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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance: Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).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: 1760

Product-Specific Guidances for Specific Products Arranged by Active Ingredient


Search by Active Ingredient or by RLD or RS Number


Newly Added Guidances since September 2019

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Acyclovir https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019909.pdf Draft Oral Suspension 019909 09/2019
Amantadine hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209410.pdf Draft Oral Tablet, Extended Release 209410 09/2019
Amoxicillin; Clavulanate potassium https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050785.pdf Draft Oral Tablet, Extended Release 050785 09/2019
Avatrombopag maleate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210238.pdf Draft Oral Tablet 210238 09/2019
Baloxavir marboxil https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210854.pdf Draft Oral Tablet 210854 09/2019
Baricitinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_207924.pdf Draft Oral Tablets 207924 09/2019
Benztropine mesylate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_009193.pdf Draft Oral Tablet 009193 09/2019
Chenodiol https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_018513.pdf Draft Oral Tablet 018513 09/2019
Chlordiazepoxide hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_012249.pdf Draft Oral Capsule 012249 09/2019
Chlorpheniramine maleate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_007638.pdf Draft Oral Tablet, Extended Release 007638 09/2019
Chlorpromazine hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_009149.pdf Draft Oral Concentrate 009149 09/2019
Chlorthalidone https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019574.pdf Draft Oral Tablet 25 mg; 15 mg 019574 09/2019
Clemastine fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_017661.pdf Draft Oral Tablet 2.68 mg 017661 09/2019
Clemastine fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020925.pdf Draft Oral Tablet 1.34 mg 020925 09/2019
Duvelisib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211155.pdf Draft Oral Capsule 211155 09/2019
Fexofenadine hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_201373.pdf Draft Oral Suspension 201373 09/2019
Fluorometholone acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019079.pdf Draft Ophthalmic Suspension, Drops 019079 09/2019
Fluticasone propionate; Salmeterol xinafoate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208799.pdf Draft Inhalation Powder 208799 09/2019
Fostamatinib disodium https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209299.pdf Draft Oral Tablet 209299 09/2019
Glycopyrronium tosylate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210361.pdf Draft Topical Cloth 210361 09/2019
Hydrogen peroxide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209305.pdf Draft Topical Solution 209305 09/2019
Hydroxyprogesterone caproate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021945.pdf Draft Intramuscular Solution 021945 09/2019
Ibrutinib https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210563.pdf Draft Oral Tablet 210563 09/2019
Ketoprofen https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019816.pdf Draft Oral Capsule, Extended Release 019816 09/2019
Lamivudine; Tenofovir disoproxil fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022344.pdf Draft Oral Tablet 022344 09/2019
Levetiracetam https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_204417.pdf Draft Oral Tablet, Extended Release 204417 09/2019
Lofexidine hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209229.pdf Draft Oral Tablet 209229 09/2019
Loteprednol etabonate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210565.pdf Draft Ophthalmic Suspension, Drops 210565 09/2019
Loteprednol etabonate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_202872.pdf Draft Ophthalmic Gel 202872 09/2019
Lovastatin https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021316.pdf Draft Oral Tablet, Extended Release 021316 09/2019
Plazomicin sulfate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_210303.pdf Draft Intravenous Solution 210303 09/2019
Sarecycline hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_209521.pdf Draft Oral Tablet 209521 09/2019
Tecovirimat https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208627.pdf Draft Oral Capsule 208627 09/2019
Thioridazine hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_011808.pdf Draft Oral Tablet 011808 09/2019

Newly Revised Guidances since September 2019

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Acyclovir https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_018604.pdf Draft Topical Ointment 018604 09/2019
Armodafinil https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021875.pdf Draft Oral Tablet 021875 09/2019
Bosutinib monohydrate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_203341.pdf Draft Oral Tablet 203341 09/2019
Budesonide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021324.pdf Draft Oral Capsule, Extended Release 021324 09/2019
Chlorthalidone https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_012283.pdf Draft Oral Tablet 50 mg; 25 mg 012283 09/2019
Colesevelam hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022362.pdf Draft Oral Powder For Suspension 022362 09/2019
Dantrolene sodium https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_017443.pdf Draft Oral Capsule 017443 09/2019
Diphenhydramine citrate; Ibuprofen https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021394.pdf Draft Oral Tablet 021394 09/2019
Duloxetine hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021427.pdf Draft Oral Capsule, Delayed Release Pellets 021427 09/2019
Fingolimod hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022527.pdf Draft Oral Capsule 022527 09/2019
Mesalamine https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022301.pdf Draft Oral Capsule, Extended Release 022301 09/2019
Metronidazole https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019737.pdf Draft Topical Gel 0.75% 019737 09/2019
Metronidazole https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020531.pdf Draft Topical Cream 020531 09/2019
Metronidazole https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020743.pdf Draft Topical Cream 020743 09/2019
Metronidazole https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021789.pdf Draft Topical Gel 1% 021789 09/2019
Metronidazole https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020901.pdf Draft Topical Lotion 020901 09/2019
Plecanatide https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208745.pdf Draft Oral Tablet 208745 09/2019
Sucralfate https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_018333.pdf Draft Oral Tablet 018333 09/2019
Tretinoin https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_016921.pdf Draft Topical Solution 016921 09/2019

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