pH evolution in solution after contact with multilayer films after different g- irradiation doses and thus reconciliation of pH and TOC with carboxylic acids detected by ion chromatography

For a number of various uses (storage, mixing, freezing, transportation, formulation, and filling) biopharmaceutical solutions are stored in sterile single-use plastic bags. Material transfers can then occur between containers and contents. These migrations, of different types, depend on the physicochemical characteristics of the material (composition, pH, solubility, viscosity, molecular weight, etc.), the nature of the product (solid, semi-solid and liquid) and the conditions of the material utilization. In the case of single-use polymers, γ-irradiation sterilization of the polymer is often carried out. The interactions could be therefore influenced by the dose and the contact time between the container and the contents. γ-sterilization of single-use systems initiates chemical reactions and complex modifications inside the plastic material, In this study, γ-irradiation doses investigated are up to 270 kGy in order to emphazise the γ-irradiation effect and to better investigate the modifications of commercial PE(Polyethylene)/EVOH(Ethylene Vinyl Alcohol)/PE-film and commercial EVA(Ethylene Vinyl Acetate)/EVOH/EVA film. This study is a part of a global investigation on γ-irradiation on multilayer films Non-specific (TOC, pH, conductivity) or specific (e.g. chromatographic, spectroscopic, gravimetric) analytical methods can be used. several approaches were used to study the impact of γ-irradiation on multilayer films, as ion chromatography to detect and quantify the ionic species, and as pH and conductivity measurements to observe the consequences of the chemical modifications.. There are few references available on the leaching of carboxylic acid species impacting aqueous solutions used in biopharmaceutical applications in contact with plastic single-use systems [[i]]. Stability studies under accelerated or real-time degradation conditions make it possible to define the shelf life and storage conditions in order to guarantee the quality of the product. The aim of the study is to identify and quantify the acid compounds that can be released from the container under normal conditions of use of the materials: the extractables. [[1]] D. Jenke, D and V.J. Barge. Factors affecting the release of extractable acetic acid from multi-layered plastic films containing ethylene vinyl acetate (EVA) and polyethylene (PE) layers. Pharm Outsourcing. 15 (2014) 56-59

Influence of γ-irradiated biopharmaceutical films

Preventing cross-contamination, saving costs and increasing configuration flexibility make the adoption of single-use technologies very attractive for the biopharmaceutical industry. The integrity and the security of bags are due to appropriate flexible and barrier polymeric materials, such as polyethylene (PE) or ethylene vinyl acetate (EVA) and polyethylene-co-vinyl alcohol (EVOH), which are barrier to water vapor and oxygen, respectively. Conventional stainless steel tanks are sterilized by steam sterilization by the end-users, whereas plastic containers are sterilized by gamma-irradiation before delivery. The major advantage of radio-sterilization is the penetration power of the γ-radiation. It is known that γ -sterilization of polyolefin based polymer leads to alterations of the material: changes in the additives or potential damage to the polymer, as reported in the literature. Irradiation of polymeric materials has been proven to initiate radiation chemical reactions inside the polymeric material, leading to either an increase or a decrease in the polymer molecular weight. The effects of γ-irradiation on polymers are well known whereas the effects of γ-irradiation on multilayer films have been little investigated. In the case of multilayer films, the acidity of the stored solution increased after gamma irradiation for instance. In another case oxidation of the solution occurred. Such observations denote the presence of acidic and oxidant compounds, which are issued either from modification of surface of the film or from the migration of by-products from core to surface. A global investigation on γ-irradiation on multilayer films is performed to investigate the γ-irradiation based modifications on PE(Polyethylene)/EVOH(Ethylene Vinyl Alcohol)/PE film and EVA(Ethylene Vinyl Acetate)/EVOH/EVA film to assess the multilayer film robustness. Several approaches could be used to study the impact of γ-irradiation on multilayer films, as ESR (Electron Spin Resonance) to observe the radicals formation, ATR-FTIR (Attenuated Total Reflection-Fourier Transform Infrared) and Raman spectroscopies to observe the structural modifications, the measurement of yellowing, the measurement of O2 transmission rate (O2TR) and water vapor transmission rate (WVTR), the measurement of pH to follow the acidity change of solution contained in the bag and the mechanical test to evaluate the toughness of film. Due to the number of data recorded, chemometric methods, such as Principal Component Analysis (PCA), are applied to enhance the weak variations brought to the γ-irradiation of the multilayer films in the different data sets. Results show that films undergo modifications at microscopic level and that they are not altered from macroscopic and application viewpoints. Results are equivalent from batch to batch assuring then a reproducibility of the films behavior for their integration in single-use systems

Exact Mesonic Vacua From Matrix Models

We investigate in detail the structure of mesonic vacua of N=1 U(Nc) supersymmetric gauge theory with Nf flavors from the matrix model. We show that the Witten index from the matrix model calculation agrees with a result from field theoretical analysis. We also discuss the relationship between a diagrammatic summation and direct matrix integration with insertion of a variable changing delta function. Using this formalism, we obtain the quantum moduli space and evidence of the Seiberg duality from the matrix models.Comment: 14 pages, 1 figure, typos corrected and note on the quamtum moduli space adde

SO(N) Superpotential, Seiberg-Witten Curves and Loop Equations

We consider the exact superpotential of N=1 super Yang-Mills theory with gauge group SO(N) and arbitrary tree-level polynomial superpotential of one adjoint Higgs field. A field-theoretic derivation of the glueball superpotential is given, based on factorization of the N=2 Seiberg-Witten curve. Following the conjecture of Dijkgraaf and Vafa, the result is matched with the corresponding SO(N) matrix model prediction. The verification involves an explicit solution of the first non-trivial loop equation, relating the spherical free energy to that of the non-orientable surfaces with topology $RP^2$.Comment: 13 pages; v2: minor typos, one equation adde

Implementing X-ray for single use systems sterilization: Current status

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Implementing X-ray for single use systems sterilization

Sterilization/decontamination by gamma irradiation is a standardized process for some medical devices, drugs and in the food field and has many advantages due to its significantly low toxicity. Many worldwide industrial sites offer gamma irradiation as a means of sterilization, and in the last decade, new irradiation modality such as X-rays or electron-beam raises. These methods make also possible the sterilization of products without significant heating and to handle them directly in their final packaging, to overcome the challenges encountered e.g., due to sterilization capacity constraints. All irradiation modalities are reliable and reproducible processes and ensure sterility over time by avoiding any possible risk of contamination. It will thus reflect on post-pandemic world solutions to build capacity with high flexibility, while looking forward to anticipating future increase in sterilization demand without negative implications/repercussions in all industries where sterilization is needed. Unfortunately, these radiation processing also present disadvantages of inducing modifications for exposed materials. Some factors could affect the observed changes, such as their chemical composition, additives, or the presence of oxygen in the environment. X-ray industrial units are beginning to emerge, and the question of a comparative study between the effects of different types of radiation and their health impact on the materials/products studied arises. This current lack of data represents a hurdle for medical device and biopharmaceutical manufacturers desiring to transition from gamma-ray sterilization modalities to X-ray or electron-beam. Communicating to the industry our approach and polymer effects results can support medical device and biopharmaceutical manufacturers to perform their own risk assessment when piloting the transition to alternative irradiation modalities. In an effort to help fill these data gaps previously enounced, physicochemical testing, mechanical testing, extractables testing, etc. will be performed on products including their polymer components previously irradiated by the different irradiation modalities (gamma and X-ray). Highlights: - Support biomanufacturers to perform their own risk assessment when piloting the supplementing of alternative irradiation modalities to ensure business continuity during sterilization processes - Comparative study between the effects at materials/components & sub-assemblies/products of different types of ionizing radiations - Understanding the parameters inducing modifications for exposed SUS to irradiation - Physicochemical testing, mechanical testing, extractables testing, functional testing, activation, etc. will be performed on products and their polymer components previously irradiated (gamma and X-ray)

Note on Matrix Model with Massless Flavors

In this note, following the work of Seiberg in hep-th/0211234 for the conjecture between the field theory and matrix model in the case with massive fundamental flavors, we generalize it to the case with massless fundamental flavors. We show that with a little modifications, the analysis given by Seiberg can be used directly to the case of massless flavors. Furthermore, this new method explains the insertion of delta functions in the matrix model given by Demasure and Janik in hep-th/0211082.Comment: 10 pages. Type fixed. Remarks adde

D-Branes in Field Theory

Certain gauge theories in four dimensions are known to admit semi-classical D-brane solitons. These are domain walls on which vortex flux tubes may end. The purpose of this paper is to develop an open-string description of these D-branes. The dynamics of the domain walls is shown to be governed by a Chern-Simons-Higgs theory which, at the quantum level, captures the classical "closed string" scattering of domain wall solitons.Comment: 23 Pages, 3 figures. v2: reference adde

Matrix Models, Monopoles and Modified Moduli

Motivated by the Dijkgraaf-Vafa correspondence, we consider the matrix model duals of N=1 supersymmetric SU(Nc) gauge theories with Nf flavors. We demonstrate via the matrix model solutions a relation between vacua of theories with different numbers of colors and flavors. This relation is due to an N=2 nonrenormalization theorem which is inherited by these N=1 theories. Specializing to the case Nf=Nc, the simplest theory containing baryons, we demonstrate that the explicit matrix model predictions for the locations on the Coulomb branch at which monopoles condense are consistent with the quantum modified constraints on the moduli in the theory. The matrix model solutions include the case that baryons obtain vacuum expectation values. In specific cases we check explicitly that these results are also consistent with the factorization of corresponding Seiberg-Witten curves. Certain results are easily understood in terms of M5-brane constructions of these gauge theories.Comment: 27 pages, LaTeX, 2 figure

Vortices, Instantons and Branes

The purpose of this paper is to describe a relationship between the moduli space of vortices and the moduli space of instantons. We study charge k vortices in U(N) Yang-Mills-Higgs theories and show that the moduli space is isomorphic to a special Lagrangian submanifold of the moduli space of k instantons in non-commutative U(N) Yang-Mills theories. This submanifold is the fixed point set of a U(1) action on the instanton moduli space which rotates the instantons in a plane. To derive this relationship, we present a D-brane construction in which the dynamics of vortices is described by the Higgs branch of a U(k) gauge theory with 4 supercharges which is a truncation of the familiar ADHM gauge theory. We further describe a moduli space construction for semi-local vortices, lumps in the CP(N) and Grassmannian sigma-models, and vortices on the non-commutative plane. We argue that this relationship between vortices and instantons underlies many of the quantitative similarities shared by quantum field theories in two and four dimensions.Comment: 32 Pages, 4 Figure