 11/2018
Adapalene (PDF - 197KB)  Revised Draft Topical Lotion 22502 11/2018

Adapalene; Benzoyl Peroxide (PDF - 159KB) Revised

 Draft Topical

Gel

207917 11/2018
Adapalene; Benzoyl Peroxide (PDF - 88 KB) Revised Draft Topical Gel 22320 11/2018

Asenapine Maleate (PDF - 90KB) Revised

 Draft  Sublingual  Tablet 22117 11/2018
Benzoyl Peroxide; Erythromycin (PDF - 212KB) Revised Draft Topical Gel 50557 11/2018
Benzoyl Peroxide; Erythromycin (PDF - 212KB) Revised Draft Topical Gel 50769 11/2018
Benzoyl Peroxide; Clindamycin Phosphate (PDF - 257KB)   Revised Draft Topical Gel 50819 11/2018
Benzoyl Peroxide; Clindamycin Phosphate (PDF - 271KB) Revised Draft Topical Gel 50756 11/2018
Benzoyl Peroxide; Clindamycin Phosphate (PDF - 325 KB) Revised Draft Topical Gel 50741 11/2018
Clindamycin Phosphate (PDF - 243KB) Revised Draft Topical Gel 50615 11/2018
Clindamycin Phosphate (PDF - 225KB) Revised Draft Topical Gel 50782 11/2018
Clindamycin Phosphate (PDF - 231KB) Revised Draft Topical Lotion 50600 11/2018

Clindamycin Phosphate; Tretinoin (PDF -138 KB) Revised

Draft Topical Gel

50802

50803

11/2018

Dapsone (PDF - 119KB) Revised

Draft Topical Gel 207154 11/2018
Dapsone (PDF - 103KB) Revised Draft  Topical Gel, 5% 21794 11/2018
Everolimus (PDF - 34KB)Revised Draft Oral Tablet 22334 11/2018

Isosorbide dinitrate  (PDF - 59KB) Revised

Draft Oral Tablet 012093 11/2018
Metaxalone (PDF - 35KB) Revised Draft Oral Tablet 13217 11/2018
Mycophenolic Acid (PDF - 15KB) Revised Draft Oral Tablet, Delayed Release 50791 11/2018
Nitazoxanide (PDF - 85KB) Revised Draft Oral Tablet 21497 11/2018
Sulfacetamide Sodium (PDF - 215KB) Revised Draft Topical Lotion (or "Suspension USP") 19931 11/2018
Sulfamethoxazole; Trimethoprim (PDF - 42KB) Revised Draft Oral Suspension 77612 11/2018
Sumatriptan (PDF - (19KB) Revised Draft Nasal Spray 20626 11/2018

Tazarotene  (PDF - 151KB) Revised

Draft Topical Aerosol, Foam 202428 11/2018
Tazarotene  (PDF - 251 KB) Revised Draft Topical Gel (0.1%) 20600 11/2018
Tretinoin (PDF - 117KB) Revised Draft Topical Cream 17340 11/2018
Tretinoin (PDF - 117KB) Revised Draft Topical Cream 17522 11/2018
Tretinoin (PDF - 117KB) Revised Draft Topical Cream 19049 11/2018
Tretinoin (PDF -133KB) (NDA 020475) Revised Draft Topical Gel (0.1%) 20475 11/2018
Tretinoin (PDF -133KB) (NDA 020475) Revised Draft Topical Gel (0.04%) 20475 11/2018
Tretinoin (PDF - 116KB) Revised Draft Topical Gel 17579 11/2018
Tretinoin (PDF - 126KB) Revised Draft Topical Gel 17955 11/2018
Tretinoin (PDF - 126KB) Revised Draft Topical Gel 22070 11/2018
Triamterene (PDF - 40KB) Revised Draft Oral Capsule 13174 11/2018

Zolmitriptan  (PDF - 26KB) Revised

Draft Nasal Spray 021450 11/2018
 
 

 

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Page Last Updated: 11/28/2018
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