Tiêu chuẩn iso 08362 5 2016

© ISO 2016 Injection containers and accessories — Part 5 Freeze drying closures for injection vials Récipients et accessoires pour produits injectables — Partie 5 Bouchons à lyophilisation pour flacon[.]

Injection c ontainers and

Part 5:

vials

Récipient et ac e ssoires p ur produits injecta le s —

Partie 5: B ouch ns à ly p ilisation p ur flaco s d’injection

T ir d edition

2 16-0 -1

Reference n mb r

COPYRIGHT PROTECTED DOCUMENT

© 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

the r eq eser

ISO c pyrig ht ofic

C de Blan on et 8 • C 4 1

CH-1 14 Vernier, Geneva, Sw itzerlan

Tel + 12 7 9 011

Fax 412 7 9 0 4

c pyrig ht@iso.or g

www.iso.or g

F reword i v

Introduction v

1 Sc ope 1

2 Nor mati ve r eferenc es 1

3 Terms and definitions 1

4 Shape and dimensions 2

5 Desig natio 4

6 Material 4

7 Per for manc e requir ements 4

7.1 General 4

7.2 Physical r eq ir ements 4

7.2.1 Hardnes 4

7.2.2 Penetrabi ity 4

7.2.3 Frag mentation 4

7.2.4 S lf-sealng and aq eous solution tig htnes 5

7.2.5 A queous solution tightnes 5

7.2.6 Resistanc to ag eing 5

7.2.7 Resid al moistur e 5

7.3 Chemical req irement 5

7.4 Biolog ical r eq irement 5

7.5 Particulate contamination r eq ir ements 5

8 Labeling 5

A nne x A (informative)Deter minatio of moistur e 6

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 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 ion, in us io a d injec tion, a d blo d

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

This third edition canc ls an r plac s the se on edition (ISO 8 6 -5:2 0 ), w hich has be n t ech icaly

r vised t o inclu e a new 7.5

ISO 8 6 consis s of the fol owing part , u de the g ene al title Injec tio c ontaine s a d ac c es s ories:

— Part 1: Injec tio v ials made o glas s tu in

— Part 2 : Clos ur s fr injec tio v ials

— Part 3 : Aluminium c aps fr injec tion vials

— Part 4: Injec tion vials made o mo lded glas s

— Part 5: Fr eze dry in clos ur s fr injec tio v ial s

— Part 6 : Ca s made o aluminium-plas tic s c ombin tio s fr injec tio v ials

— Part 7: Injec tio c aps made o aluminium-plas tic s c ombin tio s w ith ut o e la pin plas tic s p rt

Fr e e drying closur s ar put on the t op of a glas containe aft er fil ing, lea ing sufficient o enings

for the subl mation proc s an v cu m A t the end of the drying proc s , they ar 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 ific proc s r q ir ment ha e be n ad r s ed in this p rt of ISO 8 6 b spe ifying r lev nt

r q ir ment for fr e e drying closur s, inclu ing a t es method for det ermining 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, for ins anc , in ISO 1 3 8 or in the GMP Guidel nes as publshed b

the E ro ean C mmunity and the Unit ed Stat es of Ame ica

Injection c ontainers and ac c essories —

Part 5:

This p rt of ISO 83 2 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 inje tion vials, as desc ibed in ISO 8 6 -1 an ISO 8 6 -4, w hich is

used in conne 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 part of ISO 8 6 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 b strongly afected by the nature an performance of the primary packa ing

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 48, Ru be , v ulc ani zed or thermo las tic — Determin tion o h rdnes s (h rdnes s bet we n 10 IRHD

a d 10 IRHD)

ISO 3 0 – , Ru be — Tole a c es fr produc ts — Part 1: Dimens io al tole a c es

ISO 3 0 – 2, Ru be — Tole a c es fr produc ts — Part 2 : G eometric al tole a c es

ISO 76 19– , Ru be , v ulc ani zed or the mo las tic — Dete min tio o indentatio h rdnes s —

Part 1: Duromete meth d (S or h rdnes s)

ISO 88 1 1, Elas tome ic p rts fr p r nte als a d fr dev ic 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 al s a d fr devic es fr p armac eutic al us e — Part 4 : B iolo ic al

r q ir ments a d tes t meth ds

ISO 8 7 – :2 0 , Elas tome ic p rts fr p r nte al s a d fr dev ic es fr p armac eutic al us e — Part 5:

Fu c tio al r q ir ment a d tes tin

3 Terms and definitions

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

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 that ena lesthe drying of a froz n pharmac utical pr paration in a v cu m chambe

4 Shape and dimensions

4.1 The dimensions of fr ee e drying closur es shal be g iven in Ta le 1 whie Fig ur e 1 i ustrates the

g eneral desig n of a free e drying closure

Table 1 — Dimensio s of fre ze drying closures

Dimensions in milimetr es

Nominal

siz

d

1

± ,2

d

2

min

h

2

± ,2

h

3

min

h

4

min

a

The value of d

2

is ap led in that are which is defined b h

3

4.2 If not othe w ise spe ified, g eneral dimensional toler anc s shal be in ac or danc with ISO 33 2-1

and ISO 3 02-2

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

pier cing ar ea ( e Fig ure 1) The height of the sp c rs shal not exc ed 0,3 mm

NOTE The spacer in Figure 1 are shown for il ustrative p rposes only an do not form part of the

req irements of this part of ISO 8 62

The e ma be marks or in entations on the t op surfac

4.4 If the flang e of the closur e has a slghtly conical sha e, it shal be 0,3 mm max imum in relation to

the diamete in or de to faci tate pr od ction The toler anc s of the trimming edg e of the flang e shal

comply w ith the toleranc s spe ified in Ta le 1 for diamete d

1

4.5 The plug part shal pr ovide slts, chan els or othe a pr opriate means, in conju ction w ith

pr otru ing or p sitioning element at the oute diamete , which ena le inse tion on 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 closure into the ne k of the vial

4.7 The desig n of the flang e p rt in conjunction with the plug desig n shal pe mit b th the recons itution

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

means of a pier cing devic

Dimensions in milimetr es

A

A

1

1

2

∅0,7

∅d₁

∅d₂

a

Key

1 positioning element

2 spacer

a

T e in er diameter shal not b wider than the in er lumen

NOT T e total height of the fre ze drying closure, h

1 , can vary an is subject o mutual a re ment b tween

man facturer an user

Figure 1 — Example of a fre ze drying closure design

4.8 The fr ee e drying closur e shal be desig ned an man factur ed in such a wa y that the remo al of

the r econs ituted pr oduct with a hypode mic ne dle can be visualy controled in or de to minimiz the

amou t of r esid al pr od ct

4.9 When fr ee e drying closur es ar e put in plac for the ly phi zation pr oc s an the containe is

ex osed to transp rtation pr oc s es, they should ex hibit suficient shock an vibration r esistanc tha

u de reg ular pr oc s ing con itions, they do not fal of or be ome dis orted

A fr e e drying closur for inje tion vials can be designat ed b the words “ r e e drying closur ”

folowed b the n mbe of this p rt of ISO 8 6 folowed b the nominal siz

E AMP E A fre ze drying closure of nominal size 1 complying with the req irements laid down in this

part of ISO 8 62 is designated as folows:

Fr e e drying closur ISO 8 6 –5 — 1

The elast ome ic mat erial used shal me t the r q ir ment spe ified in Clause 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 if ied l mit an without impairment of it

pe formanc charact eris ics u de con itions of normal use In case othe st eri ization methods ar

used, 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 7.2.7)

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 ial r q ir ment

NOT It is cur ent practice to prefer elastomeric materials that use straight or halo enated butyl rub er

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

g s perme tion

7 P erformanc e requirements

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 hard es a r ed up n 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 76 19-1 on a spe ial t es spe imen

Alt ernatively, the hardnes can be t est ed on the closur s in ac ordanc with ISO 48 If t est ed in

ac ordanc with ISO 48, the mic ohard es shal not dife b mor than ± IRHD from the ty e sample

7.2.2 P enetrabiity

The r q ir ment of ISO 88 1-5:2 0 , 4.1 shal a ply

7.2.3 F rag mentatio

The r q ir ment of ISO 88 1-5:2 0 , 4.2 shal a ply

7.2.4 S lf-se lng and aq eo s solutio tightnes

The r q ir ment of ISO 88 1-5:2 0 , 4.3 shal a ply

7.2.5 Aqueo s solutio tig htnes

The r q ir ment of ISO 8 7 -5:2 0 , 4.4 shal a ply If the tes spe imen comples with 7.2.4, the

r q ir ment of this subclause have also be n met and sep rate tes ing ac ording to this subclause

is not ne ded

7.2.6 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-lfe of the

medicinal prod ct, w hich ist 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 ora e an han ling con itions Guidelines for st ora e of v lcanized rub er

are given in ISO 2 3

7.2.7 Residual moistur e

Up n r q es , the rub e man factur r shal give a r commen ation as to the time an t empe atur

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

en up with a pr -defined 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 A

7.3 Chemical requirements

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

7.4 Biolog ical r equirements

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

7.5 P ar ticulate c ontamination r equirements

Closur s should be man factur d such that p rticulat e contamination is minimiz d The spe if ication

an method should be a r ed upon b the man factur r of the closur an the use It is r commen ed

that closur s be t est ed in ac ordanc with ISO 8 7 -3

8 Label ing

Packed closur s that me t he r q ir ment of this p rt of ISO 8 6 can be la eled with the designation

given in Clause 5

A nnex A

A 1 Principle

The elast ome ic mat erial t o be t est ed is heat ed in a nitrog en s r am in a drying pist ol The ev porat ed

wat er is p s ed int o a titration c l w he e the amou t of wat er is det ermined coulometricaly

A 2 A pparatus

A 2.1 Kar l-Fis her c oulometric devic e

A 2.2 Dr ying pistol, with a heating sys em to adjus temperatur es betwe n 1 0 °C an 1 0 °C

A 2.3 Nitr og en suppl y, with a mole ular sieve cartridg e

A 2.4 Stainles ste l weighing b at

A 2.5 A nal ytical balanc e, ac urate to 0,1 mg

A 3 Reag ents

The r ag ent ar as spe ified in the measur ment syst em man al

A 3.1 So ium tartrate, or eq iv lent ,w ith k own wate content ( tan ar d)

A 3.2 C ntr ol solutio , 1 % (b mas )wate in or ganic solvent

A 4 Proc edure

A 4.1 A pparatus pr eparation

S t up the a paratus as in icat ed in the ins ruction man al Adjus the drying pist ol t o (140 ± 2) °C an

flush it with nitrog en at a suita le rat e

Che k the a paratus in p rticular for the folowing:

— low blan drift ;

— cor e t det ermination of wat er cont ent of control solution;

— cons ant slo e of cumulative gra h wat er/time w hen ru ning a blank ;

— cor e t det ermination of wat er in sodium tartrat e

Dai y che king is r commen ed