Performance Properties of the Population Bioequivalence Approach for In Vitro Delivered Dose for Orally Inhaled Respiratory Products
Journal Title: The AAPS Journal - Year 2014, Vol 16, Issue 1
Abstract
Regulatory agencies, industry, and academia have acknowledged that in vitro assessments serve a role in establishing bioequivalence for second-entry drug product approvals as well as innovator post-approval drug product changes. For orally inhaled respiratory products (OIPs), the issues of correctly analyzing in vitro data and interpreting the results within the broader context of therapeutic equivalence have garnered significant attention. One of the recommended statistical tests for in vitro data is the population bioequivalence method (PBE). The current literature for assessing the PBE statistical approach for in vitro data assumes a log normal distribution. This paper focuses on an assessment of that assumption for in vitro delivered dose. Concepts in development of a statistical model are presented. The PBE criterion and hypotheses are written for the case when data follows a normal distribution, rather than log normal. Results of a simulation study are reported, characterizing the performance of the PBE approach when data are expected to be normally distributed, rather than log normal. In these cases, decisions using the PBE approach are not consistent for the same absolute mean difference that the test product is from the reference product. A conclusion of inequivalency will occur more often if the test product dose is lower than the reference product for the same deviation from target. These features suggest that more research is needed for statistical equivalency approaches for in vitro data.
Authors and Affiliations
Beth Morgan, Helen Strickland
Keywords
Related Articles
- EP ID EP681046
- DOI 10.1208/s12248-013-9543-x
- Views 61
- Downloads 0
CNS drug delivery: Opioid peptides and the blood-brain barrier
Peptides are key regulators in cellular and intercellular physiological responses and possess enormous promise for the treatment of pathological conditions. Opioid peptide activity within the central nervous system (CNS)...
Supersaturated Self-Nanoemulsifying Drug Delivery Systems (Super-SNEDDS) Enhance the Bioavailability of the Poorly Water-Soluble Drug Simvastatin in Dogs
This study investigates the potential of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) to improve the bioavailability of poorly water-soluble drugs compared to conventional SNEDDS. Conventional...
Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer
Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged dele...
High glucose concentration in isotonic media alters Caco-2 cell permeability
Caco-2 cell permeability was evaluated in isotonic media containing high (25mM) or physiological (5.5mM) glucose concentrations. Transepithelial electrical resistance (TEER) and membrane fluidity were measured to assess...
Key elements of bioanalytical method validation for small molecules
Method validation is a process that demonstrates that a method will successfully meet or exceed the minimum standards recommended in the Food and Drug Administration (FDA) guidance for accuracy, precision, selectivity, s...