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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance: Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).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: 1885

Product-Specific Guidances for Specific Products Arranged by Active Ingredient


Search by Active Ingredient or by RLD or RS Number


Newly Added Guidances since March 2021

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Bremelanotide Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210557.pdf Draft Subcutaneous Solution 210557 03/2021
Calcifediol https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208010.pdf Draft Oral Capsule, Extended Release 208010 03/2021
Cysteamine Bitartrate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213491.pdf Draft Oral Granule, Delayed Release 213491 03/2021
Degarelix Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022201.pdf Draft Subcutaneous Powder 022201 03/2021
Elexacaftor, Ivacaftor, Tezacaftor; Ivacaftor https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212273.pdf Draft Oral Tablet, Tablet 212273 03/2021
Entrectinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212725.pdf Draft Oral Capsule 212725 03/2021
Ethinyl Estradiol; Levonorgestrel https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208612.pdf Draft Oral Tablet 208612 03/2021
Ethinyl Estradiol; Levonorgestrel https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209405.pdf Draft Oral Tablet 209405 03/2021
Fedratinib Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212327.pdf Draft Oral Capsule 212327 03/2021
Ferric Maltol https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212320.pdf Draft Oral Capsule 212320 03/2021
Guanfacine Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019032.pdf Draft Oral Tablet 019032 03/2021
Istradefylline https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022075.pdf Draft Oral Tablet 022075 03/2021
Ledipasvir; Sofosbuvir https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212477.pdf Draft Oral Pellets 212477 03/2021
Monomethyl Fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210296.pdf Draft Oral Capsule, Delayed Release 210296 03/2021
Octreotide Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208232.pdf Draft Oral Capsule, Delayed Release 208232 03/2021
Octreotide Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213224.pdf Draft Subcutaneous Solution 213224 03/2021
Penicillin G Benzathine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050141.pdf Draft Injection Injectable 050141 03/2021
Selinexor https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212306.pdf Draft Oral Tablet 212306 03/2021
Siponimod Fumaric Acid https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209884.pdf Draft Oral Tablet 209884 03/2021
Sofosbuvir https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212480.pdf Draft Oral Pellets 212480 03/2021
Solriamfetol Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211230.pdf Draft Oral Tablet 211230 03/2021
Testosterone Undecanoate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_206089.pdf Draft Oral Capsule 206089 03/2021

Newly Revised Guidances since March 2021

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Cannabidiol https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210365.pdf Draft Oral Solution 210365 03/2021
Ciclesonide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021658.pdf Draft Inhalation Aerosol, Metered 021658 03/2021
Doxycycline Hyclate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050533.pdf Draft Oral Tablet 050533 03/2021
Fenoprofen Calcium https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_017604.pdf Draft Oral Capsule 017604 03/2021
Ipratropium Bromide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021527.pdf Draft Inhalation Aerosol, Metered 021527 03/2021
Ivacaftor; Ivacaftor, Tezacaftor https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210491.pdf Draft Oral Tablet, Tablet 210491 03/2021
Labetalol Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_018687.pdf Draft Oral Tablet 018716 03/2021
Nitazoxanide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021497.pdf Draft Oral Tablet 021497 03/2021
Nitazoxanide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021498.pdf Draft Oral For Suspension 021498 03/2021
Pazopanib Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022465.pdf Draft Oral Tablet 022465 03/2021
Regorafenib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_203085.pdf Draft Oral Tablet 203085 03/2021
Rucaparib Camsylate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209115.pdf Draft Oral Tablet 209115 03/2021
Ursodiol https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019594.pdf Draft Oral Capsule 019594 03/2021
Ursodiol https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020675.pdf Draft Oral Tablet 020675 03/2021

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