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Introduction: Most patients with acute facial palsy initially present to emergency departments (EDs), where clinical practice guidelines (CPGs) recommend steroids, eye care, and follow-up with facial nerve specialists. Objective: To evaluate adherence to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Bell's palsy (BP) CPGs within EDs at a single academic institution. Method : We conducted a retrospective review of all patients diagnosed with acute facial palsy in the EDs of an academic tertiary care center between June 1, 2021, and June 1, 2022. Results: A total of 270 patients met inclusion criteria; most were male ( n = 150, 55.9%), diagnosed with BP ( n = 243, 90.0%), and presented to community-based emergency rooms ( n = 170, 62.96). Although most patients received steroid treatment ( n = 243, 90.0%), only 61.5% ( n = 166) received the AAO-HNS-recommended course. Older patients and those who received steroids were more likely to receive imaging ( p < 0.001 , p = 0.03). Treatment with the AAO-HNS-recommended steroid regimen was associated with a higher likelihood of receiving laboratory evaluation ( p = 0.02). Providers often advised follow-up; however, only 12.2% of patients were discharged with an electronic referral order. Conclusion : There are opportunities to standardize the treatment of patients in the ED presenting with acute facial palsy according to AAO-HNS CPGs.

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. Common approaches towards establishing dissolution safe spaces are described. This paper encourages the preparation of protocols clearly describing why and how testing is performed along with the expected pass/fail criteria prior to generating data on the materials to be evaluated. The target audience of this manuscript includes CMC regulatory scientists, laboratory analysts, as well as statisticians from industry and regulatory health agencies involved in the assessment of product quality via in vitro dissolution testing. Building upon previous publications, this manuscript provides a solution to the current ambiguity related to dissolution profile comparison. The principles outlined in this and previous manuscripts provide a basis for global regulatory alignment in the application of dissolution profile assessment to support manufacturing changes and biowaiver requests., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Recurrent Clostridiodies difficile infection (CDI) contributes to morbidity and mortality in cancer patients. Fecal microbiota transplantation (FMT) has been proven to be effective in treatment of recurrent CDI, but immunocompromised patients have been excluded from prospective studies due to safety concerns. The aim of this study was to investigate the safety of FMT for recurrent CDI in immunocompromised patients with solid tumor malignancy undergoing chemotherapy., Methods: This was a single center, prospective observational study of patients at a tertiary care cancer center of 10 patients with recurrent CDI who were at least 18 years of age, with a solid tumor malignancy who had received chemotherapy within the previous 6 months. Patients received FMT either by upper endoscopy or colonoscopy and were followed for 6 months. Safety was a primary outcome measured by infections occurring within 2 weeks of FMT. Efficacy of FMT was also evaluated., Results: Nineteen patients were evaluated. On applying exclusion criteria, 10 were included in the study. One patient requested to be off study within 2 weeks and was considered a treatment failure. Seven received FMT via upper endoscopy, three via colonoscopy. There were no infectious complications from FMT. Eight patients (80%) were cured after the first FMT. All eight patients went on to restart oncologic treatment with an average of 32.5 days after FMT., Conclusions: FMT is safe and effective for recurrent CDI in solid tumor patients undergoing chemotherapy. Patients can resume oncologic treatment after FMT., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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. Members from regulatory agencies explained that dissolution profile similarity testing is only part of the overall assessment of the acceptability of the proposed changes; decisions are usually made based on aggregate weight of evidence. Scientific shortcomings of f 2 were highlighted but no proposal on how to replace it was made. Controlling dissolution timepoint variability and application of pairwise batch-to-batch comparisons (PBC) of dissolution profiles caused considerable debate. Several industry participants suggested increased sample sizes to raise confidence in decision-making and to avoid PBC. They proposed identification of a single mathematical method with predefined acceptance criteria and suggested that dissolution timepoint selection should follow EMA and HC guidance. A majority of meeting attendees favored applying clinically relevant dissolution specifications (CRDS) and dissolution safe space to determine the impact of minor/moderate CMC changes as opposed to dissolution profile similarity assessment via statistical methods. Day 2 of the workshop highlighted the need and opportunities for global harmonization including variability, timepoint selection, role of CRDS, and statistical methods to address the ambiguity globally operating pharmaceutical companies are currently facing., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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. The analysis was validated by size-based fractionation of the LNPs with subsequent offline analysis of the fractions. Four LNPs formulated with different PEG-lipids and different lipid compositions were tested. Good agreement was observed between the online and offline size-based RNA distributions among all four LNPs, demonstrating the utility of the online method for LNP-encapsulated RNA in general, and suggesting a means for simplified biophysical quantitation of a dosing-related critical quality attribute., (Copyright © 2021 Merck Sharp & Dohme Corp., The Author(s). Published by Elsevier B.V. All rights reserved.)

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. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

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. However, once commercial benzyl alcohol is exposed to the atmosphere, formation of BDBA is possible. The synthesis and characterization of BDBA is reported. The ability of BDBA to react with alcohols to form other types of acetals, and the impact of low levels of BDBA on the quantitative analysis of pharmaceutical products, are considered.

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.