Pediatric dosing for locally acting drugs in submissions to the U.S. Food and Drug Administration between 2002 and 2020
Abstract Deriving pediatric doses for locally acting drugs (LADs) presents a unique challenge because limited systemic exposure hinders commonly used approaches such as pharmacokinetic matching to adults. This study systematically evaluated drug development practices used for pediatric dose selectio...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13611 |
| _version_ | 1797657439721488384 |
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| author | Gelareh A. Abulwerdi Anuradha Ramamoorthy Edward Bashaw Gilbert J. Burckart Rajanikanth Madabushi Elimika Pfuma Fletcher |
| author_facet | Gelareh A. Abulwerdi Anuradha Ramamoorthy Edward Bashaw Gilbert J. Burckart Rajanikanth Madabushi Elimika Pfuma Fletcher |
| author_sort | Gelareh A. Abulwerdi |
| collection | DOAJ |
| description | Abstract Deriving pediatric doses for locally acting drugs (LADs) presents a unique challenge because limited systemic exposure hinders commonly used approaches such as pharmacokinetic matching to adults. This study systematically evaluated drug development practices used for pediatric dose selection of LADs approved by the U.S. Food and Drug Administration from 2002 to 2020. The three study objectives were: (1) to determine the dose selection approach for the labeled pediatric dose, (2) to examine the studied pediatric dose(s), and (3) to evaluate the characteristics of the pediatric clinical programs used to support the labeled pediatric dose. A total of 187 pediatric submissions were characterized for the labeled and studied pediatric doses of LADs. The pediatric dose was predominantly labeled as a flat dose (91%) and at a single‐dose level (67%) similar to adults. The majority (68.4%) of the submissions had the same labeled dose for pediatrics and adults. Independent pharmacodynamic/efficacy studies in pediatric patients commonly (64.2%) provided supportive evidence for the labeled pediatric dose. Inhalation, nasal, and injectable submissions had the highest number of clinical trials, lowest usage of an extrapolation of efficacy approach, and utilized diverse approaches in selecting the studied pediatric doses. This article highlights approaches for LAD dosing in pediatric patients and can be used to inform drug development of these products in the pediatric population. |
| first_indexed | 2024-03-11T17:45:35Z |
| format | Article |
| id | doaj.art-27577306551548d5bd65d5511cbee4ed |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-03-11T17:45:35Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-27577306551548d5bd65d5511cbee4ed2023-10-18T07:31:18ZengWileyClinical and Translational Science1752-80541752-80622023-10-0116102046205710.1111/cts.13611Pediatric dosing for locally acting drugs in submissions to the U.S. Food and Drug Administration between 2002 and 2020Gelareh A. Abulwerdi0Anuradha Ramamoorthy1Edward Bashaw2Gilbert J. Burckart3Rajanikanth Madabushi4Elimika Pfuma Fletcher5Office of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAAbstract Deriving pediatric doses for locally acting drugs (LADs) presents a unique challenge because limited systemic exposure hinders commonly used approaches such as pharmacokinetic matching to adults. This study systematically evaluated drug development practices used for pediatric dose selection of LADs approved by the U.S. Food and Drug Administration from 2002 to 2020. The three study objectives were: (1) to determine the dose selection approach for the labeled pediatric dose, (2) to examine the studied pediatric dose(s), and (3) to evaluate the characteristics of the pediatric clinical programs used to support the labeled pediatric dose. A total of 187 pediatric submissions were characterized for the labeled and studied pediatric doses of LADs. The pediatric dose was predominantly labeled as a flat dose (91%) and at a single‐dose level (67%) similar to adults. The majority (68.4%) of the submissions had the same labeled dose for pediatrics and adults. Independent pharmacodynamic/efficacy studies in pediatric patients commonly (64.2%) provided supportive evidence for the labeled pediatric dose. Inhalation, nasal, and injectable submissions had the highest number of clinical trials, lowest usage of an extrapolation of efficacy approach, and utilized diverse approaches in selecting the studied pediatric doses. This article highlights approaches for LAD dosing in pediatric patients and can be used to inform drug development of these products in the pediatric population.https://doi.org/10.1111/cts.13611 |
| spellingShingle | Gelareh A. Abulwerdi Anuradha Ramamoorthy Edward Bashaw Gilbert J. Burckart Rajanikanth Madabushi Elimika Pfuma Fletcher Pediatric dosing for locally acting drugs in submissions to the U.S. Food and Drug Administration between 2002 and 2020 Clinical and Translational Science |
| title | Pediatric dosing for locally acting drugs in submissions to the U.S. Food and Drug Administration between 2002 and 2020 |
| title_full | Pediatric dosing for locally acting drugs in submissions to the U.S. Food and Drug Administration between 2002 and 2020 |
| title_fullStr | Pediatric dosing for locally acting drugs in submissions to the U.S. Food and Drug Administration between 2002 and 2020 |
| title_full_unstemmed | Pediatric dosing for locally acting drugs in submissions to the U.S. Food and Drug Administration between 2002 and 2020 |
| title_short | Pediatric dosing for locally acting drugs in submissions to the U.S. Food and Drug Administration between 2002 and 2020 |
| title_sort | pediatric dosing for locally acting drugs in submissions to the u s food and drug administration between 2002 and 2020 |
| url | https://doi.org/10.1111/cts.13611 |
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