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.

Active Ingredient(s)	Route of Administration	Dosage Form	RLD Application Number
Planned New PSGs for Complex Generic Drug Products Updated March 25, 2021
ACLIDINIUM BROMIDE; FORMOTEROL FUMARATE	INHALATION	POWDER	210595
ACYCLOVIR	OPHTHALMIC	OINTMENT	202408
ACYCLOVIR; HYDROCORTISONE	TOPICAL	CREAM	022436
AFAMELANOTIDE	SUBCUTANEOUS	IMPLANT	210797
ALBUTEROL SULFATE; IPRATROPIUM BROMIDE	INHALATION	SPRAY, METERED	021747
ASENAPINE	TRANSDERMAL	SYSTEM	212268
BECLOMETHASONE DIPROPIONATE MONOHYDRATE	NASAL	SPRAY, METERED	019389
BETAMETHASONE DIPROPIONATE; CALCIPOTRIENE	TOPICAL	CREAM	213422
CHLORHEXIDINE GLUCONATE	DENTAL	TABLET	020774
CICLESONIDE	NASAL	SPRAY, METERED	022044
CLOBETASOL PROPIONATE	TOPICAL	CREAM	209483
COLESEVELAM HYDROCHLORIDE	ORAL	BAR, CHEWABLE	210895
CYTARABINE; DAUNORUBICIN	INTRAVENOUS	POWDER	209401
DESMOPRESSIN ACETATE	NASAL	SPRAY, METERED	201656
DOXYCYCLINE HYCLATE	PERIODONTAL	SYSTEM, EXTENDED RELEASE	050751
ETHINYL ESTRADIOL; SEGESTERONE ACETATE	VAGINAL	RING	209627
EXENATIDE	SUBCUTANEOUS	SUSPENSION, EXTENDED RELEASE	209210
FERRIC DERISOMALTOSE	INTRAVENOUS	SOLUTION	208171
FIDAXOMICIN	ORAL	FOR SUSPENSION	213138
FLUNISOLIDE	NASAL	SPRAY, METERED	018148
FLUOROURACIL	TOPICAL	CREAM	022259
FLUTICASONE FUROATE; UMECLIDINIUM BROMIDE; VILANTEROL TRIFENATATE	INHALATION	POWDER	209482
FLUTICASONE PROPIONATE	NASAL	SPRAY, METERED	209022
FORMOTEROL FUMARATE; GLYCOPYRROLATE	INHALATION	AEROSOL, METERED	208294
GLUCAGON	SUBCUTANEOUS	SOLUTION	212097
GOLODIRSEN	INTRAVENOUS	SOLUTION	211970
HALOBETASOL PROPIONATE	TOPICAL	AEROSOL, FOAM	210566
HALOBETASOL PROPIONATE	TOPICAL	LOTION	209355
HEPARIN SODIUM	INJECTION	INJECTABLE	017029
HYDROCORTISONE ACETATE; PRAMOXINE HYDROCHLORIDE	TOPICAL	AEROSOL, FOAM	086457
IPRATROPIUM BROMIDE	NASAL	SPRAY, METERED	020393; 020394
IRINOTECAN HYDROCHLORIDE	INTRAVENOUS	INJECTABLE, LIPOSOMAL	207793
LEUPROLIDE ACETATE	SUBCUTANEOUS	POWDER	021343
LEUPROLIDE ACETATE	SUBCUTANEOUS	POWDER	021731
LEVODOPA	INHALATION	POWDER	209184
LEVONORGESTREL	INTRAUTERINE	INTRAUTERINE DEVICE	208224
LIDOCAINE; TETRACAINE	TOPICAL	PATCH	021623
LOTEPREDNOL ETABONATE	OPHTHALMIC	GEL	208219
MECHLORETHAMINE HYDROCHLORIDE	TOPICAL	GEL	202317
MELOXICAM	INTRAVENOUS	SOLUTION	210583
METOCLOPRAMIDE HYDROCHLORIDE	NASAL	SPRAY, METERED	209388
MICONAZOLE NITRATE; PETROLATUM, WHITE; ZINC OXIDE	TOPICAL	OINTMENT	021026
MIDAZOLAM	NASAL	SPRAY	211321
MOMETASONE FUROATE	IMPLANTATION	IMPLANT	209310
OLODATEROL HYDROCHLORIDE	INHALATION	SPRAY, METERED	203108
OLODATEROL HYDROCHLORIDE; TIOTROPIUM BROMIDE	INHALATION	SPRAY, METERED	206756
PALIPERIDONE PALMITATE	INTRAMUSCULAR	SUSPENSION, EXTENDED RELEASE	207946
PATIROMER SORBITEX CALCIUM	ORAL	POWDER	205739
PROGESTERONE	VAGINAL	SYSTEM	201110
SECRETIN SYNTHETIC HUMAN	INTRAVENOUS	FOR SOLUTION	021256
SEMAGLUTIDE	ORAL	TABLET	213051
SODIUM CHLORIDE	INHALATION	AEROSOL, METERED	019912
TEGASEROD MALEATE	ORAL	TABLET	021200
TENAPANOR HYDROCHLORIDE	ORAL	TABLET	211801
TOBRAMYCIN	INHALATION	POWDER	201688
TRIFAROTENE	TOPICAL	CREAM	211527
ZANAMIVIR	INHALATION	POWDER	021036

Planned Revised PSGs for Complex Generic Drug Products Updated March 25, 2021
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); Update the language Minor Revision: Add links or references to general guidance; Comply with Clinical Data Interchange Standards Consortium (CDISC)
ADAPALENE; BENZOYL PEROXIDE	TOPICAL	GEL	022320	Editorial Revision: Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach
ADAPALENE; BENZOYL PEROXIDE	TOPICAL	GEL	207917	Editorial Revision: Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach
AZACITIDINE	INTRAVENOUS, SUBCUTANEOUS	POWDER	050794	Editorial Revision: Correct typos
BENZYL ALCOHOL	TOPICAL	LOTION	022129	Minor Revision: Add links or references to general guidance
BETAMETHASONE DIPROPIONATE; CALCIPOTRIENE	TOPICAL	OINTMENT	021852	Editorial Revision: Correct typos; Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach
BETAMETHASONE DIPROPIONATE; CALCIPOTRIENE	TOPICAL	SUSPENSION	022185	Editorial Revision: Correct typos; Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach
BEXAROTENE	TOPICAL	GEL	021056	Minor Revision: Add links or references to general guidance
BUDESONIDE	ORAL	CAPSULE, EXTENDED RELEASE	021324	Editorial Revision: Update the language
BUTENAFINE HYDROCHLORIDE	TOPICAL	CREAM	020524	Editorial Revision: Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach
BUTENAFINE HYDROCHLORIDE	TOPICAL	CREAM	021307	Editorial Revision: Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach
CALCIPOTRIENE	TOPICAL	OINTMENT	020273	Editorial Revision: Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach
CALCIPOTRIENE	TOPICAL	CREAM	020554	Editorial Revision: Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach
CLINDAMYCIN PHOSPHATE	TOPICAL	LOTION	050600	Editorial Revision: Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach
CRISABOROLE	TOPICAL	OINTMENT	207695	Editorial Revision: Update the language Minor Revision: Add links or references to general guidance
DICLOFENAC SODIUM	TOPICAL	GEL	021005	Editorial Revision: Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach
DICLOFENAC SODIUM	TOPICAL	GEL	022122	Editorial Revision: Update the language; Update the web links Minor Revision: Add an in vitro BE option as an alternative BE approach; Comply with CDISC
DOCOSANOL	TOPICAL	CREAM	020941	Editorial Revision: Update the language Minor Revision: Add links or references to general guidance; Comply with CDISC
FERRIC CITRATE	ORAL	TABLET	205874	Minor Revision: Correct an error
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: Add an in vitro BE option as an alternative BE approach
FLUTICASONE PROPIONATE	NASAL	SPRAY, METERED	205434	Editorial Revison: Update the references
IRON SUCROSE	INTRAVENOUS	INJECTABLE	021135	Minor Revision: Provide more details on product characterization
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
LEUPROLIDE ACETATE	INJECTABLE	INJECTION	019732; 020011; 020263	Minor Revision: Clarify in vivo study design
LEUPROLIDE ACETATE	IMPLANTATION	IMPLANT	021088	Minor Revision: Clarify in vivo study design
LEUPROLIDE ACETATE	INJECTABLE	INJECTION	020517; 020708	Minor Revision: Clarify in vivo study design
LEUPROLIDE ACETATE; NORETHINDRONE ACETATE	INTRAMUSCULAR, ORAL	INJECTABLE, TABLET	203696	Minor Revision: Clarify in vivo study design
LEVONORGESTREL	INTRAUTERINE	INTRAUTERINE DEVICE	203159	Minor Revision: Clarify in vitro BE study design; Add recommendations for device comparisons Major Revision: Add in vivo BE study
LIDOCAINE	TOPICAL	OINTMENT	008048	Minor Revision: Clarify in vitro study design; Add links or references to general guidance
LIDOCAINE	TOPICAL	PATCH	207962	Minor Revision: Change study design for in vivo BE studies
LOTEPREDNOL ETABONATE	OPTHALMIC	SUSPENSION	020583	Minor Revision: Update the language
LULICONAZOLE	TOPICAL	CREAM	204153	Minor Revision: Add links or references to general guidance
MUPIROCIN CALCIUM	TOPICAL	CREAM	050746	Editorial Revision: Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach; Comply with CDISC
OXYCODONE	ORAL	CAPSULE, EXTENDED RELEASE	208090	Major Revision: Add additional in vitro feeding tube studies
OZENOXACIN	TOPICAL	CREAM	208945	Minor Revision: Add links or references to general guidance
PACLITAXEL	INJECTION	SUSPENSION	021660	Editorial Revision: Correct typos
PENCICLOVIR	TOPICAL	CREAM	020629	Minor Revision: Add links or references to general guidance
PENTOSAN POLYSULFATE SODIUM	ORAL	CAPSULE	020193	Minor Revision: Add an in vitro BE option as an alternative BE approach.
PODOFILOX	TOPICAL	GEL	020529	Minor Revision: Clarify in vivo study design
SILVER SULFADIAZINE	TOPICAL	CREAM	017381	Minor Revision: Add links or references to general guidance
SODIUM ZIRCONIUM CYCLOSILICATE	ORAL	SUSPENSION	207078	Minor Revision: Correct an error
SPINOSAD	TOPICAL	SUSPENSION	022408	Minor Revision: Clarify in vitro study design; Add links or references to general guidance
SUCROFERRIC OXYHYDROXIDE	ORAL	CHEWABLE TABLET	205109	Minor Revision: Add API sameness recommendations
TACROLIMUS	TOPICAL	OINTMENT 0.03%	050777	Editorial Revision: Update the language Minor Revision: Add links or references to general guidance; Comply with CDISC
TACROLIMUS	TOPICAL	OINTMENT 0.1%	050777	Editorial Revision: Update the language Minor Revision: Add links or references to general guidance; Comply with CDISC
TESTOSTERONE	IMPLANTATION	PELLET	080911	Major Revision: Add additional partial AUC recommendations
TRIAMCINOLONE ACETONIDE	INJECTION	INJECTABLE	012041; 014901	Editorial Revision: Correct typos Minor Revision: Add information on newly approved strengths of the RLD