The compatibility of materials with industrial technologies of sterilization

Sophie ROUIF

Manager Research & Development in IONISOS
info@ionisos.fr

There are several methods of sterilization of medical devices. The most common are the steam (or autoclave), ionizing radiations and ethylene oxide.
Among these techniques, ionizing radiations and ethylene oxide are used at the industrial scale and allow the processing of products without manipulation to either product or pallet configuration, and in high volumes. With these technologies, the products are treated in carton boxes or in pallets.

The principles of radiation and ethylene oxide induce the chemical modification of biological molecules and thus alter the microbial metabolism, resulting in the destruction of organisms (bacteria, yeast fungi ...). These chemical modifications are, at first, not necessarily specific to biological molecules, and secondary reactions on the materials of medical devices are not excluded. The metals do not present any problem of compatibility with the sterilization technologies.

Plastics may be exposed to secondary or side effects, and they also are largely used in medical applications. The knowledge of major trends and information from plastics suppliers allows the choice of suitable materials from the beginning of a new project / product.

Chamber of ethylene oxide treatment

Ionizing radiation

Radiations used for radio sterilization are gamma rays (photons emitted by a cobalt 60 source) and accelerated electrons (generated by an electron accelerator). The sterilization acts by the formation of free radicals: it cuts, modifies and distorts the DNA chains of organisms, causing the destruction of bacteria, yeasts, molds, fungi and viruses. What happens with these organisms, also occurs with the materials exposed. Free radicals formed can causesecondary or side effects on materials.

The effects of ionizing radiation are a balance between ruptures and molecular rearrangements, such as crosslinking or cyclizations. There is no general rule of behavior, but trends can be identified by considering the polymer structure and conditions of radiation.
In the structure of polymers, the most sensitive chemical bonds are affected first. This is mainly polymers with halogen atoms (fluorine, chlorine), such as polyvinyl chloride (PVC) or polytetrafluoroethylene (PTFE), and polymers presenting quaternary carbon atoms (substituted by four different groups), as butyl rubber or polypropylene (PP).
Radiolysis reactions and degradation are highly favored by the presence of oxygen, less temperature, and very little in the dose rate.

Treatment with gamma rays, which is characterized by a lower dose rate (compared to accelerated electrons) produces some degradation by oxidation of the polymer to the surface.
But the dose is the main factor of influence. The dose is the amount of energy received per kilogram of material, its unit is the kiloGray (1 kGy = 1 kJ / kg). Most polymers are resistant to sterilization doses of about 25 kGy to 75 kGy, however they deteriorate beyond. This is the case of PP, PVC and cellulose. PTFE degrades at low dose, POM from 25 kGy and butyl rubber at a slightly higher dose, depending on the grade.

The table hereafter shows the behavior under ionizing radiation doses for sterilization (between 25 kGy and 70 kGy) of polymers commonly used (non-exhaustive list).

	RESISTANT	To consider with attention	DEGRADATION
Polyolefine	PS, PE	PP, PVC
Technical thermoplastics	EVA, EVOH, ABS, ABS/PC PA 6, PA 66 PET, PBT	PMMA PC	POM
High performance thermoplastics	UHMWPE, PA46, PA11, PA12 PPA, PAA PPS, PPO PSU, PPSU PI, PAI, PEI PEEK LCP	PVDF, CTFE	PTFE
Thermoplastic elastomers (TPE)	SBS, SEBS	PP/EPDM PEBA TPU COPE (ether – ester copolymer)
Elastomers	NR, NBR, HNBR, SBR	Butyl rubber, chlorobutyl rubber, Neoprene, EPDM, EPR
High performance elastomers	Fluoroelastomers, Fluorosilicones	Silicones, AEM/ACM

With a few exceptions of polymers whose mechanical properties can decrease, the main risk of modification of plastics under ionizing radiation is yellowing. This arises from the formation of double bonds, resulting from the cuts of some polymer chains, enough to make it visible, but generally not enough to influence the mechanical properties. The yellowing is especially important when the dose is high. Generally, it is reversible: it decreases largely in the few weeks following the treatment.

Ethylene oxide (ETO)

This technique uses a sterilizing gas, which is also characterized by a high diffusivity and permeability, associated with conditions favoring these two factors: the products are brought into contact with the ETO under controlled conditions of temperature, humidity, pressure and time of exposure. It is often used when materials are sensitive to radiation and steam.
Sterilization is due to the alkylation reaction occurring at the ends of the chains of enzymes and DNA and RNA molecules. The functions -OH,-COOH,-SH and-NH react with the radical - CH₂ - CH₂ - OH of the ETO, altering the microbial metabolism.
The chemical structures of plastics (except cellulosic polymers) are not rich in functions that can react by alkylation with the ETO. Such functions can be found at the ends of polymer chains, but these are often blocked by initiators or by polymerization additives. In such conditions, the biological molecules are the most sensitive to ETO. Therefore, secondary reactionswith plastics are quite limited. Particular attention should be paid to the polystyrene (PS) and its derivative SAN (styrene-acrylonitrile). In both cases, according to the grade, a loss of mechanical properties of 30 % can be observed. This does not limit the use of the product, it will depend on the intended use of the components made of these materials. Physical conditions (temperature, pressure and humidity) of the process influence more the choice of the materials, including plastics. The steps of preparation (conditioning) and of contact with the ETO are conducted at a temperature generally between 40°C and 50°C in conditions of relative humidity of 50 % to 60 % for 6 to 8 hours. Particular attention, through a validation test, must paid to plastics whose service temperature ranges up to 70 ° C - 80 ° C, as for example polyolefins, and hydrophilic coatings, which can swell.
The ability of the material to adsorb the ETO and to allow its migration through it is the most important parameter to ensure the sterility of the whole product. This can be checked in existing tables and by trials to validate the conditions of treatment.

In conclusion, with the exception of PTFE and POM in the case of ionizing radiations, almost all plastics can be compatible with both industrial sterilization techniques.
It should be noted that a few materials commonly used in the medical sector, including PP, PS, PMMA, PC and the butyl rubber, should be paid special attention. The main risks are yellowing in the case of radiation and a slight degradation of PS in the case of ETO. We suggest to make sure from your suppliers of the compatibility of the medical grades they offer with the techniques of sterilization, and then to perform some validation trials.