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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance: Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).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: 1974

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 2020

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Ceritinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211225.pdf Draft Oral Tablet 211225 11/2020
Clobazam https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210833.pdf Draft Oral Film 210833 11/2020
Crofelemer https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_202292.pdf Draft Oral Tablet, Delayed Release 202292 11/2020
Diazepam https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211635.pdf Draft Nasal Spray 211635 11/2020
Epinephrine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_205920.pdf Draft Inhalation Aerosol, Metered 205920 11/2020
Fluorodopa F18 https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_200655.pdf Draft Intravenous Solution 200655 11/2020
Lefamulin Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211672.pdf Draft Oral Tablet 211672 11/2020
Naloxone Hydrochloride; Oxycodone Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_205777.pdf Draft Oral Tablet, Extended Release 205777 11/2020
Pretomanid https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212862.pdf Draft Oral Tablet 212862 11/2020
Prochlorperazine Maleate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_010571.pdf Draft Oral Tablet 010571 11/2020
Tafamidis https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212161.pdf Draft Oral Capsule 212161 11/2020
Tafamidis Meglumine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211996.pdf Draft Oral Capsule 211996 11/2020
Tiotropium Bromide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021936.pdf Draft Inhalation Spray, Metered 021936 11/2020
Vancomycin Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208910.pdf Draft Oral For Solution 208910 11/2020

Newly Revised Guidances since November 2020

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Azelaic Acid https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_207071.pdf Draft Topical Aerosol, Foam 207071 11/2020
Budesonide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_205613.pdf Draft Rectal Aerosol, Foam 205613 11/2020
Bupropion Hydrochloride; Naltrexone Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_200063.pdf Draft Oral Tablet, Extended Release 200063 11/2020
Calcipotriene https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022563.pdf Draft Topical Aerosol, Foam 022563 11/2020
Clobetasol Propionate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022013.pdf Draft Topical Aerosol, Foam 022013 11/2020
Desonide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021978.pdf Draft Topical Aerosol, Foam 021978 11/2020
Erythromycin Ethylsuccinate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_061904.pdf Draft Oral Tablet 061904 061905 11/2020
Erythromycin Ethylsuccinate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050207.pdf Draft Oral Granule 050207 11/2020
Erythromycin Ethylsuccinate; Sulfisoxazole Acetyl https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050529.pdf Draft Oral Granule 050529 11/2020
Fluphenazine Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_011751.pdf Draft Oral Tablet 011751 089743 11/2020
Hydrocortisone Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_017351.pdf Draft Rectal Aerosol, Metered 017351 11/2020
Isotretinoin https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021951.pdf Draft Oral Capsule 021951 11/2020
Isotretinoin https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_018662.pdf Draft Oral Capsule 076135 018662 11/2020
Levorphanol Tartrate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_008720.pdf Draft Oral Tablet 008720 11/2020
Lomitapide Mesylate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_203858.pdf Draft Oral Capsule 203858 11/2020
Methylphenidate Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_207960.pdf Draft Oral Tablet, Extended Release, Chewable 207960 11/2020
Pimavanserin Tartrate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_207318.pdf Draft Oral Tablet 207318 11/2020
Propranolol Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_016418.pdf Draft Oral Tablet 016418 11/2020
Propranolol Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021438.pdf Draft Oral Capsule, Extended Release 021438 11/2020
Propranolol Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_018553.pdf Draft Oral Capsule, Extended Release 018553 11/2020
Tofacitinib Citrate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208246.pdf Draft Oral Tablet, Extended Release 208246 11/2020

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