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This article evaluates the current gaps around the impact of post-manufacturing processes on the product qualities of protein-based biologics, with a focus on user centricity. It includes the evaluation of the regulatory guidance available, describes a collection of scientific literature and case studies to showcase the impact of post-manufacturing stresses on product and dosing solution quality. It also outlines the complexity of clinical handling and the need for communication, and alignment between drug providers, healthcare professionals, users, and patients. Regulatory agencies provide clear expectations for drug manufacturing processes, however, guidance supporting post-product manufacturing handling is less defined and often misaligned. This is problematic as the pharmaceutical products experience numerous stresses and processes which can potentially impact drug quality, safety and efficacy. This article aims to stimulate discussion amongst pharmaceutical developers, health care providers, device manufacturers, and public researchers to improve these processes. Patients and caregivers' awareness can be achieved by providing relevant educational material on pharmaceutical product handling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Protein drugs, such as monoclonal antibodies, have proved successful in treating cancer and immune system diseases. The structural complexity of these molecules requires careful handling to ensure integrity and stability of the drug. In this study, a failure mode and effects analysis was performed based on a Gemba Walk method in a Swedish University Hospital. The Gemba Walk is focused on pharmacists observing the actual supply process steps from distributor, pharmacy cleanroom to patient administration. Relevant protein drugs are chosen based on sales statistics within the hospital and the corresponding wards were observed. Further is the Double Diamond design method used to identify major risks and deliver mitigation strategies. The study identified potential stress factors such as temperature, shock by impact, shaking, vibration and light exposure. There were also risks associated with porters' and healthcare professionals' lack of awareness and access to information. These risk factors may cause loss of efficacy and quality of the protein drug, potentially leading to patient safety concerns. In this study, a simulation is also performed to list measures that theoretically should be in place to ensure the quality of the protein drug, for example validated and protocol-based compounding in cleanroom, training and validated transports., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Electrical asymmetrical flow field-flow fractionation (EAF4) is an interesting new analytical technique that separates proteins based on size or molecular weight and simultaneously determines the electrical characteristics of each population. However, until now, the research using EAF4 has not been published except for the proof-of-concept in the original publication by Johann et. al. in 2015 [1]. Hence the methods capabilities and optimized conditions need to be further investigated, such as composition of the carrier liquid, pH stability and effect of the electric field strength. The pH instability was observed in the initial method of EAF4 due to the electrolysis products when applied electric field. Therefore, we have investigated and provided a modified method for rapid pH stabilization through additional focusing step with the electric field. Then, the electrical properties such as the zeta-potential and effective net charge of the monomer and oligomers of three different proteins (GA-Z, BSA, and Ferritin) were determined based on their electrophoretic mobility from EAF4. The results showed that there were limitations to the applicability of separation by EAF4 to proteins. Nevertheless, this study shows that EAF4 is an interesting new technique that can examine the zeta-potential of individual proteins in mixtures (or monomers and oligomers) not accessible by other techniques., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Many novel pharmaceutically active substances are characterized by a high hydrophobicity and a low water solubility, which present challenges for their delivery as drugs. Tablets made from cross-linked hydrophobically modified poly (acrylic acid) (CLHMPAA), commercially available as Pemulen™, have previously shown promising abilities to control the release of hydrophobic model substances. This study further investigates the possibility to use CLHMPAA in tablet formulations using ibuprofen as a model substance. Furthermore, surfactants were added to the dissolution medium in order to simulate the presence of bile salts in the intestine. The release of ibuprofen is strongly affected by the presence of surfactant and/or buffer in the dissolution medium, which affect both the behaviour of CLHMPAA and the swelling of the gel layer that surrounds the disintegrating tablets. Two mechanisms of tablet disintegration were observed under shear, namely conventional dissolution of a soluble tablet matrix and erosion of swollen insoluble gel particles from the tablet. The effects of surfactant in the surrounding medium can be circumvented by addition of surfactant to the tablet. With added surfactant, tablets that may be insusceptible to the differences in bile salt level between fasted or fed states have been produced, thus addressing a central problem in controlled delivery of hydrophobic drugs. In other words CLHMPAA is a potential candidate to be used in tablet formulations for controlled release with poorly soluble drugs.

In this work three in vitro methods for the measurement of mucoadhesion have been compared: ellipsometry, tensile strength and rheology. The conditions used for the three methods have been as similar as possible. Six different polymers were investigated: sodium carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), chitosan, polyvinyl pyrrolidone (PVP) and two cross-linked polyacrylic acids, Noveon (hydrophobically modified) and Carbopol. The results showed that PVP did not exhibit mucoadhesion according to any of the methods used. Chitosan, Noveon, Carbopol, CMC and HEC showed good mucoadhesion in the tensile strength and the rheological measurements, but not in the ellipsometry investigation. Chitosan was the only polymer showing good mucoadhesion with the ellipsometry method. No two methods gave the same ranking of mucoadhesive strength of the polymers. The conflicting results obtained with the different methods underline the need for further improvements in existing experimental techniques and theoretical concepts for the correct assessment of mucoadhesive properties., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The present study describes the preparation of 11 batches of starch microspheres for drug delivery. Parameters such as the type of starch material, the type of protein, and the incubation time of the process were varied, and the obtained microspheres differed in yield, encapsulation efficiency and physical properties. The crystalline/ordered structure (obtained through X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC)), the microscopic appearance and the surface morphology (viewed with scanning electron microscopy (SEM)) were found to differ between the batches depending on the starch type, encapsulated protein and incubation conditions that were employed. Freeze-drying was found to have a destructive effect on the ordered structure of the starch and this effect varied with regard to preparation conditions. Drug release experiments demonstrated that the release from the starch matrix depended on the type of protein as well as on the incubation time during the manufacturing at temperatures of 6 degrees C and 37 degrees C. The enzymatic degradation of starch was slightly different between the materials depending on the crystalline/ordered structure that had formed during the preparation.