Tiêu chuẩn iso 11040 8 2016

© ISO 2016 Prefilled syringes — Part 8 Requirements and test methods for finished prefilled syringes Seringues préremplies — Partie 8 Exigences et méthodes d’essai pour seringues préremplies prêtes à[.]

Prefil ed syring es —

Part 8:

Se ing e s prér mplie s —

Partie 8: Exigence s et méth de s d’e ssai p ur sering e s prér mplie s

prê tes à l’emploi

Fir t edition

2 16-1 -1

Refer ence n mb r

ISO 1 040-8:2 16(E)

COPYRIGHT PROTECTED DOCUMENT

© ISO 2016, P blshed in Sw itz rlan

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F reword i v

Introduction v

1 Sc ope 1

2 Nor mati ve r eferenc es 1

3 Terms and definitions 2

4 Use r equirements 2

4.1 Definition of inten ed use 2

4.2 R isk manag ement 3

4.3 A pplcation of usa i ty eng ine ring 3

5 System characterizatio 3

5.1 Critical dimensions 3

5.2 Desc iption of comp nent an mate ials 4

5.2.1 General 4

5.2.2 Barr el 4

5.2.3 Plu g er s o pe s 5

5.2.4 A dditional comp nents 5

5.3 Desc iption of the content of the finished prefi ed syring e 5

6 Perfor manc e requir ements 5

6.1 General 5

6.2 Br eak lo se an ex trusion for ces 5

6.3 Burs resistanc 6

6.4 Br eak r esis anc .6

6.5 Closure sys em for ces an tor ques 6

6.6 Conne tivity with fluid p th con e tors 6

6.7 Resid al v lume 6

6.8 Ne dle penetration for ce 6

6.9 Ne dle pul-out force 6

6.1 Sharps injury pr ote tion r eq ir ements 6

6.1 Liq id leakag e bey n plu g er

7 6.1 Mar king s 7

7 Pharmac eutical requir ements 7

7.1 General 7

7.2 Drug -containe interaction 7

7.3 Biolog ical r eq irement 7

7.4 Containe closur e integ rity 7

7.5 Delverable v lume 8

7.6 Particles (visible an subvisible) 8

8 Documentation 8

Biblog raphy

9

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

For an ex lanation on the meaning of ISO spe ific t erms an ex r s ions r lated to conformity as es ment,

as wel as information a out ISO’s adhe enc to the Wor ld Trade Org nization (WTO) principles in the

Te h ical Bar ie s to Trade (TBT) se the folowing URL: www.iso.org/ iso/for word.html

The committ ee r sp nsible for this document is ISO/TC76, Tra s fus io , in us ion a d injec tion, a d blo d

proc es s in eq ipment fr medic al a d p armaceutic al us e

ISO 1 040 consis s of the folowing p rt , u de the g ene al title Pre i ed sy rin es:

— Part 1: Glas s cylnde s fr dental loc al a aes thetic c artridges

— Part 2 : Plu ge s to pe s fr dental loc al a aes thetic c artridges

— Part 3 : Seals fr dental loc al a aes thetic c artridges

— Part 4 : Glas s b r el s fr injec ta les a d s te ii zed s ub s s embled sy rin es r ady fr fi in

— Part 5: Plu ge s to pe s fr injec ta les

— Part 6 : Plas tic b r el s fr injec ta les

— Part 7: Packa in sys tems fr s te ii zed s ub s s embled sy rin es r ady f r fi in

— Part 8: R eq ir ment a d tes t meth ds fr fini shed pr fi ed sy rin es

Hist oricaly, inje ta le (par nt eral) lq id pharmac utical prod ct have be n mainly pro ided

in primary containe s ( i.e amp ules an vials) w hich r q ir d the lq id t o be trans e r d int o

a hy ode mic syring e an combined with the a pro riat e inje tion ne dle befor it final use

This proc d r is not only time-consuming, but also pr sent a gr at n mbe of p s ibi ties for

contamination and use e rors

Ove the p s seve al years, the pr sentation of l q id pharmac utical prod ct in pr filed syring es

for single use, many with s aked ne dles, is be oming mor pr v lent The simplcity of use that is

pro ided not only benef it their use in the cl nical set ing, but also ena les these t o be used b la use s

in a home set ing

The s an ardization of the r q ir ment for pr f iled syringes has be n ad r s ed b ISO/TC 7 6 in

two wa s:

— thespe if ication of the comp nent of the pr filed syring e prior t o f il ng isinclu ed in the pr vious

part of the ISO 1 040 se ies;

— the r q ir ment for the final pr fil ed syring e, pr sent ed t o the use as a f inished prod ct, ar

addr s ed in this p rt of ISO 1 040

Finished pr filed syring es r q ir marketing authorization as a drug, in some r gions as a combination

prod ct or as a medical devic , depen ing on the cont ent an the int en ed use The syring e play s a d al

role in the pr filed syring e prod ct — as a containe closur sy st em an as a del ve y devic Safety,

pe formanc an usa i ity ne d t o be conside ed, as wel in case of int en ed pr as embly, co acka ing

or la el r fe enc for use with othe devic s an eq ipment This p rt of ISO 1 040 ad r s es the

cont ent and syring e as a sy st em, with the int ent t o ensur the suc es ful pe formanc for it int en ed

purp se

The e ar othe int ernational an national s an ards an guidanc publcations an , in some

countries, national r gulations that ar a plca le t o medical devic s an pharmac uticals Their

r q ir ment might supe sede or complement this p rt of ISO 1 040 Develo e s an man factur rs

of f inished pr filed syring es ar encourag ed t o inves ig t e an det ermine w hethe the e ar any othe

r q ir ment r lev nt t o the safety or marketa i ity of their prod ct

Prefil ed syring es —

Part 8:

syring es

This p rt of ISO 1 040 is a plca le t o aseptical y f iled or t erminal y st eri iz d f inished pr filed

syring es ( int en ed for single use only)b sed on ISO 1 040-4 or ISO 1 040-6, t og ethe with ISO 1 040-5,

for p r nt eral inje tion pr p rations with focus on q al ty, fu ctional pe formanc an safety

r q ir ment , as wel as r lev nt t es methods

Finished pr filed syring es w hich ha e u de g one an ad itional pr p ration st ep b the use befor

inje tion (e.g diuent yring es that ha e be n emptied for r cons itution an in w hich the r cons itut ed

drug solution has be n aspirat ed aft er r cons itution) ar ex clu ed from the sco e of this p rt of

ISO 1 040

NOTE 1 T is part of ISO 1 040 can also b used as a guidance for other ty es,designs an / r sizes of pref il ed

syring s,e.g.d al chamb r pref iled syring s

NOTE 2 In case the f inished pref iled syring es are used in a ne dle-b sed injection system, se also

ISO 1 60 -3

NOTE 3 A tt ention is drawn t o ap lica le national or re ional re ulations such as P E r

)

, USP 2)

or JP 3)

NOT 4 Finished pref iled syring s containing so-cal ed b rderline prod cts, e.g h aluronic acid,are inclu ed

in the s ope of this part of ISO 1 040, though they are not always re ulated as a p armaceutical prod ct

2 Normati ve r eferences

The folowing document , in w hole or in p rt, ar normatively r fe enc d in this document an ar

in ispensa le for it a pl cation F or dat ed r fe enc s, only the edition cit ed a pl es F or u dat ed

r fe enc s, the lat es edition of the r fe enc d document ( inclu ing any amen ment )a pl es

ISO 1 040-4:2 1 , Pre i ed sy rin es — Part 4 : Glas s b r el s f r injec ta les a d s te ii zed s ub s s embled

sy rin es r ady fr fi in

ISO 1 040-5, Pre i ed sy rin es — Part 5: Plu ge s to pe s fr injec ta les

ISO 1 040-6, Prei ed sy rin es — Part 6 : Plas tic b r el s fr injec ta les

ISO 2 9 8, S arps injur y protec tio — R eq ir ments a d tes t meth ds — S arps protec tion featur s fr

s in le -us e hy pode mic ne dles , introduc ers fr c athete s a d ne dles used fr blo d s ampln

ISO 8 3 9-1, Smal b r c on ec tors fr lq ids a d g ses in healthc ar a plc atio s — Part 1: G ene al

r q ir ments

ISO 8 3 9-7, Smal b r c on ec tors fr liquids a d g s es in healthc ar a plc atio s — Part 7: Co nec tors

w ith 6% (L e ) ta e fr intra as c ular or hy pode mic a plc ations

1) S e http:/ w w w.ed m.eu/

2) S e http:/ w w w.usp.or g /

3) S e http:/ w w w.pmda.g o.jp

ISO 8 3 9- 20, Smal b r c on ec tors fr lq ids a d g ses in healthc ar a plc atio s — Part 2 : Commo

tes t meth ds

ISO 7 8 -1:2 1 , Ste ie hypode mic sy rin es fr s in le us e — Part 1: Syrin es fr ma u l use

IEC 6 3 6, Medic al dev ic es — Ap lc atio o us abi t y en ine rin to medic al dev ic es

3 Terms and definitions

F or the purposes of this document, the fol owing t erms and def initionsa ply

3.1

finished prefi led syring e

pr filed containe closur sy st em for p r nt eral inje tion pr p rations as it is market ed, inclu ing e.g

as embly of comp nent , t erminal st eri ization an final p cka ing

3.2

manufacturer

natural or leg l pe son holding the lc nc for the pharmac utical prod ct with r sp nsibi ty for the

design, man factur , packa ing, an la el ing of a f inished pr filed syring e, befor it is plac d on the

market or put int o se vic , r g rdles of w hethe these o e ations ar car ied out b that pe son or on

that pe son behalf b a third p rty

3.3

risk manag ement

sy st ematic a plcation of manag ement p lcies, proc d r s an practic s t o the tasks of analy sing,

ev luating, control ng an monit oring risk

[ SOURCE:ISO 149 1:2 0 , 2.2 ]

3.4

user

p tient or health car pro ide (cl nical pe son el, doct or, or la pe son) w ho pr par s and/ r uses the

finished pr f il ed syring e

4 User r equir ements

4.1 Definition ofintended use

The man factur r shal def ine the int en ed use of the f inished pr f iled syring e Aspe t t o be

conside ed shal inclu ethe folowing:

— use s inclu ing their health s atus;

— therout e of adminis ration;

— targ et tis ue;

— ad itional medical devic s or a plcation aids that ar used for a plcation, e.g ne dle-b sed inje tion

sy st ems, infusion tubes, r cons itution aids, st erie hy ode mic ne dles, plung er rod/fing er flang e;

— charact eris ics of the environment d ring transp rt, st orag e and use;

— int eractions betwe n use , environment an pr filed syring e;

— point of use, e.g hospital, home ar ;

— fr q ency of a plcation;

— c iticalty of medication, e.g medication for acut e car or for chronic diseases

4.2 Risk manag ement

Man factur rs shal folow a risk-b sed a pro ch d ring thedesign, develo ment, man factur an lfe

cycle ofthe f inished pr f iled syring e lke ex emplary desc ibed b ISO 149 1 Risk manag ement shal

conside the int ended use, int eractions betwe n cont ent an containe , an environmental con itions

This can r sult in prod ct-spe if ic r q ir ment an t es methods that dife from w hat is outl ned in

this p rt of ISO 1 040

If the pr f il ed syring e is int en ed t o be used in combination with pr at ached, co ackag ed or la el

r fe enc d devic s an eq ipment, the man factur r shal ensur that he w hole combination, inclu ing

the con e tion sy st em, is safe, usa le an does not imp ir the spe ified pe formanc s of the devic s

NOTE F or f il ing proces , se R eference [17]

4.3 A ppl cation of usabi ity eng ineering

The usa i ity of the pr filed syring e shal be conside ed an v ldat ed ac ording t o a proc s compl ant

with IEC 6 3 6

NOTE 1 F or further information, se R eference [16]

NOTE 2 T e instructions for use are part of the usa ility t esting

5.1 Critical dimensions

Critical dimensions shal be defined conside ing the int ended use of the f inished pr f iled syring e

Spe ial focus shal be given t o:

— int erfac s with othe devic s (e.g sharp injury pr vention featur s or ne dle-b sed inje tion

sy st ems, ne dleles con e tion devic s), comp nent and use s;

— conne tivity with othe devic s at the p int of use (e.g IV ac es sy st ems or ne dles);

— plu g er st op e p sition depending on the int ended use (e.g use in ne dle-b sed inje tion sy st ems)

Figur 1 inclu es ex mples on how t o measur the plung er st op e p sition on f inished pr filed

syring es

a) E ample 1 b) Example 2

Key

1 plu g er stop er

l

1

distance from the plu g er stop er to the top of the 9 ° cone (mechanical or optical gag e)

l

2

an l

3

distance from the plu g er stop er to the b ck en of the syring e

Figure 1 — Examples for me suring plung er the stop er positio for finished prefiled syring es

5.2 Des r iption of c omponents and materials

5.2.1 General

The sele t ed component and mat erials shal be suita le for the int en ed man facturing proc s es (e.g

t erminal st eri ization if a plca le)

The int erfac with othe drug delve y devic s an / r comp nent , e.g tubing or ne dle b sed inje tion

sy st ems, shal be conside ed

5.2.2 Bar r el

ISO 1 040-4 an ISO 1 040-6 shal a ply

NOTE 1 If f il lines or grad ation marks are print ed,ISO 78 6-1:2 1 , Ta le 1 can b considered

NOTE 2 ISO 1 040-6 wil b revised t o cover plastic sub s emblies re d for f iling

The b r el can inclu e a s aked ne dle The ne dle dimensions inclu ing inne an out er diamet ers

shal be consist ent with the int ended use, conside ing e.g rout e of adminis ration, use in ne dle-b sed

inje tion syst emsan cont ent viscosity

5.2.3 Plung er sto per

ISO 1 040-5 shal a ply

NOTE 1 Plu g r stop er dimensions chang e by placing it int o the syring

NOTE 2 T ere can b special aspects for co ted or laminated plu g er , as ociated e.g with plu g r placement

5.2.4 Additional c ompo ents

A dditional comp nent sup orting the int en ed use can inclu e the folowing:

— plu g er rod;

— add-on f ing er flang e;

— sharpinjury pr vention featur ac ording t o ISO 2 9 8;

— hy ode mic ne dle with 6 % Lue conical f it ing ac ording t o ISO 7 64;

— f ilt er;

— tubing;

— vial ada t er

A finished pr f iled syring es can be used in ne dle-based inje tion sy st ems The int erfac t o the

r lev nt comp nent shal be conside ed

5.3 Des ription of the c ontent ofthe finished prefi led syring e

Critical paramet ers of the cont ent hal be defined These p ramet ers can inclu e the folowing:

— viscosity;

— density;

— surfac t ension;

— f il v lume inclu ing t ole anc s;

— pH

These paramet ers ar t empe atur depen ent an can chang e over time

6 P erformanc e requir ements

The man factur r shal ensur that the finished pr filed syring e me t the a pro riat e fu ctional

r q ir ment u ti the en of it shelf lfe The t es s desc ibed in the folowing subclauses should be

conside ed but might not be al inclusive

Limit for the t es s shal bedef ined b sed on the int en ed use ( e 4.1)

6.2 Break loose and ex trusion forc es

Br ak lo se and extrusion for e t es ing shal be con uct ed with the f inal sy st em ( inclu ing as embled

plu g er an e.g at ached ne dle and as embled plu g er rod) as int en ed for use F or the t es s, the

t empe atur of thecont ent shal be the same as for a plcation