Comments on the Japanese study of the radiation resistance of the bioburden of medical devices

The findings obtained in an extensive study of the radiation resistance of microbes forming the bioburden of a number of medical devices has been carried out by Takehisa et al. and reported in this number of this Journal. The following paper reviews the expected behaviour of the reported populations under the conditions specified in ISO Standard 11137 Method 1, which is widely used in the determination of the radiation sterilization dose required for sterilization of medical devices. The populations reported for “dry” devices contain a higher proportion of more radiation resistant microbes than that found in the standard distribution of resistance (SDR) that is used for setting the sterilization dose in Method 1. A possible alternative dose setting method for more resistant microbial populations is introduced and discussed.     

Effect of γ-radiation on ointment cold cream

In this paper, Co-60γ ray was used to irradiate the ointment cold cream at room temperature (25°C). We also used FTIR, GC and thin film chromatogram to analyse various irradiated samples. It was found that the ointment cold cream can be irradiated at dose of 5–35 kGy and at dose rate from 0.2 to 0.6 kGy/h at room temperature (25°C) without evident decomposition. At dose of 5–15 kGy, the number of bacteria can be reduced to hygienic standard value. The radiation sterilization is a safe method for killing the bacteria in the ointment cold cream.     

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.”

     

A study on radiation sterilization of medical devices in the South of China

In this paper, directing at the peculiarity of south China, the technique and quality control of Co-80 r radiation sterilization of medical devices have been studied. Radiation dose setting is determined by the AAMI method. Experiment shows that radiation treatment has no effect upon the attributes of the products. Under the same condition of packing and environment, storing time of radiation sterilization is 4 times than that of sterilization by heat. Clinical appliances of 1000 carton products show that radiation sterilization products are safe and reliable.     

The research of using Co-60 γ ray to sterilize different mediums for edible fungus

The present experiment has been carried out by using different dosage of Co—60 γ ray for radiation sterilization of five kinds of cultural materials of edible fungus, The results indicated that sterilization dosage of sawdust is 22 kGy. that of cotton—seed shell and the rest are 26 kGy. We conclude that using Co-60 γ ray to sterilize the cultura 1 materials of edible fungus is a secure and saving labor and energy new method which could sterilize thoroughly.     

Status of radiation processing dosimetry

Several milestones have marked the field of radiation processing dosimetry since IMRP 7. Among them are the IAEA symposium on High Dose Dosimetry for Radiation Processing and the international Workshops on Dosimetry for Radiation Processing organized by the ASTM.

Several standards have been or are being published by the ASTM in this field, both on dosimetry procedures and on the proper use of specific dosimeter systems. Several individuals are involved in this international cooperation which contribute significantly to the broader understanding of the role of dosimetry in radiation processing.

The importance of dosimetry is emphasized in the standards on radiation sterilization which are currently drafted by the European standards organization CEN and by the international standards organization ISO. In both standards, dosimetry plays key roles in characterization of the facility, in qualification of the process and in routine process control.

As a function of the work on the standards, several issues are now receiving major attention. These include traceability and uncertainty limits of the dose measurements, calibration procedures, environmental influence and combination of influence factors such as dose rate and temperature.

The increased attention to these factors have increased the demands on existing dosimeter systems, and rather than new dosimeters, the latest years have seen improvements on established dosimeters.     

Studies of radiosterilization and radiation effect on disposable medical products and their packing materials

This report describes the studies of radiation effects in the physical and chemical properties of various disposable medical products, such as catguts, syringes and theirpacking materials; toxic tests on them; sufficient radiation conditions and radiation doses. These studies could provide the basis for production of medical products and quality assurance of radiation sterilization.     

Field evaluations of the VDmax approach for substantiation of a 25 kGy sterilization dose and its application to other preselected doses

The International and European standards for radiation sterilization require evidence of the effectiveness of a minimum sterilization dose of 25 kGy but do not provide detailed guidance on how this evidence can be generated. An approach, designated VD_max, has recently been described and computer evaluated to provide safe and unambiguous substantiation of a 25 kGy sterilization dose. The approach has been further developed into a practical method, which has been subjected to field evaluations at three manufacturing facilities which produce different types of medical devices. The three facilities each used a different overall evaluation strategy: Facility A used VD_max for quarterly dose audits; Facility B compared VD_max and Method 1 in side-by-side parallel experiments; and Facility C, a new facility at start-up, used VD_max for initial substantiation of 25 kGy and subsequent quarterly dose audits. A common element at all three facilities was the use of 10 product units for irradiation in the verification dose experiment.

The field evaluations of the VD_max method were successful at all three facilities; they included many different types of medical devices/product families with a wide range of average bioburden and sample item portion values used in the verification dose experiments. Overall, around 500 verification dose experiments were performed and no failures were observed. In the side-by-side parallel experiments, the outcomes of the VD_max experiments were consistent with the outcomes observed with Method 1.

The VD_max approach has been extended to sterilization doses >25 and <25 kGy; verification doses have been derived for sterilization doses of 15, 20, 30, and 35 kGy. Widespread application of the VD_max method for doses other than 25 kGy must await controlled field evaluations and the development of appropriate specifications/standards.     

Biomedical applications of radiation technology in Mexico

Mexican Health Institutions continuously require suitable medical grade prosthetic materials for reconstructive and plastic surgery. In particular, the requirements of polydimethylsiloxane, PDMS, for soft tissue replacements are rapidly growing. In addition to molecular weight, the properties of PDMS in biomedicine strongly depend on its purity, formulation and processing. High energy radiation has been used for both the synthesis of highly pure PDMS, free of catalyst and chemicals, and for sterilization of biomedical products. Here, are discussed the gamma radiation polymerization of different siloxane precursors to obtain PDMS with specific functionality and molecular structure as well as the radiation sterilization of amniotic membranes used as wound dressing.     

Thermal and spectroscopic analysis of florfenicol irradiated in the solid-state

The study has been undertaken to check the effect of ionising radiation on the physical and chemical properties of florfenicol, an antibiotic of a wide range of antibacterial activity. The solid-state samples were subjected to an electron beam generated by accelerator corresponding to the doses of 25, 100 and 400 kGy, and the effect of the exposure was analysed by the methods not requiring changes in the state (with no preliminary treatment), such as SEM, DSC, FTIR, XRD, EPR and HPLC. Florfenicol irradiated with a dose of 25 kGy has not changed the form or colour, however, a small increase in intensity of some absorption bands in the FTIR spectrum and of some peaks in the XRD pattern, a decrease in the melting point by 0.6°C, the appearance of free radicals and a loss in the FF content within the error of the method (0.91%) have been observed. After irradiation with greater doses (100 and 400 kGy) the changes have intensified, yellow discolouration appeared and the loss of FF content has increased to 6.39%. As follows from the results, the compound studied in solid-state undergoes radiolysis after e-beam irradiation in the doses ≥25 kGy, but lower doses (15–20 kGy) can be applied for its decontamination or sterilization with no adverse effect on its physico-chemical properties.     

Radiation effect studies on anticancer drugs, cyclophosphamide and doxorubicin for radiation sterilization

Two anticancer drugs, cyclophosphamide (CPH) and doxorubicin hydrochloride (DOXO), in powder form were exposed to a range of doses of ⁶⁰Co gamma and electron beam radiation to study the effects of ionizing radiation. Pharmacopoeia tests, discolouration, degradation products, effect of irradiation temperature and dose rate were investigated. CPH undergoes less than 2% degradation at 30 kGy. Chromatographic studies revealed formation of several trace level degradation products, discolouration and free radicals in the irradiated CPH. N,N-bis (2-chloroethyl) group in the molecule is particularly sensitive to radiation degradation. Irradiation to 5 kGy at low temperature (77 K) did not result in significant changes. DOXO was observed to be quite radiation resistant and did not undergo significant changes in its physico-chemical properties and degradation product profile. It can be radiation sterilized at normal sterilization dose of 25 kGy.     

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”.     

Experiences using IAEA Code of practice for radiation sterilization of tissue allografts: Validation and routine control

Problems of tissue allografts in using International Standard (ISO) 11137 for validation of radiation sterilization dose (RSD) are limited and low numbers of uniform samples per production batch, those are products obtained from one donor. Allograft is a graft transplanted between two different individuals of the same species. The minimum number of uniform samples needed for verification dose (VD) experiment at the selected sterility assurance level (SAL) per production batch according to the IAEA Code is 20, i.e., 10 for bio-burden determination and the remaining 10 for sterilization test. Three methods of the IAEA Code have been used for validation of RSD, i.e., method A1 that is a modification of method 1 of ISO 11137:1995, method B (ISO 13409:1996), and method C (AAMI TIR 27:2001). This paper describes VD experiments using uniform products obtained from one cadaver donor, i.e., cancellous bones, demineralized bone powders and amnion grafts from one life donor. Results of the verification dose experiments show that RSD is 15.4 kGy for cancellous and demineralized bone grafts and 19.2 kGy for amnion grafts according to method A1 and 25 kGy according to methods B and C.     

Effects of different sterilization processes on the properties of a novel 3D‐printed polycaprolactone stent

Bioresorbable stents (BRS) offer the potential to improve long‐term patency rates by providing support just long enough for the artery to heal itself. While manufacturing methods to produce BRS using the appropriate architecture, material and mechanical studies, etc., have received much attention, the effects subsequent sterilization methods have on BRS properties are overlooked. Sterilization process can change a device's properties. This work presents the effects ethanol, ultraviolet light (UV), and antibiotic sterilization processes at 0.5, 1, 2, 4, 8, and 16 hours have on a novel 3D‐printed polycaprolactone stent. The stents were analysed using sterility tests, scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, mass spectrometry, for molecular weight, and degradation tests. Results have shown ethanol to be an effective sterilization treatment as it barely affected the material's properties. On the other hand, UV had a considerable influence (mainly produced by the photodegradation of UV irradiation) on crystallinity and molecular weight. Lastly, while antibiotic sterilization did not affect crystallinity to the same degree, it did substantially reduce the molecular weight of the samples. Ethanol results in being the best sterilization method for the high material requirements that medical devices such as stents have.     

Radiation‐induced migration of additives in PVC‐based biomedical disposable devices. Part 1. Surface morphology by AFM and SEM/XEDS

Two different types of plasticized poly(vinyl chloride) (PVC) used for biomedical disposable devices—extruded and injection moulded—were studied in the non‐sterilized condition and after 25 and 50 kGy of beta irradiation. The polymer surfaces were analysed by scanning electron microscopy (SEM) equipped with an x‐ray energy‐dispersive spectroscopy (XEDS) and by atomic force microscopy (AFM). The inner surface of two parts of a venous line showed a different morphology according to their original formulation (for extrusion or injection moulding process) and reacted differently on sterilization with beta irradiation. Moulded parts were affected only slightly by the radiation step, whereas the variations were bigger for the extruded parts. In order to gain the best performances for the medical devices studied, the utmost care must be taken in the sterilization step, which should be optimized as well as the other steps of the manufacturing process. Copyright © 2003 John Wiley & Sons, Ltd.     

Dose distributions for containers electron sterilized at energies from 150–250 keV

An electron beam facility is described utilizing a 30 cm wide x 250 kV x 20 ma processor for the study of the in-line sterilization of containers for aseptic food and medical device packaging. The sterilizer permits the handling of containers of varying length to diameter ratios, ranging from 1.36 liter (46 oz) two piece cans, to 0.5 liter (16.9 oz) liquid food cartons to 3–90 ml pharmaceutical syringes and vials. The thin film dosimetric techniques used to survey these containers and the results obtained under in-line, continuous motion conditions are described.     

Organic and inorganic fouling at quartz-liquid interface in ultraviolet photoreactors during on-line sterilization of cheese whey

This article reports on lamp fouling during on-line ultraviolet (UV) sterilization of cheese whey. The extent of fouling as well as the composition of fouling materials was studied after the operation of three tubular UV reactors of different flow thicknesses (18, 13, and 6 mm) for 48 h at a 2-h residence time. Lamp fouling, which significantly affected the sterilization efficiency, was realized after an extended period of operation. The extent of lamp fouling increased with a decrease in the thickness of the flowing cheese whey (14.42, 15.31, and 25.25 g for 18-, 13-, and 6-mm thickness, respectively). A strong relationship between the extent of fouling and the steady-state outlet temperature was observed. The rouling material contained 63.51 to 77.19% protein, 12.57 to 16.49% fat and 6.51 to 9.47% minerals on dry weight bases compared with 1% protein, 0.5% fat, and 0.4% minerals in raw cheese whey. The organic and inorganic material concentrations in the fouling material increased with a decrease in the flow thickness. The fouling mechanism was owing to adsorption and direction exchange, which were enhanced by the high temperature and low pH attained in the study. Improved designs of UV reactors in which the contact between the flowing material and the quartz surface should be developed.     

The Effect of Sterilization Methods on the Structural and Chemical Properties of Fibrin Microthread Scaffolds

A challenge for the design of scaffolds in tissue engineering is to determine a terminal sterilization method that will retain the structural and biochemical properties of the materials. Since commonly used heat and ionizing energy‐based sterilization methods have been shown to alter the material properties of protein‐based scaffolds, the effects of ethanol and ethylene oxide (EtO) sterilization on the cellular compatibility and the structural, chemical, and mechanical properties of uncrosslinked, UV crosslinked, or 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide (EDC) crosslinked fibrin microthreads in neutral (EDCn) or acidic (EDCa) buffers are evaluated. EtO sterilization significantly reduces the tensile strength of uncrosslinked microthreads. Surface chemistry analyses show that EtO sterilization induces alkylation of EDCa microthreads leading to a significant reduction in myoblast attachment. The material properties of EDCn microthreads do not appear to be affected by the sterilization method. These results significantly enhance the understanding of how sterilization or crosslinking techniques affect the material properties of protein scaffolds.

     

Preparation of quaternarized N-halamine-grafted graphene oxide nanocomposites and synergetic antibacterial properties

At present, frequent outbreaks of bacteria and viruses have seriously affected people's normal lives. Therefore, the study of broad-spectrum antibacterial nanocomposites is very promising. However, most antibacterial materials have some disadvantages, such as single bactericidal mechanisms and unrepeatable use. Based on the current situation, a kind of nanocomposite with three structures of graphene oxide (GO), quaternary ammonium salt (QAs) and N-halamine was prepared, which showed synergistic effect to improve antibacterial activity and combined with a variety of sterilization mechanisms. Meanwhile, GO can provide richer ways of sterilization and high specific surface area, which is conducive to the grafting of quaternarized N-halamine. The advantages of physical sterilization of GO, charge adsorption of QAs, reuse of N-halamine and efficient sterilization are fully utilized. The results showed that the quaternarized N-halamine-grafted GO was obtained successfully. GO grafted with quaternarized N-halamine polymer showed strong speedy bactericidal activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) (99%). It had good storage and regeneration properties.