Product-Specific Guidances for Generic Drug Development

Disclaimer: Due to April 2019 systemwide upgrades to www.fda.gov, 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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance: Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).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 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 (https://www.regulations.gov/help). 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) 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.

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

 

 

 

Total number of currently published PSGs: 1939

Product-Specific Guidances for Specific Products Arranged by Active Ingredient


Search by Active Ingredient or by RLD or RS Number


Newly Added Guidances since August 2020

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Alpelisib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212526.pdf Draft Oral Tablet 212526 08/2020
Amlodipine Benzoate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211340.pdf Draft Oral Suspension 211340 08/2020
Amoxicillin; Clarithromycin; Omeprazole https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050824.pdf Draft Oral Capsule, Tablet, Capsule, Delayed Release 050824 08/2020
Amoxicillin; Omeprazole Magnesium; Rifabutin https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213004.pdf Draft Oral Capsule, Delayed Release 213004 08/2020
Bortezomib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021602.pdf Draft Intravenous, Subcutaneous Injectable 021602 08/2020
Cannabidiol https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210365.pdf Draft Oral Solution 210365 09/2020
Darolutamide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212099.pdf Draft Oral Tablet 212099 08/2020
Diroximel Fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211855.pdf Draft Oral Capsule, Delayed Release 211855 08/2020
Drospirenone https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211367.pdf Draft Oral Tablet 211367 08/2020
Empagliflozin; Linagliptin; Metformin Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212614.pdf Draft Oral Tablet, Extended Release 212614 08/2020
Erdafitinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212018.pdf Draft Oral Tablet 212018 08/2020
Esketamine Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211243.pdf Draft Nasal Spray 211243 08/2020
Gallium DOTATOC Ga 68 https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210828.pdf Draft Intravenous Solution 210828 08/2020
Glasdegib Maleate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210656.pdf Draft Oral Tablet 210656 08/2020
Lamivudine; Tenofovir Disoproxil Fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211284.pdf Draft Oral Tablet 211284 08/2020
Larotrectinib Sulfate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210861.pdf Draft Oral Capsule 210861 08/2020
Lefamulin Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211673.pdf Draft Intravenous Solution 211673 08/2020
Sumatriptan https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210884.pdf Draft Nasal Spray 210884 08/2020
Tafenoquine Succinate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210607.pdf Draft Oral Tablet 210607 08/2020
Talc https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_205555.pdf Draft Intrapleural Powder 205555 08/2020

Newly Revised Guidances since August 2020

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Abacavir Sulfate; Dolutegravir Sodium; Lamivudine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_205551.pdf Draft Oral Tablet 205551 08/2020
Amphotericin B https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050740.pdf Draft Injection Injectable, Liposomal 050740 08/2020
Budesonide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020746.pdf Draft Nasal Spray, Metered 020746 08/2020
Dolutegravir Sodium https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_204790.pdf Draft Oral Tablet 204790 08/2020
Dolutegravir Sodium; Rilpivirine Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210192.pdf Draft Oral Tablet 210192 08/2020
Esomeprazole Magnesium https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_204655.pdf Draft Oral Capsule, Delayed Release 204655 08/2020
Ketorolac Tromethamine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022382.pdf Draft Nasal Spray, Metered 022382 08/2020
Loteprednol Etabonate; Tobramycin https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050804.pdf Draft Ophthalmic Suspension/Drops 050804 08/2020
Maraviroc https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022128.pdf Draft Oral Tablet 022128 08/2020
Metoprolol Succinate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019962.pdf Draft Oral Tablet, Extended Release 019962 08/2020
Mycophenolate Mofetil https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050722.pdf Draft Oral Capsule 050722 08/2020
Mycophenolate Mofetil https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050723.pdf Draft Oral Tablet 050723 08/2020
Omega 3 Acid Ethyl Esters https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021654.pdf Draft Oral Capsule 021654 08/2020
Rivaroxaban https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022406.pdf Draft Oral Tablet 022406 08/2020
Sodium Polystyrene Sulfonate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_087859.pdf Draft Oral, Rectal Suspension 087859 08/2020
Theophylline https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_087942.pdf Draft Oral Capsule, Extended Release 081034 08/2020
Theophylline https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_085328-TabER-600MG.pdf Draft Oral Tablet, Extended Release 600 MG 040560 08/2020

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