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 11/21/2019
| Active Ingredient(s) | Route of Administration | Dosage Form | RLD Application Number |
|---|---|---|---|
| ACYCLOVIR; HYDROCORTISONE | TOPICAL | CREAM | 22436 |
| 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 | 22308 |
| BUDESONIDE | ORAL | CAPSULE | 211929 |
| BUPRENORPHINE | SUBCUTANEOUS | SOLUTION, EXTENDED RELEASE | 209819 |
| CHLORHEXIDINE GLUCONATE | DENTAL | TABLET | 20774 |
| CLEVIDIPINE | INTRAVENOUS | EMULSION | 22156 |
| CROFELEMER | ORAL | TABLET, DELAYED RELEASE | 202292 |
| CYTARABINE; DAUNORUBICIN | INTRAVENOUS | POWDER | 209401 |
| DEGARELIX ACETATE | SUBCUTANEOUS | POWDER | 22201 |
| DESMOPRESSIN ACETATE | NASAL | SPRAY, METERED | 201656 |
| EPINEPHRINE | INHALATION | AEROSOL, METERED | 205920 |
| ESKETAMINE HYDROCHOLORIDE | NASAL | SPRAY | 211243 |
| ESTRADIOL | VAGINAL | INSERT, EXTENDED RELEASE | 20472 |
| ETHINYL ESTRADIOL; SEGESTERONE ACETATE | VAGINAL | RING | 209627 |
| FISH OIL TRIGLYCERIDES | INTRAVENOUS | EMULSION | 210589 |
| FLUOROMETHOLONE | OPHTHALMIC | SUSPENSION/DROPS | 19216 |
| FLUOROURACIL | TOPICAL | CREAM | 22259 |
| GLYCOPYRROLATE; INDACATEROL MALEATE | INHALATION | POWDER | 207930 |
| GRANISETRON | SUBCUTANEOUS | INJECTION, EXTENDED RELEASE | 22445 |
| HALOBETASOL PROPIONATE | TOPICAL | AEROSOL, FOAM | 210566 |
| HALOBETASOL PROPIONATE | TOPICAL | LOTION | 209355 |
| HEPARIN SODIUM | INJECTION | INJECTABLE | 17029 |
| HYDROCORTISONE ACETATE; PRAMOXINE HYDROCHLORIDE | TOPICAL | AEROSOL, FOAM | 86457 |
| LEUPROLIDE ACETATE | SUBCUTANEOUS | INJECTABLE | 21343 |
| LEUPROLIDE ACETATE | SUBCUTANEOUS | INJECTABLE | 21731 |
| LEVONORGESTREL | INTRAUTERINE | INTRAUTERINE DEVICE | 208224 |
| LIDOCAINE; TETRACAINE | TOPICAL | PATCH | 21623 |
| LIRAGLUTIDE RECOMBINANT | SUBCUTANEOUS | SOLUTION | 22341 |
| MECHLORETHAMINE HYDROCHLORIDE | TOPICAL | GEL | 202317 |
| MOMETASONE FUROATE | IMPLANTATION | IMPLANT | 209310 |
| METRONIDAZOLE | VAGINAL | GEL | 205223 |
| MICONAZOLE NITRATE; PETROLATUM, WHITE; ZINC OXIDE | TOPICAL | OINTMENT | 21026 |
| 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 | INHALATION | POWDER | 206099 |
| TALC | INTRAPLEURAL | POWDER | 205555 |
| TIOTROPIUM BROMIDE | INHALATION | SPRAY, METERED | 21936 |
| TOBRAMYCIN | INHALATION | POWDER | 201688 |
| TRETINOIN | TOPICAL | LOTION | 209353 |
| TRETINOIN | TOPICAL | GEL 0.06%, 0.08% | 20475 |
| UMECLIDINIUM BROMIDE; VILANTEROL TRIFENATATE | INHALATION | POWDER | 203975 |
Planned Revised PSGs for Complex Generic Drug Products
Updated 11/21/2019
| 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 |
| ALBUTEROL SULFATE | INHALATION | POWDER, METERED | 205636 | Minor Revision: Remove recommendations on bronchodilatation BE study |
| AZELASTINE HCL; FLUTICASONE PROPIONATE | NASAL | SPRAY, METERED | 202236 | Editorial Revision: Correct typos |
| BECLOMETHASONE DIPROPIONATE | INHALATION | AEROSOL, METERED | 020911 | Minor Revision: Add an in vitro BE option as an alternative BE approach |
| 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 |
| 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 |
| CRISABOROLE | TOPICAL | OINTMENT | 207695 | Minor Revision: Add links or references to general guidance |
| DIHYDROERGOTAMINE MESYLATE | NASAL | SPRAY, METERED | 020148 | Editorial Revision: Correct typos |
| DOCOSANOL | TOPICAL | CREAM | 020941 | Minor Revision: Add links or references to general guidance |
| FERRIC CITRATE | ORAL | TABLET | 205874 | Major Revision: Add two new options: in-vitro BE option for similar formulations or comparative clinical endpoint BE study |
| 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 |
| FLUTICASONE FUROATE | NASAL | SPRAY, METERED | 022051 | Editorial Revision: Correct Typos |
| FLUTICASONE PROPIONATE | NASAL | SPRAY, METERED | 020121 | Editorial Revision: Correct typos |
| FLUTICASONE PROPIONATE; SALMETEROL XINAFOATE | INHALATION | AEROSOL, METERED | 021254 | Editorial Revision: Correct typos |
| 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 |
| LEVALBUTEROL TARTRATE | INHALATION | AEROSOL, METERED | 021730 | Minor Revision: Remove recommendations on bronchodilatation BE study |
| 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 |
| 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 |
| METRONIDAZOLE | VAGINAL | GEL | 021806 020208 | Minor Revision: Add an in vitro BE option as an alternative BE approach |
| MOMETASONE FUROATE | NASAL | SPRAY, METERED | 020762 | Editorial Revision: Correct typos |
| NITAZOXANIDE | ORAL | TABLET | 021497 | Minor Revision: Correction of fasted and fed state simulated intestinal fluid |
| OLSALAZINE SODIUM | ORAL | CAPSULE | 019715 | Major Revision: Add additional fasting BE study |
| 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 |
| 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 |
| 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 |
| 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) |
| TRIAMCINOLONE ACETONIDE | NASAL | SPRAY, METERED | 020468 | Editorial Revision: Correct typos |
| TRIAMCINOLONE ACETONIDE | INJECTION | INJECTABLE | 012041; 014901 | Minor revision: Add information on newly approved strength(s) of the RLD Editorial Revision: Correct typos |