381 ELASTOMERIC CLOSURES FOR INJECTIONS - USP-NF

1 Revision BulletinChemical Tests / 381 ELASTOMERIC CLOSURES for Injections1 Official May 1, 2009tempt to change a closure that does not meet com- 381 ELASTOMERIC CLOSURES pendial requirements to one that does INJECTIONST herefore, all Physicochemical Tests apply to thebase formula of such CLOSURES , as well as to thecoated or laminated closure. To obtain Physico-Change to read:chemical Tests results, the tests are to be per-formed on uncoated or non-laminated CLOSURES ofnINTRODUCTIONthe same ELASTOMERIC compound, as well as to thelaminated or coated closure. The FunctionalityElastomeric CLOSURES for containers used in theTests apply to and are to be performed using thetypes of preparations defined in the general testlaminated or coated ELASTOMERIC closure.

2 Biologi-chapter INJECTIONS 1 are made of materials ob-cal Tests apply to the lamination or coating mate-tained by vulcanization (cross-linking) polymeri-rial, as well as to the base formula. Biologicalzation, polyaddition, or polycondensation ofTests may be performed on the laminated or coatedmacromolecular organic substances (elastomers).closure, or they may be performed on the laminate/Closure formulations contain natural or syntheticcoating material and the uncoated or non-lami-elastomers and inorganic and organic additives tonated CLOSURES of the same ELASTOMERIC or control vulcanization, impart physical andIn the latter case, the results are to be reported sep-chemical properties or color, or stabilize the clo-arately.

3 The base formula used for physicochemi-sure or biological tests intended to support the com- This chapter applies to CLOSURES used for long-pendial compliance of a barrier-coated closureterm storage of preparations defined in the generalshould be similar to the corresponding coated clo-test chapter INJECTIONS 1 . Such CLOSURES are typi-sure in configuration and used as part of a vial, bottle, or pre-fill sy-For all ELASTOMERIC CLOSURES for Injection 381 ringe package system. (RB 1-May-2009)tests performed on any closure type, it is importantThis chapter applies to CLOSURES formulated withto document the closure being tested, including anatural or synthetic ELASTOMERIC substances.

4 Thisfull description of the elastomer, and any lubrica-chapter does not apply to CLOSURES made from sili-tion, coating, laminations, or treatments ap-cone elastomer; however, it does apply to closuresplied. (RB 1-May-2009)treated with silicone ( , Dimethicone, NF).This chapter states test limits for Type I andWhen performing the tests in this chapter, it is notType II ELASTOMERIC CLOSURES . Type I CLOSURES arerequired that CLOSURES be treated with silicone, al-those used for aqueous preparations. Type II clo-though there is no restriction prohibiting the use ofsures are typically intended for nonaqueous prepa-siliconized and are those which, having properties op- This chapter also applies to CLOSURES coated withtimized for special uses, may not meet allother lubricious materials ( , materials chemi-requirements listed for Type I CLOSURES because ofcally or mechanically bonded to the closure) thatphysical configuration, material of construction, orare not intended to, and in fact do not provide, aboth.

5 If a closure fails to meet one or more of thebarrier to the base elastomer. When performingType I test requirements, but still meets the Typethe tests, CLOSURES with lubricious non-barrier coat-II requirements for the test(s), the closure is as-ings are to be tested in their coated a final classification of Type following comments relate solely to closuresThis chapter is intended as an initial screen tolaminated or coated with materials intended to pro-identify ELASTOMERIC CLOSURES that might be appro-vide, or in fact function as, a barrier to the basepriate for use with injectable preparations on theelastomer ( , PTFE or lacquer coatings).

6 It isbasis of their biological compatibility, their aque-not permissible to use a barrier material in an at-Copyright 2008 The United States Pharmacopeial ConventionAll Rights 381 ELASTOMERIC CLOSURES for INJECTIONS / Chemical TestsRevision BulletinOfficial May 1, 2009ous extract physicochemical properties, and theirpossible closure presentations. However, it is thefunctionality. All ELASTOMERIC CLOSURES suitable forresponsibility of the closure supplier and the in-use with injectable preparations comply with eitherjectable product manufacturer (the end user) toType I or Type II test limits.

7 However, this speci-verify the closure ELASTOMERIC formulation and anyfication is not intended to serve as the sole evalua-coating or laminate materials used according totion criteria for the selection of such identification tests. Examples of some ofThe following closure evaluation requirementsthe analytical test methodologies that may be usedare beyond the scope of this chapter:include specific gravity, percentage of ash analy- The establishment of closure identificationsis, sulfur content determination, FTIR-ATR test,tests and specificationsthin-layer chromatography of an extract, UV ab- The verification of closure product physico-sorption spectrophotometry of an extract, or IR ab-chemical compatibilitysorption spectrophotometry of a pyrolysate.

8 The identification and safety determination ofChange to read:closure leachables found in the packagedproductTEST PROCEDURES The verification of packaged product closurefunctionality under actual storage and useElastomeric CLOSURES shall conform to biological,conditionsphysicochemical, and functionality requirementsThe manufacturer of the injectable product (theboth as they are shipped by the closure supplier toend user) must obtain from the closure supplier anthe injectable product manufacturer (the end user),assurance that the composition of the closure doesand in their final ready-to-use state by the endnot vary and that it is the same as that of the used during compatibility testing.

9 When theFor those ELASTOMERIC CLOSURES processed by thesupplier informs the end user of changes in thesupplier prior to distribution to the end user, thecomposition, compatibility testing must be re-supplier shall demonstrate compendial conform-peated, totally or partly, depending on the natureance of CLOSURES exposed to such processing and/orof the changes. CLOSURES must be properly stored,sterilization steps. Similarly, if ELASTOMERIC clo-cleaned for removal of environmental contami-sures received by the end user are subsequentlynants and endotoxins, and sterilized prior to use inprocessed or sterilized, the end user is responsiblepackaging injectable demonstrating the continued conformance ofclosures to compendial requirements subsequent toCHARACTERISTICS such processing and/or sterilization conditions( , in their ready-to-use state).

10 This is especiallyElastomeric CLOSURES are translucent or opaqueimportant if CLOSURES shall be exposed to processesand have no characteristic color, the latter depend-or conditions that may significantly impact the bi-ing on the additives used. They are homogeneousological, physicochemical, or functionality charac-and practically free from flash and adventitiousteristics of the closure ( , gamma irradiation).materials ( , fibers, foreign particles, and wasteFor CLOSURES that are normally lubricated withrubber.)silicone (RB 1-May-2009) prior to use, it is permissible toperform physicochemical testing on non-lubricatedIDENTIFICATION CLOSURES , in order to avoid potential method inter- CLOSURES are made of a wide variety of elasto-ference and/or difficulties in interpreting test re-meric materials and optional polymeric For CLOSURES supplied with other lubriciousFor this reason, it is beyond the scope of this chap-non-barrier coatings.