title: Regulatory Perspectives on Strength-Dependent Dissolution Profiles and Biowaiver Approaches for Immediate Release (IR) Oral Tablets in New Drug Applications.
abstract: Dissolution profile comparisons are used by the pharmaceutical industry to assess the similarity in the dissolution characteristics of two formulations to decide whether the implemented changes, usually minor/moderate in nature, will have an impact on the in vitro/in vivo performance of the drug product. When similarity testing is applied to support the approval of lower strengths of the same formulation, the traditional approach for dissolution profile comparison is not always applicable for drug products exhibiting strength-dependent dissolution and may lead to incorrect conclusions about product performance. The objective of this article is to describe reasonable biopharmaceutic approaches for developing a biowaiver strategy for low solubility, proportionally similar/non-proportionally similar in composition immediate release drug products that exhibit strength-dependent dissolution profiles. The paths highlighted in the article include (1) approaches to address biowaiver requests, such as the use of multi-unit dissolution testing to account for sink condition differences between the higher and lower strengths; (2) the use of a single- vs. strength-dependent dissolution method; and (3) the use of single- vs. strength-dependent dissolution acceptance criteria. These approaches are cost- and time-effective and can avoid unnecessary bioequivalence studies.
authors.affiliation: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA. Sandra.Suarez@fda.hhs.gov.
authors.forename: Sandra
authors.identifier: 0000-0002-9274-9224
authors.initials: S
authors.lastname: Suarez-Sharp
authors.affiliation: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Poonam R
authors.initials: PR
authors.lastname: Delvadia
authors.affiliation: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Angelica
authors.initials: A
authors.lastname: Dorantes
authors.affiliation: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: John
authors.initials: J
authors.lastname: Duan
authors.affiliation: Division of Pharmaceutical Analysis, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, St. Louis, Missouri, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Externbrink
authors.affiliation: Division of Pharmaceutical Analysis, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, St. Louis, Missouri, USA.
authors.forename: Zongming
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Tapash
authors.initials: T
authors.lastname: Ghosh
authors.affiliation: Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Sarah Pope
authors.initials: SP
authors.lastname: Miksinski
authors.affiliation: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Seo
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D001702:Biopharmaceutics / Q000331:legislation & jurisprudence / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000331:legislation & jurisprudence / Q000379:methods*; D017277:Drug Approval / Q000331:legislation & jurisprudence / Q000379:methods*; D065546:Drug Liberation; D006801:Humans; D012995:Solubility; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D013607:Tablets
keywords: biowaivers; immediate release oral dosage forms; multi-unit dissolution testing; strength-dependent dissolution acceptance criteria; strength-dependent dissolution profiles