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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance:  Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).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 (23 New; 41 Revisions) updated  12/28/2018

Active Ingredient
(link to Specific Guidance)
TypeRoute of AdministrationDosage FormRLD Application Number
(link to Orange Book)
Date Recommended
 

Amphetamine (PDF - 55KB)

 DraftOral

Suspension, Extended Release

20432511/2018

Atropine sulfate; Diphenoxylate HCl (PDF - 40KB)

 DraftOral

Tablet

01246211/2018

Dichlorphenamide (PDF - 42KB)

 DraftOral

Tablet

01136611/2018

Doxepin hydrochloride (PDF - 52KB)

 DraftTopical

Cream

02012611/2018

Ertugliflozin; Metformin HCl (PDF - 42KB)

 DraftOral

Tablet

20980611/2018

Ertugliflozin; Sitagliptin phosphate (PDF - 42KB)

 DraftOral

Tablet

20980511/2018

Ertugliflozin (PDF - 40KB)

 DraftOral

Tablet

20980311/2018

Estradiol (PDF - 36KB)

 DraftTransdermal

Gel

02203811/2018

Latanoprostene bunod (PDF - 41KB)

 DraftOphthalmic

Solution/drops

20779511/2018

Letermovir (PDF - 40KB)

 DraftIV (infusion)

Solution

20994011/2018

Letermovir (PDF - 40KB)

 DraftOral

Tablet

20993911/2018

Levothyroxine sodium (PDF - 49KB)

 DraftOral

Capsule

02192411/2018

Lifitegrast (PDF -41KB)

 DraftOphthalmic

Solution/drops

20807311/2018
Linaclotide (PDF - 118KB) DraftOralCapsule20281112/2018

Macimorelin acetate (PDF -36KB)

 DraftOral

Solution

20559811/2018

Metoprolol succinate (PDF - 45KB)

 DraftOral

Capsule, Extended Release

21042811/2018

Netarsudil dimesylate (PDF -41KB)

 DraftOphthalmic

Solution/drops

20825411/2018

Nitazoxanide (PDF -100KB)

 DraftOral

Suspension

02149811/2018

Penicillamine(PDF - 40KB)

 DraftOral

Tablet

1985411/2018

Plecanatide (PDF - 114KB)

 DraftOral

Tablet

20874511/2018

Reserpine (PDF - 42KB)

 DraftOral

Tablet

00983811/2018

Ribociclib succinate (PDF - 40KB)

 DraftOral

Tablet

20909211/2018

Thiothixene (PDF - 41KB

 DraftOral

Capsule

01658411/2018

Newly Revised Guidances since November 1, 2018

Active Ingredient
(link to Specific Guidance)
TypeRoute of AdministrationDosage FormRLD Application Number
(link to Orange Book)
Date Recommended
 
Acetaminophen; Butalbital; Caffeine (PDF-17 KB) RevisedDraftOralCapsule

89007 

40885

11/2018
Acetaminophen; Butalbital; Caffeine (PDF-17 KB) RevisedDraftOralTablet

40511

11/2018
Acetaminophen; Oxycodone Hydrochloride (PDF - 17 KB) RevisedDraftOralTablet

40330

 

11/2018

 

Adapalene(PDF - 88 KB) RevisedDraftTopicalCream2074811/2018
Adapalene (PDF - 88 KB) RevisedDraftTopicalGel2038011/2018
Adapalene (PDF - 88 KB) RevisedDraftTopicalGel2175311/2018
Adapalene (PDF - 197KB)  RevisedDraftTopicalLotion2250211/2018

Adapalene; Benzoyl Peroxide (PDF - 159KB) Revised

 DraftTopical

Gel

20791711/2018
Adapalene; Benzoyl Peroxide (PDF - 88 KB) RevisedDraftTopicalGel2232011/2018

Asenapine Maleate (PDF - 90KB) Revised

 Draft Sublingual Tablet2211711/2018
Benzoyl Peroxide; Erythromycin (PDF - 212KB) RevisedDraftTopicalGel5055711/2018
Benzoyl Peroxide; Erythromycin (PDF - 212KB) RevisedDraftTopicalGel5076911/2018
Benzoyl Peroxide; Clindamycin Phosphate (PDF - 257KB)   RevisedDraftTopicalGel5081911/2018
Benzoyl Peroxide; Clindamycin Phosphate (PDF - 271KB) RevisedDraftTopicalGel5075611/2018
Benzoyl Peroxide; Clindamycin Phosphate (PDF - 325 KB) RevisedDraftTopicalGel5074111/2018
Clindamycin Phosphate (PDF - 243KB) RevisedDraftTopicalGel5061511/2018
Clindamycin Phosphate (PDF - 225KB) RevisedDraftTopicalGel5078211/2018
Clindamycin Phosphate (PDF - 231KB) RevisedDraftTopicalLotion5060011/2018

Clindamycin Phosphate; Tretinoin (PDF -138 KB) Revised

DraftTopicalGel

50802

50803

11/2018

Dapsone (PDF - 119KB) Revised

DraftTopicalGel20715411/2018
Dapsone (PDF - 103KB) RevisedDraft TopicalGel, 5%2179411/2018
Everolimus (PDF - 34KB)RevisedDraftOralTablet2233411/2018

Isosorbide dinitrate  (PDF - 59KB) Revised

DraftOralTablet01209311/2018
Metaxalone (PDF - 35KB) RevisedDraftOralTablet1321711/2018
Mycophenolic Acid (PDF - 15KB) RevisedDraftOralTablet, Delayed Release5079111/2018
Nitazoxanide (PDF - 85KB) RevisedDraftOralTablet2149711/2018
Sulfacetamide Sodium (PDF - 215KB) RevisedDraftTopicalLotion (or "Suspension USP")1993111/2018
Sulfamethoxazole; Trimethoprim (PDF - 42KB) RevisedDraftOralSuspension7761211/2018
Sumatriptan (PDF - (19KB) RevisedDraftNasalSpray2062611/2018

Tazarotene  (PDF - 151KB) Revised

DraftTopicalAerosol, Foam20242811/2018
Tazarotene  (PDF - 251 KB) RevisedDraftTopicalGel (0.1%)2060011/2018
Tretinoin (PDF - 117KB) RevisedDraftTopicalCream1734011/2018
Tretinoin (PDF - 117KB) RevisedDraftTopicalCream1752211/2018
Tretinoin (PDF - 117KB) RevisedDraftTopicalCream1904911/2018
Tretinoin (PDF -133KB) (NDA 020475) RevisedDraftTopicalGel (0.1%)2047511/2018
Tretinoin (PDF -133KB) (NDA 020475) RevisedDraftTopicalGel (0.04%)2047511/2018
Tretinoin (PDF - 116KB) RevisedDraftTopicalGel1757911/2018
Tretinoin (PDF - 126KB) RevisedDraftTopicalGel1795511/2018
Tretinoin (PDF - 126KB) RevisedDraftTopicalGel2207011/2018
Triamterene (PDF - 40KB) RevisedDraftOralCapsule1317411/2018

Zolmitriptan  (PDF - 26KB) Revised

DraftNasalSpray02145011/2018
 
 

 

Resources

Page Last Updated: 01/08/2019
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