Speed up biopharma devices’ release to market

It is a challenge in the biopharma industry to attain appropriate qualification protocols for devices. The manufacturers necessitate device storage that lasts for an extended period of time. Single-use devices may need storage for up to 6 years before their functional lifetime actually starts. In other words, every product completes its unique journey before it can be functionally used by the customer. At this point, the manufacturer needs to provide a quality certificate that guarantees the device’s safety and robustness during its life cycle. Likewise, package material aging information is needed to ensure package integrity, satisfy FDA validation requirements, and provide evidence of sterility and fitness for use over a product’s life cycle. To decrease the time necessary for testing prior to commercialization, or in other words to speed up product’s market release; manufacturers perform accelerated-aging studies on the product/ package combination. These studies are performed at elevated temperatures, so to simulate the realistic life span of the product. Life span of every product is unique in line with its application requirements and consists of sections such as storage of components, assembly and irradiation, storage of the irradiated product and finally application. Polymers are similar to living organisms and their properties are time, temperature and stress dependent, making the job of simulating the life cycle very complicated and difficult. As Sartorius Stedim Biotech, we are taking this challenge and adapt our aging methodology to each polymers. Our method will be shared to show how we can speed product introduction to market. Biography Dr. Nazli Gulsine Ozdemir has received her PhD from Kingston University London, UK at the age of 28 and following her graduation she worked as a postdoctoral researcher at University of Bristol, UK. Currently she works as a materials specialist, at Sartorius Stedim Biotech in the United Kingdom. She has published 10 papers as first author in reputable journals. She has also given speeches in many polymer engineering and materials science conferences across the globe. Nelly Montenay has received a degree in Engineering from the ITECH Lyon Engineering School. She is specialized in polymers science and plastic transformation. She is Platform Manager for Single Use Systems in Sartorius Stedim Biotech Research and Development Group, with 14 years of experience in polymer science, film development and product qualification testing

Embedded particles in single-use films: Cosmetic defect or integrity risk?

Single-use films make up a large fraction of the surface area of single-use systems, and thus must meet stringent requirements not required for typical packaging films: high mechanical integrity and low levels of chemical leachables. Consequently, typical single-use films are relatively thick and contain much reduced levels of chemical additives (processing aids and stabilizers). Reduction of additives may result in a higher probability for finding gel particles embedded within the film. Gel particles, described as translucent unmixed or “un-melted” polymer resin perhaps with increased cross-linking or molecular weight, appear as “fish eye” shaped defects in the film. High temperatures within the extrusion process may chemically degrade gel particles, which then become amber, brown or black in color. In addition, the industrial scale and complex nature of film extrusion processes increases the risk for embedded foreign particle contamination in the film. Are embedded particles in single-use films cosmetic defects, or do they represent significant risk to process reliability (process integrity) or risk to product purity? In an attempt to quantify risk to integrity, tensile testing, flexural durability testing, and a unique pressure burst test were applied to single-use films with varying type and size of embedded particles. For embedded gels, the results show that only extraordinarily large gels impact tensile test results, and only very large gels impact burst test results. Limited evidence shows similar effects for embedded foreign particles. After flexural durability testing, no pinholes were found even when multiple embedded gel particles were present in the film. The test methods applied generate extreme stresses and strains compared to those found in real applications. In addition, the effects appear only with gels much larger than the detection capabilities of on-line inspection systems. Thus the risk of embedded particles to single-use film integrity appears low. Risk of embedded particles in film to product purity is addressed in a separate paper in this conference addressing overall particle contamination risk factors

Particulate contamination in single-use systems: real versus perceived risk

Certainly final drug products must be “essentially free” of visible particulate contamination and visual inspection systems must meet USP 790 criteria. In addition, final drug products must meet USP 788 limits for sub-visible particles. It is however important to distinguish final drug product standards from requirements for single-use process containers and equipment, even though it is common to claim single-use systems (SUS) “meet USP 788 requirements”. USP 788 does not describe a method for determination of particulate counts in SUS process containers and equipment (1). Visible particles are “visible” and thus a visual indicator of SUS quality, and consequently sometimes lead to visceral reactions and the perception of major or even critical risk to product safety. However, guidance from PDA TR66 (2), ASME BPE-2016 (3) and the BPSA (4) published in the last few years provide valuable information on assessment of particulate risk in SUS processes. In most situations where SUS are currently applied, filtration and purification steps occur downstream, which essentially reduces the risk to zero for transfer of particulate contamination from SUS to the final drug product. However, any applications of SUS after final filtration (such as in ascetic processes or final filling operations) present significant risk to drug substance or drug product. So is risk to final drug product from SUS an essentially a binary situation: Prior to final filtration low risk, and after final filtration high risk? While assembly of SUS is a “clean build” process usually done in ISO 7 classified cleanrooms, incoming components and cleanroom processes such as cutting, welding and human assembly are unfortunately not particulate-free with current SUS manufacturing technologies. In addition, visual inspection of SUS components and assemblies is nowhere near 100% effective at detecting visible particles, especially for large complex assemblies or stirred tank reactor systems. Sartorius is currently implementing a “Visible Particle Test” (VPT: liquid extraction and microscopy) for process monitoring and continuous improvement efforts. Thus while most SUS manufactures strive to minimize particulate contamination, absence of particulates remains a goal but is not a currently feasible SUS specification. Particle contaminants may lie within the interior surfaces of SUS (in the fluid contact path), may be embedded within bag films or plastic components, or lie on the exterior surfaces of SUS. Particulates fall into two general categories: intrinsic (particles from SUS manufacturing process and component materials) and extrinsic (particles from human operators or the environment). Extrinsic particles potentially contain microbiological or viral contamination. These classifications of location and particle type lead to different assessments of risk. One concern are potential “secondary effects” of particulate contamination. Particle contamination could potentially nucleate protein aggregation. Particles embedded in SUS films or plastic components, or on the interior surfaces of the SUS assemblies could potentially leach out chemicals or release microbiological or viral contamination into the bioprocess fluids. In this presentation, the topic of particulate contamination risk is approached holistically and scientifically using literature data along with calculations. The goal of the presentation is to gain feedback from end users, and to facilitate the discussion between suppliers and end users based upon real rather than perceived risks. (1) Particulate Contamination in Single-Use Systems, J. D. Vogel and K. Wormuth, Bioprocess International, 15(9) 2017 (2) Application of Single-Use Systems in Pharmaceutical Manufacturing, PDA Technical Report No. 66, 2014 (3) Bioprocessing Equipment, ASME BPE-2016, American Society of Mechanical Engineers, 2016 Recommendations for Testing, Evaluation and Control of Particulates from Single-Use Process Equipment, Bio Process Systems Alliance, 201

Standardization of visible particles measurement in single-use systems, an advantage for the emerging applications

The use of single-use systems (SUS) in biopharmaceutical and biotechnological industries has recently become much more common. SUS assemblies include plastic bags, tube lines and components. As much as possible, SUS should be “essentially free” of visible particles (≥100µm). The presence of visible particles inside the SUS is a visual indicator regarding the quality of product. During the biopharmaceutical manufacturing process, interactions between the drug substance contained in the bag and visible particles might lead to product quality issues. However, SUS free of particles remains a challenge due to the SUS manufacturing process which requires several steps of assembly and the presence of different components. The adoption of SUS can be a solution for the emerging applications, like vaccines and cell and gene therapy, especially in the pandemic time with a need to have products quickly and with a particulates level very low. For this reason, it is important to be able to extract, measure, characterize, and reduce the particles. SUS manufacturers need to demonstrate continuous improvement of their manufacturing process in order to limit visible particulate matter. Due to the complexity of the SUS (bags, tube lines, components, transparency, size ...), it is difficult to do a visual inspection of the entire product. To overcome this issue, the development of a visible particle test method is necessary to assess the number of visible particles contained inside the SUS, which then allows assessment of any risks linked to particle matter. This method allows to extract, count and size the particles inside SUS, and to identify particles according to their shape, color and infrared and/or Raman spectrum. That is why Sartorius co-worked with ASTM to develop a standard practice [[i]] for the extraction of particulate matter from the surfaces of single-use components and assemblies designed for use in biopharmaceutical manufacturing

Approches politiques de la situation du français dans le monde

This paper presents the main points of La langue française, arme d’équilibre de la mondialisation (The French language, a weapon to balance globalization), Les Belles-Lettres, Paris, 2015. This book examines the impact of extrinsic events (wars, revolutions...) as well as intrinsic systems (demography, economics, North-South cooperation...) on the worldwide use of French. It then analyses how this language is rooted in Africa and the crucial importance of the coming years in African countries for French’s worldwide destiny. But helping the training in French of those hundreds of millions of (more or less) French-speaking people, exceeds what the traditional cooperation with France and other northern francophone countries is able to do, while, simultaneously, those African countries attract the interests of foreign economic actors, even those opposed to the spread of French. The paper will also point up how companies and private business does root the use of French, but sometimes also spread the use of English

III. Un récit des événements de Toulouse en 1814

Montenay (de) S. III. Un récit des événements de Toulouse en 1814. In: Annales du Midi : revue archéologique, historique et philologique de la France méridionale, Tome 82, N°98, 1970. pp. 301-304

Interactions dans les agrégats de constituants des acides nucléiques et d’acides aminés aromatiques

La congélation de solutions aqueuses diluées de constituants d'acides nucléiques et d’acides aminés aromatiques entraîne la formation d’agrégats, les molécules de soluté s’insérant dans les interstices du réseau de la glace.L'étude spectroscopique permet de mettre en évidence les modifications de la luminescence des molécules dans les agrégats en fonction de la concentration, de l’addition de solvants organiques, ou de sels.Cette étude est une étape préliminaire à la compréhension ultérieure des interactions intermoléculaires apparaissant dans les agrégats mixtes

ANALYSE NUMERIQUE DE L'AEROTHERMIQUE D'AUBAGES ET DE CAVITES DE TURBOREACTEUR

PARIS-BIUSJ-Physique recherche (751052113) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF