1、BS ISO 18562-1:2017Biocompatibility evaluation of breathing gas pathways in healthcare applicationsPart 1: Evaluation and testing within a risk management processBSI Standards PublicationWB11885_BSI_StandardCovs_2013_AW.indd 1 15/05/2013 15:06BS ISO 18562-1:2017 BRITISH STANDARDNational forewordThis
2、 British Standard is the UK implementation of ISO 18562-1:2017. The UK participation in its preparation was entrusted to TechnicalCommittee CH/121/9, Lung Ventilators permanent exposure: 30 d.These times have been chosen to be consistent with the ISO 10993 series categories A, B and C for duration o
3、f use.Subclause 6.3 Deriving a permitted concentration from a tolerable exposureData for minute ventilation in infants and children are found in Reference 9. It has reference data for respiratory parameters in children, which were referenced from two publications, References 12 and 13. These data ar
4、e summarized in Table A.1.The default body weight values used in this document are 0,5 kg for neonate, 3,5 kg for infant, 10 kg for paediatric and 70 kg for adult patient. The default breathing volumes are 0,21 m3/d, 2 m3/d, 5 m3/d, and 20 m3/d, respectively.Table A.1 Ventilation data by body sizePa
5、tient sizeBody weight (BW)kgProposed total ventilation for voc dosem3/dNeonate 0,21 0,5Infant 3,5 2,0Paediatric 10 5,0Adult (19 years old)70 2018 ISO 2017 All rights reservedBS ISO 18562-1:2017ISO 18562-1:2017(E)Clause 7 Deriving allowable limitsThe choice of a ttc level (adult with 70 kg body weigh
6、t) for unknown substances of 360 g/d (limited exposure), 120 g/d (prolonged exposure) and 1,5 g/d (permanent contact) was discussed at length by the committee. For lower body weight patients, a patient-specific ttc value (g/d) based on the patient body weight from Table A.1 should be derived.The inh
7、alation ttc value for prolonged (24 h to 30 d) exposure to vocs released into the gas pathway is based on: the 5th percentile of a distribution of noncancer tolerable intake (ti) values derived from inhalation NOAEL (no observed adverse effect level) and LOAEL (lowest observed adverse effect level)
8、values (exposure duration 30 d) reported in the RepDose database (135 g/d)14; the acceptable intake of an individual mutagenic impurity in a pharmaceutical product with exposure to the patient for 30 d, per the IC H M7 guidance15(120 g/d).The lower of the two values, 120 g/d, was selected as the inh
9、alation ttc value for prolonged exposure and this value is intended to be protective for both cancer and noncancer effects.Recognizing that exposure limits can be adjusted to permit higher levels of exposure for shorter durations, the prolonged inhalation ttc was adjusted upwards to derive a limited
10、 exposure duration ttc of 360 g/d using a modification of Habers Rule (C Tn= k)16. Briefly, an exponent of n = 0.33 was used to estimate an airborne concentration (C) of a voc that produces an equivalent toxicological response in 24 h to that seen after inhalation exposure to 120 g/d for 30 d. The t
11、hree-fold increase in the limited exposure duration ttc compared to the ttc for prolonged exposure is consistent with similar efforts to extrapolate exposure limits from longer to shorter durations.Lastly, the committee considered permanent exposure limits for adults (70 kg) and proposed 40 g/d.Taki
12、ng a practical approach, the committee discussed the levels at which it was currently possible to measure concentrations using established, standardized laboratory techniques. The current detection limit for vocs using standardized test methods is 2 g/m3. Thus, a proposed limit of 2 g/m3as a concent
13、ration is as low as possible to measure. A concentration of 2 g/m3gives a total dose-to-patient for an adult (who breathes 20 m3/d) of 40 g. Thus, if any ttc limit below 40 g/d were to be proposed, it would be meaningless, as it would not be possible to measure it.It is recognized that these limits
14、can be adjusted in the future as more knowledge becomes known and analytical measurement techniques improve. However, on the balance of probabilities, the committee felt that the proposed limits of 360 g/d (limited exposure duration), 120 g/d (prolonged exposure duration) and 40 g/d (permanent expos
15、ure duration) were reasonably conservative and would not expose patients to unacceptable risks.These limits apply only to substances added by the medical device to gases supplied to patients. The proposed limits are not relevant to any other type of patient exposure. ISO 2017 All rights reserved 19B
16、S ISO 18562-1:2017ISO 18562-1:2017(E)Annex B (informative) Reference to the essential principlesThis document has been prepared to support the essential principles of safety and performance of gas pathways as components of medical devices according to ISO 16142-16. This document is intended to be ac
17、ceptable for conformity assessment purposes.Compliance with this document provides one means of demonstrating conformance with the specific essential principles of ISO 16142-16. Other means are possible. Table B.1 maps the clauses and subclauses of this document with the essential principles of ISO
18、16142-1.Table B.1 Correspondence between this document and the essential principlesEssential principles of ISO 16142-16Corresponding clause(s)/ subclause(s) of this documentQualifying remarks/notes8.1 a) Clause 4, Clause 5, Clause 6, Clause 7, Clause 8, Clause 9Only the part relating to toxicity is
19、addressed.8.1 b) Clause 4, Clause 5, Clause 6, Clause 7, Clause 8, Clause 98.2 Clause 4, Clause 5, Clause 6, Clause 7, Clause 8, Clause 98.4 Clause 4, Clause 5, Clause 6, Clause 7, Clause 8, Clause 98.5 Clause 4, Clause 5, Clause 6, Clause 7, Clause 8, Clause 9Only the part relating to egress of sub
20、stances from the medical device is addressed.20 ISO 2017 All rights reservedBS ISO 18562-1:2017ISO 18562-1:2017(E)Annex C (informative) Terminology Alphabetized index of defined termsNOTE The ISO Online Browsing Platform (OBP) and the IEC Electropedia provide access to many of these terms and defini
21、tions.Term Sourceaccessory 3.1accompanying document ISO 14971:2007, 2.1authority having jurisdiction ISO 16142-1:2016, 3.1biocompatibility 3.2expected service life 3.3formulation 3.4gas pathway 3.5hazard ISO 14971:2007, 2.3intended use ISO 14971:2007, 2.5leachable substance 3.6manufacturer ISO 14971
22、:2007, 2.8medical device 3.7medical gas pipeline system ISO 7396-1:2016, 3.36normal condition 3.8normal use 3.9particulate matter 3.10particulates 3.10patient 3.11pm 3.10process ISO 14971:2007, 2.13residual risk ISO 14971:2007, 2.15risk ISO 14971:2007, 2.16risk analysis ISO 14971:2007, 2.17risk asse
23、ssment ISO 14971:2007, 2.18risk management ISO 14971:2007, 2.22risk management file ISO 14971:2007, 2.23te 3.13threshold of toxicological concern 3.12ti 3.14til 3.14tolerable exposure 3.13tolerable intake 3.14tolerable intake level 3.14ttc 3.12type test 3.15voc 3.16 ISO 2017 All rights reserved 21BS ISO 18562-1:2017ISO 18562-1:2017(E)Term Sourcevolatile organic compound 3.16very volatile organic compound 3.17vvoc 3.1722 ISO 2017 All rights reserved
