Drugs

Product-Specific Guidances for Generic Drug Development

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initial step for selecting methodology for generic drug product development, applicants are referred to the following draft guidance:  Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application (ANDA) (Dec. 2013).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

The Agency is seeking feedback and considers comments to the docket on these guidances.  The comments should be submitted to the Division of Dockets Management (DDM) under Docket FDA-2007-D-0369-0015.  For electronic comments, refer to the website http://www.regulations.gov OR mail your written comments to DDM (HFA-305), FDA, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.  Please contact the Regulations.gov Help Desk at 1-877-378-5457 (toll free) for assistance regarding submissions.   

For additional information on development of generic drug products, please refer to FDA’s webpage on biopharmaceutics guidances.
 
1GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2018-2022 (GDUFA II Commitment Letter) available at https://www.fda.gov/downloads/forindustry/userfees/genericdruguserfees/ucm525234.pdf
 

 

Product-Specific Guidances Arranged by Active Ingredient

A  B  C  D  E  F  G  H  I  J  K  L  M  N  O  P  Q  R  S  T  U  V  W  X  Y  Z

Newly Added Guidances since September 1, 2018 (42 New; 12 Revisions) updated  9/13/2018

Active Ingredient
(link to Specific Guidance)
TypeRoute of AdministrationDosage FormRLD Application Number
(link to Orange Book)
Date Recommended
 

Abemaciclib (PDF - 41KB) 

 DraftOral

Tablet

2087169/2018

Albuterol sulfate (PDF - 117KB) 

 Draft Inhalation

Powder, metered

2056369/2018

 Allopurinol; Lesinurad (PDF - 41KB)

 DraftOralTablet2092039/2018

 Amantadine HCl (PDF - 40KB)

DraftOralCapsule, Extended Release2089449/2018

 Amphetamine Aspartate; Amphetamine Sulfate; Dextroamphetamine Saccharate; Dextroamphetamine Sulfate (PDF - 56KB)

DraftOralCapsule, Extended Release0220639/2018

Azelaic acid (PDF - 96KB)

 DraftTopical Foam, Aerosol2070719/2018

Benznidazole (PDF - 44KB)  

DraftOralTablet2095709/2018

Brigatinib (PDF - 41KB)

DraftOralTablet2087729/2018

 Brimonidine tartrate; Timolol maleate (PDF - 41KB) 

DraftOphthalmicSolution/drops0213989/2018

 Chlorzoxazone (PDF - 41KB)

DraftOralTablet0115299/2018

 Ciprofloxacin HCl (PDF - 101KB)

DraftOphthalmicOintment0203699/2018

Dapagliflozin propanediol; Saxagliptin HCl (PDF - 42KB)

DraftOralTablet2090919/2018

 Delafloxacin meglumine (PDF - 40KB)

DraftOralTablet2086109/2018

 Desonide (PDF - 39KB)

Draft

Topical

Gel

021844

9/2018

 Deutetrabenazine (PDF - 60KB)

DraftOralTablet2080829/2018

 Diazepam (PDF - 61KB)

DraftOralTablet0132639/2018

 Efinaconazole (PDF - 44KB) 

DraftTopicalSolution2035679/2018

Enasidenib mesylate (PDF - 54KB)

DraftOralTablet2096069/2018

Glecaprevir; Pibrentasvir (PDF - 41KB)

DraftOralTablet2093949/2018

Ibuprofen; Pseudoephedrine HCl (PDF - 39KB)

DraftOralTablet0197719/2018

 Ivermectin (PDF - 103KB)

DraftTopicalLotion2027369/2018

Lamotrigine (PDF - 54KB)

DraftOralTablet, Disintegrating0222519/2018

 Luliconazole (PDF - 107KB)

DraftTopicalCream

204153

9/2018

 Midostaurin (PDF - 42KB)

DraftOralCapsule

207997

9/2018

 Miltefosine (PDF - 62KB)

DraftOralCapsule2046849/2018

 Morphine sulfate (PDF - 63KB)

DraftOralCapsule2086039/2018

 Neratinib maleate (PDF - 41KB)

DraftOralTablet2080519/2018

 Olaparib (PDF - 43KB)

DraftOralTablet2085589/2018

 Olive Oil; Soybean Oil (PDF - 42KB)

DraftInjectionInjectable2045089/2018

 Oxycodone HCl (PDF - 61KB)

DraftOralTablet2097779/2018

 Penciclovir (PDF - 49KB)

DraftTopicalCream0206299/2018

 Perflutren (PDF - 45KB)

DraftIntravenousInjectable0210649/2018

 Pilocarpine HCl (PDF - 41KB)

DraftOphthalmicSolution2008909/2018

 Pitavastatin magnesium (PDF - 40KB)

DraftOralTablet2083799/2018

 Pitavastatin sodium (PDF - 39KB)

DraftOralTablet2098759/2018

 Pregabalin (PDF - 42KB)

DraftOralTablet, Extended Release2095019/2018

 Secnidazole (PDF - 41KB)

DraftOralGranules2093639/2018

 Sofosbuvir; Velpatasvir; Voxilaprevir (PDF - 53KB)

DraftOralTablet2091959/2018

 Spironolactone (PDF - 39KB)

DraftOralSuspension2094789/2018

 Sulfur hexafluoride lipid-type A microsphere (PDF - 45KB)

DraftIntravenousSuspension2036849/2018

 Talc (PDF - 38KB)

DraftIntrapleuralAerosol0205879/2018

Tavaborole (PDF - 44KB)

DraftTopicalSolution2044279/2018
 

Newly Revised Guidances since September 1, 2018

Active Ingredient
(link to Specific Guidance)
TypeRoute of AdministrationDosage FormRLD Application Number
(link to Orange Book)
Date Recommended
 
Acetazolamide (PDF - 17 KB)RevisedDraftOralTablet0089439/2018
Chlorpromazine Hydrochloride (PDF - 45KB) Revised Draft OralTablet

084112

084114

 9/2018
Doxorubicin Hydrochloride (PDF-66KB)RevisedDraftInjectionInjectable, Liposomal507189/2018

Morphine sulfate (PDF - 43KB)Revised

DraftOralTablet, Extended Release2065449/2018

Nicotine Polacrilex (PDF - 25KB) Revised

DraftBuccalChewing Gum20066

18612

9/2018
Nicotine Polacrilex (PDF - 35KB) RevisedDraftOralTroche/lozenge223609/2018

Nicotine Polacrilex (PDF - 41KB)Revised

DraftOralTroche/lozenge213309/2018
Nisoldipine (PDF - 38KB)
Revised
DraftOralTablet, Extended Release203569/2018

Oxycodone (PDF - 54KB)  Revised

DraftOralCapsule, Extended Release2080909/2018
Raltegravir Potassium (PDF - 28KB) RevisedDraftOralTablet221459/2018
Tacrolimus (PDF - 80KB) RevisedDraftTopicalOintment 0.1%507779/2018
Tacrolimus (PDF - 77KB) RevisedDraftTopicalOintment 0.03%507779/2018

 

 

 

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