ISO radiation sterilization standards

This presentation provides an overview of the current status of the ISO radiation sterilization standards. The ISO standards are voluntary standards which detail both the validation and routine control of the sterilization process. ISO 11137 was approved in 1994 and published in 1995. When reviewing the standard you will note that less than 20% of the standard is devoted to requirements and the remainder is guidance on how to comply with the requirements.

Future standards developments in radiation sterilization are being focused on providing additional guidance. The guidance that is currently provided in informative annexes of ISO 11137 includes: device/packaging materials, dose setting methods, and dosimeters and dose measurement, currently, there are four Technical Reports being developed to provide additional guidance:

1. 1. AAMI Draft TIR, “Radiation Sterilization Material Qualification”

2. 2. ISO TR 13409-1996, “Sterilization of health care products — Radiation sterilization — Substantiation of 25 kGy as a sterilization dose for small or infrequent production batches”

3. 3. ISO Draft TR, “Sterilization of health care products — Radiation sterilization Selection of a sterilization dose for a single production batch” li]4. ISO Draft TR, “Sterilization of health care products — Radiation sterilization-Product Families, Plans for Sampling and Frequency of Dose Audits.”

     

The radiation resistance of the bioburden from medical devices

An extensive study of the radiation resistance of microbial species constituting the bioburden of a number of different medical devices obtained from Japanese medical device manufacturers has been carried out. A standard protocol for determining radiation resistance was used and validated at the fourteen centres involved in the study. Individual microbial isolates from the bioburden obtained from seven different devices manufactured in these centres were studied. A total of 3742 unselected isolates were obtained, of which 197 failed to survive long enough for subsequent radiation resistance studies. The remainder were subjected to an initial screen test to identify those organisms that were sensitive to the lethal effects of radiation with a D₁₀ of < 1.5kGy. The 465 isolates that survived the screen doses were then tested for survival in an incremental series of radiation doses using methods similar to those of Whitby (1979) and Yan and Tallentire(1995). The isolates from “dry” devices were more resistant than those obtained from the one water filled (“wet”) device studied. The overall distribution of radiation resistance among the isolates was considered to be similar to that forming the “Standard Distribution of Resistance” (SDR) included in the ISO International Standard 11137 “Sterilization of Health Care Products — Requirements for validation and routine control — Radiation sterilization”.     

The effects of γ-radiation on the thermal, mechanical, and segmental dynamics of a silica filled, room temperature vulcanized polysiloxane rubber

RTV-5370 is a filled polydimethylsilxoane–polymethylphenylsiloxane copolymer system originally developed by Dow Corning and now supplied by Rhone Poulenc. There is a desire to develop lifetime assessments of this material for certification programs and as a model system for understanding other filled siloxane polymer systems. We have initiated aging studies on these materials by employing accelerated aging tests with exposure to Co-60 γ-radiation. The effects of radiation exposure have been investigated by thermal (differential scanning calorimetry), mechanical (dynamic mechanical analysis), chemical (solvent swelling), and segmental dynamics (nuclear magnetic resonance) methods. The data show that RTV-5370 undergoes predominately radiation-induced crosslinking reactions over the dose range investigated. These reactions reduce the molecular weight between crosslinks, thereby hardening the composite and reducing the motional dynamics of segmental motion. DSC studies show dose dependent crystallization phenomena.     

The “Facilitated Transition” hypothesis as an explanation for the gemdialkyl effect

A new technique of searching the conformational space of transition states was used to explore the cause of the rate acceleration in the gem-dialkyl effect in intramolecular cyclization reactions. Several previous hypotheses were discarded and a new hypothesis was advanced based on this new data. This hypothesis, the “Facilitated Transition” hypothesis, states that increased steric hindrance reduces the overall activation energy by facilitating rotation through the transition state. The older “Reactive Rotamer” hypothesis was eliminated by generating all conformations of the starting materials using the and computer programs and demonstrating that no relationship is found between rate increase and a change in the concentration of “reactive rotamers”.     

Moment Analysis in Non-Linear Frontal-Elution and Elution Chromatography

Analytical formulae are presented for the statistical moments of an output chromatographic curve for non-linear distribution isotherms at a very narrow feed band (“elution chromatography”). Non-linear “frontal-elution chromatography”, i.e., the case of a very wide feed band, is also considered. The analytical expressions characterize the position and the width of sorption and desorption boundaries of the output curve. The column length at which a constant configuration of the sorption (or desorption) boundary is attained is dependent in the curvature of the isotherm and on the plate height. The results have been confirmed experimentally.     

Protein-coated β-ferric hydrous oxide particles: An electrokinetic and electrooptic study

Using microelectrophoresis and electric light scattering techniques, we investigated the adsorption characteristics, surface coverage and surface electric parameters of superstructures from two isoforms of plastocyanin, PCa and PCb, in an oxidized state adsorbed on β-ferric hydrous oxide particles. The surface electric charge and electric dipole moments of the composite particles and the thickness of the protein adsorption layer are determined in a wide pH range, at different ionic strengths and concentration ratios of PC to β-FeOOH. The adsorption of the two proteins was found to shift the particles’ isoelectric point and to alter the total electric charge and the electric dipole moments of the oxide particles to different extent. A “reversal” in the direction of the permanent dipole moment is observed at lower pH for PCb- than for PCa-coated oxide particles. Strict correlation is found between the changes in the electrokinetic charge of the composite particles and the variation in their “permanent” dipole moments. Data suggest that the adsorption of the proteins is driven by electrostatic and/or hydrophobic interactions with the oxide surfaces dependent on pH. The adsorption behaviour is consistent with the involvement of the “eastern” and “northern” patches of the plastocyanin molecules in their adsorption on the oxide surfaces that are differently charged depending on pH.     

Kosmotrope character of maltose in water mixtures

It is well known that water plays a fundamental role for living beings, because the nature of water transformations provides for the ability to preserve biostructures. Solute can be classified as “kosmotropes” or “chaotropes” depending on the interaction strength with water. In the case of solutes destroying the natural hydrogen bonded network of water, called “kosmotropes” or “structure-makers”, the denaturation processes can be inhibited.

The aim of this work is to investigate the vibrational behaviour of maltose/H₂O mixtures in order to characterise the changes induced by the sugar on the H₂O hydrogen-bonded network. The obtained findings point out that maltose has a destructuring effect on the water tetrahedral network and emphasise its kosmotrope character.     

With radiation crosslinking of engineering plastics into the next millennium

Much basic research has been done on the crosslinking behaviour of so-called “engineering plastics”. Up to now the industrial conversion to actual manufacture of multifunctional electronic components has gained ever increasing importance in the plastics industry and will continue to do so in the coming years. Examples of this are SMD (surface mounted device) technology, and 3D-MID (3-dimensional moulded interconnected devices) technology. These techniques require materials with high short-term temperature stability. In this paper it will be discussed which engineering plastics are significant for the radiation crosslinking process, for both technical and commercial reasons. The main topics will be the crosslinking behaviour of Polybutylenterephthalate (PBT) and Polyamide (PA). The importance and the challenges to the irradiation industry, as well as practical applications, will be shown.     

Determination of copper, lead and cadmium in whole blood by stripping voltammetry with the use of graphite electrodes

The problem with toxic metal ion determination in blood is the adsorption of organic compounds on the electrode surface and the formation of complexes between metal ions and organic constituents of blood. This is the reason why usually preliminary acid digestion or other sample pretreatment is used. Two kinds of electrodes have been used: “Ultra-Trace Electrode”, made from impregnated graphite (I), and thick film graphite disposable electrodes (II). The analysis of whole blood with different sample preparation methods shows, that chemical digestion is not necessary for the analysis. Electrochemical two-stage sample preparation provides the possibility for analysing whole blood with the mentioned electrodes. Thick film disposable electrodes are less sensitive to the interference of organic constituents of blood. These electrodes give the possibility to determine total cadmium, lead and copper concentration in whole blood without special sample pretreatment. The application of “Ultra-Trace Electrode” for blood analysis is possible only after preliminary pretreatment of blood by chemical digestion or electrochemical sample preparation.     

The quantitative determination of fission and nuclear reaction products

Definitions are given to the terms “per cent atom burn-up” and “per cent atoms consumed” as applied to nuclear fuel analysis at the Argonne National Laboratory. The radiochemical and analytical methods which have been adapted and developed especially for this type of analysis are discussed. The analysis of nuclear reaction products by paper chromatographic methods and scintillation spectrometry is emphasised and demonstrated.     

Prediction of paper permanence by accelerated aging II. Comparison of the predictions with natural aging results

Accelerated aging tests are credible and useful to predict paper permanence only if such tests can be shown to correlate with natural aging. In the first part of this study, a kinetic model was developed based on the accelerated aging results. In this report, we have shown that this kinetic model can indeed predict the natural aging results of lignin-free sheets with a statistical confidence. This is the first quantitative comparison of accelerated aging with natural aging.     

Chemical analysis of precipitates in metallic alloys using coincidence Doppler broadening of positron annihilation radiation

Two-detector coincidence Doppler broadening (CDB) method of positron annihilation radiation is applied to the study of precipitates in metals. As the first step, the CDB spectra for many kinds of elements are measured to obtain the “fingerprint” of each element for the chemical analysis of the precipitates in metals. Utilizing the fingerprint of Cu, we made chemical analysis of nano-particles formed in the initial stage of thermal aging in a Fe–Cu alloy, and found that the particles are consisting of Cu only and free from vacancies, which demonstrates the usefulness of this method in the study of the precipitates.     

Tungstate-mediated In-situ Passivation of Grain Boundary Grooves in Perovskite Solar Cells

Possessed with advantageous optoelectronic properties, perovskites have boosted the rapid development of solution-processed solar cells. The performance of perovskite solar cells (PSCs) is significantly weakened by the carrier loss at grain boundary grooves (GBGs); however, it receives limited attention and there lacks effective approach to solve this issue. Herein, for the first time, we constructed the tungstate/perovskite heterointerface via a “two step” in situ reaction approach that provides effective defect passivation and ensures efficient carrier dynamics at the GBGs. The exposed perovskite at grain boundaries is converted to wide-band-gap PbWO₄ via an in-situ reaction between Pb²⁺ and tungstate ions, which passivate defects due to the strong ionic bonding. Moreover, recombination loss is further suppressed via the heterointerface energetics modification based on an additional transformation from PbWO₄ to CaWO₄. PSCs based on this groove modification strategy showed good universality in both normal and inverted structure, with an improved efficiency of 23.25 % in the n-i-p device and 23.33 % in the p-i-n device. Stable power output of the modified device could maintain 91.7 % after around 1100 h, and the device efficiency could retain 92.5 % after aging in air for around 2110 h, and 93.1 % after aging at 85 °C in N₂ for 972 h.     

Reply to “Comments on the paper entitled ‘The formulation and modelling of the anodic dissolution of zinc through adsorbed intermediates’ ” by C. Cachet et al.

The points raised in the paper entitled “Comments on the paper entitled ‘The formulation and modelling of the anodic dissolution of zinc through adsorbed intermediates”’ have been discussed. It has been shown that, in contrast to the statements in the “Comments”, most of the papers concerning the reaction schemes suggested for the interpretation of the dissolution or deposition of metals, which were considered as a support for the opinion of the Authors of the “Comments”, support the views expressed in our original paper [J. Electroanal. Chem. 583 (2005) 148]. On the other hand, it has been stressed again that the criticism expressed in the original paper refers to dubious conclusions drawn on the basis of transient measurements.     

Design and application of process control charting methodologies to gamma irradiation practices

The relationship between the contract irradiation facility and the customer has historically been based upon a “PASS/FAIL” approach with little or no quality metrics used to gage the control of the irradiation process. Application of process control charts, designed in coordination with mathematical simulation of routine radiation processing, can provide a basis for understanding irradiation events. By using tools that simulate the physical rules associated with the irradiation process, end-users can explore process-related boundaries and the effects of process changes. Consequently, the relationship between contractor and customer can evolve based on the derived knowledge. The resulting level of mutual understanding of the irradiation process and its resultant control benefits both the customer and contract operation, and provides necessary assurances to regulators.

In this article we examine the complementary nature of theoretical (point kernel) and experimental (dosimetric) process evaluation, and the resulting by-product of improved understanding, communication and control generated through the implementation of effective process control charting strategies.     

Concerning the theory of chirality functions : Part I. Construction and discussion of chirality functions by means of [2.2] metacyclophanes

By means of [2.2]metacyclophane (skeleton symmetry C_2h) the construction of qualitatively-complete chirality functions via the first and second “Naherungsansatze” is demonstrated. In this context, a detailed comment concerning the algebraic theory of chirality functions is given. As the first term of the chirality function (“abridged Ansatz”), both methods furnish a simple superposition rule (“quadrant rule”). The second component as deduced via the method of polynomials is of third degree in ligand specific parameters. A particular property of the second approximation method is derived. The consequences with respect to observables of the chirality phenomenon, in the case of the approximations being valid, are discussed.     

Application of nonparametric statistics to the estimation of the accuracy of Monte Carlo confidence intervals in regression analysis

Confidence intervals and their uncertainties for nonlinear regression parameters are obtained using nonparametric statistical methods. The confidence intervals are calculated by means of a Monte Carlo procedure. Their uncertainties depend on the confidence level desired and on the number of Monte Carlo simulations of the data set. They are obtained by calculating the uncertainties in the boundaries of the confidence intervals using a generalization of the nonparametric method used to calculate confidence intervals for medians. The method described here provides reliable confidence intervals at relatively low computational expense. It seems especially suited to the statistical analysis of nonlinear regression problems that are difficult to deal with using conventional methods.     

Optical potential theory of diatom-diatom scattering. II. Indistinguishable molecules

The theory of vibro-rotational energy exchange in “indistinguishable” diatom-diatom scattering is formulated in terms of effective potentials. Due the necessity of considering both “symmetric” and “antisymmetric” molecular two-particle states, the formalism has a characteristic (two-by-two matrix structure. A mathematical generalization of Schwinger's theory of sources allows a compact derivation of exact and approximate expressions for t “optical” and “transition” potentials of elastic and inelastic processes, respectively. Finally, considerations based on a partial wave analysi of the working equations, suggest that the present theory should be more readily amenable to numerical implementations than the close coupling approach     

Zur nomenklatur der phane—II

The new term “Phanes” has been clearly defined and a nomenclature system tentatively developed. This system is comprehensible and of general application and at the same time relatively simple. The notations “nucleus”, “bridge”, “number of bridge members” and “number of ring members” are defined. In order to get a definite characterisation of the phanes which contain a carbocyclic nucleus, a carbocyclic and heterocyclic bridge the following terms: “carbophanes”, “carba-phanes” and “hetera-phanes” have been newly introduced. The prefix “hetera-” has been proposed as a general expression and as a representative term for the syllables “aza-”, “oxa-”, “thia-” and so on. The so called “a-nomenclature” is clearly called “hetera-nomenclature”. The new expressions “heteralogous” and “substitulogous” are explained. As the various examples will show, the “Phane-Nomenclature” can also be applied to the naming of complicated metallocenophanes.     

10MeV 25KW industrial electron LINAC

A 10MeV 25KW plus class electron LINAC was developed for sterilisation of medical devices. The LINAC composed of a standing wave type single cavity prebuncher and a 2m electro-plated travelling wave guide uses a 5MW 2856MHz pulse klystron as an RF source and provides 25KW beam power at the Ti alloy beam window stably after the energy analysing magnet with 10MeV plus-minus 1 MeV energy slit. The practical maximum beam power reached 29 KW and this demonstrated the LINAC as one of the most powerful S-band electron LINACs in the world. The control of the LINAC is fully automated and the “One-Button Operation” is realised, which is valuable for easy operation as a plant system. 2 systems have been delivered and are being operated stably.