Dissolution Profile Similarity Assessment-Best Practices, Decision Trees and Global Harmonization.

During the write-up of the meeting summary reports from the 2019 dissolution similarity workshop held at the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI), several coauthors continued their discussions to develop a "best-practice" document defining the steps required to assess dissolution profiles in support of certain biowaivers and postapproval changes. In previous reports, current challenges related to dissolution profile studies were discussed such that the steps outlined in the two flow charts ("decision trees") presented here can be applied. These decision trees include both recommendations for the use of equivalence procedures between reference and test products as well as application of the dissolution safe space concept.

Current Approaches for Dissolution Similarity Assessment, Requirements, and Global Expectations.

This report summarizes podium presentations and breakout sessions from the second day of the 2019 M-CERSI workshop on In Vitro Dissolution Similarity Assessment in Support of Drug Product Quality: What, How, and When? Presenters from the U.S. Food and Drug Administration (FDA), Health Canada (HC), European Medicines Agency (EMA), Brazilian Health Surveillance Agency (ANVISA), and the pharmaceutical industry shared experiences/concerns with dissolution profile similarity assessment supporting minor/moderate Chemistry, Manufacturing and Control (CMC) changes.

Enabling online determination of the size-dependent RNA content of lipid nanoparticle-based RNA formulations.

The potential of lipid nanoparticles (LNPs) as nucleic acid delivery vehicles has been demonstrated in recent years, culminating in the emergency use approval of LNP-based mRNA SARS-CoV-2 vaccines in late 2020. The determination of RNA content relative to LNP size can be important to the understanding of efficacy and adverse effects. This work presents the first description of a facile and rapid analytical method for online, size-dependent RNA payload distribution measurement using data from multi-angle light scattering, ultraviolet and refractive index detectors following separation of the LNPs by size-exclusion chromatography.

Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data.

Concerning the stability of benzyl alcohol: formation of benzaldehyde dibenzyl acetal under aerobic conditions.

An impurity in benzyl alcohol was identified as benzaldehyde dibenzyl acetal (BDBA). The component BDBA is reversibly formed by the reaction of benzyl alcohol with benzaldehyde, an oxidative degradation product of benzyl alcohol. Whereas, BDBA is a known chemical entity, it is not typically controlled in commercial benzyl alcohol since it cannot be formed in the absence of benzaldehyde, which is itself generally controlled.

Development and validation of an automated extraction method (accelerated solvent extraction) and a reverse-phase HPLC analysis method for assay of ivermectin in a meat-based chewable formulation.

A new method for monitoring ivermectin content in HEARTGARD CHEWABLES has been developed and validated. The method consists of the automated extraction of ivermectin from the meat-based formulation under conditions of elevated temperature and pressure (accelerated solvent extraction, ASE, and determination of the active by reverse-phase high performance liquid chromatography (HPLC). The method resolves both active species of ivermectin (components H(2)B(1a) and H(2)B(1b)) from the formulation matrix.