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 October 21, 2022
|
Active Ingredient(s) |
Route of Administration |
Dosage Form |
RLD or RS Application Number |
|---|---|---|---|
| AFAMELANOTIDE | SUBCUTANEOUS | IMPLANT | 210797 |
| AMMONIUM LACTATE | TOPICAL | CREAM | 075774 |
| AMMONIUM LACTATE | TOPICAL | LOTION | 019155 |
| ARIPIPRAZOLE | ORAL | TABLET | 207202 |
| BIMATOPROST | OPHTHALMIC | IMPLANT | 211911 |
| BUDESONIDE | ORAL | CAPSULE, DELAYED RELEASE | 215935 |
| CABOTEGRAVIR | INTRAMUSCULAR | SUSPENSION, EXTENDED RELEASE | 215499 |
| CABOTEGRAVIR; RILPIVIRINE | INTRAMUSCULAR | SUSPENSION, EXTENDED RELEASE | 212888 |
| CALCITONIN SALMON | INJECTION | INJECTABLE | 017808 |
| CASIMERSEN | INTRAVENOUS | SOLUTION | 213026 |
| CITRIC ACID; LACTIC ACID; POTASSIUM BITARTRATE | VAGINAL | GEL | 208352 |
| CLINDAMYCIN PHOSPHATE | VAGINAL | GEL | 215650 |
| CLOBETASOL PROPIONATE | TOPICAL | CREAM | 209483 |
| CLOBETASOL PROPIONATE | TOPICAL | LOTION | 213691 |
| DESMOPRESSIN ACETATE | NASAL | SPRAY, METERED | 201656 |
| DEXTROAMPHETAMINE | TRANSDERMAL | SYSTEM | 215401 |
| DIHYDROERGOTAMINE MESYLATE | NASAL | SPRAY, METERED | 213436 |
| DONEPEZIL HYDROCHLORIDE | TRANSDERMAL | SYSTEM | 212304 |
| ETEPLIRSEN | INTRAVENOUS | SOLUTION | 206488 |
| ETHINYL ESTRADIOL; SEGESTERONE ACETATE | VAGINAL | RING | 209627 |
| FERRIC DERISOMALTOSE | INTRAVENOUS | SOLUTION | 208171 |
| FERRIC PYROPHOSPHATE CITRATE | INTRAVENOUS | SOLUTION | 212860 |
| FIDAXOMICIN | ORAL | FOR SUSPENSION | 213138 |
| FLUTICASONE PROPIONATE | NASAL | SPRAY, METERED | 209022 |
| FORMOTEROL FUMARATE; GLYCOPYRROLATE | INHALATION | AEROSOL, METERED | 208294 |
| GIVOSIRAN SODIUM | SUBCUTANEOUS | SOLUTION | 212194 |
| GLUCAGON | NASAL | POWDER | 210134 |
| GOLODIRSEN | INTRAVENOUS | SOLUTION | 211970 |
| HYDROCORTISONE | RECTAL | ENEMA | 016199 |
| HYDROCORTISONE ACETATE; PRAMOXINE HYDROCHLORIDE | TOPICAL | AEROSOL, METERED | 086457 |
| INOTERSEN SODIUM | SUBCUTANEOUS | SOLUTION | 211172 |
| LANREOTIDE ACETATE | SUBCUTANEOUS | SOLUTION | 215395 |
| LEUPROLIDE MESYLATE | SUBCUTANEOUS | EMULSION | 211488 |
| LEVODOPA | INHALATION | POWDER | 209184 |
| LEVONORGESTREL | INTRAUTERINE | INTRAUTERINE DEVICE | 208224 |
| LIDOCAINE; TETRACAINE | TOPICAL | PATCH | 021623 |
| LOXAPINE | INHALATION | POWDER | 022549 |
| MAGNESIUM SULFATE; POTASSIUM CHLORIDE; SODIUM SULFATE | ORAL | TABLET | 213135 |
| MANNITOL | INHALATION | POWDER | 202049 |
| MANNITOL | INHALATION | POWDER | 022368 |
| MECHLORETHAMINE HYDROCHLORIDE | TOPICAL | GEL | 202317 |
| MICONAZOLE NITRATE; WHITE PETROLATUM; ZINC OXIDE | TOPICAL | OINTMENT | 021026 |
| MITOMYCIN | PYELOCALYCEAL | POWDER | 211728 |
| MOMETASONE FUROATE | IMPLANTATION | IMPLANT | 209310 |
| MOMETASONE FUROATE | NASAL | SPRAY, METERED | 215712 |
| NALOXONE HYDROCHLORIDE | INJECTION | INJECTABLE | 215457 |
| OBEVIXIBAT | ORAL | CAPSULE | 215498 |
| PATIROMER SORBITEX CALCIUM | ORAL | POWDER | 205739 |
| PATISIRAN SODIUM | INTRAVENOUS | SOLUTION | 210922 |
| PEGCETACOPLAN | SUBCUTANEOUS | SOLUTION | 215014 |
| RUXOLITINIB PHOSPHATE | TOPICAL | CREAM | 215309 |
| SIROLIMUS | INTRAVENOUS | POWDER | 213312 |
| SIROLIMUS | TOPICAL | GEL | 213478 |
| TESTOSTERONE | NASAL | GEL, METERED | 205488 |
| TOBRAMYCIN | INHALATION | POWDER | 201688 |
| TRIAMCINOLONE ACETONIDE | INJECTION | SUSPENSION | 211950 |
| TRIAMCINOLONE ACETONIDE | INTRA-ARTICULAR | FOR SUSPENSION, EXTENDED RELEASE | 208845 |
| VARENICLINE TARTRATE | NASAL | SOLUTION | 213978 |
| VILTOLARSEN | INTRAVENOUS | SOLUTION | 212154 |
| VOSORITIDE | SUBCUTANEOUS | POWDER | 214938 |
| ZANAMIVIR | INHALATION | POWDER | 021036 |
Planned Revised PSGs for Complex Generic Drug Products
Updated October 21, 2022
| Active Ingredient(s) | Route of Administration | Dosage Form | RLD or RS Application | Planned Revision Category (Brief Reason) |
|---|---|---|---|---|
| ACYCLOVIR | BUCCAL | TABLET | 203791 | Editorial Revision: Update language Minor Revision: Clarify in vivo study |
| AZELAIC ACID | TOPICAL | GEL | 021470 | Minor Revision: Add an in vitro BE option as an alternative BE approach |
| BENZOYL PEROXIDE; CLINDAMYCIN PHOSPHATE | TOPICAL | GEL | 050819 | Minor Revision: Add an in vitro BE option as an alternative BE approach |
| DAUNORUBICIN CITRATE | INJECTION | INJECTABLE, LIPOSOMAL | 050704 | Editorial Revision: Correct typos Minor Revision: Clarify in vivo study design |
| DICLOFENAC EPOLAMINE | TOPICAL | SYSTEM | 021234 | Editorial Revision: Update the language Minor Revision: Add links or references to general guidance; Comply with CDISC |
| FERRIC OXYHYDROXIDE (Previous active ingredient name: Iron Dextran) |
INJECTION | INJECTABLE | 017441 | Editorial Revision: Update the active ingredient name Minor Revision: Provide more details on product characterization; Add additional in vivo study design option |
| FERRIC OXYHYDROXIDE (Previous active ingredient name: Sodium Ferric Gluconate Complex) |
INJECTION | INJECTABLE | 020955 | Editorial Revision: Update the active ingredient name Minor Revision: Provide more details on product characterization; Add additional in vivo study design option |
| FERUMOXYTOL | INTRAVENOUS | SOLUTION | 022180 | Editorial Revision: Correct typos; Update the language Minor Revision: Clarify in vivo study design |
| FLUOROURACIL | TOPICAL | CREAM | 020985 | Minor Revision: Add an in vitro BE option as an alternative BE approach |
| GOSERELIN ACETATE | IMPLANTATION | IMPLANT | 019726 | Editorial Revision: Update the language Minor Revision: Clarify in vivo study design Major Revision: Add additional partial Area Under the Curve (pAUC) recommendations |
| GOSERELIN ACETATE | IMPLANTATION | IMPLANT | 020578 | Editorial Revision: Update the language Minor Revision: Clarify in vivo study design Major Revision: Add additional pAUC recommendations |
| ICOSAPENT ETHYL | ORAL | CAPSULE | 202057 | Minor Revision: Add information on newly approved strengths of the Reference Listed Drug (RLD) |
| LANREOTIDE ACETATE | SUBCUTANEOUS | SOLUTION | 022074 | Editorial Revision: Update the language Minor Revision: Add recommendations for device comparisons |
| LEVONORGESTREL | INTRAUTERINE | INTRAUTERINE DEVICE | 203159 | Minor Revision: Clarify in vitro and in vivo BE study designs |
| 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 |
| OXYCODONE | ORAL | CAPSULE, EXTENDED RELEASE | 208090 | Editorial Revision: Update the language Minor Revision: Add links or references to general guidance Major Revision: Add additional in vitro feeding tube studies |
| PALIPERIDONE PALMITATE | INTRAMUSCULAR | SUSPENSION, EXTENDED RELEASE | 022264 | Minor Revision: Clarify in vivo study design |
| PROGESTERONE | VAGINAL | GEL | 020701 | Editorial Revision: Update the language Minor Revision: Add an in vitro BE option as an alternative BE approach; Clarify in vivo study design; Add recommendations for device comparisons; Comply with CDISC |
| RIFAXIMIN | ORAL | TABLET | 021361 | Major Revision: Add in vivo BE study |
| SODIUM PHOSPHATE, DIBASIC, ANHYDROUS; SODIUM PHOSPHATE, MONOBASIC, MONOHYDRATE | ORAL | TABLET | 021892 | Editorial Revision: Update language |
| SUCRALFATE | ORAL | SUSPENSION | 019138 | Minor Revision: Provide more details on in vitro testing |
| SUCRALFATE | ORAL | TABLET | 018333 | Minor Revision: Provide more details on in vitro testing |
| SUMATRIPTAN SUCCINATE | SUBCUTANEOUS | INJECTABLE | 020080 | Minor Revision: Clarify in vitro study design |