Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union
Abstract
:1. Introduction
2. Legal Basis
3. Composition Sameness (Q1/Q2) for the Development of Second-Entry Topical Products
4. Physicochemical and Structural (Q3) Characterization of Second-Entry Topical Products
4.1. General Requirements
- (a)
- Appearance and texture, including the look, feel and smell of the dispensed product;The EMA draft guideline [5] has indicated only appearance but the scope is the same.
- (b)
- Phase states, including high-resolution micrographs to show the absence or presence of undissolved particles to identify single-phase and multiple-phase products;
- (c)
- Structural organization of the matter, including particle size distribution and crystal habit, and/or emulsion globule size distribution and identification of the type of emulsion, e.g., oil in water or water in oil;
- (d)
- Polymorphic form of the active substance within the product for products with a suspended active substance.The EMA draft guideline [5] indicates the particle size distribution and polymorphism for suspensions and the globule size distribution for emulsions, but crystal habit is not mentioned; however, it is mentioned as a factor that may affect bioavailability and should be included in stability studies;
- (e)
- Rheological behavior of liquid and semisolid dosage forms, including
- Complete flow curves plotting shear stress vs. shear rate, and viscosity vs. shear rate until low or high-shear plateaus are achieved. Apparent viscosity should be reported at least at low, middle, and high shear rates.The EMA draft guideline specifies that these shear stress flow sweep experiments should comprise multiple data points across the range of increasing and decreasing shear rates so that any linear portions of the up-curves or down-curves are clearly identified. In contrast to the US FDA, for the EMA, the resulting curves should be characterized by fitting to (modified) power law equations so that numerical data can be produced [15]; however, the minimum of the three share rates to estimate apparent viscosities is not defined, only the need to measure the apparent viscosity at specified shear rates across the rheograms, e.g., η100, and the quantification of the thixotropic relative area (SR) if appropriate.
- Yield stress, if the products exhibit plastic flow behavior.
- Linear viscoelastic response (storage and loss moduli vs. frequency).The EMA draft guideline specifies that viscoelastic storage and loss moduli (G’ and G”), and loss tangent (tan δ) should be determined in these oscillatory strain sweep (shear strain oscillatory amplitude sweep) experiments [15] to obtain parameters that can be compared objectively. The EMA draft guideline also mentions the creep test.
- (f)
- Water activity and/or drying rate, relevant for products with volatile excipients including water;
- (g)
- pH and buffering for products with an aqueous component;
- (h)
- Oleaginous components, which should be characterized according to the tests listed in the US Pharmacopeia;
- (i)
- Specific gravity (density);
- (j)
- Metamorphosis of the product when dispensed from the containers.
4.2. Product-Specific Requirements
4.2.1. Solutions
4.2.2. Suspensions
- (a)
- the drug has a narrow therapeutic index (NTI), but none have been classified as NTI in this route of administration;
- (b)
- the drug exhibits dose-related systemic toxicity, but this can be addressed by comparing systemic exposure with conventional PK BE studies;
- (c)
- the means by which the active substance reaches the local site of action is not established or understood; this is not expected presently and, moreover, it might be claimed that if the formulation is considered to be simple and an extended pharmaceutical equivalence is met, the applied product will be therapeutically equivalent in any case;
- (d)
- the method of administration is not the same, which might be a limitation only if the application device/method is patented;
- (e)
- the product cannot be fully characterized with respect to quality attributes, but this is not foreseen if the reference product has been authorized recently;
- (f)
- it is not possible to measure a quantifiable permeation kinetic or PD event for the product; however, a stratum corneum sampling/tape stripping (TS) study might be used; and
- (g)
- in vitro and in vivo permeation kinetic and PD studies are not applicable or are considered insufficiently predictive of clinical response, e.g., products indicated for the treatment of open wounds and ulcers, which would apply only for complex formulations as explained above. If the formulation is considered simple and extended pharmaceutical equivalence is met, the applied product will be therapeutically equivalent in any case. Therefore, the main limitation is the possibility of developing sensitive IVRT or an in vitro permeation test (IVPT), or the reproducibility of the TS technique.
4.2.3. Gels
4.2.4. Ointments
Drug | RS | Q | AT | M | PS | GS | AV | FC | YS | LVR | WA | pH | SG | DR | OC | IVRT | IVPT |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Acyclovir [75] | 18604 | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||||
Betamethasone Dipropionate; Calcipotriene [68] | 21852 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||
Calcipotriene [76] | 20273 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Crisaborole [77] | 207695 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Gentamicin Sulfate [70] | 62351 | ||||||||||||||||
Mupirocin [69] | 50591 | √ | √ | √ | √ | √ | √ | √ | √ | ||||||||
Nitroglycerin [78] | 21359 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||||
Nystatin [71] | 62124 | ||||||||||||||||
Nystatin; Triamcinolone Acetonide [74] | 63305 | ||||||||||||||||
Tacrolimus [79] | 50777 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Tacrolimus [80] | 50777 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Tirbanibulin [81] | 213189 | √ | √ | √ | √ | √ | √ | √ | √ | ||||||||
Triamcinolone Acetonide [71] | 087385 | ||||||||||||||||
Triamcinolone Acetonide [73] | 08995 |
4.2.5. Creams
4.2.6. Lotions
4.2.7. Other Topical Dosage Forms
- (a)
- Microscopic birefringence analysis of the dispensed foam after complete collapse, in order to determine whether any crystals of undissolved active substance form during dispensing.
- (b)
- Time to break (from dispensing to complete foam collapse) analysis, conducted at 30 °C, 33 °C, 35 °C, and 40 °C under controlled relative humidity conditions.
- (c)
- Weight per volume of uncollapsed foam.
5. Statistical Comparison of Physicochemical Properties
6. In vitro Release Tests (IVRT)
7. Kinetic Studies to Address Local Availability
8. Pharmacodynamic and Clinical Endpoints
9. Decision Tree for the Development of Second-Entry Topical Products
10. Development of Additional Strengths
11. Virtual Bioequivalence
12. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Brominidine tartrate. Gel; Topical. September 2015. 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Brimonidine%20tartrate_topical%20gel_204708_RC09-15.pd (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Clobetasol propionate. Gel; Topical. October 2016. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Clobetasol%20Propionate_topical%20gel%200.05_RLD%2075368_RC09-16.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Desonide. Gel; Topical. September 2018. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Desonide_draft_Topical%20gel_RLD%20021844_RC09-18.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Betamethasone Dipropionate; Calcipotriene. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021852.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Mupirocin. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_018604.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Gentamicin Sulfate. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_060463.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Nystatin. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_060571.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Triamcinolone Acetonide. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_011600.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Triamcinolone Acetonide. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_011600-Oin-0.05P.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Nystatin; Triamcinolone Acetonide. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_060572.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Acyclovir. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050591.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Calcipotriene. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020273.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Crisaborole. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_207695.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Nitroglycerin. Ointment; Intra-Anal. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021359.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Tacrolimus. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050777-Oin-0.1P.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Tacrolimus. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050777-Oin-0.03P.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Tirbanibulin. Ointment; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213189.pdf (accessed on 17 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Acyclovir. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021478.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Acyclovir; Hydrocortisone. Cream; topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022436.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Ammonium lactate. Cream; Topical. November 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020508.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Betamethasone Dipropionate; Calcipotriene. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_213422.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Butenafine Hydrochloride. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020524.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Butenafine Hydrochloride. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021307.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Calcipotriene. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020554.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Docosanol. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020941.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Doxepin Hydrochloride. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020126.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Fluocinolone Acetonide. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_012787.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Fluorouracil. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_016988.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Fluorouracil. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022259.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Gentamicin Sulfate; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_060462.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Ivermectin. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_206255.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Ketoconazole. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019084.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Luliconazole. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_204153.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Metronidazole. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020531.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Metronidazole. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020743.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Mupirocin Calcium. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050746.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Nystatin. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_060575.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Nystatin; Triamcinolone Acetonide. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_060576.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Oxymetazoline Hydrochloride. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208552.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Ozenoxacin. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208945.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Penciclovir. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020629.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Pimecrolimus. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021302.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Silver Sulfadiazine. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_017381.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Tazarotene. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021184-Cre-0.05P.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Tazarotene. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021184-Cre-0.1P.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Triamcinolone Acetonide. Cream; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_011601.pdf (accessed on 26 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Fluorouracil. Cream; Topical. February 2019. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Fluorouracil%20Topical%20Cream%20NDA%20020985%20RV%20Feb%202019.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Ammonium Lactate. Lotion; Topical. November 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_019155.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Abametapir. Lotion; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_206966.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Benzyl Alcohol. Lotion; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_022129.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Clindamicin Phosphate. Lotion; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050600.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Miconazole nitrate; White petrolatum; Zinc oxide. Lotion; Topical. November 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021026.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Triamcinolone Acetonide. Lotion; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_011602.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Malathion. Lotion; Topical. June 2012. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Malathion_draft_Topical%20lotion_RLD%2018613_RC06-12.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Mometasone furoate. Lotion; Topical. April 2016. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Mometasone%20furoate_topical%20lotion_RLD%2019796_RC04-16.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Halobetasol. Lotion; Topical. October 2016. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Halobetasol_topical%20lotion_RLD%20208183_RC%2009-16.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Ivermectin. Lotion; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_202736.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Metronidazole. Lotion; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020901.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Tazarotene. Lotion; Topical. October 2022. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_211882.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Clindamycin phosphate. Aerosol, foam; Topical. June 2020. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050801.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Nystatin. Powder; Topical. August 2021. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_060578.pdf (accessed on 23 December 2022).
- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Ciclopirox. Shampoo/Topical. February 2010. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Ciclopirox_shmp_21159_RC2-10.pdf (accessed on 23 December 2022).
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- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Clobetasol Propionate. Spray/Topical. February 2010. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Clobetasol_Propionate_spray_21835_RC2-11.pdf (accessed on 23 December 2022).
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- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Erythromycin. Swab; Topical. February 2020. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Erythromycin_swab_64126_RC2-10.pdf (accessed on 23 December 2022).
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- U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Draft Guidance on Tretinoin. Gel; Topical. June 2020. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_020475.pdf (accessed on 23 December 2022).
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Drug | RS | Q1Q2 | A | V | pH | SG | DR | ST |
---|---|---|---|---|---|---|---|---|
Calcipotriene [20] | 020611 | √ | ||||||
Clindamycin Phosphate [30] | 050537 | √ | ||||||
Clobetasol Propionate [21] | 019966 | √ | ||||||
Clotrimazole [31] | 018181 | √ | ||||||
Diclofenac sodium [32] | 204623 | √ | ||||||
Diclofenac sodium [22] | 020947 | √ | ||||||
Efinaconazole [35] | 203567 | √ | √ | √ | √ | √ | √ | |
Erythromycin [23] | 064187 | √ | ||||||
Fluorouracil [24] | 016831 | √ | ||||||
Fluorouracil [25] | 016831 | √ | ||||||
Hydrocortisone [26] | 081271 | √ | ||||||
Hydrogen peroxide [37] | 209305 | √ | √ | √ | √ | √ | √ | |
Minoxidil [27] | 019501 | √ | ||||||
Minoxidil [28] | 020834 | √ | ||||||
Podofilox [29] | 019795 | √ | ||||||
Tavaborole [36] | 204427 | √ | √ | √ | √ | √ | ||
Tretinoin [33] | 016921 | √ | √ |
Drug | RS | Q | AT | M | PS | GS | AV | FC | YS | LVR | WA | pH | SG | DR | OC | IVRT | IVPT |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Betamethasone Dipropionate; Calcipotriene [38] | 22185 | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||||
Spinosad [40] | 22408 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Drug | RS | Q | AT | M | PS | GP | AV | FC | YS | LVR | WA | pH | SG | DR | OC | IVRT | IVPT |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Adapalene [43] | 20380 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||||
Adapalene [44] | 21753 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||||
Adapalene, Benzoyl Peroxide [45] | 22320 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||||
Adapalene, Benzoyl Peroxide [46] | 207917 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||||
Bexarotene [47] | 21056 | √ | √ | √ | √ | √ | √ | √ | √ | ||||||||
Clindamycin Phosphate [48] | 50782 | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||||
Clindamycin Phosphate [49] | 50615 | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||||
Clindamycin Phosphate; Tretinoin [50] | 50802 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||||
Clindamycin Phosphate; Tretinoin [51] | 50803 | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||||
Dapsone [52] | 207154 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||
Dapsone [53] | 21794 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||
Diclofenac Sodium [54] | 22122 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Diclofenac Sodium [55] | 21005 | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||||
Ketoconazole [56] | 21946 | √ | √ | √ | √ | √ | √ | √ | √ | ||||||||
Metronidazole [57] | 19737 | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||||
Metronidazole [58] | 21789 | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||||
Podofilox [59] | 20529 | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||||
Tazarotene [60] | 20600 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||||
Tretinoin [61] | 17579 | √ | √ | √ | √ | √ | √ | √ | √ | ||||||||
Tretinoin [62] | 22070 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||||
Tretinoin [63] | 17955 | √ | √ | √ | √ | √ | √ | √ | √ |
Drug | RS | Q | AT | M | PS | GS | AV | FC | YS | LVR | WA | pH | SG | DR | OC | IVRT | IVPT |
Acyclovir [82] | 21478 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Acyclovir, Hydrocortisone [83] | 22436 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||
Ammonium Lactate [84] | 20508 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Betamethasone Dipropionate; Calcipotriene [85] | 213422 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Butenafine Hydrochloride [86] | 20524 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Butenafine Hydrochloride [87] | 21307 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Calcipotriene [88] | 20554 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Docosanol [89] | 20941 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Doxepin Hydrochloride [90] | 20126 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Fluocinolone Acetonide [91] | 12787 | ||||||||||||||||
Fluorouracil [92] | 16988 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Fluorouracil [93] | 22259 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Gentamicin Sulfate [94] | 62307 | ||||||||||||||||
Ivermectin [95] | 206255 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Ketoconazole [96] | 19084 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Luliconazole [97] | 204153 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Metronidazole [98] | 20531 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Metronidazole [99] | 20743 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Mupirocin Calcium [100] | 50746 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||
Nystatin [101] | 64022 | ||||||||||||||||
Nystatin; Triamcinolone Acetonide [102] | 62364 | ||||||||||||||||
Oxymetazoline Hydrochloride [103] | 208552 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Ozenoxacin [104] | 208945 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Penciclovir [105] | 20629 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||
Pimecrolimus [106] | 21302 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Silver Sulfadiazine [107] | 17381 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||
Tazarotene [108] | 21184 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Tazarotene [109] | 21184 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Triamcinolone Acetonide [110] | 11601 |
Drug | RS | Q | AT | M | PS | GS | AV | FC | YS | LVR | WA | pH | SG | DR | OC | IVRT | IVPT |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Abametapir [113] | 206966 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||
Ammonium Lactate [112] | 19155 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Benzyl Alcohol [114] | 22129 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||
Clindamycin Phosphate [115] | 50600 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||
Halobetasol Propionate [120] | 209355 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Ivermectin [121] | 202736 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||
Malathion [118] | 018613 | √ | |||||||||||||||
Metronidazole [122] | 20901 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Miconazole Nitrate; White Petrolatum; Zinc Oxide [116] | 21026 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | |||||
Mometasone Furoate [119] | 019796 | √ | |||||||||||||||
Tazarotene [123] | 211882 | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | ||||
Triamcinolone Acetonide [117] | 11602 |
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García-Arieta, A.; Gordon, J.; Gwaza, L.; Merino, V.; Mangas-Sanjuan, V. Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union. Pharmaceutics 2023, 15, 601. https://doi.org/10.3390/pharmaceutics15020601
García-Arieta A, Gordon J, Gwaza L, Merino V, Mangas-Sanjuan V. Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union. Pharmaceutics. 2023; 15(2):601. https://doi.org/10.3390/pharmaceutics15020601
Chicago/Turabian StyleGarcía-Arieta, Alfredo, John Gordon, Luther Gwaza, Virginia Merino, and Víctor Mangas-Sanjuan. 2023. "Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union" Pharmaceutics 15, no. 2: 601. https://doi.org/10.3390/pharmaceutics15020601