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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance: Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).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: 1711

Product-Specific Guidances for Specific Products Arranged by Active Ingredient


Search by Active Ingredient or by RLD or RS Number


Newly Added Guidances since May 2019

Active Ingredient (link to Specific Guidance) URL Type Route Dosage Form RLD or RS Number Date Recommended
Acetaminophen; Codeine Phosphate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Acetaminophen; Codeine Phosphate Tablet ANDA 085055 PSG Page RC May 2019.pdf Draft Oral Tablet 085055 05/2019
Apalutamide https://www.accessdata.fda.gov/drugsatfda_docs/psg/Apalutamide Oral Tablets NDA 210951 PSG Page RC May 2019.pdf Draft Oral Tablet 210951 05/2019
Beclomethasone Dipropionate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Beclomethasone dipropionate Inhalation Aerosol Metered NDA 207921 PSG Page RC May 2019.pdf Draft Inhalation Aerosol, Metered 207921 05/2019
Benoxinate hydrochloride; Fluorescein sodium https://www.accessdata.fda.gov/drugsatfda_docs/psg/Benoxinate hydrochloride; Fluorescein sodium Ophthalmic solution drops 0.25-0.45 NDA 208582 PSG Page RC May 2019.pdf Draft Topical Solution, Drops 208582 05/2019
Bictegravir Sodium; Emtricitabine; Tenofovir Alafenamide Fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Bictegravir Sodium, Emtricitabin, Tenofovir Alafenamide Fumarate Oral Tablet NDA 210251 page RC May 2019.pdf Draft Oral Tablet 210251 05/2019
Brimonidine Tartrate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Brimonidine tartrate ophthalmic solution 0.025 NDA 208144 PSG Page RC May 2019.pdf Draft Ophthalmic Drops, Solution 208144 05/2019
Budesonide https://www.accessdata.fda.gov/drugsatfda_docs/psg/Budesonide Nasal Spray Metered NDA 020746 PSG Page RC May 2019.pdf Draft Nasal Spray, Metered 020746 05/2019
Chlorpheniramine Maleate; Ibuprofen; Pseudoephedrine Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/Chlorpheniramine maleate; Ibuprofen; Pseudoephendrine HCl Tablet 2mg; 200mg; 30mg NDA 021441 PSG Page RC May 2019.pdf Draft Oral Tablet 021441 05/2019
Cyclosporine https://www.accessdata.fda.gov/drugsatfda_docs/psg/Cyclosporine ophthalmic solution 0.09 NDA 210913 PSG Page RC May 2019.pdf Draft Ophthalmic Drops, Solution 210913 05/2019
Desloratadine; Pseudoephedrine Sulfate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Desloratadine_Pseudoephedrine_Oral_Extended_Release_Tablet_NDA_021313_PSG_Page_RC_May_2019.pdf Draft Oral Tablet, Extended Release 021313 05/2019
Desmopressin Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Desmopressin acetate Sublingual Tablets NDA 022517 PSG Page RC May 2019.pdf Draft Sublingual Tablet 022517 05/2019
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Efavirenz Lamivudine Tenoforvir Dsisoproxile Funarate Tablets NDA208255 PSG Page RC May 2019.pdf Draft Oral Tablet 208255 05/2019
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Efavirenz-Lamivudine-Tenofovir Disoproxil Fumarate Oral Tablet NDA 022142 page RC May 2019.pdf Draft Oral Tablet 022142 05/2019
Eravacycline Dihydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/ERAVACYCLINE DIHYDROCHLORIDE POWDER INTRAVENOUS NDA 211109 PSG Page RC May 2019.pdf Draft Intravenous Powder 211109 05/2019
Estradiol; Levonorgestrel https://www.accessdata.fda.gov/drugsatfda_docs/psg/Estradiol Levonorgestrel transdermal extended release film NDA 021258 PSG Page RC May 2019.pdf Draft Transdermal Film, Extended Release 021258 05/2019
Fluticasone Furoate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Fluticasone furoate nasal spray metered NDA 022051 PSG Page RC May 2019.pdf Draft Nasal Spray, Metered 022051 05/2019
Fluticasone Propionate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Fluticasone Propionate Inhalation Powder NDA 208798 PSG Page RC May 2019.pdf Draft Inhalation Powder 208798 05/2019
Fluticasone Propionate; Salmeterol Xinafoate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Fluticasone Propionate; Salmeterol Xinafoate Inhalation Aerosol Metered NDA 021254 PSG Page RC May 2019.pdf Draft Inhalation Aerosol, Metered 021254 05/2019
Fosnetupitant Chloride Hydrochloride; Palonosetron Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/Fosnetupitant and Palonosetron Hydrochloride, powder for injection NDA 210493 PSG Page RC May 2019.pdf Draft Intravenous Powder 210493 05/2019
Halcinonide https://www.accessdata.fda.gov/drugsatfda_docs/psg/Halcinonide topical ointment NDA 017824 PSG Page RC May 2019.pdf Draft Topical Ointment 017824 05/2019
Lamivudine; Tenofovir Disoproxil Fumarate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Lamivudine-Tenofovir Disoproxil Fumarate Oral Tablet NDA 022141 PSG page RC May 2019.pdf Draft Oral Tablet 022141 05/2019
Naproxen https://www.accessdata.fda.gov/drugsatfda_docs/psg/Naproxen Oral Suspension NDA 018965 PSG Page RC May 2019.pdf Draft Oral Suspension 018965 05/2019
Omeprazole Magnesium https://www.accessdata.fda.gov/drugsatfda_docs/psg/Omeprazole magnesium oral delayed release suspension NDA 022056 PSG Page RC May 2019.pdf Draft Oral Granules, Delayed Release 022056 05/2019
Primidone https://www.accessdata.fda.gov/drugsatfda_docs/psg/Primidone Tablets NDA 009170 PSG Page RC May 2019.pdf Draft Oral Tablet 009170 05/2019
Timolol Maleate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Timolol Maleate Ophthalmic Solution NDA 018086 PSG Page RC May 2019.pdf Draft Ophthalmic Drops, Solution 018086 05/2019
Tobramycin https://www.accessdata.fda.gov/drugsatfda_docs/psg/Tobramycin ophthalmic ointment 0.3 NDA 050555 PSG Page RC May 2019.pdf Draft Ophthalmic Ointment 050555 05/2019

Newly Revised Guidances since May 2019

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/Azelaic Acid Cream 20 NDA 020428 PSG Page RV May 2019.pdf Draft Topical Cream 020428 05/2019
Azelaic Acid https://www.accessdata.fda.gov/drugsatfda_docs/psg/Azelaic Acid Gel 15 NDA 021470 PSG Page RV May 2019.pdf Draft Topical Gel 021470 05/2019
Betaxolol Hydrochloride https://www.accessdata.fda.gov/drugsatfda_docs/psg/BETAXOLOL HYDROCHLORIDE ophthalmic suspensiondrops NDA 019845 PSG Page RV May 2019.pdf Draft Ophthalmic Suspension, Drops 019845 05/2019
Brimonidine Tartrate; Brinzolamide https://www.accessdata.fda.gov/drugsatfda_docs/psg/BRIMONIDINE TARTRATE BRINZOLAMIDE ophthalmic suspension drops NDA 204251 PSG Page RV May 2019.pdf Draft Ophthalmic Drops, Suspension 204251 05/2019
Brinzolamide https://www.accessdata.fda.gov/drugsatfda_docs/psg/BRINZOLAMIDE ophthalmic suspension drops NDA 020816 PSG Page RV May 2019.pdf Draft Ophthalmic Suspension, Drops 1% 020816 05/2019
Fosfomycin Tromethamine https://www.accessdata.fda.gov/drugsatfda_docs/psg/Fosfomycin Tromethamine Oral Solution NDA 050717 PSG Page RV May 2019.pdf Draft Oral Suspension 050717 05/2019
Ivermectin https://www.accessdata.fda.gov/drugsatfda_docs/psg/Ivermectin Topical Cream 1 NDA 206255 PSG Page RV May 2019.pdf Draft Topical Cream 206255 05/2019
Methylprednisolone https://www.accessdata.fda.gov/drugsatfda_docs/psg/Methylprednisolone Oral Tablet NDA 11153 PSG Page RV May 2019.pdf Draft Oral Tablet 011153 05/2019
Prednisolone Acetate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Prednisolone acetate Ophthalmic suspension RLD 017011 PSG Page RV May 2019.pdf Draft Ophthalmic Suspension, Drops 017011 05/2019
Tofacitinib Citrate https://www.accessdata.fda.gov/drugsatfda_docs/psg/Tofacitinib Citrate Oral Tablet NDA 203214 PSG Page RV May 2019.pdf Draft Oral Tablet 203214 05/2019

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