ISO 10993-7:2008/Amd 1:2019
Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals — Amendment 1: Applicability of allowable limits for neonates and infants

Standard No.

ISO 10993-7:2008/Amd 1:2019

Release Date

2019

Published By

International Organization for Standardization (ISO)

Latest

ISO 10993-7:2008/Amd 1:2019

Introduction

Core changes in the standard revision

Revision elements	2008 original version	2019 amendment	Clinical significance
Contact time classification	Unclear time period constraints	Added 24h/30d phased dose limit	More accurately control early exposure risks
Neonatal TI value	Not specially specified	EO:0.02mg/kg/day ECH:0.029mg/kg/day	Reduce the risk of toxicity in premature infants
Analytical methods	Basic requirements only	Six new validation guidelines including ICH Q2	Improve the reliability of test results

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Key points for limit adjustment for special populations

The amendment clarifies for the first time the tolerance thresholds (TI values) for premature infants, newborns and children:

• Permanent contact devices: EO limit reduced to 1/15 of the adult standard (0.02 vs 0.3mg/kg/day)
• Ethylene chloride (ECH): The limit for newborns is 2.2 times stricter than that for adults (0.029 vs 0.064mg/kg/day)

Clinical application examples

The residual limit of the neonatal breathing circuit system needs to be recalculated: Assuming that the premature infant weighs 2kg, the daily EO exposure limit = 2kg × 0.02mg/kg = 0.04mg/day, which is only 0.4% of the standard equipment for adults

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Technical implementation recommendations

1. Contact time verification: Cumulative contact time assessment is required for multi-component devices
2. Analytical method upgrade: It is recommended to use GC-MS combined with headspace sampling technology, and the detection limit must be ≤0.1ppm
3. Document management: The use of CEF/PEF coefficients must be clearly recorded in the technical documents

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Background of standard evolution

This revision is based on 22 reports on adverse reactions to neonatal devices issued by the EU EMA and the US FDA between 2015 and 2018, mainly involving:

• Extracorporeal membrane oxygenation (ECMO) circuit hemolysis incident
• Issue of premature infant incubator sealing material release

ISO 10993-7:2008/Amd 1:2019 Referenced Document

• ISO 10993-1:2018 Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process

ISO 10993-7:2008/Amd 1:2019 history

• 2019 ISO 10993-7:2008/Amd 1:2019 Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals — Amendment 1: Applicability of allowable limits for neonates and infants
• 2009 ISO 10993-7:2008/cor 1:2009 Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals; Technical Corrigendum 1
• 2008 ISO 10993-7:2008 Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals
• 1995 ISO 10993-7:1995 Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals

Standard and Specification