An examination of process models and model risk frameworks for pharmaceutical manufacturing.

Process models are a growing tool for pharmaceutical manufacturing process design and control. The Industry 4.0 paradigm promises to increase the amount of data available to understand manufacturing processes.

Regulatory workshop on challenge strain development and GMP manufacture - A stakeholder meeting report.

Within the Innovative Health Initiative (IHI) Inno4Vac CHIMICHURRI project, a regulatory workshop was organised on the development and manufacture of challenge agent strains for Controlled Human Infection Model (CHIM) studies. Developers are often uncertain about which GMP requirements or regulatory guidelines apply but should be guided by the 2022 technical white paper "Considerations on the Principles of Development and Manufacturing Qualities of Challenge Agents for Use in Human Infection Models" (published by hVIVO, Wellcome Trust, HIC-Vac consortium members). Where those recommendations cannot be met, regulators advise following the "Principles of GMP" until definitive guidelines are available.

Report of the European Medicines Agency Conference on RNA-Based Medicines.

RNA-based medicines have potential to treat a large variety of diseases, and research in the field is very dynamic. Proactively, The European Medicines Agency (EMA) organized a virtual conference on February 2, 2023 to promote the development of RNA-based medicines. The initiative addresses the goal of the EMA Regulatory Science Strategy to 2025 to "catalyse the integration of science and technology in medicines development.

Variability of in vivo potency assays of whole-cell pertussis, inactivated polio, and meningococcal B vaccines.

For the batch release of vaccines, potency release assays are required. Non-animal in vitro tests have numerous advantages and are preferred; however, several vaccines are still released using in vivo assays. Their major drawback is the inherent variability with its practical implications.

Directing the Selectivity of Oxygen Reduction to Water by Confining a Cu Catalyst in a Metal Organic Framework.

Electrocatalysis is to play a key role in the transition towards a sustainable chemical and energy industry and active, stable and selective redox catalysts are much needed. Porous structures such as metal organic frameworks (MOFs) are interesting materials as these may influence selectivity of chemical reactions through confinement effects. In this work, the oxygen reduction catalyst Cu-tmpa was incorporated into the NU1000 MOF.

Rational arguments for regulatory acceptance of consistency testing: benefits of non-animal testing over release testing of vaccines.

Introduction: There are rational arguments to replace existing potency and safety assays for batch release testing of vaccines with more advanced non-animal techniques to measure critical quality attributes. However, the introduction of alternatives to replace release assays of authorized vaccines is challenging.

Areas Covered: This report describes the hurdles encountered in substituting assays and ways to overcome these and provides arguments why more advanced alternatives are superior, not only as a tool to monitor the quality of vaccines but also from a practical, economical, and ethical point of view.

Development of a cell line-based in vitro assay for assessment of Diphtheria, Tetanus and acellular Pertussis (DTaP)-induced inflammasome activation.

Safety and potency assessment for batch release testing of established vaccines still relies partly on animal tests. An important avenue to move to batch release without animal testing is the consistency approach. This approach is based on thorough characterization of the vaccine to identify critical quality attributes that inform the use of a comprehensive set of non-animal tests to release the vaccine, together with the principle that the quality of subsequent batches follows from their consistent production.

Interfacial Characterization of Ruthenium-Based Amphiphilic Photosensitizers.

Nonreactive surfactant molecules have long been used and characterized for a wide range of applications in industries, life science, and everyday life. Recently, new types of functional amphiphilic molecules have emerged that bear another function, for example, a light-absorbing action, or catalytic properties. However, the surfactant properties of these molecules remain to date essentially unknown.

Shorter Alkyl Chains Enhance Molecular Diffusion and Electron Transfer Kinetics between Photosensitisers and Catalysts in CO -Reducing Photocatalytic Liposomes.

Covalent functionalisation with alkyl tails is a common method for supporting molecular catalysts and photosensitisers onto lipid bilayers, but the influence of the alkyl chain length on the photocatalytic performances of the resulting liposomes is not well understood. In this work, we first prepared a series of rhenium-based CO -reduction catalysts [Re(4,4'-(C H ) -bpy)(CO) Cl] (ReC ; 4,4'-(C H ) -bpy=4,4'-dialkyl-2,2'-bipyridine) and ruthenium-based photosensitisers [Ru(bpy) (4,4'-(C H ) -bpy)](PF ) (RuC ) with different alkyl chain lengths (n=0, 9, 12, 15, 17, and 19). We then prepared a series of PEGylated DPPC liposomes containing RuC and ReC , hereafter noted C , to perform photocatalytic CO reduction in the presence of sodium ascorbate.

Overcoming scientific barriers in the transition from to non-animal batch testing of human and veterinary vaccines.

Introduction: Before release, vaccine batches are assessed for quality to evaluate whether they meet the product specifications. Vaccine batch tests, in particular of inactivated and toxoid vaccines, still largely rely on methods. Improved vaccine production processes, ethical concerns, and suboptimal performance of some tests have led to the development of alternatives.

Evaluation of a Head-Tongue Controller for Power Wheelchair Driving by People With Quadriplegia.

The head-tongue controller (HTC) is a multimodal alternative controller designed for people with quadriplegia to access complex control capabilities by combining tongue and head tracking to offer both discrete and proportional controls in a single controller. In this human study, 17 patients with quadriplegia and current users of alternative controllers were asked to perform four trials of either simple driving tasks or advanced maneuvers in a custom-designed course. Completion time and accuracy were compared between their personal alternative controller (PAC) and various combinations of driving modalities with the HTC.

Variability of in vivo potency tests of Diphtheria, Tetanus and acellular Pertussis (DTaP) vaccines.

For batch release of legacy vaccines such as DTaP, in vivo potency release assays are required. We quantified the variability of in vivo potency release assays for four DTaP (Diphtheria, Tetanus, acellular Pertussis) products of different manufacturers. With their large CV (Coefficients of Variance) ranging from 16% to 132%, these in vivo assays are of limited value to ensure their potency is consistent and similar to the clinical batches used for the marketing authorisation.

Estimation of manufacturing development costs of cell-based therapies: a feasibility study.

Background Aims: Cell-based therapies (CBTs) provide opportunities to treat rare and high-burden diseases. Manufacturing development of these innovative products is said to be complex and costly. However, little research is available providing insight into resource use and cost drivers.

What does cell therapy manufacturing cost? A framework and methodology to facilitate academic and other small-scale cell therapy manufacturing costings.

Background Aims: Recent technical and clinical advances with cell-based therapies (CBTs) hold great promise in the treatment of patients with rare diseases and those with high unmet medical need. Currently the majority of CBTs are developed and manufactured in specialized academic facilities. Due to small scale, unique characteristics and specific supply chain, CBT manufacturing is considered costly compared to more conventional medicinal products.

Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised.

Regulatory T cells (Tregs) have a prominent role in the control of immune homeostasis. Pharmacological impact on their activity or balance with effector T cells could contribute to (impaired) clinical responses or adverse events. Monitoring treatment-related effects on T cell subsets may therefore be part of (pre-)clinical studies for medicinal products.

Pragmatic rules for comparability of biological medicinal products.

Comparability is a key concept in the evaluation of both manufacturing changes and biosimilars. It constitutes a pragmatic and flexible approach which recognises that biologicals are inherently variable and that minor variations in quality attributes are often clinically irrelevant. In this discussion paper, we argue that comparability exercises rely on a number of pragmatic criteria.

Regulatory perspective on in vitro potency assays for human dendritic cells used in anti-tumor immunotherapy.

Dendritic cells (DCs) are key connectors between the innate and adaptive immune system and have an important role in modulating other immune cells. Therefore, their therapeutic application to steer immune responses is considered in various disorders, including cancer. Due to differences in the cell source and manufacturing process, each DC medicinal product is unique.

Regulatory perspective on in vitro potency assays for human T cells used in anti-tumor immunotherapy.

The adaptive immune system is known to play an important role in anti-neoplastic responses via induction of several effector pathways, resulting in tumor cell death. Because of their ability to specifically recognize and kill tumor cells, the potential use of autologous tumor-derived and genetically engineered T cells as adoptive immunotherapy for cancer is currently being explored. Because of the variety of potential T cell-based medicinal products at the level of starting material and manufacturing process, product-specific functionality assays are needed to ensure quality for individual products.

Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: An analysis from the EAACI AIT Guidelines Project.

Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality.

Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products.

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US).

Regulatory perspective on in vitro potency assays for human mesenchymal stromal cells used in immunotherapy.

Mesenchymal stromal cells (MSCs) are multipotent cells derived from various tissues that can differentiate into several cell types. MSCs are able to modulate the response of immune cells of the innate and adaptive immune system. Because of these multimodal properties, the potential use of MSCs for immunotherapies is currently explored in various clinical indications.

Characteristics of product recalls of biopharmaceuticals and small-molecule drugs in the USA.

Compared with chemically synthesized small-molecule drugs, the manufacturing process of biopharmaceuticals is more complex. Unexpected changes to product characteristics following manufacturing changes have given rise to calls for robust systems to monitor the postauthorization safety of biopharmaceuticals. We compared quality-related product recalls in the USA of biopharmaceuticals and of small molecules.

Dendritic cell-based in vitro assays for vaccine immunogenicity.

Dendritic cells (DC) are pivotal in the induction of adaptive immune responses because they can activate naive T-cells. Moreover, they steer these adaptive immune responses by integrating various stimuli, such as from different pathogen associated molecular patterns and the cytokine milieu. Immature DC are very well capable of ingesting protein antigens, whereas mature DC are efficient presenters of peptides to naive T cells.