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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance: Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (August 2021).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 esub@fda.hhs.gov. Questions regarding submission of datasets to CDER may be sent to edata@fda.hhs.gov.

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 regulations.gov website (www.regulations.gov). 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 Regulations.gov Help Desk at 1-877-378-5457 (toll free) or at (www.regulations.gov/support) 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 guidance document database.

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

Total number of currently published PSGs: 1948

Product-Specific Guidances for Specific Products Arranged by Active Ingredient


Search by Active Ingredient or by RLD or RS Number


Newly Added Guidances since November 2021

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Artesunate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213036.pdf Draft Intravenous Powder 213036 11/2021
Beclomethasone Dipropionate Monohydrate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019389.pdf Draft Nasal Spray, Metered 019389 11/2021
Bempedoic Acid https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211616.pdf Draft Oral Tablet 211616 11/2021
Bempedoic Acid; Ezetimibe https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211617.pdf Draft Oral Tablet 211617 11/2021
Cenobamate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212839.pdf Draft Oral Tablet 212839 11/2021
Ciclesonide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022004.pdf Draft Nasal Spray, Metered 022004 11/2021
Clascoterone https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213433.pdf Draft Topical Cream 213433 11/2021
Colesevelam Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210895.pdf Draft Oral Bar, Chewable 210895 11/2021
Diclofenac Potassium https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020142.pdf Draft Oral Tablet 020142 11/2021
Dicyclomine Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_007409-Tab.pdf Draft Oral Tablet 007409 11/2021
Glucagon https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212097.pdf Draft Subcutaneous Solution 212097 11/2021
Lactitol https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211281.pdf Draft Oral For Solution 211281 11/2021
Lemborexant https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212028.pdf Draft Oral Tablet 212028 11/2021
Lurbinectedin https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213702.pdf Draft Intravenous Powder 213702 11/2021
Minocycline Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212379.pdf Draft Topical Aerosol, Foam 212379 11/2021
Minocycline Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213690.pdf Draft Topical Aerosol, Foam 213690 11/2021
Minocycline Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209269.pdf Draft Oral Tablet, Extended Release 209269 11/2021
Opicapone https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212489.pdf Draft Oral Capsule 212489 11/2021
Pemigatinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213736.pdf Draft Oral Tablet 213736 11/2021
Potassium Phosphate, Dibasic; Potassium Phosphate, Monobasic https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212832.pdf Draft Intravenous Solution 212832 11/2021
Potassium Phosphate, Dibasic; Potassium Phosphate, Monobasic https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212121.pdf Draft Intravenous Solution 212121 11/2021
Remimazolam Besylate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212295.pdf Draft Intravenous Powder 212295 11/2021
Riluzole https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209080.pdf Draft Oral Suspension 209080 11/2021
Rimegepant Sulfate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212728.pdf Draft Oral Tablet, Orally Disintegrating 212728 11/2021
Sodium Iodide I-131 https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_016517.pdf Draft Oral Capsule 016517 11/2021
Tenapanor Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211801.pdf Draft Oral Tablet 211801 11/2021
Tucatinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213411.pdf Draft Oral Tablet 213411 11/2021

Newly Revised Guidances since November 2021

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Alprazolam https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021726.pdf Draft Oral Tablet, Orally Disintegrating 021726 11/2021
Aripiprazole https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021729.pdf Draft Oral Tablet, Orally Disintegrating 021729 11/2021
Carbidopa; Levodopa https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_076699.pdf Draft Oral Tablet, Orally Disintegrating 078690 11/2021
Cetirizine Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022578.pdf Draft Oral Tablet, Orally Disintegrating 022578 11/2021
Colesevelam Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021176.pdf Draft Oral Tablet 021176 11/2021
Colesevelam Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022362.pdf Draft Oral For Suspension 022362 11/2021
Desloratadine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021312.pdf Draft Oral Tablet, Orally Disintegrating 021312 11/2021
Donepezil Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021720.pdf Draft Oral Tablet, Orally Disintegrating 021720 11/2021
Lansoprazole https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021428.pdf Draft Oral Tablet, Delayed Release, Orally Disintegrating 021428 11/2021
Leuprolide Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021088.pdf Draft Implantation Implant 021088 11/2021
Leuprolide Acetate; Norethindrone Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_203696.pdf Draft Intramuscular, Oral Injectable, Tablet 203696 11/2021
Loratadine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020704.pdf Draft Oral Tablet, Orally Disintegrating 020704 11/2021
Methylphenidate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_205489.pdf Draft Oral Tablet, Orally Disintegrating, Extended Release 205489 11/2021
Metoclopramide Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022246.pdf Draft Oral Tablet, Orally Disintegrating 022246 11/2021
Mirtazapine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021208.pdf Draft Oral Tablet, Orally Disintegrating 021208 11/2021
Olanzapine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021086.pdf Draft Oral Tablet, Orally Disintegrating 021086 11/2021
Ondansetron https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020781.pdf Draft Oral Tablet, Orally Disintegrating 020781 11/2021
Risperidone https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021444.pdf Draft Oral Tablet, Orally Disintegrating 021444 11/2021
Rizatriptan Benzoate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020865.pdf Draft Oral Tablet, Orally Disintegrating 020865 11/2021
Triamcinolone Acetonide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_012041.pdf Draft Injection Injectable 012041 014901 11/2021
Zolmitriptan https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021231.pdf Draft Oral Tablet, Orally Disintegrating 021231 11/2021

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