Biological evaluation of medical devices —Part 7: Ethylene oxide sterilization residuals
1 Scope
This part of GB/T 16886 specifies allowable limits for residual ethylene oxide (EO) and ethylene chlorohydrin (ECH) in individual EO-sterilized medical devices, procedures for the measurement of EO and ECH, and methods for determining compliance so that devices may be released. Additional background, including guidance and a flowchart showing how this document is applied, are also included in the informative annexes.
EO-sterilized devices that have no patient contact (e.g., in vitro diagnostic devices) are not covered by this part.
Note: This part does not specify limits for ethylene glycol (EG).
2 Normative references
The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 10993-1 Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk management process
ISO 10993-3 Biological evaluation of medical devices — Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
ISO 10993-10 Biological evaluation of medical devices - Part 10: Tests for irritation and delayed-type hypersensitivity
ISO 10993-12 Biological evaluation of medical devices - Part 12: Sample preparation and reference materials
ISO 10993-17 Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 10993-1, ISO 10993-17 and the following apply.
3.1
simulated-use extraction
extraction to demonstrate compliance with the requirements of this part of ISO 10993, by evaluating residue levels available to the patient or user from devices during the routine use of a device with water extraction to simulate product use
3.2
exhaustive extraction
extraction until the amount of EO or ECH in a subsequent extraction is less than 10 % of that detected in the first extraction, or until there is no analytically significant increase in the cumulative residue levels detected
Note: As it is not possible to demonstrate the exhaustive nature of residual recovery, the definition of exhaustive extraction adopted is as above.
4 Requirements
4.1 General
Note: Information on the derivation of the limits in this part of ISO 10993 as well as other important background information and guidance relevant to the use of this document is contained in the informative annexes.
This clause specifies maximum allowable residues for ethylene oxide (EO) for each individual medical device sterilized with EO. As noted in the introduction to ISO 11135-1:2007, when determining the suitability of EO for sterilization of medical devices, it is important to ensure that the levels of residual EO, ethylene chlorohydrin (ECH) and ethylene glycol (EG) pose a minimal risk to the patient in normal product use. Moreover, when the choice for EO sterilization has been made, irrespective of the provisions of this standard, exposure to EO residues should be minimized. Maximum allowable residues for ECH, when ECH has been found to be present in medical devices sterilized with EO, are also specified. Local effects (e.g., irritation) have been considered and are incorporated in the tolerable contact limit (TCL) as discussed in 4.3.5.2 and Annex G for EO, and 4.3.5.3 and Annex H for ECH. No device limits are specified for EG because a risk assessment (Annex I) indicates that calculated allowable levels are higher than those likely to occur in a medical device. However, the potential exists for acute haemodynamic and haemolytic effects to occur following rapid intravenous administration of hyperosmolar compounds like EG. Ethylene oxide sterilization of medical devices would not be expected to produce hyperosmolar solutions. Methods for the determination of EO and ECH are given in 4.4.
The requirements in this part of ISO 10993 are in addition to the biological evaluation and testing requirements for medical device as indicated in ISO 10993-1. For devices sterilized using ethylene oxide, attention shall be paid in particular to ISO 10993-3 and ISO 10993-10. All applicable requirements of ISO 10993-1 shall take into account the EO residual level at the time of release for each individually designed medical device.
Results of the biological assessment of the device may dictate more stringent limits than those specified in 4.3, which are designed to protect against systemic effects.
4.2 Categorization of devices
Foreword i
Introduction iv
1 Scope
2 Normative references
3 Terms and definitions
4 Requirements
4.1 General
4.2 Categorization of devices
4.3 Allowable limit
4.4 Determination of EO and ECH residuals
5 Product release
5.1 General
5.2 Release of products without dissipation curve data
5.3 Procedure for product release using residue dissipation curves
Annex A (Normative) Evaluation of gas chromatograms
Annex B (Informative) Gas chromatographic determination for EO and ECH
Annex C (Informative) Flowchart and guidance for the application of this part of ISO 10993 series of standards to the determination of EO and ECH residuals in medical devices
Annex D (Informative) Factors influencing product residual
Annex E (Informative) Extraction conditions for determination of residual EO
Annex F (Informative) Rationale for the provisions of this part of ISO 10993
Annex G (Informative) Establishment of allowable limits for EO
Annex H (Informative) Establishment of allowable limits for ECH
Annex I (Informative) Establishment of allowable limits for EG
Annex J (Informative) Preparation of EO and ECH standards
Annex K (Informative) Ethylene oxide residue measuring methods
Bibliography
