Tiêu chuẩn iso 18562 1 2017

Howeve , the ISO 1 99 se ies does not suff iciently ad r s the biolo ical ev luation of the gas pathways of medical devices.. medical devic ins rument, a p ratus, implement, machine, a p

Bioc ompatibility evaluation of

Part 1:

Év lu tion de la biocomp tibilité des v ies de g z re spiratoire s da s

le s a plications de soins de santé —

Partie 1: Év lu tion et essais a s ein d’u proc ssus de ge stion du

COPYRIGHT PROTECTED DOCUMENT

© ISO 2017, P blshed in Sw itz rlan

A ll rig hts r eserved Unles otherw ise spe ified, nopar of this p blc tion ma y be r epr od c d or utilz d otherw ise in an form

or b an me ns, ele tr onic or me hanic l, inclu in p oto opying , or postin on the internet or an intranet , w ithout prior

written permis ion Permis ion c n be req esed from either ISO at the ad r es below or ISO’s member bod y in the c u try of

F reword i v

Introduction v

1 Sc ope 1

2 Nor mati ve r eferenc es 2

3 Terms an definitions 2

4 General pr inciples ap l ying to biocomp tibilit evaluatio of medica l devic s 6

4.1 General 6

4.2 Ty pe t sts 7

4.3 Biocompatibilit ha za r d identification 8

4.4 Ex tent of risk asses ment 8

4.5 Biocompatibilit ev luation plan 9

4.6 S le tion of tes s 1

4.7 Subseq ent ev luation 1

5 Co taminatio of br eathing gas fr om ga s p thwa s 11

5.1 * Duration of use 1

5.2 Pa rticulat mat er (pm)emis ions 1

5.3 Volatile orga niccomp und (voc) emis ions 1

5.4 L acha ble substa nces in con ensate 1

6 Adjustment for difer ent p tient g roups 13

6.1 General considerations 1

6.2 A djustment for b dy weight 1

6.3 * De iving a pe mited conc ntration from a t ler a ble ex posur e 14

7 * Der i ving alowable l mits 14

7.1 General proces .14

7.2 For medica l devices inten ed for lmited ex posur e use (≤ 4 h) 1

7.3 For medica l devices inten ed for pr olong ed ex osur e use (> 4 h but < 0 d) 1

7.4 For medica l devices inten ed for pe manent contact (≥ 0 d) 1

8 Risk benefit anal ysis 16

9 A sses the biocomp tibilit of the medica l devic 17

A nne x A (informative)Rationale and g uidanc e 18

A nne x B (informative)Referenc e to the es ential pr inciples 20

A nne x C (informative) Terminolog y — A lphabetized index of defined ter ms 21

Biblog raphy 23

ISO (he Int ernational Org nization for Stan ardization) is a worldwidefede ation of national s an ards

b dies (ISO membe b dies) The work of pr p ring Int ernational Stan ards is normaly car ied out

through ISO t ech ical committ ees Each membe b dy int er st ed in a subje t for w hich a t ech ical

committ ee has be n es a lshed has the right t o be r pr sent ed on that committ ee Int ernational

org nizations, g ove nmental an non-g ove nmental, in laison with ISO, also take part in the work

ISO cola orat es closely with the Int ernational Ele trot ech ical C mmis ion (IEC) on al matt ers of

ele trot ech ical s an ardization

The proc d r s used t o develo this document an those int en ed for it furthe maint enanc ar

desc ibed in the ISO/IEC Dir ctives, Part 1 In p rticular the dife ent a pro al c it eria ne ded for the

dife ent ty es of ISO document should be not ed This document was draft ed in ac ordanc with the

edit orial rules of the ISO/IEC Dir ctives, Part 2 ( e www iso org dir ctives)

A tt ention is drawn t o the p s ibi ity that some of the element of this document ma be the subje t of

p t ent right ISO shal not be held r sponsible for identifying any or al such p t ent right Detais of

any p t ent right identified d ring the develo ment of the document wi be in the Introd ction an / r

on the ISO ls of p t ent de larations r c ived ( e www iso org p t ent )

Any trade name used in this document is information given for the convenienc of use s an does not

cons itut e an en orsement

F or an ex lanation on the voluntary natur of ISO s an ards, the meaning of ISO spe if ic t erms an

ex r s ions r lat ed t o conformity as es ment, as wel as information a out ISO’ s adhe enc t o the

World Trade Org nization (WTO) principles in the Te hnical Bar ie s t o Trade (TBT) se the folowing

URL: www iso org iso / for word html

The committ ee r sp nsible for this document is ISO/TC 1 1, An es thetic a d r s pirator y eq ipment,

Subcommitt ee SC3, L n ventiators a d r lated eq ipment

A l s of al p rt in theISO 1 5 2 se ies can be fou d on the ISO websit e

This document r pr sent the a plcation of the bes -k own scienc , in orde t o impro e patient

safety, b ad r s ing the risk of pot ential y hazardous subs anc s being conveyed t o the p atient b

the g s s r am

This document is int ended t o co e the biolo ical ev luation of gas pathways of medical devices within

a risk ma a gement proces , as p rt of the o e al medical device ev luation an develo ment This

a pro ch combines the r view an ev luation of exis ing data from al sour es with, w he e ne es ary,

the sele tion an a plcation of ad itional t es s

In g ene al, the ISO 1 9 3 se ies is int en ed t o co e the biolo ical ev luation of medical devices

Howeve , the ISO 1 99 se ies does not suff iciently ad r s the biolo ical ev luation of the gas

pathways of medical devices

Befor this document was develo ed, some a uthorities ha ing jurisdiction int erpr t ed the

ISO 1 99 -1:2 0 , Ta le A.1 t o mean that mat erials in the gas pathway form “indir ct contact” with

the patient, an should be subje t ed t o t es s eq iv lent t o those r q ir d for tis ue contact p rt of

medical devices This int erpr tation can lead t o t es s with q es iona le benef it an also t o pos ible

hazar s not being det ect ed

ISO 1 9 3-1:2 0 s at es that it is not int en ed t o pro ide a rigid set of t es methods as this might r sult

in an u ne es ary cons raint on the develo ment and use of no el medical devices ISO 1 9 3-1:2 0

also s at es w he e a p rticular a plcation war ant it, ex e t in the prod ct or in the ar a of a plcation

conc rned can cho se t o es a l sh spe ific t es s an c it eria, desc ibed in a prod ct-spe if ic ve tical

s an ard This new se ies of s andards is int en ed t o ad r s the spe if ic ne ds for the ev luation of

gas p athways that ar not adeq at ely co e ed b ISO 1 99 -1:2 0

This document pro ides a guide to the develo ment of a biolo ical ev luation plan that minimiz s

the n mbe an ex osur of tes animals b giving pr fe enc to chemical cons ituent tes ing an

in vitro models

The initial ve sion of this se ies of s an ards was int en ed t o co e only the mos commonly fou d

p t ential y harmful subs anc s It was felt that it was bes t o g et a functioning document publshed

that would t es for the bulk of the cur ently k own subs anc s of int er s W ith the use of the t c

(threshold of t xicolo ical concern) a pro ch, this document has the p t ential t o be used

t o as es the safety of es entialy any comp u d r leased from the gas pathways of r spirat ory

medical devices, with ve y few ex ceptions (e.g PCBs, dio ins), an not jus the mos commonly fou d

p t ential y harmful subs anc s L t er amen ment an ad itional p rt ar planned t o ex lcitly co e

les common subs anc s

In this document, the fol owing print y es ar used:

— r q ir ment an def initions: roman ty e;

— tes t s pec ific atio s: italc t ype;

— informative mat erial a pearing out ide of ta les, such as not es, ex mples an r fe enc s:in smale

ty e Normative t ext of ta lesis also in a smale ty e;

— t erms defined in Cla use 3 of this document or as not ed: smal ca itals

In this document, the conju ctive “or” is used as an “inclusive or” so a s at ement is true if any

combination of the con itions is true

The ve b l forms used in this document conform t o usag e desc ibed in An ex H of the ISO/IEC

Dir ctives, Part 2 F or the purposes of this document, the auxi ary ve b:

— “ hal” means that complanc with a r q ir ment or a t es is man at ory for compl anc with this

documen

— “ hould” means that complanc with a r q ir ment or a t es is r commended but is not man at ory

for compl anc with this documen

— “ ma ”is used t o desc ibe a pe mis ible wa t o achieve complanc with a r q ir ment or t es

An ast erisk ( ) as the f irs charact er of a title or at the begin ing of a p ra ra h or ta le title in icat es

that he e is guidanc or rationale r lat ed t o that it em in Annex A

The att ention of Membe Bodies is drawn t o the fact that eq ipment man factur rs an t es ing

org nizations ma ne d a transitional pe iod folowing publcation of a new, amen ed or r vised ISO

or IEC publcation in w hich t o make prod ct in ac ordanc with the new r q ir ment an t o eq ip

themselves for con ucting new or r vised t es s It is the r commen ation of the committ ee that the

cont ent of this publcation be ado t ed for implementation nationaly not earle than 3 years from

the dat e of publcation for eq ipment new ly designed an not earle than 5 years from the dat e of

publcation for eq ipment alr ady in prod ction

Bioc ompatibility evaluation ofbr eathing gas pathways in

Part 1:

This document pe ifies:

— the g ene al principles g overning the biolo ical ev luation within a risk mana gement proces of

the gas p athways of a medical device, it p rt or a cces ories, w hich ar int en ed t o pro ide

r spirat ory car or sup ly subs anc s via the r spirat ory tract t o a p atient in al environment ;

— theg ene al cat eg orization of gas pathways b sed on the natur an d ration of their contact with

theg s s r am;

— theev luation of exis ing r lev nt data from al sour es;

— theidentif ication of g psin the a ai a le data set on the b sis of a risk analysis;

— the identif ication of ad itional data set ne es ary t o analy se the biolo ical safety of the gas

p athway;

— theas es ment of the biolo ical safety of the gas pathway

This document co e s g ene al principles r g rding biocomp atibility as es ment of medical device

mat erials, w hich make up the gas pathway, but does not co e biolo ical hazar s arising from any

me hanical faiur , unles the faiur introd c s a t oxicity risk (e.g b g ene ating p ar ticulat s) The

othe p rt of ISO 1 5 2 co e spe if ic t es s that ad r s p t ential y hazardous subs anc s that ar

ad ed t o the r spira le g ss r am an es a lsh ac eptanc c it eria for these subs anc s

This document ad r s es p t ential contamination of the g s s r am arising from the gas p athways

within the medical device, w hich might then be con uct ed t o the p atient

This document a ples o e the e p ct d ser vice life of the medical device in normal use an takes

int o ac ou t theefe t of any int en ed proc s ing or r proc s ing

This document does not ad r s biolo ical ev aluation of the surfac s of medical devices that ar in dir ct

conta ct with the patient The r q ir ment for dir ct contact surfa ces ar foun in the ISO 1 9 3 se ies

Medical devices, part or a cces ories containing gas pathways that ar ad r s ed b this document

inclu e, but ar not l mit ed t o, ventiat ors, anaes hesia works ations ( inclu ing g s mix ers), br athing

sy st ems, o y g en conse ving eq ipment, o y g en conc ntrat ors, nebulz rs, low-pr s ur hose

as embl es, h midif ie s, heat an mois ur ex chang ers, r spirat ory g smonit ors, r spiration monit ors,

masks, mouth pie es, r suscitat ors, br athing tubes, br athing sy st em filt ers an Y-pie es as wel as

any br athing a cces ories int en ed t o be used with such medical devices The enclosed chambe of

an incub t or, inclu ing the mat r s , an the inne surfac of an o y g en ho d ar conside ed t o be gas

pathways and ar also ad r s ed b this document

This document does not ad r s contamination alr ady pr sent in the g s sup led from the g s sour es

w hi e medical devices ar in normal use

E AMP E Contamination ar iving at he medical devic from g s sour es such as medical g s pip line

syst ms (inclu ing the non-return valv es in the pipeline outlets ), outlets of pres ure re ulator con ected or

inte ral to a medical g s cylin er, or ro m air taken into the medical devic is not ad res ed by ISO 1 562

(al parts )

Futur part might be ad ed t o ad r s othe r lev nt aspe t of biolo ical t es ing inclu ing ad itional

contamination that might arise from the gas p athway be a use of the pr senc of drugs an anaes hetic

ag ent ad ed t o the g ss r am

NOTE 1 S me a utho ities h vin ju isdic io req ire evaluation of these risks as part of a biolo ical

evaluation

NOTE 2 This document has b en prepared t o ad res the relevant es ential principles of safety an

performance as in icated in An e B

2 Normati ve referenc es

The folowing document ar r fe r d t o in the t ext in such a wa that some or al of their cont ent

cons itut es r q ir ment of this document F or dat ed r fe enc s, only the edition cit ed a ples F or

un at ed r fe enc s, the lat es edition of the r fe enc d document ( inclu ing any amendment ) a ples

ISO 7 9 -1:2 1 , Medic al g s pipelne sys tems — Part 1: Pipelne sys tems fr c ompr s sed medic al g ses

ISO 149 1:2 0 , Medic al dev ic es — Ap lc atio o ri sk ma a ement to medic al dev ic es

ISO 1 5 2- 2, B ioc omp tibi t y ev lu tion o br athin g s p thwa s in healthc ar a plc atio s — Part 2 :

Tes ts fr emi s s io s o p rtic ulate mat e

ISO 1 5 2-3, B ioc omp tibi t y ev lu tio o br athin g s p thwa s in healthc ar a plc atio s — Part 3 :

Tes ts fr emi s s io s o v latie org nic c omp u ds (VOCs)

ISO 1 5 2-4, B ioc omp tibi t y ev lu tio o br athin g s p thways in healthc ar a plc atio s — Part 4:

Tes ts fr leacha les in c ondens ate

3 Terms and definitions

F or the purp ses of this document, the t erms an def initions given in ISO 7 9 -1, ISO 149 1 an the

folowing a ply

ISO an IEC maintain t erminolo ical data ases for use in s an ardization at the folowing ad r s es:

— IECEle tro edia: a aia le at ht p:/ www ele tro edia org

— ISO Onlnebrow sing plat orm:a ai a le at ht p:/ www iso org o p

NOTE For convenience, an alp a etized in e of al def ined terms an their sour es used in this document is

— achieve the int nded use,

— ada t it t o some spe ial use,

— faci itat e it use,

— enhanc it pe formanc , or

— ena le it fu ction t o be int egrat ed with those of othe medical devices

[ SOURCE:IEC6 6 1-1:2 0 , 3.3, modified — subs itut ed “medical device” for “eq ipment”]

3.2

biocomp tibility

a i ity t o be in contact with a lving sy st em without prod cing an u ac epta le adve seefe t

Note 1 t o entry: Medical devic s may prod ce some level of adver e efect, but that level may b determined t o

b ac epta le when considering the b nef its provided by the medical devic

3.3

expe ted ser vic lif

ma imum pe iod of useful lfe as def ined b thema ufa cturer

[ SOURCE:IEC6 6 1-1:2 0 +AMD1: 2 1 , 3.2 ]

3.4

b se p lyme or alo , inclu ing ad itives, colours, et c used t o es a lsh a pro e ty or the s a i ty of

the mat erial

Note 1 t o entry: T is do s not inclu e proces ing aids, mould rele se a ents, resid al contaminants, or other

man facturing aids that are not inten ed to b a part of the material

Note 2t o entry: T e term “ hemical composition” is commonly used as a sy on m for fo mulatio

[ SOURCE:US FDA 5 0(k) Memoran um #K97-1]

3.5

gas p thway

int erior surfac s, o e w hich g ses or lq ids that can be inspir d, in a medical device b u ded b

the p rt through w hich g ses or lq ids ent er an lea e the medical device inclu ing the patient

int erfac or the int erior surfac s of enclosur s that ar in contact with g ses or lq ids that can be

inspir d

Note 1 to entry: p atient contact surfaces such as the outer surfaces of a trache l tub or the cushion of a mask

are evaluated ac ording t o the ISO 1 9 3series

E AMP E 1 T e ventilator bre thing system, inlet f ilt er, g s mix r, blower an internal piping

E AMP E 2 E closed chamb r of an incub t or inclu ing the mat res or the in er surface of an o y gen ho d

E AMP E 3 T e in er surfaces of bre thing tub s, trache l tub s or masks an mouth ieces

3.6

l a chabl subst anc

chemical r mo ed from a medical device b the action of wat er, othe lq ids or othe g ses (e.g

anaes hetic ag ent or inhalational drugs) r lat ed t o the use of the medical device

E AMP E Ad itives, sterilant resid es, pr oc s resid es, de radation prod cts, solvents, plasticizer ,

lubricants, catalysts, sta ilizer , anti o idants, colouring a ents, f iler an monomer , among other

[ SOURCE: ISO 1 9 3-17 :2 0 , 3.1 , modif ied — ad ed “or othe g ses (e.g anaes hetic ag ent or

inhalational drugs) ]

medical devic

ins rument, a p ratus, implement, machine, a pl anc , implant, r ag ent for in vitro use, sof war ,

mat erial or othe simiar or r lat ed article, int en ed b the ma ufa cturer t o be used, alone or in

combination, for h man beingsfor one or mor of the folowing spe if ic purp se( ) of:

— dia nosis, pr vention, monit oring, tr atment or aleviation of disease;

— dia nosis, monit oring, tr atment, aleviation of or compensation for an injury;

— inves ig tion, r plac ment, modif ication, or sup ort of the anat omy or of a phy siolo ical proces ;

— sup orting or sus aining lfe;

— control of conc ption;

— disinfe tion of medical devices;

— pro iding information b means of in v itro ex mination of spe imensde ived from the h man body;

an does not achieve it primary int en ed action b pharmacolo ical, immu olo ical or meta olc

means, in or on the h man b dy, but w hich ma be as ist ed in it fu ction b such means

Not e 1to entry: Prod cts which may b considered t o b medical devic s in some jurisdictions but not in other

inclu e:

— disinfection substances;

— aids for per ons with disa ilities;

— devices incorporating animal an / r h man tis ues;

— devices for in v itr fertilization or as ist ed reprod ction t ech olo ies

[ SOURCE:ISO 1 48 :2 1 , 3.1 ]

3.8

normal condition

con ition in w hich al means pro ided for prot ection a ains hazar s ar intact

[ SOURCE:IEC6 6 1-1:2 0 , 3.7 ]

3 9

normal use

o e ation, inclu ing routine inspe tion an adjus ment b any use , an s an -b , ac ording t o the

ins ructions for use

Not e 1 t o entry: No mal use should not b confused with int n ed use While b th inclu e the concept of use as

inten ed by the ma ufa ctu er,int n ed use focuses on the medical p rpose while n rmal use incorporates

not only the medicalp rpose but maintenance,service, transport, etc as wel

[ SOURCE:IEC6 6 1-1:2 0 +AMD1: 2 1 , 3.9 , modif ied — r plac d “o erat r” with “ use ”]

l ving h man u de g oing a medical, surgical, or dental proc d r

[ SOURCE:IEC6 6 1-1:2 0 +AMD1: 2 1 , 3.7 6, modif ied — r mo ed r fe enc t o animal

threshold of t xicological conc rn

ttc

level of ex osur for al chemicals, k own or u k own, below w hich it is conside ed the e is no

a pr cia le risk t o h man health

Note 1 t o entry: A t c is used as an ac epta le value for a t for an u k own or insuff iciently characterized

compou d

3.13

tol rabl exp sure

te

t otal amou t of a subs anc ( in unit of µg d) that a patient can be ex osed t o pe 24 h pe iod that is

conside ed t o be without a pr cia le harm t o health

Note 1to entry: Te is also refer ed t o as “alowed dose t o patient T is amou t is specif ic t o a particular p atient

or p atient grou of a given b d weight

Note 2t o entry: Te is calculated by multiplying tol r b e inta e by the b d mas

t otal amou t of a subs anc pe kio ram of body weight ( in u it of µg kg b dy weight/d) that a

patient can be ex osed t o pe 24 h pe iod that is conside ed t o be without a pr cia le harm t o health

Note 1t o entry: T is amou t is ap lica le for al p atient grou s

3.1

type test

t es on a r pr sentative sample of the medical device with the o je tive of det ermining if the medical

device, as designed an man factur d, can me t the r q ir ment of this document

Note 1 to entry: If the f inal medical devic is not used for the as es ments, al diferences b tween the

“ representative sample” an the f inal medical devic ne d t o b des rib d an a justif ication provided for wh

the diferences do not afect he outcome of the testing

[ SOURCE: IEC 6 6 1-1:2 0 , 3.1 5, modif ied — subs itut ed “medical device” for “ me eq ipment” an

ad ed Not e 1]

3.1

v la il organic compound

v c

org nic comp u d w hose b i ing p int is in the rang e of 5 °C t o 2 0 °C

Note 1 t o entry: There are man varied def initions of voc For the p rposes of this document, a voc is a compou d

that has a b iling point in the rang e of 5 °C to 260 °C, at a stan ard atmosp eric pres ure of 1 1,3 k a

Note 2 to entry: Boiling points of some compou ds are diff icult or impos ible t o determine b cause they

decompose b fore they b il at atmosp eric pres ure

Note 3 to entry: Compou ds stil ex ert a vapour pres ure, an so could enter the bre thing g s, at t emperatures

lower than their b iling point

Note 4 to entry: voc do s not inclu e ver y volatil or ga ic compo nds (vv ocs) nor semivolatile org nic

compou ds ( SV Cs) Ad itional parts of this document might b developed t o ad res these substances in

the future S me a uth rities ha in ju isdic io req ire evaluation of these risks as part of a biolo ical

evaluation

3.1 7

ver y v la il or ganic compound

vv c

org nic comp u d w hose b i ing p int is in the rang eof 0 °C t o 5 °C

Not e 1 to entry: Boiling points of some compou ds are diff icult or impos ible to determine b cause they

decompose b fore they b il at atmosp eric pres ure

4 General pr inciples appl ying to biocompatibility e aluation ofmedica l devices

The biocompatibility ev luation of any mat erial or medical device, part or a cces or y int en ed for

use with patients shal form part of a s ructur d biocompatibility ev luation pro ramme within

a risk mana gement proces The biocomp atibilit ev luation shal be plan ed, car ied out an

document ed b k ow ledg ea le an ex e ienc d profes ionals Figur 1i lus rat es this proces

The ev luation pro ramme shal inclu e document ed, informed de isions that as es the

adv ntag es /disadv ntag es and r lev nc of:

— the physical an chemical charact eris ics of the v rious can idat e mat erials o e the e p ct d

ser vice life of the medical device;

NOT Where this information is alre d documented within the risk ma a ement fil for the

medical devic , it can b inclu ed by reference

— any hist ory of h man ex osur data;

— any exis ing t oxicolo y an othe biocompatibility safety data on prod ct and comp nent

mat erials, br ak down prod ct an meta olt es

Al medical devices should be ev luat ed for biocomp atibilit , but ev luation does not ne es ariy

imply t es ing eve ything Depen ing on the f inal formulation, man facturing or a plcation, an

ev luation ma r sult in the conclusion that no t es ing or no ad itional tes ing is ne ded

E AMP E T e medical devic has a demonstra le similarity in a specif ied fu ction an p y sical form, has

identical fo mulatio , contains no ad itional chemicals, uses the same man facturing pr oc s es, so that it is

eq ivalent t o a medical devic , part or ac es or y that has alre d b en evaluat ed

Check c ompla c e b ins pec tio o the risk manag ement pla a d risk manag ement file

Figure 1 — Risk ma a gement proc s for biological evaluatio of gas p thway s

4.2 Type tests

The t es s desc ibed in this document ar ty e t sts Ty e t sts ar pe formed on the f inal medical

device, a comp nent of the medical device or a r pr sentative sample of the medical device, p rt

or a cces or y being ev luat ed If r pr sentative samples ar used ( i.e man factur d an proc s ed

b eq iv lent methods), conside ation should be given t o w hethe or not the dife enc s between

the r pr sentative sample and the f inal medical device or component could afe t the r sult of the

t es Tes ing of r pr sentative samples (man factur d an proc s ed b eq iv lent methods) inst ead

of the final medical device should be sup ort ed b a desc iption of any dife enc s betwe n the

r pr sentative sample an the f inal medical device, an a detaied rationale for w hy each dife enc is

not ex e t ed t o impact he biocompatibility of the f inal medical device

NOTE S me a uth rities ha in ju isdic io evaluate these diferences an rationales

4.3 Biocomp tibility ha za rd identification

Identify al the p s ible biocomp atibilit -r lat ed hazar s that might r ach the p atient via the gas

pathways d ring the use of the medical device

Al k own p s ible biocompatibility-r lat ed hazards shal be taken int o ac ou t for eve y mat erial

an final medical device, part or a cces or y This does not imply that t es ing for al p s ible hazar s

is ne es ary or practical ISO 1 9 3-1:2 09, Cla use 5 and Clause 6 ha e ad itional r q ir ment for

ad itional ty es an d rations of p atient ex osur

E AMP E F or a medical devic (such as a mask)that has direct p atient contact in ad ition to g s p athway

contact, as es ment for compliance to b th ISO 1 562-1 an ISO 1 9 3-1 can b req ired

In the sele tion of mat erials t o be used in gas pathway man factur , the f irs conside ation should

be fitnes for purp se with r g rd t o charact eris ics an pro e ties ofthe mat erial, w hich inclu es

phy sical, me hanical, chemical an t oxicolo ical pro e ties

Mat erials used t o man factur the comp nent in the gas p athways should be suita le for the

int nded use, an use mat erials with demons ra le hist ory of safe use in the int en ed or comp ra le

a plcation w he ever p s ible

The fol owing shal be taken int o ac ou t for their r lev nc t o the o e al biolo ical ev luation of the

gas pathway:

— themat erial() of man factur ;

— int en ed ad itives, proces contaminant an r sid es;

— subs anc s r leased in normal use;

— degradation prod ct from normal use that might p s int o the p atient via the gas p athways;

contain req irements for de radation prod cts from polymer , ceramic an

metals, respectively If t esting for de radation using dry he t only, then ISO 1 9 3-1 , ISO 1 9 3-14 an

ISO 1 9 3-1 ne d not ap ly

NOT 2 No mal use can inclu e use with he ted an h midif ied bre thing g s Tests are done on the

“wor t case” conf iguration.T is can me n t esting with an without he t an h midif ication t o esta lish the

wor t case

— othe comp nent and their int eractions in the final medical device, part or a cces or y;

— thepe formanc an charact eris ics of the final medical device, p rt or a cces or y;

— phy sical charact eris icsof the f inal medical device, p rt or a cces or y inclu ing, but not l mit ed t o,

porosity, p rticle siz and sha e;

— theefe t of any hy gienic proc s ing st eps r q ir d befor use or r -use, if a plca le

Check c ompla c e b ins pec tio o the risk manag ement pla a d risk manag ement file

4.4 Ex tent of risk a sses ment

An analy sis shal be made of the haza ds identified in 4.3, and the risk that the hazard p ses t o the

patient det ermined The r sult shal be document ed

The rig our ne es ary in the biolo ical ev luation is princip ly det ermined b the d ration an

fr q ency of the ex osur an the hazards identified for the medical device The information ne ded

t o sup ort a biolo ical ev luation, inclu ing any t es data, shal take int o ac ount the physical an

chemical charact eris ics of the mat erials, the ele trome hanical natur of the medical device, as wel

as the fr q ency, d ration an con itionsof ex osur of the p atient t o the g s from the gas pathway

This ena les the cat eg orization of uses t o faci tat e the sele tion of a pro riat e t es s, if r q ir d

NOTE 2 ISO 1 9 3-1:2 0 , Clause contains ad itional req irements

4.5 Biocomp tibility evaluation plan

Ha ing identified the p s ible biocompatibility hazards an det ermined the risks that they might

p se t o the patient, a biocompatibility ev luation plan shal be c eat ed

This plan shal detai w hat is cur ently k own a out the mat erial formulation, ad itives an proces

aids used in the man factur of the gas pathways of the medical device, an the efor identify g ps

in k ow ledg e that hal be f iled b furthe work

If a p t ential hazar has be n identified, but the risk it p ses t o the patient can be shown t o be

neglgible (for ex mple, the dose the patient r c ives is les than the t lerable e p sure), then no

furthe work on the haza d is r q ir d The de ision shal be document ed

If a p t ential hazar has be n identif ied, but the risk it p ses t o the patient is not neglgible, or the

risk is u k own, then furthe work t o charact eriz or mitig t e the hazar is r q ir d This st ep ma

inv lve r fe ring t o pr vious simi ar medical devices an man facturing methods, ac es ing r la le

information in the publc domain, or pe forming t es s t o g the the data

Al medical devices should be ev luat ed for biocomp atibilit , but ev luation does not aut omaticaly

imply t es ing Depen ing on the final formulation, man facturing an a pl cation, an ev luation ma

r sult in the conclusion that no t es ing or no additional t es ing is ne ded

E AMP E T e medical devic has a demonstra le similarity in a specif ied fu ction an p ysical form, has

identical fo mulatio , contains no ad itional chemicals, uses the same man facturing pr oc s es, so that it is

eq ivalent o a medical devic , part or a cc s o y that has alre d b en evaluated

To r d c animal t es ing for gas pathways that can contact lq ids, identification of mat erial chemical

cons ituent an conside ation of chemical charact erization shal be u de taken, an only if r sult

show the pr senc of subs anc s, w hich do not ha e suff icient t oxicolo ical data t o alow risk

as es ment, should any biolo ical t es ing be conside ed

NOTE 1 S me local efects inclu ing cyt oto icity, ir itation, an sensitization might not b adeq ately

as es ed using a chemical characterization/risk as es ment ap ro ch As a result, it can b neces ary to

con uct biolo ical testing to as es these en points Syst emic efects inclu ing acute, sub cute, subchronic an

chronic to icity, reprod ctive an developmental to icity, g noto icity an car inog enicity can oft en b as es ed

using a chemical characterization/risk as es ment ap ro ch

An ev luation of particulat mat er shal be inclu ed in the biocompatibility ev luation

Tes r sult cannot guarant ee fr edom from p t ential biolo ical haza ds Th s, biolo ical

inves ig tions shal be folowed b car ful o se v tions for unex e t ed adve se r actions or event in

h mans d ring use of the final medical device, p rt or a cces or y

NOTE 2 T e rang of pos ible biolo ical haza ds is wide an can inclu e short-term efects, as wel as long

-term or specif ic to ic efects

The biolo ical ev luation of a gas pathway shal take int o ac ou t the natur and mo i ity of the

chemical cons ituent in the mat erials used t o man factur the medical device, part or a cces or y an