Product-Specific Guidances for Generic Drug Development

Disclaimer: Due to April 2019 systemwide upgrades to, the filenames for product-specific guidances on this web page may not match the corresponding guidance titles. In such cases, the name on the document correctly identifies the title of the guidance. These discrepancies will be corrected as soon as possible.

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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance: Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (August 2021).

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 Investigational New Drug (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 Questions regarding submission of datasets to CDER may be sent to

COMMENTS: The Agency is seeking feedback and considers comments to the docket on these guidances. You may submit comments on any guidance at any time as follows: Submit electronic comments to Docket FDA-2007-D-0369. For further information on submitting electronic comments, refer to the website ( You may also mail your written comments to DDM (HFA-305), FDA, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All submissions received must include the Docket No. [FDA-2007-D-0369]. Please contact the Help Desk at 1-877-378-5457 (toll free) for assistance regarding submissions.

The FDA posts plans for issuing new or revised product-specific guidances on the Upcoming Product-Specific Guidances for Complex Generic Drug Product Development web page.

For additional information on development of generic drug products, please refer to FDA’s biopharmaceutics guidances.

1GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2018-2022 (GDUFA II Commitment Letter)




Total number of currently published PSGs: 1921

Product-Specific Guidances for Specific Products Arranged by Active Ingredient

Search by Active Ingredient or by RLD or RS Number

43 record(s) found for 'H'

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Halcinonide cream_RLD 017556_RC12-16.pdf Draft Topical Cream 017556 12/2016
Halcinonide topical ointment NDA 017824 PSG Page RC May 2019.pdf Draft Topical Ointment 017824 05/2019
Halobetasol Propionate lotion_RLD 208183_RC 09-16.pdf Draft Topical Lotion 208183 10/2016
Halobetasol Propionate propionate_topical cream_NDA 19967_RC04-16.pdf Draft Topical Cream 019967 04/2016
Halobetasol Propionate propionate_topical ointment_NDA 19968_RC04-16.pdf Draft Topical Ointment 019968 04/2016
Haloperidol Oral Tablets NDA 015921 RV Feb 2019.pdf Draft Oral Tablet 015921 02/2019
Homatropine Methylbromide; Hydrocodone Bitartrate;_Hydrocodone_Bitartrate_tabs_88508_RC12-09.pdf Draft Oral Tablet 005213 12/2009
Hydralazine Hydrochloride Draft Oral Tablet 008303 07/2008
Hydralazine Hydrochloride; Isosorbide Dinitrate;_Isosorbide_tab_20727_RC12-09.pdf Draft Oral Tablet 020727 12/2009
Hydrochlorothiazide Draft Oral Tablet 011835 05/2010
Hydrochlorothiazide Final Oral Capsule 020504 05/2008
Hydrochlorothiazide; Lisinopril Draft Oral Tablet 019888 019778 12/2012
Hydrochlorothiazide; Losartan Potassium; Losartan potassium_oral tablet_RLD 20387_Final 08-17.pdf Final Oral Tablet 020387 08/2017
Hydrochlorothiazide; Metoprolol Tartrate;_HCTZ_tab_18303_RC08-10.pdf Draft Oral Tablet 018303 08/2010
Hydrochlorothiazide; Moexipril Hydrochloride Draft Oral Tablet 020729 07/2014
Hydrochlorothiazide; Olmesartan Medoxomil Final Oral Tablet 021532 05/2008
Hydrochlorothiazide; Quinapril Hydrochloride;_Quinapril_HCl_tabs_20125_RC07-10.pdf Draft Oral Tablet 020125 07/2010
Hydrochlorothiazide; Spironolactone Draft Oral Tablet 012616 12/2009
Hydrochlorothiazide; Telmisartan Draft Oral Tablet 021162 07/2008
Hydrochlorothiazide; Triamterene Draft Oral Tablet 019129 06/2013
Hydrochlorothiazide; Triamterene triamterene_oral capsule_RLD 016042, 073191_Final 08-17.pdf Final Oral Capsule 016042 073191 08/2017
Hydrochlorothiazide; Valsartan; Valsartan_Oral Tablet_RLD 20818_Final 08-17.pdf Final Oral Tablet 020818 08/2017
Hydrochlorothiazide;Irbesartan Draft Oral Tablet 020758 03/2012
Hydrochlorothiazide;Metoprolol Succinate Draft Oral Tablet, Extended Release 021956 04/2014
Hydrocodone Bitartrate bitartrate_oral ER cap_RLD 202880_RC09-16.pdf Draft Oral Capsule, Extended Release 202880 10/2016
Hydrocodone Bitartrate bitartrate_oral ER tablet_NDA 206627_RV07-18.pdf Draft Oral Tablet, Extended Release 206627 07/2018
Hydrocodone Bitartrate; Ibuprofen BITARTRATE; IBUPROFEN_oral tablet_RLD 020716_Final 08-17.pdf Final Oral Tablet 020716 08/2017
Hydrocortisone cream_ANDA 089414_RC03-17.pdf Draft Topical Cream 089414 05/2017
Hydrocortisone solution_RLD 81271_RC06-16.pdf Draft Topical Solution 081271 06/2016
Hydrocortisone oral tablet_ RLD 008697_Final 08-17.pdf Final Oral Tablet 008697 08/2017
Hydrocortisone Acetate Draft Rectal Aerosol, Metered 017351 11/2020
Hydrocortisone Butyrate butyrate_topical lotion_RLD 022076_RC03-17.pdf Draft Topical Lotion 022076 05/2017
Hydrocortisone Valerate valerate_topical ointment_RLD 070543_RC09-16.pdf Draft Topical Ointment 018726 10/2016
Hydrocortisone Valerate valerate_topical cream_NDA 017950_RC11-17.pdf Draft Topical Cream 017950 02/2018
Hydrogen Peroxide Draft Topical Solution 209305 09/2019
Hydromorphone Hydrochloride Draft Oral Tablet, Extended Release 021217 07/2014
Hydromorphone Hydrochloride HCl_oral tablet_RLD 19892_Final 08-17.pdf Final Oral Tablet 019892 08/2017
Hydroxychloroquine Sulfate Final Oral Tablet 009768 04/2020
Hydroxyprogesterone Caproate Draft Intramuscular Solution 021945 09/2019
Hydroxyurea Draft Oral Capsule 016295 08/2008
Hydroxyzine Hydrochloride Draft Oral Tablet 088617 088618 088619 06/2010
Hydroxyzine Pamoate Final Oral Capsule 011459 10/2011
Hydroxyzine Pamoate Final Oral Suspension 011795 10/2011

Newly Added Guidances since August 2021

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Acyclovir Draft Ophthalmic Ointment 202408 08/2021
Albuterol Sulfate; Ipratropium Bromide Draft Inhalation Spray, Metered 021747 08/2021
Amisulpride Draft Intravenous Solution 209510 08/2021
Avapritinib Draft Oral Tablet 212608 08/2021
Carbinoxamine Maleate Draft Oral Tablet 008915 08/2021
Cefiderocol Sulfate Tosylate Draft Intravenous Powder 209445 08/2021
Copper Dotatate Cu-64 Draft Intravenous Solution 213227 08/2021
Esomeprazole Magnesium Draft Oral Tablet, Orally Disintegrating, Delayed Release 214278 08/2021
Estradiol Draft Transdermal Gel, Metered 021166 08/2021
Ethinyl Estradiol; Levonorgestrel Draft Transdermal System 204017 08/2021
Fostemsavir Tromethamine Draft Oral Tablet, Extended Release 212950 08/2021
Indomethacin Draft Rectal Suppository 017814 08/2021
Ipratropium Bromide Draft Nasal Spray, Metered 020393 020394 08/2021
Lasmiditan Succinate Draft Oral Tablet 211280 08/2021
Leuprolide Acetate Draft Subcutaneous Powder 021343 08/2021
Loteprednol Etabonate Draft Ophthalmic Gel 208219 08/2021
Olodaterol Hydrochloride Draft Inhalation Spray, Metered 203108 08/2021
Osilodrostat Phosphate Draft Oral Tablet 212801 08/2021
Ozanimod Hydrochloride Draft Oral Capsule 209899 08/2021
Paliperidone Palmitate Draft Intramuscular Suspension, Extended Release 207946 08/2021
Semaglutide Draft Oral Tablet 213051 08/2021
Sufentanil Citrate Draft Sublingual Tablet 209128 08/2021
Tazemetostat Hydrobromide Draft Oral Tablet 211723 08/2021

Newly Revised Guidances since August 2021

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Bexarotene Draft Oral Capsule 021055 08/2021
Budesonide Draft Oral Capsule, Delayed Release 021324 08/2021
Eltrombopag Olamine Draft Oral Tablet 022291 08/2021
Eltrombopag Olamine Draft Oral For Suspension 207027 08/2021
Ferric Citrate Draft Oral Tablet 205874 08/2021
Ferric Oxyhydroxide Draft Oral Tablet, Chewable 205109 09/2021
Ferric Oxyhydroxide Draft Intravenous Injectable 021135 09/2021
Letrozole Draft Oral Tablet 020726 08/2021
Leuprolide Acetate Draft Injection Injectable 019732 020011 020263 08/2021
Leuprolide Acetate Draft Injection Injectable 020517 020708 08/2021
Liothyronine Sodium Draft Oral Tablet 010379 08/2021
Loteprednol Etabonate Draft Ophthalmic Suspension/Drops 020583 08/2021
Nystatin Draft Topical Powder 065203 08/2021
Orlistat Draft Oral Capsule 020766 021887 08/2021
Paclitaxel Draft IV Infusion For Suspension 021660 08/2021
Podofilox Draft Topical Gel 020529 08/2021
Sodium Zirconium Cyclosilicate Draft Oral For Suspension 207078 08/2021
Tazarotene Draft Topical Cream 0.05% 021184 08/2021

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