What is ISO 10993-7

ISO 10993-7 is a standard developed by the International Organization for Standardization (ISO) that outlines the requirements for testing the biocompatibility of medical devices. This standard specifies the requirements for testing the residual levels of ethylene oxide, a commonly used sterilization method, in medical devices. It is used to ensure that the residual levels of ethylene oxide on a medical device are safe for patient use and that the device has been properly sterilized. The standard provides guidance on the test method, limits for residual ethylene oxide, and the acceptance criteria for the test results.

Why is Ethylene Oxide Residual Testing Important?

Ethylene oxide (EO) residual testing is required for medical devices because EO is a commonly used sterilization method, but it can leave residue on the device that can be harmful to patients. EO is a known carcinogen and mutagen, and exposure to EO residues on medical devices can cause skin irritation and allergic reactions. Therefore, testing for residual EO is necessary to ensure that medical devices are safe for patient use and have been properly sterilized.

ISO 10993-7 provides the guidelines and procedures for measuring the amount of residual EO on a medical device, and it specifies the allowable limits for EO residues based on the intended use and route of administration of the device. By performing EO residual testing in accordance with ISO 10993-7, manufacturers can ensure that their devices meet the requirements for biocompatibility and patient safety.

Additionally, regulatory agencies such as FDA, in the US, and other international regulatory bodies have specific requirements for residual EO testing, and manufacturers must comply with these regulations in order to market their devices.

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Categories of Medical Device based on ISO 10993-7

ISO 10993-7 document groups medical devices into 3 major categories depending on the duration of contact with the patient.

A) Limited Exposure Devices are those that are used within 24 hours. These devices have a lower allowable limit of EO residues and are intended for short-term use. Examples include single-use devices such as surgical gloves and dressings.

B) Prolonged Exposure Devices are medical devices which are in contact with patients between 24 hours to 30 days. These devices have a slightly higher allowable limit of EO residues and are intended for intermediate-term use. Examples include catheters and wound dressings.

C) Permanent Contact devices are those that are placed on patients for more than 30 days. These devices have the highest allowable limit of EO residues and are intended for long-term use. Examples include implantable devices such as pacemakers and artificial joints.

It's important to note that these limits are based on specific test methodologies, as outlined in ISO 10993-7, and are not absolute values, other factors such as the duration of contact with the device and the patient health condition could be considered.

Ethylene Oxide Residual Limits Based on ISO 10993-7:2008

ISO 10993-7:2008 classified medical devices into several categories based generally on allowable limit of EO residues.

First three general categories are;

1. Limited Exposure Devices

These are devices which are used or applied to patients with contact up to 24 hours either in single or multiple use. The average daily exposure limit for ethylene oxide (EO) is 4mg while average daily exposure limit for ethylene chlorohydrin (ECH) is 9mg.

2. Prolonged Exposure Devices

These are devices used on a patient or have patient contact of more than 24 hours but not exceeding 30 days either in single or multiple uses. The allowable limit for ethylene oxide is 4mg for first 24 hours and 60mg for up to 30 days of patient contact. It is also required that the average daily dose to a patient should not exceed 2mg/day. The allowable limit for ethylene chlorohydrin is 9mg for first 24 hours and 60mg for 30 days of patient contact.

3. Permanent Contact Devices

These are devices used long term on a patient which exceed 30 days either in a single or multiple use.

The allowable limits for ethylene oxide are;

i) Average Daily Dose of 0.1mg/day

ii) First 24 hours limit of 4mg/device

iii) First 30 days limit of 60mg/device

iv) Lifetime exposure limit of 2. g

The allowable limits for ethylene chlorohydrin are;

i) Average Daily Dose of 0.4mg/day

ii) First 24 hours limit of 9mg/device

iii) First 30 days limit of 60mg/device

iv) Lifetime exposure limit of 10g

Besides these 3 categories, there are medical devices which will not or difficult to comply with the set allowable limit. These devices are placed under special categories including;

Intraocular Lens which normally contain chlorine (they are kept in saline solution) will have high ECH level. In fact it was estimated that the resulting ECH toxicity was four times greater than the EO corresponding level. The EO limit in intraocular lenses was set so not to exceed 0.5ug/lens/day or 1.25ug per lens. However, the suggestion by several sources that the limit for ECH in intraocular lenses to be 4 times that of corresponding EO level is WRONG! The statement in ISO 10993-7 is ...

"The acceptability of ECH levels in intraocular devices made from viscoelastic materials that contain chlorine may need to be evaluated, as the level of ECH that results in ocular toxicity is about four times greater than the corresponding EO level"

The statement clearly says that ECH limit in intraocular lenses need to be evaluated and no limit has been set for ECH in intraocular lenses. Probably, the revision of ISO 10993-7 will address this issue.

Blood cell separator: For blood cell separators used in patient and donor blood collection, the maximum allowable dose of EO is 10mg and the maximum allowable dose of ECH shall not exceed 22mg.

Blood Oxygenators: For blood oxygenators and blood separators, the maximum allowable dose of EO to patient is 60mg and the maximum allowable dose of ECH shall not exceed 45mg.

Devices used in Cardiopulmonary bypass: Any medical devices used in cardiopulmonary bypass procedures should contain maximum allowable limit of 20mg for EO and 9mg for ECH.

Extracorporeal Blood Purification Devices: These devices should should contain at most 4.6mg/device for both EO and ECH.

Drapes, Gowns, OT Table Clothes: For these large surface areas devices which are meant to have skin contact only, tolerable contact limit (TCL) may be applied. TCL is expressed as total amount of residues per centimeter square of contact surface area of devices. Manufacturers will have to determine the contact surface areas of their devices and should verify that the contact surfaces would exhibit negligible irritation as specified in ISO 10993-10. The allowable TCL for drapes, gowns and table cloths are 10ug/cm2 for EO and 5mg/cm2 for ECH.