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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance: Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).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: 1832

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 2020

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Albuterol Sulfate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019604.pdf Draft Oral Tablet, Extended Release 019604 03/2020
Amifampridine Phosphate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208078.pdf Draft Oral Tablet 208078 03/2020
Amino Acids;Calcium Chloride;Dextrose;Magnesium Sulfate;Potassium Chloride;Sodium Acetate;Sodium Glycerophosphate;Soybean Oil https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_200656.pdf Draft Intravenous Emulsion 200656 03/2020
Besifloxacin Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022308.pdf Draft Ophthalmic Suspension/Drops 022308 03/2020
Binimetinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210498.pdf Draft Oral Tablet 210498 03/2020
Budesonide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211929.pdf Draft Oral Capsule, Extended Release 211929 03/2020
Clevidipine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022156.pdf Draft Intravenous Emulsion 022156 03/2020
Dacomitinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211288.pdf Draft Oral Tablet 211288 03/2020
Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210874.pdf Draft Oral Tablet, Extended Release 210874 03/2020
Diltiazem Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_018602.pdf Draft Oral Tablet 018602 03/2020
Doravirine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210806.pdf Draft Oral Tablet 210806 03/2020
Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210807.pdf Draft Oral Tablet 210807 03/2020
Duloxetine Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212516.pdf Draft Oral Capsule, Delayed Release 212516 03/2020
Edaravone https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209176.pdf Draft Intravenous Solution 209176 03/2020
Elagolix Sodium https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210450.pdf Draft Oral Tablet 210450 03/2020
Granisetron https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022445.pdf Draft Subcutaneous Injection, Extended Release 022445 03/2020
Ivacaftor; Lumacaftor https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211358.pdf Draft Oral Granule 211358 03/2020
Liraglutide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022341.pdf Draft Subcutaneous Solution 022341 03/2020
Lusutrombopag https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210923.pdf Draft Oral Tablet 210923 03/2020
Mexiletine Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_018873.pdf Draft Oral Capsule 074377 03/2020
Moxidectin https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210867.pdf Draft Oral Tablet 210867 03/2020
Propranolol Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021438.pdf Draft Oral Capsule, Extended Release 021438 03/2020
Rifamycin Sodium https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210910.pdf Draft Oral Tablet, Delayed Release 210910 03/2020
Selenious Acid https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209379.pdf Draft Intravenous Solution 209379 03/2020
Semaglutide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209637.pdf Draft Subcutaneous Solution 209637 03/2020
Stiripentol https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_206709.pdf Draft Oral Capsule 206709 03/2020
Stiripentol https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_207223.pdf Draft Oral For Suspension 207223 03/2020
Sumatriptan Succinate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_206099.pdf Draft Nasal Powder 206099 03/2020
Tacrolimus https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210115.pdf Draft Oral For Suspension 210115 03/2020
Tiopronin https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211843.pdf Draft Oral Tablet, Delayed Release 211843 03/2020
Tolvaptan https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_204441.pdf Draft Oral Tablet 204441 03/2020
Umeclidinium Bromide; Vilanterol Trifenatate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_203975.pdf Draft Inhalation Powder 203975 03/2020
Upadacitinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211675.pdf Draft Oral Tablet, Extended Release 211675 03/2020

Newly Revised Guidances since March 2020

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Albuterol Sulfate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020503.pdf Draft Inhalation Aerosol, Metered 020503 021457 020983 03/2020
Albuterol Sulfate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_205636.pdf Draft Inhalation Powder, Metered 205636 03/2020
Beclomethasone Dipropionate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020911.pdf Draft Inhalation Aerosol, Metered 020911 03/2020
Calcitonin Salmon https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020313.pdf Draft Nasal Spray, Metered 020313 03/2020
Dapagliflozin; Metformin Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_205649.pdf Draft Oral Tablet, Extended Release 205649 03/2020
Edoxaban Tosylate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_206316.pdf Draft Oral Tablet 206316 03/2020
Ibrutinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_205552.pdf Draft Oral Capsule 205552 03/2020
Levalbuterol Tartrate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021730.pdf Draft Inhalation Aerosol, Metered 021730 03/2020
Olsalazine Sodium https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019715.pdf Draft Oral Capsule 019715 03/2020
Selexipag https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_207947.pdf Draft Oral Tablet 207947 03/2020

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