Ethylene oxide residues

Thermolabile medical devices are generally sterilised by exposure to ethylene oxide. Any surplus ethylene oxide will be removed during the aeration phase. Afterwards, the products must be tested for ethylene oxide residues. The reliable quality control of medical devices is, as a result, a requirement for production that corresponds to international standards as well as for the successful marketing of your products. Testing for sterilisation residues in medical products is regulated in EN ISO 10993-7. Methods for analysis and the statutory limit values are to be found here.

As a GMP-certified contract laboratory in Switzerland, accredited in accordance with ISO 17025, we will test your products for sterilisation residues (ethylene oxide and ethylene chlorohydrin). We will carry out quality inspection of your products quickly and competently.

Do you have any question on the interpretation of EN ISO 10993-7 and what should be observed in the quality inspection of medical devices?

Why is ethylene oxide used for sterilisation?

Traditionally, sterilisation took place mainly in steam sterilisers at a high temperature and at excess pressure. Many modern products cannot be sterilised in a steam chamber as a result of their thermolability.

Sterilisation of these medical devices normally takes place by exposure to ethylene oxide. This method is firmly established as the standard method in this area.

What are the advantages of the ethylene oxide method?

The EO molecule is smaller than water or formaldehyde and as a result possesses good penetrating capabilities. Additionally, EO has a sterilising effect even at low temperatures. 

The good penetrating capabilities of ethylene oxide into cells makes the exposure of DNA, proteins, vitamins and enzymes possible. The killing of micro-organisms is carried out chemically by an alkylation reaction of the molecules named.

What are the disadvantages of the ethylene oxide method?

The process takes longer than heat sterilisation and the toxicity of the ethylene oxide means that additional measures for the degassing of the treated products are necessary. Therefore, a ventilation phase of several hours takes place to eliminate the sterilisation residues.

Testing of the residues in accordance with iso 10993-7

After aeration, the products must be tested with regard to ethylene oxide and ethylene chlorohydrin (a degradation product of EO). ISO 10933-7 serves as the guideline for the determination. Allowable analysis methods and limit values for ethylene oxide residues and its degradation product ethylene chlorohydrin are regulated here.

When will testing be done?

Sterilisation will be carried out in a separate work phase in special facilities after the production of a medical device. After exposure to ethylene oxide comes the aeration phase. Afterwards, the samples will be analysed either in-house or will be sent by courier to a specialised service laboratory for analysis.

What should be observed during transportation?

Transportation is also regulated in ISO 10933-7 and is generally performed in dry ice. Losses due to evaporation will be minimised as a result. Cooling using freezing packs is not permissible. It is particularly important that untreated control samples are sent protected and separately. Only in this way can contamination from the treated samples be avoided.

The advantages of external testing by a contract laboratory

There are many years of technical expertise available in a service laboratory. The high sample throughput allows testing of the samples to usually be cost-effective. In the event of questions or problems, then there are experienced and competent technical experts available to act as contact people for the customer.

How will analysis be performed?

The analysis will be implemented by performing an extraction and following it with content determination using GC-FID. Depending on the intended use of the medical device, different methods will be used.

Extraction by simulated application

Products with a short term patient contact (<24 hours) fall into this category, category A. Here, contact of the product with the patient is simulated. For this simulation, the surfaces will be rinsed with water and the sterilisation in the rinse water will be determined.

Exhaustive extraction

Products with a longer period of patient contact (<30 days) fall into this category. The process has the goal of investigating the complete residual content of a medical device. Extraction will be performed until less than 10% of the content ascertained in the first extraction is obtained or until the analytical data indicate that there will be no more significant increase in the cumulated residual content. This process is used for example, for implants that remain for a long period of time in the body.

As the amount of work required can vary greatly depending on the number of extraction rounds, the costs are very different according to the type of product and cannot be calculated exactly in advance.

What is the purpose of measuring untreated products, blind samples or blanks?

Further chemical constituents could be found within the sample matrix that, in the event of a gas chromatographic separation, lead to signals with the same retention time as the sterilisation residues. As a result, there is the danger of obtaining false-positive findings. By measuring blank samples, it will be guaranteed that these are not false-positive measurement results.

The specifics when planning the market launch of a new product

Further tests should be carried out along with routine testing. In accordance with ISO 10993-7, paragraph 5.3, dissipation curves must be prepared for a minimum of three production batches.

Do you require additional information?

Please read the unabridged version in our technical article (see the right-hand column) or ask for advice from our customer services.

Our services in detail:

• Consultation on ISO 10993-7
• Testing for ethylene oxide and ethylene chlorohydrin
• Determination of dissipation curves
• Additional services are according to directory of services or upon request.