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  1. Guidances (Drugs)

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)