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Upcoming Product-Specific Guidances for Complex Generic Drug Product Development

Introduction

This web page provides information related to upcoming new and revised product-specific guidances (PSGs) to support the development and approval of safe and effective complex generic drug products.

What is a complex generic drug product?

As described in the GDUFA II Commitment Letter, a complex generic drug product generally means the following—

  • A product with:
    • a complex active ingredient(s) (e.g., peptides, polymeric compounds, complex mixtures of APIs, naturally sourced ingredients)
    • a complex formulation (e.g., liposomes, colloids)
    • a complex route of delivery (e.g., locally acting drugs such as dermatological products and complex ophthalmological products and otic dosage forms that are formulated as suspensions, emulsions or gels)
    • a complex dosage form (e.g., transdermals, metered dose inhalers, extended release injectables)
  • Complex drug-device combination products (e.g., auto injectors, metered dose inhalers); and
  • Other products where complexity or uncertainty concerning the approval pathway or possible alternative approaches would benefit from early scientific engagement.

How often does FDA publish new and revised PSGs?

To support generic drug development and generic drug approval, FDA issues new and revised PSGs on a quarterly and as needed basis. These PSGs, including PSGs for complex generic drug products, when finalized, describe FDA’s current thinking and expectations on how to develop generic drug products to specific reference listed drugs and are intended to assist the generic pharmaceutical industry with identifying the most appropriate methodology and evidence needed to support a specific generic drug’s approval. The published PSGs are announced in the Federal Register and made available to the public on FDA’s website.

What information is being provided on this web page?

For new PSGs for complex generic drug products under development, this web page provides information on the active ingredient(s), the route of administration and dosage form, and the reference listed drug (RLD) application number. In addition to this information, the list of PSGs for complex generic products under revision also includes the planned revision categories. This web page only describes FDA’s plans for issuing new and revised PSGs for these complex generic drug products.

What do the different planned revision categories mean?

For revised PSGs, the planned revision categories briefly describe the nature of the anticipated revisions. Planned revision categories are defined as the following:

  • Major revision: A PSG is being revised to include additional bioequivalence studies or evidence recommended to support FDA approval.
  • Minor revision: Any revision that is not considered major, including but not limited to when a PSG is to be revised to remove certain studies, to provide alternative (less burdensome) approaches to the currently recommended studies, to add information on newly approved strengths of the RLD, or to make other recommendations that would not generally result in additional recommended bioequivalence studies or evidence by an ANDA applicant.
  • Editorial revision: A PSG is being revised to include non-substantive changes such as updating external references, correcting grammatical issues, and streamlining the format of existing recommendations.

FDA will also provide specific information on the planned revision when such information is available for public release.

How often does FDA update this web page?

This web page will be updated each time FDA issues a new quarterly PSG batch. Each update removes the published PSGs and adds any new PSG under development or revision. This advance notice will help generic drug companies to plan for their development of complex generic drug products.  

New and Revised PSGs for Complex Generic Drug Products

Below is the list of PSGs for complex generic drug products that FDA plans to issue and the list of PSGs that FDA plans to revise in the coming year. While this list reflects FDA’s effort to be transparent regarding current plans for developing PSGs for complex generic drug products, it should be noted that timing may be subject to change.

 

Planned New PSGs for Complex Generic Drug Products
Updated 11/21/2019

Active Ingredient(s) Route of Administration Dosage Form RLD Application Number
ACYCLOVIR; HYDROCORTISONE TOPICAL CREAM 22436
AMINO ACIDS; CALCIUM CHLORIDE; DEXTROSE; MAGNESIUM SULFATE; POTASSIUM CHLORIDE; SODIUM ACETATE; SODIUM GLYCEROPHOSPHATE; SOYBEAN OIL INTRAVENOUS EMULSION 200656
APREPITANT INTRAVENOUS EMULSION 209296
BESIFLOXACIN HYDROCHLORIDE OPHTHALMIC SUSPENSION/DROPS 22308
BUDESONIDE ORAL CAPSULE 211929
BUPRENORPHINE SUBCUTANEOUS SOLUTION, EXTENDED RELEASE 209819
CHLORHEXIDINE GLUCONATE DENTAL TABLET 20774
CLEVIDIPINE INTRAVENOUS EMULSION 22156
CROFELEMER ORAL TABLET, DELAYED RELEASE 202292
CYTARABINE; DAUNORUBICIN INTRAVENOUS POWDER 209401
DEGARELIX ACETATE SUBCUTANEOUS POWDER 22201
DESMOPRESSIN ACETATE NASAL SPRAY, METERED 201656
EPINEPHRINE INHALATION AEROSOL, METERED 205920
ESKETAMINE HYDROCHOLORIDE NASAL SPRAY 211243
ESTRADIOL VAGINAL INSERT, EXTENDED RELEASE 20472
ETHINYL ESTRADIOL; SEGESTERONE ACETATE VAGINAL RING 209627
FISH OIL TRIGLYCERIDES INTRAVENOUS EMULSION 210589
FLUOROMETHOLONE OPHTHALMIC SUSPENSION/DROPS 19216
FLUOROURACIL TOPICAL CREAM 22259
GLYCOPYRROLATE; INDACATEROL MALEATE INHALATION POWDER 207930
GRANISETRON SUBCUTANEOUS INJECTION, EXTENDED RELEASE 22445
HALOBETASOL PROPIONATE TOPICAL AEROSOL, FOAM 210566
HALOBETASOL PROPIONATE TOPICAL LOTION 209355
HEPARIN SODIUM INJECTION INJECTABLE 17029
HYDROCORTISONE ACETATE; PRAMOXINE HYDROCHLORIDE TOPICAL AEROSOL, FOAM 86457
LEUPROLIDE ACETATE SUBCUTANEOUS INJECTABLE 21343
LEUPROLIDE ACETATE SUBCUTANEOUS INJECTABLE 21731
LEVONORGESTREL INTRAUTERINE INTRAUTERINE DEVICE 208224
LIDOCAINE; TETRACAINE TOPICAL PATCH 21623
LIRAGLUTIDE RECOMBINANT SUBCUTANEOUS SOLUTION 22341
MECHLORETHAMINE HYDROCHLORIDE TOPICAL GEL 202317
MOMETASONE FUROATE IMPLANTATION IMPLANT 209310
METRONIDAZOLE VAGINAL GEL 205223
MICONAZOLE NITRATE; PETROLATUM, WHITE; ZINC OXIDE TOPICAL OINTMENT 21026
PATIROMER SORBITEX CALCIUM ORAL POWDER 205739
RIFAMYCIN ORAL TABLET, DELAYED RELEASE 210910
SEMAGLUTIDE SUBCUTANEOUS SOLUTION 209637
SODIUM ZIRCONIUM CYCLOSILICATE ORAL FOR SUSPENSION 207078
SUMATRIPTAN NASAL SPRAY 210884
SUMATRIPTAN SUCCINATE INHALATION POWDER 206099
TALC INTRAPLEURAL POWDER 205555
TIOTROPIUM BROMIDE INHALATION SPRAY, METERED 21936
TOBRAMYCIN INHALATION POWDER 201688
TRETINOIN TOPICAL LOTION 209353
TRETINOIN TOPICAL GEL 0.06%, 0.08% 20475
UMECLIDINIUM BROMIDE; VILANTEROL TRIFENATATE INHALATION POWDER 203975

 

Planned Revised PSGs for Complex Generic Drug Products
Updated 11/21/2019

Active Ingredient(s) Route of Administration Dosage Form RLD Application Number Planned Revision Category (Brief Reason)
ACYCLOVIR TOPICAL CREAM 021478 Editorial Revision: Reorganize information on In-Vitro Release Test (IVRT) and In Vitro Permeation Test (IVPT); Minor Revision: Add links or references to general guidance
ALBUTEROL SULFATE INHALATION POWDER, METERED 205636 Minor Revision:  Remove recommendations on bronchodilatation BE study
AZELASTINE HCL; FLUTICASONE PROPIONATE NASAL   SPRAY, METERED 202236 Editorial Revision:  Correct typos
BECLOMETHASONE DIPROPIONATE INHALATION AEROSOL, METERED 020911 Minor Revision:  Add an in vitro BE option as an alternative BE approach
BENZYL ALCOHOL TOPICAL LOTION 022129 Minor Revision: Add links or references to general guidance
BEXAROTENE TOPICAL GEL 021056 Minor Revision: Add links or references to general guidance
BUDESONIDE NASAL SPRAY, METERED 020746 Editorial Revision:  Correct typos  
BUPRENORPHINE TRANSDERMAL FILM, EXTENDED RELEASE 021306 Minor Revision: Clarify in vivo study design
CALCITONIN SALMON NASAL SPRAY, METERED 020313 Minor Revision: Clarify in vivo study design; Add recommendations for device comparisons
CRISABOROLE TOPICAL OINTMENT 207695 Minor Revision: Add links or references to general guidance
DIHYDROERGOTAMINE MESYLATE NASAL SPRAY, METERED 020148 Editorial Revision: Correct typos
DOCOSANOL TOPICAL CREAM 020941 Minor Revision: Add links or references to general guidance
FERRIC CITRATE ORAL TABLET 205874 Major Revision:  Add two new options: in-vitro  BE option for similar formulations or comparative clinical endpoint BE study
FLUOROURACIL TOPICAL CREAM 016831 Minor Revision: Add an in vitro BE option as an alternative BE approach
FLUOROURACIL TOPICAL CREAM 020985 Minor Revision: Add an in vitro BE option as an alternative BE approach
FLUOROURACIL TOPICAL CREAM 016988 Minor Revision: Clarify in vitro studies
FLUTICASONE FUROATE NASAL SPRAY, METERED 022051 Editorial Revision:  Correct Typos
FLUTICASONE PROPIONATE NASAL SPRAY, METERED 020121 Editorial Revision:  Correct typos  
FLUTICASONE PROPIONATE;  SALMETEROL XINAFOATE INHALATION AEROSOL, METERED 021254 Editorial Revision:  Correct typos  
IVERMECTIN TOPICAL LOTION 202736 Minor Revision: Add links or references to general guidance
IVERMECTIN TOPICAL CREAM 206255 Minor Revision: Add links or references to general guidance
LEVALBUTEROL TARTRATE INHALATION AEROSOL, METERED 021730 Minor Revision:  Remove recommendations on bronchodilatation BE study
LEVONORGESTREL INTRAUTERINE INTRAUTERINE DEVICE 203159 Major Revision: Clarify in vitro BE study design; Add in vivo BE study; Add recommendations for device comparisons
LEVONORGESTREL INTRAUTERINE INTRAUTERINE DEVICE 021225  Major Revision: Clarify in vitro study design; Clarify in vivo study design; Add recommendations for device comparisons
LIDOCAINE TOPICAL OINTMENT 008048 Minor Revision: Clarify in vitro study design; Add links or references to general guidance
LOTEPREDNOL ETABONATE; TOBRAMYCIN OPHTHALMIC SUSPENSION/ DROPS 050804 Major Revision:  Add additional in-vitro BE Study
LULICONAZOLE TOPICAL CREAM 204153 Minor Revision: Add links or references to general guidance
METRONIDAZOLE VAGINAL GEL 021806 020208 Minor Revision:  Add an in vitro BE option as an alternative BE approach
MOMETASONE FUROATE NASAL SPRAY, METERED 020762 Editorial Revision:  Correct typos  
NITAZOXANIDE ORAL TABLET 021497 Minor Revision: Correction of fasted and fed state simulated intestinal fluid
OLSALAZINE SODIUM ORAL CAPSULE 019715 Major Revision: Add additional fasting BE study
OZENOXACIN TOPICAL CREAM 208945 Minor Revision: Add links or references to general guidance
PENCICLOVIR TOPICAL CREAM 020629 Minor Revision: Add links or references to general guidance
SILVER SULFADIAZINE TOPICAL CREAM 017381 Minor Revision: Add links or references to general guidance
SPINOSAD TOPICAL SUSPENSION 022408 Minor Revision: Clarify in vitro study design; Add links or references to general guidance
TACROLIMUS TOPICAL OINTMENT 0.03% 050777 Minor Revision: Add links or references to general guidance
TACROLIMUS TOPICAL OINTMENT 0.1% 050777 Minor Revision: Add links or references to general guidance
TESTOSTERONE IMPLANTATION PELLET 080911 Major Revision: Add additional partial AUC recommendation(s)
TRETINOIN TOPICAL CREAM 017340 Editorial Revision: Update weblinks and typos; Minor Revision: Add an in vitro BE option as an alternative BE approach
TRETINOIN TOPICAL CREAM 017522 Editorial Revision: Update weblinks and typos; Minor Revision: Add an in vitro BE option as an alternative BE approach
TRETINOIN TOPICAL CREAM 019049 Editorial Revision: Update weblinks and typos; Minor Revision: Add an in vitro BE option as an alternative BE approach
TRETINOIN TOPICAL GEL 017955 Editorial Revision: Update weblinks and typos; Minor Revision: Add an in vitro BE option as an alternative BE approach
TRETINOIN TOPICAL GEL 017579 Editorial Revision: Update weblinks and typos; Minor Revision: Add an in vitro BE option as an alternative BE approach
TRETINOIN TOPICAL GEL 0.04%,  0.1% 020475 Editorial Revision: Update weblinks and typos; Minor Revision: Reorganize information to include all strengths within a single PSG
TRETINOIN TOPICAL GEL 022070 Editorial Revision: Update weblinks and typos; Minor Revision: Add an in vitro BE option as an alternative BE approach
TRETINOIN TOPICAL CREAM 021108 Minor Revision: Add an in vitro BE option as an alternative BE approach; Comply with Clinical Data Interchange Standards Consortium (CDISC)
TRETINOIN TOPICAL CREAM 019963 Minor Revision: Add an in vitro BE option as an alternative BE approach; Comply with Clinical Data Interchange Standards Consortium (CDISC)
TRIAMCINOLONE ACETONIDE NASAL SPRAY, METERED 020468 Editorial Revision:  Correct typos  
TRIAMCINOLONE ACETONIDE INJECTION INJECTABLE 012041; 014901 Minor revision: Add information on newly approved strength(s) of the RLD
Editorial Revision: Correct typos