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  1. Guidance, Compliance, & Regulatory Information

Upcoming Product-Specific Guidances for Complex Generic Drug Product Development

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 5/23/2019

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

BAZEDOXIFENE ACETATE; ESTROGENS,
CONJUGATED

ORAL

TABLET

022247

BESIFLOXACIN HYDROCHLORIDE

OPHTHALMIC

SUSPENSION/DROPS

022308

BETAMETHASONE DIPROPIONATE;
CALCIPOTRIENE

TOPICAL

AEROSOL, FOAM

207589

BUDESONIDE

ORAL

CAPSULE, EXTENDED RELEASE

211929

BUPRENORPHINE

SUBCUTANEOUS

SOLUTION, EXTENDED RELEASE

209819

BUPRENORPHINE

SUBCUTANEOUS

INJECTION, EXTENDED RELEASE

210136

CHLORHEXIDINE GLUCONATE

DENTAL

TABLET

020774

CLEVIDIPINE

INTRAVENOUS

EMULSION

022156

COPPER

INTRAUTERINE

INTRAUTERINE DEVICE

018680

CROFELEMER

ORAL

TABLET, DELAYED RELEASE

202292

CYTARABINE

INJECTION

INJECTABLE, LIPOSOMAL

021041

CYTARABINE; DAUNORUBICIN

INTRAVENOUS

POWDER

209401

DEGARELIX ACETATE

SUBCUTANEOUS

POWDER

022201

DESMOPRESSIN ACETATE

NASAL

SPRAY, METERED

201656

EPINEPHRINE

INHALATION

AEROSOL, METERED

205920

ESTRADIOL

VAGINAL

INSERT, EXTENDED RELEASE

020472

EXENATIDE

SUBCUTANEOUS

SUSPENSION, EXTENDED RELEASE

209210

FISH OIL TRIGLYCERIDES

INTRAVENOUS

EMULSION

210589

FLUOROMETHOLONE ACETATE

OPHTHALMIC

SUSPENSION/DROPS

019079

FLUOROURACIL

TOPICAL

CREAM

022259

FLUTICASONE PROPIONATE;
SALMETEROL XINAFOATE

INHALATION

POWDER

208799

GLYCOPYRROLATE ; INDACATEROL MALEATE

INHALATION

POWDER

207930

GLYCOPYRRONIUM TOSYLATE

TOPICAL

CLOTH

210361

GRANISETRON

SUBCUTANEOUS

INJECTION, EXTENDED RELEASE

022445

HALOBETASOL PROPIONATE

TOPICAL

AEROSOL, FOAM

210566

HYDROCORTISONE ACETATE;
PRAMOXINE HYDROCHLORIDE

TOPICAL

AEROSOL, METERED

086457

HYDROXYPROGESTERONE CAPROATE

INTRAMUSCULAR

SOLUTION

021945

LEVONORGESTREL

INTRAUTERINE

INTRAUTERINE DEVICE

208224

LIDOCAINE

TOPICAL

PATCH

207962

LIDOCAINE; TETRACAINE

TOPICAL

PATCH

021623

LOTEPREDNOL ETABONATE

OPHTHALMIC

GEL

202872

LOTEPREDNOL ETABONATE

OPHTHALMIC

SUSPENSION/DROPS

210565

LUTETIUM DOTATATE LU-177

INTRAVENOUS

SOLUTION

208700

MECHLORETHAMINE HYDROCHLORIDE

TOPICAL

GEL

202317

METRONIDAZOLE

VAGINAL

GEL

205223

MICONAZOLE NITRATE;
PETROLATUM, WHITE; ZINC OXIDE

TOPICAL

OINTMENT

021026

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 SUCCINATE

INHALATION

POWDER

206099

SUMATRIPTAN SUCCINATE

SUBCUTANEOUS

INJECTABLE

020080

TESTOSTERONE

TRANSDERMAL

GEL, METERED

204399

TIMOLOL MALEATE

OPHTHALMIC

SOLUTION, GEL FORMING/DROPS

020330

TOBRAMYCIN

INHALATION

POWDER

201688

TRETINOIN

TOPICAL

LOTION

209353

UMECLIDINIUM BROMIDE;
VILANTEROL TRIFENATATE

INHALATION

POWDER

203975

Planned Revised PSGs for Complex Generic Drug Products
Updated 5/23/2019

Active Ingredient(s)

Route of Administration

Dosage Form

Application Number

Planned Revision Category: Brief Reason

ACYCLOVIR

TOPICAL

OINTMENT

018604

Minor Revision: Provide more details on product characterization

ACYCLOVIR

TOPICAL

CREAM, 5%

021478

Editorial Revision: Reorganize information on In-Vitro Release Test (IVRT) and In Vitro Permeation Test (IVPT)

BUDESONIDE

ORAL

CAPSULE

021324

Major Revision: Add additional sprinkle BE study

CALCITONIN SALMON

NASAL

SPRAY, METERED

020313

Minor Revision: Clarify in vivo study design; Add recommendations for device comparisons

COLESEVELAM HYDROCHLORIDE

ORAL

POWDER FOR SUSPENSION

022362

Editorial Revision: Correct typos

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

LEVONORGESTREL

INTRAUTERINE

INTRAUTERINE DEVICE

203159

Major Revision: Clarify in vitro BE study design; Add in vivo BE study

MESALAMINE

ORAL

CAPSULE, EXTENDED RELEASE

022301

Minor Revision: Change partial AUC parameters

METRONIDAZOLE

TOPICAL

GEL

019737

Minor Revision: Add an in vitro BE option as an alternative BE approach; Comply with Clinical Data Interchange Standards Consortium (CDISC)

METRONIDAZOLE

TOPICAL

CREAM

020531

Minor Revision: Add an in vitro BE option as an alternative BE approach; Comply with Clinical Data Interchange Standards Consortium (CDISC)

METRONIDAZOLE

TOPICAL

CREAM

020743

Minor Revision: Add an in vitro BE option as an alternative BE approach; Comply with Clinical Data Interchange Standards Consortium (CDISC)

METRONIDAZOLE

TOPICAL

LOTION

020901

Minor Revision: Add an in vitro BE option as an alternative BE approach; Comply with Clinical Data Interchange Standards Consortium (CDISC)

METRONIDAZOLE

TOPICAL

GEL

021789

Minor Revision: Add an in vitro BE option as an alternative BE approach; Comply with Clinical Data Interchange Standards Consortium (CDISC)

OMEGA-3-ACID ETHYL ESTERS

ORAL

CAPSULE

021654

Minor Revision: Clarify in vitro study design

PIMECROLIMUS

TOPICAL

CREAM

021302

Minor Revision: Provide more details on clinical study design

PLECANATIDE

ORAL

TABLET

208745

Editorial Revision: Correct typos

SCOPOLAMINE

TRANSDERMAL

FILM, EXTENDED RELEASE

017874

Minor Revision: Change partial AUC parameters

SUCRALFATE

ORAL

TABLET

018333

Minor Revision: Remove recommendation for a comparative clinical endpoint BE study; Add API sameness recommendations

TRETINOIN

TOPICAL

GEL 0.04%,
0.10%

020475

Minor Revision: Reorganize information to include all strengths within a single PSG

TRETINOIN

TOPICAL

GEL 
 

022070

Minor Revision: Add an in vitro BE option as an alternative BE approach

TRETINOIN

TOPICAL

GEL 
 

017955

Minor Revision: Add an in vitro BE option as an alternative BE approach

TRETINOIN

TOPICAL

GEL 
 

017579

Minor Revision: Add an in vitro BE option as an alternative BE approach

TRETINOIN

TOPICAL

CREAM 

019049

Minor Revision: Add an in vitro BE option as an alternative BE approach

TRETINOIN

TOPICAL

CREAM 
 

017522

Minor Revision: Add an in vitro BE option as an alternative BE approach

TRETINOIN

TOPICAL

CREAM
 

017340

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)