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 6/03/2020

Active Ingredient(s)	Route of Administration	Dosage Form	RLD Application Number
ACYCLOVIR; HYDROCORTISONE	TOPICAL	CREAM	022436
BREMELANOTIDE ACETATE	SUBCUTANEOUS	SOLUTION	210557
CHLORHEXIDINE GLUCONATE	DENTAL	TABLET	020774
CLOBETASOL PROPIONATE	TOPICAL	CREAM	209483
CROFELEMER	ORAL	TABLET, DELAYED RELEASE	202292
CYTARABINE; DAUNORUBICIN	INTRAVENOUS	POWDER	209401
DEGARELIX ACETATE	SUBCUTANEOUS	POWDER	022201
DESMOPRESSIN ACETATE	NASAL	SPRAY, METERED	201656
DOXYCYCLINE HYCLATE	PERIODONTAL	SYSTEM, EXTENDED RELEASE	050751
EPINEPHRINE	INHALATION	AEROSOL, METERED	205920
ESKETAMINE HYDROCHOLORIDE	NASAL	SPRAY	211243
ETHINYL ESTRADIOL; SEGESTERONE ACETATE	VAGINAL	RING	209627
EXENADITE	SUBCUTANEOUS	SUSPENSION, EXTENDED RELEASE	209210
FERRIC DERISOMALTOSE	INTRAVENOUS	SOLUTION	208171
FIDAXOMICIN	ORAL	FOR SUSPENSION	213138
FLUTICASONE PROPIONATE	NASAL	SPRAY, METERED	209022
FLUOROURACIL	TOPICAL	CREAM	022259
GLUCAGON	SUBCUTANEOUS	SOLUTION	212097
HALOBETASOL PROPIONATE	TOPICAL	AEROSOL, FOAM	210566
HALOBETASOL PROPIONATE	TOPICAL	LOTION	209355
HEPARIN SODIUM	INJECTION	INJECTABLE	017029
HYDROCORTISONE ACETATE; PRAMOXINE HYDROCHLORIDE	TOPICAL	AEROSOL, FOAM	086457
IRINOTECAN HYDROCHLORIDE	INTRAVENOUS	INJECTABLE, LIPOSOMAL	207793
LEUPROLIDE ACETATE	SUBCUTANEOUS	INJECTABLE	021343
LEUPROLIDE ACETATE	SUBCUTANEOUS	INJECTABLE	021731
LEVODOPA	INHALATION	POWDER	209184
LEVONORGESTREL	INTRAUTERINE	INTRAUTERINE DEVICE	208224
LIDOCAINE; TETRACAINE	TOPICAL	PATCH	021623
MECHLORETHAMINE HYDROCHLORIDE	TOPICAL	GEL	202317
MOMETASONE FUROATE	IMPLANTATION	IMPLANT	209310
MICONAZOLE NITRATE; PETROLATUM, WHITE; ZINC OXIDE	TOPICAL	OINTMENT	021026
MIDAZOLAM	NASAL	SPRAY	211321
MOMETASONE FUROATE	IMPLANTATION	IMPLANT	209310
NALOXONE HYDROCHLORIDE; OXYCODONE HYDROCHLORIDE	ORAL	TABLET, EXTENDED RELEASE	205777
OCTREOTIDE ACETATE	SUBCUTANEOUS	SOLUTION	213224
OLODATEROL HCL; TIOTROPIUM BROMIDE	INHALATION	SPRAY; METERED	206756
PATIROMER SORBITEX CALCIUM	ORAL	POWDER	205739
PENICILLIN G BENZATHINE	INJECTION	INJECTABLE	050141
SECRETIN SYNTHETIC HUMAN	INTRAVENOUS	FOR SOLUTION	021256
SEMAGLUTIDE	ORAL	TABLET	213051
SUMATRIPTAN	NASAL	SPRAY	210884
TALC	INTRAPLEURAL	POWDER	205555
TENAPANOR HYDROCHLORIDE	ORAL	TABLET	211801
TIOTROPIUM BROMIDE	INHALATION	SPRAY, METERED	021936
TOBRAMYCIN	INHALATION	POWDER	201688
VANCOMYCIN HYDROCHLORIDE	ORAL	FOR SOLUTION	208910

 

 

Planned Revised PSGs for Complex Generic Drug Products
Updated 6/3/2020

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
AMPHOTERICIN B	INJECTION	INJECTABLE, LIPOSOMAL	050740	Minor Revision: Clarify in vitro study design; clarify in vivo study design. Editorial Revision:  Correct typos
AZACITIDINE	INTRAVENOUS, SUBCUTANEOUS	POWDER	050794	Editorial Revision:  Correct 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
BUDESONIDE	NASAL	SPRAY, METERED	020746	Editorial Revision:  Correct typos
BUDESONIDE	ORAL	CAPSULE, DELAYED RELEASE	021324	Editorial Revison:  Correct typos
CLINDAMYCIN PHOSPHATE	TOPICAL	LOTION	050600	Minor Revision: Add an in vitro BE option as an alternative BE approach Editorial Revision:  Update the language (changing to common language)
CRISABOROLE	TOPICAL	OINTMENT	207695	Minor Revision: Add links or references to general guidance
DOCOSANOL	TOPICAL	CREAM	020941	Minor Revision: Add links or references to general guidance
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
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
KETOROLAC TROMETHAMINE	NASAL	SPRAY, METERED	022382	Editorial Revision:  Correct Typos; Update the language (changing to common language)
LEVONORGESTREL	INTRAUTERINE	INTRAUTERINE DEVICE	203159	Major Revision: Clarify in vitro BE study design; Add in vivo BE study; 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
NITAZOXANIDE	ORAL	TABLET	021497	Minor Revision: Correction of fasted and fed state simulated intestinal fluid
OMEGA-3-ACID EHTYL ESTERS	ORAL	CAPSULE	021654	Minor Revision: Provide more details on product characterization
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
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.
SILVER SULFADIAZINE	TOPICAL	CREAM	017381	Minor Revision: Add links or references to general guidance
SODIUM POLYSTYRENE SULFONATE	ORAL/RECTAL	SUSPENSION	087859	Minor Revision: Provide more details on product characterization
SPINOSAD	TOPICAL	SUSPENSION	022408	Minor Revision: Clarify in vitro study design; Add links or references to general guidance
TACROLIMUS	TOPICAL	OINTMENT 0.03%	050777	Editorial: Update the language (changing to common language); Minor Revision: Add links or references to general guidance; Comply with Clinical Data Interchange Standards Consortium (CDISC)
TACROLIMUS	TOPICAL	OINTMENT 0.1%	050777	Editorial Revision: Update the language (changing to common language); Minor Revision: Add links or references to general guidance; Comply with CDISC
TESTOSTERONE	IMPLANTATION	PELLET	080911	Major Revision: Add additional partial AUC recommendation(s)
TRIAMCINOLONE ACETONIDE	INJECTION	INJECTABLE	012041; 014901	Editorial Revision: Correct typos; Minor Revision: Add information on newly approved strength(s) of the RLD
TRIPTORELIN PAMOATE	INTRAMUSCULAR	INJECTION	022437 021288 022437	Editorial Revision:  Add additional RLD (208956)