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Document Text Contents
Page 147

Sterilization by Ethylene O"ide 135

Secondary packaging malerials are usually made from corrugated card-
board; the grade and the direction of fluting can have serious effeclS on
sterility assurance and on sterility maintenance. Absorption of moisture in
secondary packaging may divert the 3vailabilily of elhylene oxide from ilS
target sites. lnsufficienl structural rigidity of secondary packaging may
lead 10 damage to primary packaging during or after sterilization with con-
sequent loss of sterililY.

(b) Seals. Primary packs must be sealed in a manner that wiU prevent
microbiological ingress. withstand the rigors of the sterilization cycle. and
still be easily openable by the customer at point of use. Within some packs
there may be more than one type of seal. some intended to be opened.
others intended to be permanenlly closed. Syringe packs usually direct the
user to the openable seal by a printed instruction. Often this is disregarded
in clinical practice, where users have found it easier to burst the packets
open. The characteristics of good microbiological seals and of equipment
that is capable of producing consislenl seal qualily can only be evalual,ed
empirically.

A. Validation of Ethylene Oxide Sterilization Processes

The overall scheme of validation of ethylene oxide sleriliztllion is no different
from validation of any other process. With new equipment it requires careful
consideration of design before specification (Design Qualification), confirmation
that received equipment conforms 10 its specification (Installation Qualif'ic.alion),
and continuation that received equipment can perform its specified functions
when assembled. plumbed in, and linked up to local services (Opemtional Quali-
fication).

Process qualification of ethylene oxide sterilization is both slerilizer
specific and product specific. II is particularly directed toward the measurable
parameters of the whole sleri,lization cycle. If external preconditioning is used.
validation should address the measurable parameters of aU combinations of
preconditioning chamber and sterilizer. Where one preconditioning chamber
may serve two or more sterilizers. or where one sterilizer may be served by two
or more preconditioning chambers. cycie-to-cycJe variability should be minimal.
The essence of successful ethylene oxide sterilization lies in Ihe establishment of
a complete process specification with very light lolerances. The integral effeclS
of me specified conditions on assurance of sterilily can only be validated by
reference to biological monitors.

J. Load SpecijicQlion: The product and its primary and secondary packaging
must be specified. The loading pallem of primary packs ;n'o shelf packs should
be specitied. Occlusi()[) of gas-permeable surfaces one against lhe other should
be avoided if slerility is to be assured.

a

Page 148

136 Chapter 6

The loading pattern of shelf packs on pallets mu.. also he specified. Pal-
terns thai allow good circulation of gas to all pans of the load. designed with free
space and "chimneys." are best from :1 sterilization standpoint but may connici
with commercial considerations. Sterilit,y assurance, cycle duriltion. sterilizer
capacity. and throughput rates are inextricably linked to validated loading pat-
lems for ethylene oxide sterilization. A further factor involved in det~rmining
loading pauerns is the rigors of ethylene oxide sterilization, which can affect the
strenglh of corrugated cardboard. Panial or lotal collapse of a stacked pallet
may involve some compromise of sterility. The use of "dividers" 10 give greater
slfUctural suppon to Slacked pallets may impede gas penetrmion. All of these
factors c::m only be addressed empirically; any significant change to a successful
loading pallem mu t be validated thoroughly.

If more lhan one product is to be sterilized at the same time in the same
sterilizer. process validat'ion should be completed for each combinatjon. 1lle lot
size in many manufacturing operations is "tailored" to sterilil..er capacity. and in
such instances it should not be difficult to avoid mixed load. This may be more
difficult for conlmet sterilization operations. Ethylene oxide sterilil..3tion can·
tracts should address the validation of mixed loads or prohibit them. Both roules
have cost implications.

The types of patlets should be specified-wood. aluminum, or some other
material. Ethylene oxide is nOl absorbed by metal pallets. but the: same cannot
be said for wood. Wood is commonly used but difflCuh 10 control. Hard woods
may absorb differently from soft woods. and some pallets may be water satu-
rated, while others may be quite dry. Some of the unexpected and unpredictable
sterilization failures seen in ethylene oxide sterilil.lllion may be associated with
use of wood pallets. Once validated. change from one IYpe of material to
another should nOl be permiued.

2. Equipment Specification: Any change in process equipment or any intro-
duction of new process equipment should be considered for validation. Biologi.
cal validation may not always be necessary if there is sufficient physical or
chemical evidence 10 demonstT:lte equivalence. All equip~nl should be identi·
fied: peciflC:l1ions, drawing. and instruction and maintenance manuals hould
be obtained and referenced in validation docu~nlation. No list of equipment
requiring validation can profess (0 be comprehensive. All functional equipment
should be subject to scheduled inspection and prevenlative mainlenance pro-
grams. All measuring devices must be calibrated and scheduled for regular
recalibration.

a. External Preconditioning Chambers. External preconditioning cham·
bers are nOI required to be as elaborat'e as sterilizers. This may in some cases
lead to the belief that they are of only minor significance 10 the assurance of
sterility. This is not correct. Due care and attention must be given 10 the design
and specification of external preconditioning chambers.

Page 294

about tha book . • •

DeuiJing the scientific priDciples uDderlying the ochievement ofsterlJity, this unique
ref= exlmioes both I broad spectrum of pradkaJ, commooly used sterilizatioD
procedures and the methods .vailable to CODfirm .lerility-......ing the .trengths
aad limitatioDl of each tecboology.

Deli",,'iDg OIITOIIt regulatory requin:meIl15 for sterlJity, AdWIIIJIg SI"UJIy IJJ
Mtdk:4J tutd Ph4rrruJautlalJ Protluch dis<:uIseo steriJizaliOD approach.. thai utilize
I8IUr8l<ld steam ... dry heal ... ethyl..... oxide ... gamma radialiaD ... sterile filtratioD
•.• aDd more.

ContaiDing more thaa 200 up-to-<!ale IilUalUre citatioDl, usefUl equatiODl, aDd
iDlightful tsbles aDd drawiDg., Ath/,lIillg SI'rlJIJ] /11 Mtdk:4J tutd P1uJnruu:IutiaIJ
ProtIUdJ i. aa ....Dtial resource for pbarmacis15, pbarmacologisl5, cIiDk:al micro-
biologisl5, virologisl5, quality ...u18..... aDd productioD maoagen in the pbarm_u.
tical iDdustry, sterilization scientists and eGli.DCCil, biochemists, and upper·level
undergraduate aDd graduate ItudeD15 iD these discipli.....

about tho author • • .

NIGEL A. HAu..s is Head of Biolop:aJ Quality at Olexo MaaufacturiDg Servioea,
COUDty Durham, United Kingdom. Dr. Hal1J is • FeUow of both the lnstilllte of
Biology (U.K.) aDd the l..tilllte of Quality Assurance (U.K.) as well as • member
of the Society for Applied Bacleriology (U.K.). He received the B.Tech. degree
(1968) in biological science from the Univ....ity of Bradford and the Ph.D. degree
(1972) in applied microbiology from the Univenity of Bath, both in the United
KiDgdom.

PrlNtd In the Uniltd StalCs ofAmerica ISBN: 0-8247-9014-6

morcel dekker. Inc.lnew york' basel' hong kong

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