Application of Clinical Pharmacology Principles in Drug Development of Modified-Release Products: Leveraging Exposure-Response Information to Support Approval.
bioequivalence
exposure response
extended release
modified release
Journal
Journal of clinical pharmacology
ISSN: 1552-4604
Titre abrégé: J Clin Pharmacol
Pays: England
ID NLM: 0366372
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
06
03
2020
accepted:
14
04
2020
pubmed:
27
5
2020
medline:
13
8
2021
entrez:
27
5
2020
Statut:
ppublish
Résumé
The development of modified-release (MR) drug products aims to address a clinical need such as improving patient compliance. There are multiple pathways and development strategies for the registration and approval of MR products. The development strategy of an MR product is usually dependent on the availability and pharmacokinetic/pharmacodynamics (PK/PD) characteristics of the reference drug product, that is, an immediate-release (IR) product or a reference MR. Compared with a reference IR product, an MR product is likely to have a different PK profile over the least common dosing time due to unequal dosing intervals. In case of differences in PK profiles between the MR product and the reference product, confirmatory efficacy and safety studies may be needed to support registration. In some cases, however, a thorough clinical PK/PD characterization may provide sufficient basis to support the approval of the proposed MR product without the need for additional safety and efficacy studies. This article summarizes the US Food and Drug Administration experience and the regulatory considerations supporting the approval of MR products in the past 6 years and discusses cases in which clinical pharmacology and PK/PD information were leveraged to support approval without the need for additional clinical studies. Details of all these cases are available in the public domain. In 2 cases a well-characterized exposure-response relationship provided sufficient justification that differences in the shape of the PK profiles were not clinically relevant. In the remaining 3 cases a thorough characterization of the PK profile along with a risk-based approach provided bases for approval.
Substances chimiques
Delayed-Action Preparations
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1441-1452Informations de copyright
Published 2020. This article is a U.S. Government work and is in the public domain in the USA.
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