Tiêu Chuẩn Iso 08871-5-2016.Pdf

© ISO 2016 Elastomeric parts for parenterals and for devices for pharmaceutical use — Part 5 Functional requirements and testing Éléments en élastomère pour administration parentérale et dispositifs à[.]

Elastomeric parts for par enterals and

Part 5:

Élément en élastomè e p ur administration p r ntérale et dis positifs

à usage p armac utique —

Partie 5: Exigence s fnction e lles et e ssais

S con edition

2 16-1 -1

COPYRIGHT PROTECTED DOCUMENT

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F reword i v

Introduction v

1 Sc ope 1

2 Nor mati ve r eferenc es 1

3 Terms an definitions 1

4 Req irements 2

4.1 Penetrabi ty 2

4.2 Frag mentation 2

4.3 S lf-sealng an aq eous solution tig htnes 2

4.4 A queous solution tightnes 2

5 Preparatio of elastomer ic closur es for testing 2

5.1 Sampl ng 2

5.2 Cleaning 2

5.3 Ste i zation 2

A nne x A (normative) Test for penetrabiity 3

A nne x B (normative) Test for frag mentation 4

A nne x C (normative) Test for self-se lng and d ye solutio tightnes 6

A nne x D (normative) Test for d ye solutio tightnes 8

Biblog raphy 10

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 sp nsible 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 meaning of ISO spe ific 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 WTO principles in the Te h ical

Bar ie s t o Trade (TBT) se the fol owing URL: F or word - Sup lementary information

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

This se on edition canc ls an r plac s the firs edition (ISO 88 1-5:2 0 ), w hich has be n t ech icaly

r vised

ISO 88 1 consis s of the folowing part , u de the g ene al title Elas tome ic p rts fr p r nte als a d fr

dev ic es fr p armac eutic al use:

— Part 1: Ex trac ta les in a ueo s a tocla ates

— Part 2 : Identific atio  a d charac te i zation

— Part 3 : Dete min tion o r leased-p rticle c ou t

— Part 4 : B iolo ic al r q ir ments a d tes t meth ds

— Part 5: Fu c tio al r q ir ments a d tes tin

Elast ome ic or rub e closur s for pharmac utical use ar used in combination with vials an many

times in conjunction with pie cing devic s The e ar thr e fu ctional p ramet ers w hich ar imp rtant

t o the pie cing proc s These ar penetra i ity, fra mentation an self-seal ng The thr e fu ctional

t es s desc ibed in this p rt of ISO 8 7 can be used as a r fe enc method for t es ing elast ome ic

closur s that ar pie c d using inje tion ne dles made from metal In ad ition, the aq eous solution

tightnes t es can be used t o ve ify the efe tivenes of the sealng of a spe if ic closure /vial combination

Elastomeric parts for par enterals and for devic es for

Part 5:

This p rt of ISO 8 7 spe ifies r q ir ment an t es methods for functional paramet ers of elast ome ic

closur s used in combination with vials an w hen pie c d b an inje tion ne dle

NOTE F nctional testing with spikes is specif ied in ISO 8 36-2 an in ISO 8 36-6

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 7 64, Ste ie hypode mic ne dles fr s in le us e

ISO 8 6 -1, Injec tion c ontaine s a d acc es s ories — Part 1: Injec tio v ials made o glas s tu in

ISO 8 6 -3, Injec tio c ontaine s a d ac c es s ories — Part 3: Aluminiumc aps fr injec tio v ials

ISO 8 6 -4, Injec tio c ontaine s a d ac c es s ories — Part 4 : Injec tio v ial s made o mo lded glas s

ISO 8 6 -6, Injec tio c ontaine s a d ac c es sories — Part 6 : Ca s made o aluminium-plas tic s c ombin tio s

fr injec tion vials

3 Terms and definitions

F or the purposes of this document, the folowing t ermsand definitions a ply

3.1

penetrabi ity

for e r q ir d for pie cing an elast ome ic closur

3.2

fra mentatio

measur of the n mbe of elast ome ic particles w hich ar g ene at ed b the pie cing proc s

3.3

self-se l ng

measur of the r seal ng ef iciency of elas ome ic closur s folowing penetration and with rawal of

a ne dle

3.4

aqueous solutio tightnes

measur for the efe tive sealng of a spe if ic elast ome ic closure /vial combination

4 Requir ements

4.1 Penetrabi ity

When t est ed in ac ordanc with Annex A, the for e r q ir d for pie cing shal not be gr at er than 1 N

for each closur

4.2 Frag mentation

When t est ed in ac ordanc with Annex B, the n mbe of elast ome ic fra ment pe 48 pie cings visible

with the naked eye shal not be gr at er than 5

4.3 S lf-seal ng and aqueous solution tig htnes

When t est ed in ac ordanc with An ex C, none of the vials shal contain any trac of colour d solution

w hen o se ved with the naked eye This r q ir ment a ples t o multi-dose containe s only, i.e

containe s w hich uti z elast ome ic closur sthat ar pie c d multiple times

Mat erials that me t the r q ir ment ar not r q ir d t o u de g o furthe t es ing in ac ordanc with 4.4

4.4 Aque us solution tightnes

When t est ed in ac ordanc with Annex D, none of the vials shal contain any trac of colour d solution

w hen o se ved with the naked eye

5 Preparation ofelastomeric closures for testing

5.1 S mpl ng

The n mbe of closur s r q ir d for each t es is as folows

— S lf-seal ng an aq eous solution tightnes : 1

In practic , it is r commen ed that mor than the minimum r q ir d n mbe of closur s be pr p r d

for t es ing

5.2 Cle ning

Closur s shal be st eri iz d in the as-del ve ed con ition If samples from r gular prod ction cleaning

proc s es ar not a aia le, the st op e s shal be cleaned in ac ordanc with the folowing proc d r

Introd c an a pro riat e n mbe of rub e closur s in a suita le glas containe , co e with p

article-fr e wat er, boi for 5 min, then rinse f ive times with cold p rticle-fr e wat er

5.3 Steri ization

The closur sshal be t est ed aft er ha ing be n subje t ed t o the st eri ization method actual y used

A nne x A

(normative)

Test for penetrabi ity

A 1 General

Many elast ome ic closur s for pharmac utical use ar used in conjunction with inje tion ne dles The

for e ne es ary t o penetrat e or pie c a rub e closur is an imp rtant p ramet er in ev luating the

suita i ty of the closur for it int en ed use

A 2 Principle

The for e ne es ary t o complet ely pie c an elast ome ic closur is measur d using a suita le a p ratus

A 3 A pparatus, equipment and reag ents

A 3.1 1 closur es, pr ep r ed in ac or danc with Clause 5

A 3.2 1 cle n vials, in ac or danc w ith ISO 8 6 -1 or ISO 8 6 -4, ne k finish siz to match the siz of

closur es (A 3.1) (e.g 1 mm, 2 mm)

A 3.3 1 aluminium or plastic/ luminium cr imp se ls, in ac or danc w ith ISO 8 62-3 or ISO 8 6

-6, siz d to match the siz of closures (A 3.1) (e.g 1 mm, 2 mm), an c imping a p ratus

A 3.4 1 lubricated lo g -bevel [bevel angle (1 ± 2) ]metal h ypo er mic ne dles, ex te nal diamete

of 0,8 mm in ac or danc with ISO 78 4

A 3.5 A pparatus, ca a le of measuring a for ce of 1 N w ith an ac ur acy of ±0,2 N

A 4 Procedure

A 4.1 Close thevials (A 3.2) with the closur es (A.3.1) to be tes ed an se ure with a c imp seal (A 3.3)

A 4.2 Fit the for ce-measuring a p ratus(A 3.5) with a hypode mic ne dle (A.3.4)and pier ce a closur e

pe pen icular to the surfac Re ord the max imum force Use a new ne dle for each of the 9 r emaining

closur es and r epeat he pr oc d re

A 5 Ex pres ion of results

Re ord the for e r q ir d for pie cing each closur and comp r the tes r sult with the

r q ir ment in 4.1

A nne x B

(normative)

Test for frag mentation

Many elast ome ic closur s for pharmac utical use ar used in conju ction with inje tion ne dles

Elast ome ic fra ment ma be r leased upon penetration with these inje tion ne dles The n mbe

an siz of thesefra ment can afe t he q alty of drug prod ct with w hich the elast ome ic closur s

ar used

B.2 Principle

Elast ome ic closur s for inje tion vials ar pie c d with an inje tion ne dle Elast ome ic fra ment

w hich have be n ca used b pie cing ar cole t ed on a f ilt er an cou t ed

B.3 A pparatus, equipment and r eag ents

B.3.1 12 closures, pr ep r ed in ac or danc with Clause 5

B.3.2 12cle n vials, in ac or danc with ISO 8 6 -1 or ISO 8 6 -4, ne k finish siz to match the siz of

closur es (B.3.1) (e.g 1 mm, 2 mm)

B.3.3 12 aluminium or plastic/ luminium c imp se ls, in ac or danc with ISO 8 6 -3 or ISO 8 6

-6, siz to match the siz of closur es (B.3.1)(e.g 1 mm, 2 mm), and c imping a p ratus

B.3.4 P ar ticle-fr ee water, to fit the fi v lumes of the vials (B.3.2) an syring e (B.3.6)

B.3.5 12lubricated lo g -bevel [bevel ang le (1 ± 2) ]metal hypo er mic ne dles, ex te nal diamete

of 0,8 mm in ac ordanc w ith ISO 7 64

B.3.6 S yr ing e, ca a le of being fited w ith the ne dles in B.3.5

B.3.7 Fiter , with a por e siz of 0,5µm

B.3.8 Fiter ing apparatus, ca a le of holding a fite (B.3.7) w ith a p r e siz of 0,5 µm

B.3.9 Laborator y micr osc ope or a mag nificatio g las , with a minimum mag nification of 6

B.4 Proc edure

B.4.1 Plac in each of the 1 clean vials (B.3.2) a v lume of particle-fr ee wate (B.3.4) eq iv lent o the

nominal v lume min s 4 ml (e.g plac 2 ml in a 2 ml vial) Close the vials w ith the closur es (B.3.1) to

be tes ed an se ur e with a c impseal (B.3.3)

B.4.2 Pier ce each closur e using a hypode mic ne dle (B.3.5) fited to a clean syring e (B.3.6) fi ed w ith

p rticle-fr ee wate (B.3.4), an inje t into the vial 1 ml of wate an r emo e 1 ml of air C r y out this

o eration four times for each closur e, piercing each time at a diferent site Use a new ne dle for each

closur e an che k that he ne dle is not blu ted d ring the test

B.4.3 Pas the lq id fr om each of the 1 vials thr ough a fite (B.3.7) ha ving a p re siz of 0,5 µm an

cou t the n mbe of p rticles visible with the naked eye The cou t is b sed on the as umption that

fr ag ment with a diamete eq al to or g r eate than 50 µm ar e visible with the naked eye In cases of

doubt or dispute, cou t the rub e fr ag ment with a micr osco e or mag nifying g las (B.3.9) to ve ify

their siz an natur e

B.5 Ex pres ion of results

R ecord the t otal n mbe of fra ment an comp r t o the lmit given in 4.2

A nne x C

(normative)

Test for self-seal ng and d ye solution tig htness

C.1 General

Elast ome ic closur s for pharmac utical use ar commonly used in conjunction with vials The closur

ensur s an a pro riat e seal with the vial Po r closure /vial seal int egrity an / r p or self-seal ng can

afe t the st eri ty of the vial cont ent , prod ct v lume an conc ntration of doses

Many elast ome ic closur s for pharmac utical use ar used in conju ction with inje tion ne dles F or

multiple-dose containe s, the closur s ma be pie c d many times o e the course of del ve ing al the

doses S lf-sealng or r seal of the incision made b the ne dle is imp rtant t o the containe int egrity

C.2 Principle

Elast ome ic closur s for inje tion vials ar pie c d several times with an inje tion ne dle an ex mined

for leakag e for ed b a pr s ur dife ential ac os the closur

C.3 A pparatus, equipment and r eag ents

C.3.1 1 closures, pr ep r ed in ac or danc with Clause 5

C.3.2 1 cle n vials, in ac or danc with ISO 8 6 -1 or ISO 8 6 -4, ne k finish siz to match the siz of

closur es (C.3.1) (e.g 1 mm, 2 mm)

C.3.3 1 aluminium or plastic/ luminium c imp se ls, in ac or danc with ISO 8 6 -3 or ISO 8 6

-6, siz to match the siz of closur es (C.3.1) (e.g 13 mm, 2 mm), an c imping a p r atus

C.3.4 P ar ticle-fr ee water, to fit the fi v lumes of the vials (C.3.2)

C.3.5 Solutio of meth ylene blue, 1 g /l

NOTE T e presence of surfactants can chang e the le king b haviour of a liq id,an therefore, it is ad isa le

t o avoid it

C.3.6 1 lubricated lo g -bevel [bevel ang le (1 ± 2) ]metal hypo er mic ne dles, ex te nal diamete

of 0,8 mm in ac ordanc w ith ISO 7 64

C.3.7 Vacuum chamber, ca a le of maintaining a pr es ur e (27 k Pa below atmosphe ic pr es ur e)

for 1 min

C.4 Proc edure

C.4.1 Plac in each of the 1 clean vials (C.3.2) a v lume of p rticle-fr ee wate (C.3.4) eq iv lent to the

nominal v lume (e.g plac 2 ml in a 2 ml vial) Close thevials w ith the closures (C.3.1) to be tes ed an

se ur e w ith a c imp seal (C.3.3)

C.4.2 Using a new h ypoder mic ne dle (C.3.6) for each closure, pierce each closure 1 times, piercing

each time at a diferent site within the tar g et area Immer se the vials upr ight in a containe holding the

solution of meth ylene blue (C.3.5) E sure that the vials are completely immer sed in the solution Plac the

containe of vials in a v cu m chambe (C.3.7) an red c the pres ure b 2 k a Hold the v cu m for

1 min, then res ore to atmospher ic pres ure A llow the vials to remain immer sed in the meth ylene blue

solution for an ad itional 3 min, then remo e them from the chambe Rinse the out ide of the vials with

wate Inspe t the vial content visualy for an y trac s of the blue-coloured solution of meth ylene blue

C.5 Ex pres ion of results

R eport if the vials contain any trac of colour d solution an comp r t o the r q ir ment in 4.3