Tiêu chuẩn iso 08536 6 2016

© ISO 2016 Infusion equipment for medical use — Part 6 Freeze drying closures for infusion bottles Matériel de perfusion à usage médical — Partie 6 Bouchons à lyophilisation pour flacons de perfusion[.]

Infusion equipment for medical use —

Part 6:

Matérie l de pe f sion à usage médical —

Partie 6 : B ouch ns à ly p ilisation p ur flaco s de pe fsion

© ISO 2016, 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 1

3 Terms an definitions 1

4 Shape and dimensions 2

5 Desig natio 3

6 Material 3

7 Req irements 4

7.1 General 4

7.2 Physical r eq ir ements 4

7.2.1 Hardnes 4

7.2.2 Frag mentation (coring ) 4

7.2.3 Spike penetr ation for ce 4

7.2.4 Spike penetr ation/seala i ty 4

7.2.5 Resistanc to ag eing 4

7.2.6 Resid al moistur e 4

7.3 Chemical req irement 4

7.4 Biolog ical r eq irement 5

8 Labeling 5

A nne x A (normative) Deter mination of fr ag ments 6

A nne x B (normative) Deter mination of spike penetratio for c e 8

A nne x C (normative) Spike retentio /se labiity 10

A nne x D (normative) Closure piercing devic e 12

A nne x E (informative) Determination of r esidual moistur e 13

Biblog raphy 16

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

This third edition canc ls an r plac s the se on edition (ISO 8 3 -6:2 09), w hich has be n t ech icaly

Fr e e drying closur s ar put on the t op of infusion b t les aft er fil ng, lea ing suff icient o eningsfor

the subl mation proc s and v cu m A t the en of the drying proc s , they can be ful y inse t ed int o

the glas containe b hydraulc or me hanical means in the v cu m chambe

Fr e e drying closur s can pick up wat er d ring ship ing, st orag e, washing an st eam st eri ization

cycles, w hich is diff icult t o r mo e in a subseq ent drying cycle As a conseq enc , the fr e e drying

closur s ar usual y lo ded with r sid al mois ur Depending up n the mas of the fr e e-dried

prod ct an the degr e of it sensitivity t o wat er, the r sid al mois ur in therub e mat erial can spoi

the fr e e-dried pr p ration d ring st orag e

These spe if ic proc s r q ir ment ha e be n ad r s ed in this document b spe ifying r lev nt

r q ir ment for fr e e drying closur s inclu ing a t es method on det ermination of r sid al mois ur

Primary p cka ing component made of elast ome ic mat erials ar an int egral p rt of medicinal

prod ct an th s the principles of cur ent Go d Man facturing Practic s (cGMP) a ply t o the

man facturing of these component

Principles of cGMP ar desc ibed in, for ex mple, ISO 1 3 8 or GMP Guidelnes as publshed b the

Euro ean Commu ity an the Unit ed Stat es of Ame ica

Infusion equipment for medical use —

Part 6:

This document spe if ies the sha e, dimensions, mat erial, pe formanc r q ir ment an la el ng for

the ty e of closur for infusion b t les, as desc ibed in ISO 8 3 -1, that is used in con e tion with the

fr e e-drying (or ly phi zation)of drugs an biolo ical mat erials

The dimensional r q ir ment ar not a plca le t o b r ier-co t ed closur s

Closur s spe ified in this document ar int en ed for single use only

NOTE T e pot ency, p rity, sta ility an safety of a medicinal prod ct d ring its man facture an stora e

can strongly b afected by the nature an performance of the primary packa ing

2 Normati ve r eferences

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 amen ment ) a ples

ISO 3 0 (al p rt ), R ub e — Tole a c es fr produc ts

ISO 76 19-1, Ru be , v ulc ani zed or the mo las tic — Dete min tion o indentatio h rdnes s — Part 1:

Duromete meth d (S or h rdnes s)

ISO 8 3 -1, In us io eq ipment fr medic al use — Part 1: In us ion glas s b ttles

ISO 8 3 -3, In us io eq ipment fr medic al us e — Part 3: Aluminium c aps fr in us io b t les

ISO 8 7 -1, Elas tome ic p rts f r p r nte als a d fr devic es fr p armac eutic al us e — Part 1: Ex trac ta les

in a ueo s a tocla ates

ISO 8 7 -4, Elas tome ic p rts fr p r nte als a d fr devic es fr p armac eutic al use — Part 4 : B iolo ic al

r q ir ments a d tes t meth ds

3 Terms and definitions

F or the purposes of this document, the folowing t ermsand definitions 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 Onlne brow sing plat orm:a ai a le at ht p:/ www.iso.org o p

3.1

fre ze-drying

ly phi izatio

drying proc s designed t o r mo e solvent from b th aq eous an non-aq eous sy st ems b

subl mation an desorption

fre ze drying closure

closur w hich ena les the drying of a froz n pharmac utical pr p ration in a v cu m chambe

4 Shape and dimensions

4.1 The dimensions of free e drying closur es shal be as g iven in Ta le 1 Fig ure 1 i us rates the

g eneral desig n of a free e drying closure

Dimensions in milimetr es

man facturer an user

Figure 1 — Example to i lustrate a fre ze drying closure design

Table 1 — Dimensio s of fre ze drying closures

Dimensions in milimetr es

4.2 If not othe w ise spe ified, g eneral dimensional toleranc s shal be in ac or danc with ISO 3 0

(al p rts)

2

4.3 If spac rs ar e located on the to of the flang e, they shal not inte fer e with the mar ks for the

inje tion site The height of the sp c rs shal not exc ed 0,3mm

On the t op surfac , the e ma be marks or in entations

4.4 If the flang e of the closure has a slght conical sha e, the conicity shal be 0,8 mm max in relation

to the diamete in or de to faci tate pr oduction T e toleranc s of the trimming edg e of the flang e shal

comply with the toler anc s spe ified in Ta le 1 for the diamete d

1

4.5 The plug p rt shal pr ovide slt , channels or othe a propriate means in conju ction with

pr otru ing or positioning elements at the oute diamete , which ena le inse tion in a drying (halfwa y)

p sition d ring the sublmation pr oc s

4.6 The desig n of the p sitioning element to hold the fr ee e drying closur e firmly in the sublmation

p sition should not compr omise the ful inse tion of the closur e

4.7 The desig n of the flang e p rt in conjunction w ith the plug design shal pe mit b th the r econstitution

of the fr ee e-dried pr od ct with the a pr opriate solvent an the r emo al of the dis olved pr od ct b

means of a pier cing devic

4.8 When free e drying closur es are put in plac for the ly phi zation pr oc s an the containe is

ex posed to transp rt proc s es, they should exhibit suficient hock an vibr ation r esis anc that u de

r eg ular pr oc s ing con itions they do not fal of nor be ome dis or ted

4 9 Al edg es of the closur ma be rou ded

A fr e e drying closur for infusion b t les can be designat ed b the words “ r e e drying closur ”

folowed b the n mbe of this document olowed b the nominal siz

E AMP E A fre ze drying closure for infusion b t les of nominal size 3 complying with the req irements

laid down in this document is designated as folows:

Fr e e drying closur ISO 8 3 -6 - 3

The elast ome ic mat erial used shal me t the r q ir ment spe if ied in Cla use 7

The elast ome ic mat erial shal withs an two st eri ization cycles w hen aut ocla ing in saturat ed st eam

at (1 1 ± 2) °C for 3 min without ex ce ding the spe ified l mit an without the imp irment of it

pe formanc charact eris ics un e the con itions of normal use In case of othe st eri ization methods,

e.g ir adiation, the suita i ity of the mat erial shal be ev luat ed

W ith r g rd t o the spe ial r q ir ment for low r sid al mois ur , the drying proc s shal be inclu ed

in the ev luation of the mat erial’s pe formanc charact eris ics ( e also 7.2.5)

Closur s shal be made from the elast ome ic formulation originaly t est ed an a pro ed b the en

-use The closur man factur r shal ensur the conformanc of each delve y with the ty e sample an

the complanc with pr viously a r ed fu ctional an compen ium r q ir ment

NOTE It is cur ent practice to prefer elastomeric materials which use straight or halo enat ed butyl rub er

as a b se polymer, since this clas of materials e hibits an ex celent b r ier fu ction a ainst water vapour an

g s perme tion

7 Requir ements

The r q ir ment spe if ied in 7.2 t o 7.4 r pr sent minimum r q ir ment w hich r fe t o the con ition

of the elast ome ic closur s on r c ipt b the use

7.2 Physical r equir ements

7.2.1 Har dnes

The hardnes a r ed betwe n man factur r an use shal not dife from the nominal v lue b mor

than ± Shor A w hen t est ed in ac ordanc with ISO 7619-1 on spe ial t es spe imen Alt ernatively,

the hardnes can be t est ed on the closur s ac ording t o ISO 48 If t est ed ac ording t o ISO 48, the

mic ohardnes shal not dife b mor than ± IRHD from the ty e sample

7.2.2 F rag mentatio (c or ing )

When t est ed for fra mentation in ac ordanc with An ex A, not mor than 2 fra ment of diamet er

eq al t o or gr at er than 5 µm pe 1 pie cings shal be o se ved

7.2.3 Spike penetratio for c e

When t est ed for penetra i ty in ac ordanc with An ex B, the for e ne ded t o penetrat e the closur

shal not ex ce d 8 N, an the a e ag e v lue shal be les than 7 N No closur shal be pushed int o the

b t le d ring pie cing

7.2.4 Spike penetratio /se labiity

When t est ed in ac ordanc with Annex C, complet e penetration shal be achieved (no closur shal be

pushed int o the b t le) in al cases an no signs of leakag e shal a pear betwe n the spike an the

closur for a pe iod 4 h;nor shal the spikebe pul ed from the closur d ring thistime pe iod

7.2.5 Resistanc e to ag eing

The ma imum time betwe n the dat e of man factur an the pharmac utical use should be a r ed

up n betwe n the man factur r of the closur s an the use

The closur s shal maintain their pe formanc charact eris ics throughout the entir shelf l fe of the

medicinal prod ct w hich is t est ed as p rt of the s a i ity t es b the use

NOTE Ag ing depen s u on the st orag e an han ling con itions A guide t o st ora e of v lcanized rub er is

given in ISO 2 3

7.2.6 Residual moisture

Up n r q es , the rub e man factur r shal give a r commen ation at w hat time and t empe atur

( ime /t empe atur profile) the use can r d c r sid al mois ur from fr e e drying closur s t o en

up with a pr -def ined mois ur level, as ex osur t o dry heat ma damag e the elast ome ic mat erial

R esid al mois ur can be det ermined in ac ordanc with An ex E

7.3 Chemical r equir ements

The r q ir ment in ISO 8 7 -1 shal a ply

4

7.4 Biolog ical r equirements

The r q ir ment in ISO 8 7 -4 shal a ply

Packed closur s w hich me t the r q ir ment of this document can be la eled with the designation

given in Clause 5

A nnex A

(normative)

A 1 Principle

The purp se of the t es is t o measur the r lative coring t en encies of dife ent rub e closur s The

v lues o tained can be significantly afe t ed b many fact ors, such as prior proc s ing of the closur s,

ty e of c imping devic , seal ng for e, design of thespike, it sharpnes , the amou t of lubrication of the

spike an the keen es of the o e at or’ s sight

It is, the efor , ne es ary t o control these v ria les in orde t o o tain compara le r sult In this cont ext,

a subseq ent t es with closur s of k own fra mentation pro e ties can be inclu ed (r fe enc t es ),

i.e in a firs ru the closur s of w hich the fra mentation should be ev luat ed ar t est ed Immediat ely

aft erwards in a se on ru , closur s with k own fra mentation beha iour ar t est ed (r fe enc )

This subseq ent t es ing should be inclu ed from time t o time t o ensur a pro riat e han lng an

fu ctioning of the t es sy st em

If the fra mentation of the r fe enc samples is fou d t o be in the rang e of k own r sult the t es ing is

r co niz d as v ld

A 2 A pparatus

A 2.1 Ten infusion b t les, in ac or danc w ith ISO 8 3 -1 (2 infusion b ttles ar e r eq ir ed, should

refer enc tes ing be included)

A 2.2 Capping devic e an aluminium caps in ac or danc with ISO 8 3 -3, an which fit the infusion

b tles to be used in the test

A 2.3 Membrane fite set

A 2.4 One test spike, in ac or danc with A nnex D

The same t es spike should be used for al r fe enc an sample t es ing

A 2.5 Ste m autoclave ca a le to maintain (1 1 ± 2) °C

A 3 Proc edure

A 3.1 C le t a sample of 1 closur es fr om the type or lot to be tes ed Subje t the closure to s eam

s e i zation for 3 min at (1 1± 2)°C, folowed b drying for 1 h at 7 °C

NOTE If the closures in practice are subjected to a sterilization proces other than ste m sterilization, use

that st erilization proces to sterilize the closures an dis e ard B.3.1

A 3.2 Prep re 1 infusion b tles in ac ordanc with ISO 8 3 -1, of an y siz , fi ed with min 5 % of the

nominal v lume of wate Close these 1 infusion b tles with s er ilz d closures of the type to be tes ed

A 3.3 Fix the closures with aluminium ca s that me t he r eq ir ement of ISO 8 36-3

6