Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union
The development of second-entry topical products is hampered by several factors. The excipient composition should be similar to the reference product because excipients may also contribute to efficacy. Conventional pharmacokinetic bioequivalence studies were not considered acceptable because drug co...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/2/601 |
| _version_ | 1797618665466626048 |
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| author | Alfredo García-Arieta John Gordon Luther Gwaza Virginia Merino Víctor Mangas-Sanjuan |
| author_facet | Alfredo García-Arieta John Gordon Luther Gwaza Virginia Merino Víctor Mangas-Sanjuan |
| author_sort | Alfredo García-Arieta |
| collection | DOAJ |
| description | The development of second-entry topical products is hampered by several factors. The excipient composition should be similar to the reference product because excipients may also contribute to efficacy. Conventional pharmacokinetic bioequivalence studies were not considered acceptable because drug concentrations are measured downstream after the site of action. There was no agreed methodology to characterize the microstructure of semisolids, and waivers of therapeutic equivalence studies with clinical endpoints were not possible. Only the vasoconstrictor assay for corticosteroids was accepted as a surrogate. This paper describes the implementation of the European Union’s stepwise approach for locally acting products to cutaneous products, discusses the equivalence requirements of the EMA Draft Guideline on the Quality and Equivalence of Topical Products, and compares them with the US Food and Drug Administration recommendations. Step 1 includes the possibility of waivers for simple formulations based on in vitro data only (Q1 + Q2 + Q3 + IVRT). Step 2 includes step 1 requirements plus a kinetic study (TS/IVPT/PKBE) to compare the local availability of complex formulations. Step 3 refers to clinical studies with pharmacodynamic/clinical endpoints. As excipients may affect the local tolerability and efficacy of the products, the similarity of excipient composition is required in all steps, except where clinical endpoints are compared. |
| first_indexed | 2024-03-11T08:16:47Z |
| format | Article |
| id | doaj.art-52a4d5d5634d499cb5aa518a28c6be29 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:16:47Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-52a4d5d5634d499cb5aa518a28c6be292023-11-16T22:42:09ZengMDPI AGPharmaceutics1999-49232023-02-0115260110.3390/pharmaceutics15020601Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European UnionAlfredo García-Arieta0John Gordon1Luther Gwaza2Virginia Merino3Víctor Mangas-Sanjuan4Área de Farmacocinética y Medicamentos Genéricos, División de Farmacología y Evaluación Clínica, Departamento de Medicamentos de Uso Humano, Agencia Española de Medicamentos y Productos Sanitarios, 28022 Madrid, SpainDivision of Biopharmaceutics Evaluation, Bureau of Pharmaceutical Sciences, Pharmaceutical Drugs Directorate, Health Canada, Ottawa, ON K1A 0K9, CanadaNorms and Standards for Pharmaceuticals, Health Products Policy and Standards, Access to Medicines and Health Products Division, World Health Organization, 1211 Geneva, SwitzerlandDepartment of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, SpainDepartment of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, SpainThe development of second-entry topical products is hampered by several factors. The excipient composition should be similar to the reference product because excipients may also contribute to efficacy. Conventional pharmacokinetic bioequivalence studies were not considered acceptable because drug concentrations are measured downstream after the site of action. There was no agreed methodology to characterize the microstructure of semisolids, and waivers of therapeutic equivalence studies with clinical endpoints were not possible. Only the vasoconstrictor assay for corticosteroids was accepted as a surrogate. This paper describes the implementation of the European Union’s stepwise approach for locally acting products to cutaneous products, discusses the equivalence requirements of the EMA Draft Guideline on the Quality and Equivalence of Topical Products, and compares them with the US Food and Drug Administration recommendations. Step 1 includes the possibility of waivers for simple formulations based on in vitro data only (Q1 + Q2 + Q3 + IVRT). Step 2 includes step 1 requirements plus a kinetic study (TS/IVPT/PKBE) to compare the local availability of complex formulations. Step 3 refers to clinical studies with pharmacodynamic/clinical endpoints. As excipients may affect the local tolerability and efficacy of the products, the similarity of excipient composition is required in all steps, except where clinical endpoints are compared.https://www.mdpi.com/1999-4923/15/2/601topicalcutaneousstepwise approachqualitative samenessquantitative similaritymicrostructure |
| spellingShingle | Alfredo García-Arieta John Gordon Luther Gwaza Virginia Merino Víctor Mangas-Sanjuan Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union Pharmaceutics topical cutaneous stepwise approach qualitative sameness quantitative similarity microstructure |
| title | Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union |
| title_full | Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union |
| title_fullStr | Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union |
| title_full_unstemmed | Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union |
| title_short | Regulatory Requirements for the Development of Second-Entry Semisolid Topical Products in the European Union |
| title_sort | regulatory requirements for the development of second entry semisolid topical products in the european union |
| topic | topical cutaneous stepwise approach qualitative sameness quantitative similarity microstructure |
| url | https://www.mdpi.com/1999-4923/15/2/601 |
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