270 651 Congealing Temperature / Physical Tests

1 270 651 Congealing Temperature / Physical TestsUSP 35 When the test specimen has cooled to about 5 above itscontains and protects the article. This includes primary pack-expected Congealing point, adjust the bath to a tempera-aging components and secondary packaging components, ifture 7 to 8 below the expected Congealing point. Stir thethe latter is intended to provide additional continuously during the remainder of the test byContainer:A receptacle that holds an intermediate com-moving the loop up and down between the top and bot-pound, active pharmaceutical ingredient, excipient, or dos-tom of the specimen, at a regular rate of 20 complete cy-age form and is in direct contact with the per Component:Any single part of the package orCongelation frequently may be induced by rubbing thecontainer closure system including the container ( ,inner walls of the test tube with the thermometer, or byampules, prefilled syringes, vials, bottles); container linersintroducing a small fragment of the previously congealed( , tube cartridge liners); closures ( , screw caps, stop-substance.)

2 Pronounced supercooling may cause deviationpers); ferrules and overseals; closure liners; inner seals; ad-from the normal pattern of Temperature changes. If the lat-ministration ports; overwraps; administration accessories;ter occurs, repeat the test, introducing small particles of theand under test in solid form at 1 intervals as the tem-Primary Packaging Component:Packaging componentsperature approaches the expected Congealing are in direct contact or may become in direct contactRecord the reading of the test tube thermometer every 30with the Continue stirring only so long as the temperatureSecondary Packaging Component:Packaging compo-is gradually falling, stopping when the Temperature be-nents that are not and will not be in direct contact with thecomes constant or starts to rise slightly.

3 Continue recordingarticle but may provide additional Temperature in the test tube every 30 seconds for atleast 3 minutes after the Temperature again begins to fallTertiary Packaging:Packaging components that are not inafter remaining contact with the article but facilitate the handling andThe average of not less than four consecutive readingstransport in order to prevent damage from Physical han-that lie within a range of constitutes the congealingdling and storage conditions to which the article istemperature. These readings lie about a point of a maximum, in the Temperature -time curve, that occursMaterials of Construction:Refers to the materials ( ,after the Temperature becomes constant or starts to rise andglass, plastic, elastomers, metal) used to manufacture abefore it again begins to fall.

4 The average to the nearestpackaging is the Congealing (also referred to as multi-dose):A packag-ing system that permits withdrawal of successive portions ofan article for parenteral administration without changing thesafety, strength, quality, or purity of the remaining Multi-Dose Containers in Injections 1 , Determination ofVolume of Injection in :A packaging system that permits with-drawal of successive portions of an article without changingAdd the following:the safety, strength, quality, or purity of the 659 PACKAGING ANDS ingle-Unit:A packaging system that holds a quantity ofan article intended for administration as a single dose or aSTORAGE REQUIREMENTS single finished device intended for single (see also Injections 1 , Containers for Injections):A single-unit package for an article intended for parenteraladministration.

5 Examples of single-dose containers includeEvery monograph in the USP and NF shall have packagingprefilled syringes, cartridges, fusion-sealed containers, andand storage requirements. For the packaging portion of theclosure-sealed containers when so , the choice of containers is given in this drug product packaging requirements, definitions areUnit-Dose:A single-unit packaging system for an articleprovided to guide selection and adaptation. For active phar-intended for administration by other than the parenteralmaceutical ingredients (APIs), the choice would be tight,route as a single , or, where needed, a light-resistant :A packaging system that contains a specificFor excipients, given their typical presentation as large-vol-quantity of an article that is intended to be dispensed asume commodity items (containers ranging from drums tosuch without further modification except for the addition oftank cars), a well-closed container is an appropriate labeling.

6 Unit-of-Use packaging may not be re-Where no specific directions or limitations are provided inpackaged for article s labeling, articles shall be protected from mois-Pharmacy Bulk Package:A container of a sterile prepara-ture, freezing, and excessive heat, and where necessary,tion for parenteral use that contains many single doses. Thefrom light during shipping and distribution. Drug sub-contents are intended for use in a pharmacy admixture pro-stances are exempt from this and are restricted to the preparation of admixtures forinfusion or, through a sterile transfer device, for the filling ofempty sterile constitution, the closure shall be penetrated onlyone time with a suitable sterile transfer device or dispensingPackaging must not interact physically or chemically withset that allows measured dispensing of the contents.

7 Theofficial articles in any way that causes their safety, identity,Pharmacy Bulk Package is to be used only in a suitable workstrength, quality, or purity to fail to conform to require-area such as a laminar flow hood (or an equivalent clean airments. This chapter provides definitions of both packagingcompounding area).and as a Pharmacy Bulk Package is limited to Injec-tions, for Injection, or Injectable Emulsion as defined underInjections 1 , DEFINITIONSP harmacy Bulk Packages, although containing more thanone single dose, are exempt from the multiple-dose con-Packaging System (also referred to as a container closuretainer volume limit of 30 mL and the requirement that theysystem):The sum of packaging components that togethercontain a substance or suitable mixture of substances toOfficial from May 1, 2012 Copyright (c) 2011 The United States Pharmacopeial Convention.

8 All rights from by nEwp0rt1 on Fri Dec 02 21:02:12 EST 2011 USP 35 Physical Tests / 659 Packaging and Storage271prevent the growth of microorganisms. Where a container isface. Under ideal conditions of use, the volume erroroffered as a Pharmacy Bulk Package, the label shall (a) stateincurred in measuring liquids for individual dose administra-prominently Pharmacy Bulk Packages Not for direct infu-tion by means of such graduated components should besion, (b) contain or refer to information on proper tech-not greater than 10% of the indicated amount of the liquidniques to help assure safe use of the product, and (c) bear apreparation with which the graduated component will bestatement limiting the time frame in which the containerused. Few liquid preparations have the same surface andmay be used once it has been entered, provided it is heldflow characteristics.

9 Therefore, the volume delivered variesunder the labeled storage from one preparation to and ingredients added to polymers that areSmall-Volume Injections:A single-dose injection that is in-used in the fabrication of associated components must con-tended for intravenous use and is packaged in containersform to the requirements in the applicable sections of thelabeled as containing 100 mL or of Federal Regulations, Title 21, Indirect Food Injections:A single-dose injection that is in-Dosing Cups:A measuring device consisting of a smalltended for intravenous use and is packaged in containerscup that is packaged with oral liquid articles or that may belabeled as containing more than 100 and purchased :A packaging system designed or con-Dosing Spoon:A measuring device consisting of a bowlstructed to meet Consumer Product Safety Commissionand a handle that is packaged with oral liquid articles orstandards pertaining to opening by children (16 CFR that may be sold and purchased separately.)

10 The handle ).be a graduated :A packaging system designed or con-Medicine Dropper:A measuring device consisting of astructed to meet Consumer Product Safety Commissiontransparent or translucent barrel or tube that is generallystandards pertaining to opening by senior adults (16 CFR fitted with a collapsible bulb. It is packaged with oral ).articles or may be sold and purchased :A packaging system that may not be ac-Droppers typically vary in capacity; however, the deliverycessed without obvious destruction of the seal or some por-end should be a round opening having an external diametertion of the packaging about 3 mm. The barrel may be graduated. [NOTE FewTight:A packaging system that protects the articles frommedicinal liquids have the same surface and flow character-contamination by extraneous liquids, solids, or vapors; fromistics as water, and therefore the size of drops varies materi-loss of the article; and from efflorescence, deliquescence, orally from one preparation to another.]