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 9/16/2019

 

Active Ingredient(s)	Route of Administration	Dosage Form	RLD Application Number
ACYCLOVIR; HYDROCORTISONE	TOPICAL	CREAM	022436
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	022308
BETAMETHASONE DIPROPIONATE; CALCIPOTRIENE	TOPICAL	AEROSOL, FOAM	207589
BUDESONIDE	ORAL	CAPSULE	211929
BUPRENORPHINE	SUBCUTANEOUS	SOLUTION, EXTENDED RELEASE	209819
CHLORHEXIDINE GLUCONATE	DENTAL	TABLET	020774
CLEVIDIPINE	INTRAVENOUS	EMULSION	022156
COPPER	INTRAUTERINE	INTRAUTERINE DEVICE	018680
CROFELEMER	ORAL	TABLET, DELAYED RELEASE	202292
DEGARELIX ACETATE	SUBCUTANEOUS	POWDER	022201
DESMOPRESSIN ACETATE	NASAL	SPRAY, METERED	201656
EPINEPHRINE	INHALATION	AEROSOL, METERED	205920
ESKETAMINE	NASAL	SPRAY	211243
ESTRADIOL	VAGINAL	INSERT, EXTENDED RELEASE	020472
ETHINYL ESTRADIOL; SEGESTERONE ACETATE	VAGINAL	RING	209627
FISH OIL TRIGLYCERIDES	INTRAVENOUS	EMULSION	210589
FLUOROURACIL	TOPICAL	CREAM	022259
GLYCOPYRROLATE; INDACATEROL MALEATE	INHALATION	POWDER	207930
GRANISETRON	SUBCUTANEOUS	INJECTION, EXTENDED RELEASE	022445
HALOBETASOL PROPIONATE	TOPICAL	AEROSOL, FOAM	210566
HALOBETASOL PROPIONATE	TOPICAL	LOTION	209355
HYDROCORTISONE ACETATE; PRAMOXINE HYDROCHLORIDE	TOPICAL	AEROSOL, FOAM	086457
LEUPROLIDE ACETATE	SUBCUTANEOUS	INJECTABLE	021343
LEVONORGESTREL	INTRAUTERINE	INTRAUTERINE DEVICE	208224
LIDOCAINE	TOPICAL	PATCH	207962
LIDOCAINE; TETRACAINE	TOPICAL	PATCH	021623
LUTETIUM DOTATATE LU-177	INTRAVENOUS	SOLUTION	208700
MECHLORETHAMINE HYDROCHLORIDE	TOPICAL	GEL	202317
METRONIDAZOLE	VAGINAL	GEL	205223
OXYMETAZOLINE HYDROCHLORIDE	TOPICAL	CREAM	208552
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	SUBCUTANEOUS	INJECTABLE	020080
SUMATRIPTAN SUCCINATE	INHALATION	POWDER	206099
TALC	INTRAPLEURAL	POWDER	205555
TIMOLOL MALEATE	OPHTHALMIC	SOLUTION, GEL FORMING/DROPS	020330
TOBRAMYCIN	INHALATION	POWDER	201688
TRETINOIN	TOPICAL	LOTION	209353
TRETINOIN	TOPICAL	GEL 0.06%, 0.08%	020475
UMECLIDINIUM BROMIDE; VILANTEROL TRIFENATATE	INHALATION	POWDER	203975

Planned Revised PSGs for Complex Generic Drug Products
Updated 9/16/2019

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
ADAPALENE	TOPICAL	CREAM	020748	Editorial Revision: Update weblinks and typos
ADAPALENE	TOPICAL	GEL	020380	Editorial Revision: Update weblinks and typos
ADAPALENE	TOPICAL	GEL	021753	Editorial Revision: Update weblinks and typos
ADAPALENE	TOPICAL	LOTION	022502	Editorial Revision: Update weblinks and typos
ADAPALENE; BENZOYL PEROXIDE	TOPICAL	GEL	022320	Editorial Revision: Update weblinks and typos
ADAPALENE; BENZOYL PEROXIDE	TOPICAL	GEL	0207917	Editorial Revision: Update weblinks and typos
AZACITIDINE	INTRAVENOUS, SUBCUTANEOUS	POWDER	050794	Editorial Revision: Update the language
BENZOYL PEROXIDE; CLINDAMYCIN PHOSPHATE	TOPICAL	GEL	050741	Editorial Revision: Update weblinks and typos
BENZOYL PEROXIDE; CLINDAMYCIN PHOSPHATE	TOPICAL	GEL	050756	Editorial Revision: Update weblinks and typos
BENZOYL PEROXIDE; CLINDAMYCIN PHOSPHATE	TOPICAL	GEL	050819	Editorial Revision: Update weblinks and typos
BENZOYL PEROXIDE; ERYTHROMYCIN	TOPICAL	GEL	050557	Editorial Revision: Update weblinks and typos
BENZOYL PEROXIDE; ERYTHROMYCIN	TOPICAL	GEL	050769	Editorial Revision: Update weblinks and typos
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
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
CAPSAICIN	TOPICAL	PATCH	022395	Minor Revision: Clarify in vivo study design
CLINDAMYCIN PHOSPHATE	TOPICAL	GEL	050782	Editorial Revision: Update weblinks and typos; Minor Revision: Add an in vitro BE option as an alternative BE approach
CLINDAMYCIN PHOSPHATE	TOPICAL	GEL	050615	Minor Revision: Clarify in vitro study design; Add links or references to general guidance Editorial Revision: Update weblinks and typos
CLINDAMYCIN PHOSPHATE	TOPICAL	LOTION	050600	Editorial Revision: Update weblinks and typos; Minor Revision: Add an in vitro BE option as an alternative BE approach
CLINDAMYCIN PHOSPHATE; TRETINOIN	TOPICAL	GEL	050802 050803	Editorial Revision: Update weblinks and typos
CLONIDINE	TRANSDERMAL	FILM, EXTENDED RELEASE	018891	Minor Revision: Clarify in vivo study design
CRISABOROLE	TOPICAL	OINTMENT	207695	Minor Revision: Add links or references to general guidance
DAPSONE	TOPICAL	GEL	021794	Minor Revision: Clarify in vitro study design; Add links or references to general guidance; Editorial Revision: Update weblinks and typos
DAPSONE	TOPICAL	GEL	207154	Minor Revision: Clarify in vitro study design; Add links or references to general guidance; Editorial Revision: Update weblinks and typos
DICLOFENAC EPOLAMINE	TOPICAL	PATCH	021234	Minor Revision: Clarify in vivo study design
DIHYDROERGOTAMINE MESYLATE	NASAL	SPRAY, METERED	020148	Editorial Revision: Correct typos
DOCOSANOL	TOPICAL	CREAM	020941	Minor Revision: Add links or references to general guidance
DOXEPIN HYDROCHLORIDE	TOPICAL	CREAM	020126	Minor Revision: Clarify in vitro study design; Add links or references to general guidance; Editorial Revision: Update weblinks and typos
ESTRADIOL	TRANSDERMAL	GEL	022038	Editorial Revision: Update weblinks and typos
ESTRADIOL	TRANSDERMAL	FILM, EXTENDED RELEASE	203752	Minor Revision: Clarify in vivo study design
ESTRADIOL	TRANSDERMAL	FILM, EXTENDED RELEASE	020538	Minor Revision: Clarify in vivo study design
ESTRADIOL	TRANSDERMAL	FILM, EXTENDED RELEASE	019081	Minor Revision: Clarify in vivo study design
ESTRADIOL	TRANSDERMAL	FILM, EXTENDED RELEASE	020375; 021674	Minor Revision: Clarify in vivo study design
ESTRADIOL; LEVONORGESTREL	TRANSDERMAL	FILM, EXTENDED RELEASE	021258	Minor Revision: Clarify in vivo study design
ESTRADIOL; NORETHINDRONE ACETATE	TRANSDERMAL	FILM, EXTENDED RELEASE	020870	Minor Revision: Clarify in vivo study design
ETHINYL ESTRADIOL; NORELGESTROMIN	TRANSDERMAL	FILM, EXTENDED RELEASE	021180	Minor Revision: Change in inclusion/exclusion criteria; Clarify in vivo study design
FENTANYL	TRANSDERMAL	FILM, EXTENDED RELEASE	019813	Minor Revision: Clarify in vivo study design
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
GRANISETRON	TRANSDERMAL	FILM, EXTENDED RELEASE	022198	Minor Revision: Clarify in vivo study design
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
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
LIDOCAINE	TOPICAL	PATCH	020612	Minor Revision: Clarify in vivo study design
LULICONAZOLE	TOPICAL	CREAM	204153	Minor Revision: Add links or references to general guidance
MENTHOL; METHYL SALICYLATE	TOPICAL	PATCH	022029	Minor Revision: Clarify in vivo study design
METHYLPHENIDATE	TRANSDERMAL	FILM, EXTENDED RELEASE	021514	Minor Revision: Clarify in vivo study design
NICOTINE	TRANSDERMAL	FILM, CONTROLLED RELEASE	020076 020165	Minor Revision: Clarify in vivo study design
NITAZOXANIDE	ORAL	TABLET	021497	Minor Revision: Correction of fasted and fed state simulated intestinal fluid
NITROGLYCERIN	TRANSDERMAL	FILM, EXTENDED RELEASE	020144	Minor Revision: Clarify in vivo study design
NITROGLYCERIN	TRANSDERMAL	FILM, EXTENDED RELEASE	020145	Minor Revision: Clarify in vivo study design
OLSALAZINE SODIUM	ORAL	CAPSULE	019715	Major Revision: Add additional fasting BE study
OXYBUTYNIN	TRANSDERMAL	FILM, EXTENDED RELEASE	021351	Minor Revision: Clarify in vivo study design
OXYBUTYNIN	TRANSDERMAL	FILM, EXTENDED RELEASE	202211	Minor Revision: Clarify in vivo study design
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
PIMECROLIMUS	TOPICAL	CREAM	021302	Minor Revision: Add an in vitro BE option as an alternative BE approach; Add more details on clinical study design
RIVASTIGMINE	TRANSDERMAL	FILM, EXTENDED RELEASE	022083	Minor Revision: Clarify in vivo study design
ROTIGOTINE	TRANSDERMAL	FILM, EXTENDED RELEASE	021829	Minor Revision: Clarify in vivo study design
SCOPOLAMINE	TRANSDERMAL	FILM, EXTENDED RELEASE	017874	Minor Revision: Change partial AUC parameters; Clarify in vivo study design
SELEGILINE	TRANSDERMAL	FILM, EXTENDED RELEASE	021336	Minor Revision: Clarify in vivo study design
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
SULFACETAMIDE SODIUM	TOPICAL	LOTION	019931	Editorial Revision: Update weblinks and typos
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
TAZAROTENE	TOPICAL	AEROSOL, FOAM	202428	Editorial Revision: Update weblinks and typos
TAZAROTENE	TOPICAL	GEL	020600	Editorial Revision: Update weblinks and typos
TESTOSTERONE	TRANSDERMAL	FILM, EXTENDED RELEASE	020489	Minor Revision: Clarify in vivo study design
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)