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`| rae uniren STATES PHARMACOPEIA
`USP 27
`
`NF 22_| THE NATIONAL FORMULARY
`
`| By authority of the United States Pharmacopeial ©"
`|.Convention, inc., meeting. at Washington,D.C...
`April 12-16, 2000. PreparedbythéCouncil ofExperts
`- and.published,bythe BoardofTrustees
`Officialfrom January 1, 2004
`
`The designation on the cover of thispublication, “USP.NE.
`2004,”is for case of identification only. The publication re
`contains two separate compendia: The Pharmacopeia of the =...
`United States Twenty-seventh Revision, and theNational,
`Formulary, Twenty-second Edition: “°° 0 0°
`
`UNITED STATES PHARMACOPEIAL CONVENTION,INC.
`12601 Twinbrook Parkway, Rockville, MD 20852
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`PROPERTY OF
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`MYLAN EXHIBIT 1016
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`—
`ConcerningUS-Patentor Trademark Rights °;
`The inclusion inthe PharmacopeiaorintheNational Tormulary ofa-monograph on-any dngintrespectto
`which patent of trademarkrights inayexist.shall not be-deemed, andis not intended as,.a grant of, or
`authority to exercisé, any-right or privilege protected by suchpatentor tradematk.All such, rights and.
`privileges arevested in thepatent ortrademark owner,‘andno otherpérsoh mayexercisethe samewithout
`express permission, authority, ot license secured from sugh patent or trademark owner,
`77
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`
`:"*
`
`Concerning Use of USP or NF Text
` ‘Uge ofthe USP-NF is subjectto the terms and conditions ofthe USP--NE License Agreement. Attention
`is-called tothe fact that USPandNF textis fully copyrighted. Authors and others wishing to use portions
`of the fext should tequest permission to do so from the Secretary of the USPC Board of Trustees.
`Copyright © 2003 TheUnited StatesPharmgcopeial Convention,Inc.
`.
`12601 Twinbrodk Patkway; Rockville,MD'20852"" 8 Bo
`All rights reserved.
`7 0 80 Se Ie ne SO
`ISSN 0195-7996bt ee ,
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`ISBN 1-889788-19-8
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`Printed in Canada by Webcom Limited,Toronto,Ontario... |
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`

`General Notices
`
`
`
`edGeneralNoticesand
`
`
`ae _ Requirements
`Applying to) Staridards, Tests,
` es“Nseate andOther Specifications
`. ofthe United StatesPharmacopeia
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`5
`................
`Ingredients and Processes
`3.
`eee ete eee e teens
`A 6
`Meohol Poppers teens eee ees To trsnsss
`3
`“Official” and “Official Articles”
`........
`8
`DehydratedAteohol Set ees 6
`3
`Products Not Marketed in the United States
`.,....
`Nutritional and Other Dietary Supplements ....... eeekneeCUT TT Tat tat tte nenes3
`
`
`Denatured Alcohol 2... eee eae
`6
`
`Atomic Weights and Chemical Formulas
`3
`Nuttitional and Dietary Supplements ...........
`6
`.
`‘
`*
`Added Substances .......00.0. 0.000000
`6
`Additional Ingredients 2.0.0.0. cae 6
`Abbreviations
`..........,.,........-....
`4
`Inert Headspace Gases oo... ee eee 6
`Abbreviated Statements in Monographs
`.........
`4
`Colors oo cece eee
`6
`Ointments and Suppositories
`............04.,
`6
`Significant Figures and Tolerances .........
`4
`Equivalence Statements in Tittimetric Procedtites
`4
`‘Tests and ASSAYS 2.00. ee cece een.
`6
`Tolerances 0... cece eevee
`4
`Apparatus 2.6.0... ec cee eee a
`6
`Interpretation of Requivementg ..............,
`4
`Steam Bath oo... ect ene
`6
`Water Bath oe ee een eae
`6
`General Chapters 000.0000, 000.0 ..0.000.
`4
`Foreign Substances and Impurities ...........
`6
`Other Impurities 2... eee ee
`7
`Pharmacopeial Forum ...................
`5
`Procedures... 0.00.0. e ev acv as
`7
`*harmacopeial Previews
`........-.0000.00..
`5
`Blank Determination «66... 6s eee :
`In-Process Revision
`...............00.,...
`5 Di Pet ee ee ee ee
`8
`Stimuli to the Revision Process
`.....,........
`5
`DeviWOON Sprite tee eae moet eee es
`omenclature 6. ee eee eee nes
`5
`Drying to Constant Weight
`............4..4.
`8
`Interim Revision Announcement
`......,......
`5
`yarationti
`, cf stsreCO ee eee ee
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`Official Reference Standards
`................
`5
`Sieve
`mehdedia= eek
`5
`Ignition to Constant Weight ..............0.,
`8
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`upplement.00... oe cece cece cee. Indicators we ee,rrSs &
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`Logarithms 2... eee eens
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`R.
`Microbial Strains 6. eee 8
`Cagent Stafidards
`................000005
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`Negligible 2.0... ccc ee cee na as
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`Pressure Measutements 6.0... 00.00.00 .0200 0,
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`rence Reagents
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`Solutions oo... eee tne es
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`Usp Reference Standards
`................
`5
`Temperatures 0. eee eee ae
`8
`8
`Specific Gravity 6 cc eee
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`Time Limit 0... cee eect nee evnas
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`VACUUM eee teas
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`Sof Potency
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`Water ect cece eect aveeee.
`8
`Water and Loss on Drying ook eee 8
`‘Test Results, Statistics, and Standards ....... .
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`8
`Description 2.0... ee cee eveee
`9
`Solubility .....0...0......... beeen een
`9
`Interchangeable Methods ............rare
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`USP 27
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`Storage under Nonspecific Conditions ..... pee
`peer tees
`Labeling
`....-..---06
`AmountofIngredient per,Dosage,Unit.
`Zeros...
`“Use of Leading and Terminal
`Labeling of Salts of Drugs.
`» Labeling Vitamin-Containing Products
`.....
`.., “Labeling Parenteral and Jopical Preparations
`’ Labeling Blectrolytes «6... eee eee ees .
`Labeling Alcohol... eeeDee ee eee
`Special Capsules and Tablets “....-. ate eee
`ee eee
`Expiration Date and Beyond-Use Date
`Pharmaceutical Compounding
`Vegetable and Animal Substances
`Foreign Matter ©... 0-000 e eee tess
`Preservation . 0.00 0c ee es
`
`eooocoa
`
`........--0-00 0020
`_ Weights and Measures
`Concentrations Deeb epee n been nnn eeeneees
`
`-Percentage Measurements
`Percent Weight in Weight
`‘Percent Weight in Volume «1... eee re eee
`‘Percent Volume in Volume
`
`and Dispensing .....---.....-:
`Prescribing
`Preservation,Packaging, Storage, and
`Labeling .
`Containers ..6 0. eee eee ate geneet
`Tamper-Resistant Packaging’ Laadhe case geile
`Light-Resistant Cositainer 1... ee eee bees
`Well-Closed Container
`TightContainer,
`6.6 eee es
`Hetietic Container
`
`Single-Unit Container”
`
`........ tees beeen
`Single-Dose Container
`Unit-Dose Container 6.6. ee es os
`Unit-of-Use Container 2... cee tee
`-Multiple-Unit Container
`....... been ateenean
`Multiple-Dose Container .......-: rrr
`Storage Temperatureand Humatality wens hae,
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`Heat oi. ee eee Laces
`Excessive
`Protection from Freezing 6. eve ee eee ees
`Dry Place eea
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`General Notices
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`

`

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`
`
`The full title of this publication, including its supplentents, is The
`Pharmacopeia ofthe United. States of America, Twenty-Seventh
`Revision.,This title may, beabbreviated:to UnitedStates Pharmago-
`peia, ‘Twenty-Seventh. Revision,or to. GSP,.27, :The: United.States
`Pharmacopeia,:/‘Twenty-Seventh, Revision,. supersedes, -all earlier
`eyisions. Where-theterm-USP is used,-withoutfurther qualification,
`during the periodin which this Pharmacopelais official;itrefers.only
`to USP. 27-and-any supplement(s)thereta.;The sametitles; with-no
`oe ts
`further distinction, apply. equally. to print or electronic presentation: of
`these contents.
`calbn
`Changetoréad:
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`TREE
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`General Notices
`
`3
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`aA
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`« “ATOMIC WEIGHTSAND CHEMICAL'FORMULAS"=! * |
`.
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`eG Pesce che ha teen tl,
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`The atomic weights used'in computing’ molecular weights:and‘the
`factors in the: assays’ and elsewhere. are:those recommendedin'1997
`by: ‘the TUPAGCominission .on Atomic’ Weights ‘and’ Tsotopi¢
`Abundances:'Chemical:formulas,otherthan those'in the Definitions,
`tests, and assays, ate given for purposes. ofinformation and
`calculation. The format within.a given monographis such.that.after
`‘the. official title, the primarily informational. portions of the text
`appearfirst, followed. by the text comprising requirements,the latter
`
`“.. The: General Notices and Requirements. (hereinafter referred to-as
`the General Notices) and general requirements appearing in General
`‘Chapters. provide in. summary form. the -basic. guidelines for the
`jfiterpretation and application ofthe standards,tests, assays, and-other
`specifications of the United States Pharinacopeiaand:eliminate the
`si¢ed.:to repeat throughout .the book: those -requireménts. that.dre
`pertinent in numerousinstances. Whereno specific language: is ‘given
`fo:the contrary, -the requirements.vinder:the “General Nofices and
`‘General Chapters apply.
`-
`000000 2) te tte tanita 8
`i. Where-exceptions-to the.General Notices or General Chapters are
`made, the wordingin the individual monograph takes precedence-and
`specifically: indicates the directions or the intent. To emphasize that
`such exceptions do exist, theGeneral Notices or General Chapters in
`soineplaces employ where indicated a qualifying expression such as
`‘unless. otherwise specified.” In .the individual -monographs,it =is
`anderstood.that thespecific 4vording of standards,tests,assays, and
`other specifications 1s binding wherever deviations from the General
`‘Notices.or. General..Chapters:-éxist whether or nota.
`statement of
`: meh
`exception is-made.: lo i LK
`
`
` ee8 BITE
`
`:
`
`rticles listed herein are official and the standardsset forth in:the
`monographs apply tc them enly when the articles are intended or
`labeled for use as drugs, as nutritional or dietary supplements, or as
`medital devices and ‘when bought,- sold, or dispensed for these
`purposes or when labeled as conforming to this Pharmacopcia.
`-.An article is deemed to be-recognized in,this Phatmacopeia when a
`monographfor the articlé is published in it, includingits supplements,
`addenda,orotherinfetim revisions, and an official date is generally or
`specifically assigned to it.
`Cee,
`__ :Thefollowing terminology is used-for distinguishing the articles
`for which monographs are provided:an officialsubstance is an active
`drugentity, a recognized nutrient,a dietary-supplementingredient, or
`a. pharmaceutic ingredient (see also. NF 22) or a component of a
`finished: device for :whichthe, monogtaphtitle.includes no indication
`ofthe nature-of the finishedform; an official_preparationisadrug
`product, a nutritional supplement, dietarysupplement, or afinished
`device, It is thefinished or partially finished (e.g.,:as.in the caseof a
`sterile solid, to: be,,constituted into a solution for administration)
`preparation or product of one or more officialsubstances formulated
`for use on-or for the patient. or consumer; an arficle.is.an item for
`which a monographis provided,whether'an official substanceot an
`‘official prepatation. geeee
`‘Designating Conformance, with Official Standards—When the
`letters “USP” or “NE” or “USP-NE”are utilized on the label ofan
`article to indicate compliancewithcompendial standards, the. letters
`shallappear,inconjunction withthe officialtitle ofthearticle orwhen
`appropriate, with theingredientscontained therein. The letters are not
`to be enclosedin any symbol, such as.a circle, square, etc., and.must
`appear in blockcapitalletters... ... |
`ray,
`If a dietary supplement putports to.be or is represented as.an
`official product andsuchclainyis determined by USP not to be made
`in good faith, it is the.policyofthe. USPto, seck appropriate legal
`redress,gusper ope so Ee
`24
`Products Not Marketed ti the United States—Inierest in the USP
`outside the: United States: has always: existed. From time. to-timné,
`monographs may. be.adopted forarticles‘notlegally marketed inthe
`United States as a service to-mithorities:inother countries where-USP
`standards are recognized and-applied.Appearance of any such
`monographdoes-not grant any marketing rights whatsoever,andthe
`status ofthe article in the United States omist be checked with the U.S.
`reference hereto, is synonymous with {PI
`Food and Drug Administration in the event of any. question.
`.
`“USP”, and with “compendial”.
`...
`-:,
`-
`Nutritional and-Other Dietary’Supplements—The designation of
`“~The désigtatior “USP” in, conjunction with the offici
`
`an official preparation containing.oné ormore recognized nutrients or
`4 monograph is
`elsewhere.on the label of an atticle “indicates that
`dietary supplemént- ingrédients ‘as’ “USP” or
`the use of -the
`ipicludedinthe USP andthatthearticlegyspazpurportsto-cortiply with
`designation “USP”iticonjutiction,with thetifleof such nutritional
`
`
`gall “applicablesdse27, USP stattdatds. “The4dcsp27 désignation
`or dietary supplement preparation may be made only if the
`“USP”ausp7 on the label
`“maynot and,ys, does not constitute a
`preparation meets “allarsps7 the applicable requirements contajned
`repredentation, endorsément, or incorporation by the manufacturer’s
`
`in thé individual‘mOrdgraph‘and ‘Beneral, chaptérs."“Any language
`labeling of the informational material contaiiéd’.in “the USP
`modifyingor: limiting this teptesentation’shall te accompaniedbya
`mondgraph, nor does itconstituté_ assurance by USP that the article
`‘staitefentindicating that thearticle is“*notUSP”,and indicating how
`is known to complywith USP standards. An article may only purport
`the atticle ‘differs ‘fromthestandards of strength, quality, or purity as
`to comply with a USP standard “or other requirements)jspi/When the
`détertined by thé application ofthe tests and ‘assays setforthin: the
`articleis recognized'in the USP. The standards apply equally to
`compendia.4sez, Any additional'ingredientih sucharticlethatisnot
`articles bearing theofficialtitles or names derived by transposition of
`recognized in the Pharmacopeia and for which nutritional value is
`the definitive wordsdfofficial titles or transposition in the order ofthe
`claimed shall not be represented nor imply that such ingredient is of
`namés of two ormore activeirigredients in official titles, whether or
`USP qualityofrecignized by USP.If a preparation doesnot comply
`not the: added designation“USP” is used. Names consideredto. be
`with
`“allausez7 applicable requirements but contains nutrients or
`synonyms ofthe official titles may not be used for official titles.
`‘diétai’y;supplement ingredientsthat are-recognized in the “USP, the
`~ Although both compendia, the United States Pharmacopeia and
`‘atticle may not designate thé ‘individualnutrients of-ingrédients’ as
`the National Formulary, currently are published under one cover,
`ésinplying with USP statidards’ or ‘beitig ‘of: USP! quality ‘without
`they remain separate compendia.Thedesignation USP-NFor similar
`désighating’ onthe label that the articléitself does not Complywith
`combination may be usedonthelabel ofdn article, provided the iabel
`USP standards. Tb SOREa UE
`also bears a statement such as “Meets NF standards aspublished by
`
`theUSP,”indicating the particular comperidiuts, to' Whichthe aiticle
`putports to apply.” ee
`_,Whereanarticle differs fromthe standards ofstiéngth,quality,and
`purity, as determiried by.the applicationof the assays,and tests set
`forth for it in the Phiatmacopeia,its difference shallbeplainlystated
`onits label, Whete an atlicle’failS to comply:in ‘identity with-the
`identity prescribedii the USP, or containsan added, substance that
`dnterféres‘with the ‘prescribed’assay8 afidtests, such article ‘shail"be
`
`
`desipnated bya'namethat is clearlydistinguishingand differentiating
`
`-foin‘anynamerécognizedin, thePhaimacopeia,
`° es
`
`
`
`

`

`é
`except where it is indicated otherwise. The use of the molecular
`section of the monograph being introduced by a boldface double-
`formula for the active ingredient(s) named in defining the required
`arrow symbol >». (Graphic formulas and chemical nomenclature
`strength of a Phartnacopeial article is intended to designate the
`provided as information in the individual monographis ate discussed
`chemical entity or entities,-as given in the complete chemical name of
`inthe Preface)? 05 00ee
`the article, having absolute (100 percent) purity,
`‘> A dosage form shall be formulated with the intent to provide 100
`
`percent of the quantity of each ingredient declared on the label.The
`_ ABBREVIATIONS°,
`tolerances and limits stated in the definitions in themonographs for
`Pharmacopeial articles.allow. for. analytical error, for unavoidable
`The term RS iefers to'd USP Reference Standard’as stated under
`variations in manufacturing and compounding, and for deterioration
`Reference Standards in these Gerieral’ Notices (ses also USP
`io an extent considered-acceptable under practical conditions. Where
`Reference Standards ‘(ily for a -comiprehensive ‘discussion of
`the minimum amountof'a substance present in a nutritional or dietary
`refererice miaterials.
`PE ly EE
`supplement is required to be higher than the lower tolerance limit
`The teims CS and‘ TS refer to Colorimetric’Solition and Test
`allowed’ for in “the” monograph .because of ‘applicable ‘legal
`Solution, respectively (sée- undet- Reagents, Indicators, and “Solu-
`requirements, - then the upper tolerance limit contained in-the
`tions). The term VS sefers to Volumetric Solution’as stated under
`monogtaph shall be increased by a corresponding amount...
`7
`Solutionsin the General Notices,"
`i tree reek Ce OSD
`The specified tolerances are based upon such atéributes.of quality
`‘The term PF ‘refers to ‘Pharmdcopeial Forum, the joutnal of
`‘as might beexpected to characterize anarticle produced from suitable
`standards ‘development atid official compendia revision (see Phar-
`raw materials under-recognized principles of good manufacturing
`macopeial Forum-in these General Notices).° De
`practice. ~ re wot es
`: Abbreviations’ for the nanies' of thany institutions, orgaiizations,
`The existence of- compendial’limits or ‘tolerances does not
`and publi¢ationsare vised for convenience ‘throughout USP and NF,
`constitute a basis for a claim that an official substancethat more
`An alphabetized tabulationfollows. ™-
`me
`an
`nearly approaches 100 percent purity “exceeds” the Pharmacopeial
`Institution, Organization, or Publication|
`quality. Similarly, the fact that an article has been prepared to closer
`. Abbreviation «
`tolerances that those specified in the monograph does not constitute a
`AAMT |
`” Association for the Advancement of Medical
`basis for a claim that
`the article “exceeds” the Pharmacopeial
`po.
`27
`oe) 8 8 Tnstromentation
`requirements: 6° 0.05 oe
`. an
`“ACS °--
`> °'» -Amigiicaii Chemical Society
`» ‘Interpretation ofRequirements—Analytical results observedin the
`ANSTO" 0 “AmericanNationalStandards Institute
`laboratory: (or’ calculated. ‘from experimental measutements} are
`AOAC.
`- AOACInternational (formerly Associationof
`‘compared with stated limits. to“ détermine whether there is
`wd _ Official Analytical Cheimists)
`coiiformance with compendial assay or
`test requirements, ‘The
`-ASTM' «|
`Amneériéan‘Sociétyfor Testingand, Materials
`observed‘or‘calculated-values. usuallywill contain more significant
`ATCC ©
`American Type Culture Collection
`-
`fignires thati there’are in the statéd limit, and an observed or ‘caléulited
`CAS CC
`: Chemical Abstracts Service ¢
`:
`result is to be rounded‘offto the umberofplaces that isin agreement
`CFR - *?
`-U:8, Codeof Federal Regulations
`withthelimitexpressionby thefollowing procedure. [NoTk—Limits,
`4
`EP os
`°"'* Europeari Pharmacopoeia 7
`which are fixed numbers, are not rounded off} ae
`= -°
`EPA
`U.S. Environmental Protection Agency
`When rounding off is required, consider only one digit in the
`.:
`FCC.
`:
`.
`iv). Food Cherhicals Codex. °F
`decimalplaceto the right of the last place in the limit expression, If
`:
`“USFood and Drug Administration
`DA + «vt
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`this digit is smaller than5,it is eliminated and the preceding digit is
`<°) .) +Health:Industry Manufacturers Association-
`‘HIMA:
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`unchanged. If this digit is.greater than 5, it is eliminated and the
`4
`. ‘International Organization for
`TSQ0ure
`hata
`preceding digit:is increased by one. If this digitequals 5, the 5 is
`noi
`_ Standardization .--
`cv e0 "): beet:
`2
`eliminated and the preceding digit is increased by one.
`TUPAC...
`:, International Union ofPure and Applied:
`Tllustration of Routiding Numerical’ Values for Comparison *
`
`-_with Requirements ©
`.
`““Compehdial ““ “Unrotinded = Rounded
`
`:
`Requirement "Vaile Result _
`Confornis |
`"Assaylimit >98.0% + 97.96%;.
`..- 98,0%
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`Assay limit <101.5%,
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`0.015%
`0.02%
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`OO 2 9.027%... 003%. No...
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`Limit test,<3 ppm:
`, -0.00035% © -0.0004% —..No:.
`a ee 9,60025% —. 0,0003% ©.Yes.
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`6.00028%
`0.0003% -__. Yes
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`General Notices
`
`USP 27
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`©
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`Japanese Pharmacopoeia:
`JP
`NationalInstitute of Standards and
`NIST .
`ine 2. Technology... 0... hohe.
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`-USAN .. «. x United States Adopted Names...
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`
`_. World Health Organization -
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`WHQ 5...
`
`.. Abbreviated Statements in.Monographs—Incomplete sentences are
`employed in various ‘portionsof the monographs,for directness, and
`brevity. Where thelimit tests are soabbreviated,itis to,be understood
`thatthe chapter numbers (shown Jn angle:brackets) designate the
`owed, andthat the values. specified
`
`respective procedures to be followe
`
`afterthe colon.atethe required limits.
`
`
`SIGNIFICANTFIGURES AND TOLERANCES. - -
`. Where limits ere expressed numerically berein, the upper and
`lower limits-of a range include.the two values themselves and. all
`intermediate. values, but no values outside the limits. The limits
`expressed in monograph definitions and. tests, regardless. of whether
`the values are expressed as percentages or as absolute numbers, are
`-considered significant to the last digit shown,
`uo
`Equivalence Statements in Titrimetric Procedures—The directions
`for titrimetric procedures.conclude withastatementofthe weight of
`the analyte thatis equivalent to each mL ofthe standardizedtitrant, In
`such at, equivalence statement,.it is to be understoodthat:the number
`of significant figures-in the concentration ofthe titrant corresponds to
`the number of significant figures in the weight ofthe analyte. Blank
`corrections aré to be madeforalltitrimetric assays where appropriate
`(see Titrimetry (541).
`ta
`:
`a oe
`Tolerances—The limits specified in the’ monographs “for
`Pharmacopeial articles are- established with avview:to the use of
`thesé articles as drugs, nutritional or dietary supplements, ordevices,
`
`a GENERAL. CHAPTERS
`_ Each general chapter is assigited‘a numberthat appears in brackets
`adjacentto the chapternanie (¢.g., (621) Chromtatography). Genéral
`“chaptersthatinclude general requirements for tests and assays are
`numberedfrorix (1) to (999), chapters that are informationalare
`numbered from (1600} "to(1999), and’ chapters pertaining to
`muitritional supplements are numbered above'{2000),.,
`“The ‘use of the géneral chapter numbers’ is éncouraged for te
`identificationand rapid access {9 géneral tests‘and information,It is
`especially helpful where monograph section headings and chapter
`
`hameés are not the same(e.g., Ultraviolet Absorption (197U) inh a
`monograph refers to method
`(197U) under general
`tests chaptet
`{197} Spectrophotometric Identification Tests, Specific rotation
`
`

`

`
`
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`
`
`‘USP 27
`
`GeneralNotices
`
`5
`
`-(7818) in a monograph refers to method (781S} under generaltests
`chapter (781) Optical Rotation; and Calcium (191) in a monograph
`refers ‘to the tests for Calcium undergeneral tests:*chapter191)
`Mentification Tests-~General).
`-
`“4
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`PHARMACOPEIAL FORUM.
`
`‘Pharmacopeial Forum (PF). 1s. the.“USP journal of ‘standards
`development and official compendia revision. Pharmacopeial Forum
`is. the, working document.of.the USP Committee of Revision..It is
`intended.to-provide public’portions of. commiunications- within’ the
`General Committee of Revision ‘and public.notice of proposed new
`‘andrevised standardsof:the USP and NFand to afford opportunity
`‘for. comment thereon. The organization of PF includes, but is not
`Himitedto, the followingsections. Subsections occurwhere oeeded
`for Drugs and Phamiaceutic Ingredients (Excipients) and. for
`Nutritional Stipplements.
`- Pharmacopeial Previews——Possible revisions or new monographs
`or chapters that are considered to be in a-preliminary stage of
`development.
`.
`.
`A(dn-Process‘Revision—New or revisedmonographs tor chaptersthat
`are proposed for adoption:as officialUSP or NFstandards.
`Stimuli to the Revision:ProcessReports, :statements, articles;or
`cammentaies relating to compendialiissués,
`°"Nomenclature—Articles: and ‘announcements relevant to
`
`compendial nomenclature issues and listings of suggested and new
`United ‘States Adopted Nariies (USAN) and International Noppro-
`prietary Names (INN).
`“.
`Interim Revision Aniiounicemént (iifpresent)—Official revisions
`‘aad’their effective’ dates, announcement of the availability offew
`USPReference Standards, and announcement of assays or teststhat
`are heldin abeyance pending availability ofrequired USP Reference
`‘Standards.
`Official Reference StandardsCatalog of current lots of, USP
`‘Reference Standards, with ordering. information. and names,and
`addresses ofworldwide suppliers.
`wo
`fosSUPPLEMENT a
`"Supplementsto officialtext.are publishedperiodicallyandinclude
`text previously published inPF, whichis ready to be made official,
`1
`
`| REAGENT|STANDARDS
`is The proper conduct ofthe:Pharmacopeiat-tests and assays and the
`reliability of the results: depend, in.part, upon the ‘quality .of the
`reagents used in-the performanceofthe procedures. Unless.otherwise
`specified, reagents are to be used that conform to the specifications set
`forth in the current edition of Reagent. Chemicals:published. by. the
`American, Chemical Society. Where such ACS reagent specifications
`aré not available ‘or wherefor various reasons the requiredpurity
`differs, compendial specifications’ for reagentsof acceptable quality
`‘ate’ provided (seeReagents, Indicators, arid Solutions). Listing of
`these réagerits, including the indicators and solutions’employed a5
`Teagents,
`in no way implies that
`they have therapeuticutility;
`firthermore, any ‘reference to USP-or'NF-in their’ labeling:shall
`include also theterm “reagent” or ‘_reagent grade.” oe
`oor,
`
`REFERENCE,REAGENTS©
`“* Some’‘compendial | tests or assays fequite‘the:usé of spétific
`Tédgents, These’ ate supplied by USP when they might’ not, be
`‘generally commercially available.orbecause theyare necessary for
`the!‘testing.and éare available only totheoriginator ofthe testsorassay.
`Wye
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`
`USPREFERENCE STANDARDS
`USPReference Standards are‘guthentic, specimensthat havebeen
`approved by the USP Reference StandardsCommittee.as suitable for
`use as comparison standards.in USP or NF tests andassays. (See USP
`Reference Standards (1 1).} Currently official. fots ofUSP Reference
`Standards are published in Pharmacopeial }Forum..
`. Where a-USPReferenceStandardis referred to ina monogtaph or
`chapter, the words. “Reference Standard” are abbreviated to: “RS”
`(see USP ReferenceStandards. (11): |.
`« Where a iest or anassay calls for.the.use ofta compendial.article
`rather.than for a USP Reference:Standard as.a material standard of
`reference, a substance meeting all of the_compeiidial monograph
`requirementsfor thatarticle is to be used,
`,
`The requirerhents forany ‘new USP o¢ NEF staridards; tests, or
`assays for which a new USP Reference Standardjis specified are not
`in éffect untilthe specified USP Reference Standardis available. The
`availability ofnew,USPReference Standardsandthe official dates of
`the USP of Ni standards, tests, or assaysrequiring their use are
`announcedvia Suppleinenitsor Interin RevisionAnnouncements.
`“UNITS OFPOTENCY.
`For substances that’ cannot be conipistely chaiacterized. by
`chemical and physical means,
`it. may be necessary to express
`quantities ofactivity in‘biologicalnits offpotency, each defined by an
`authoritative, designated referencestaridard.
`Units of ‘biological potency defined by the World ‘Health
`Organization (WHO)for International’ Biological Standards and
`International Biological Reference Prepatations are-termed Interna-
`tional Units (TU). Units defined by USP Reference Standards are USP
`Units, and the individualmonographsrefer to these, Unless otherwise
`indicated, USP Units.are equivalent to.the corresponding Interna-
`tional Units, where such exist, Such -equivalence: isusually
`established on the. basis solely of the: compendial: assay, for the
`substance,
`Forbiological.products,‘whetherornotInternationalUnits orUSP
`Units doexist (see Biologics (1041), units ofpotency aredefinediby
`the corresponding US Standard establisheddbythe.FDA.
`.
`Change toread:
`INGREDIENTSAND PROCESSES. _
`Official drug products andfinisheddevices’ are piepated from
`ingredientsthat meettherequirements ofthe comperidial monographs
`fot those individual ‘ingredients for which imonographis are provided
`(see also WF 22), Generally, nutritional and dietarysupplements are
`prepared fromr ingredients that meet’ requiteménts of the comipendial
`monographs forthose’ ingredients ‘for’ ‘Which ‘monographs are
`provided, except that ‘substances of acceptable food. grade quality
`maybe utilizedintheevent of a ‘differetice.
`Official suibstarices.aré preparéd according to recognizedprinciples
`‘ofgodd manufacturing ptactice‘and from ingredients complying with
`specificationsdesigned to assure that‘theresultant substatices meet
`thé’ réquirements of the coimpendial monographs (see ‘alsoForeigh
`Substaricesand Impurities under Tests aidAssays).
`-.Preparations for which a complete'‘cortiposition is”given. in this
`Phatmacopeia, ‘unless specifically. exempted herein‘ or in the.
`individual monogtaph, are to’ éontain only the ingrédients named in
`the formulas. However, there may be-“deviation, fromthe ‘specified
`procesies ‘or methods of “cqmpounding;: though’. net. from the
`ingredientsor progortionsthereof, provided thefinished: préparation
`conformsto the relevant standards ‘laid ‘down: Herein. and: to
`preparations produced: by following thespecified process.
`-
`" Thetolerances ‘specified in- individual. Hiorogtaplis and in the
`‘getieral chapters: for compounded: preparations ate:‘based on those
`attributés ‘of quality as: might -be-ekpected-fo characterize -an. article
`cotapounded ‘from: suitable bulk drug’substances and ingredierits in
`accordance with the procedires provided or -under -recognized
`principles of good phartnaceutical-practice as described in.this
`Pharmacopeia (see. “Pharmaceutical Compounding—Nonsterile
`Preparationsaosp27 (795)) and elsewhere...
`.
`:Monographsfor preparationsintended tobe compounded pursuant
`to prescription may contain assay methods. Assay methods are‘not
`intended for evaluating a compounded preparation prior to
`
`
`
`

`

`-USP.27
`
`_. Inert Headspace’ Gases-—The air-in a container. of:an article for
`parenteral use may" be evacuated or be replaced bycarbon dioxide,
`helium, or nitrogen, or by-a mixture.of these. gases, which fact néed
`not be declared in the labeling. Bo cae Tt
`Colors—Added substances employed solely to impart color may
`be incorporated inte official preparations, except those intended for
`parenteral or ophthalmic.use; in ‘accordance with the regulations
`pertaining to the useof colors issued by the FDA provided such
`added substances are GtHerwisd appropriate in-all respects. (See. also
`‘Added Substances underInjections (1).)- Be aE
`
` Oihimenis andSuppositortes—tn the prepatationofcintitientsadd
`suppositories,thepropoitionsofthesubstances constituting the base
`may be varied to-maintain,‘a suitable’ consistency underdifferent
`‘Glimaticconditions, provided the concentrations ofactive ingredients
`faredot varied arid:thebioavailability, therapeutic efficacy orsafety of
`the’pieparation isttotimpaired, ts
`
` General Notices
`
`dispensing. Assay methods are intendedto-setve as the official test
`methodsin the event of a question of dispute as to whether or not the
`compounded préparation complies. with official'standards. »
`- Where-a monogtaph ‘on a preparation calls foran ingredient inan
`‘amountexpressed on the dried basis, the ingredient need notbe dried
`priorto tise if due-allowance'is made for the water or other volatile
`substances present itthe quantity taken, | toe
`~ Unless.specifically exempted elsewhere in this Phatmacopeia,the
`identity, strength; quality, and’ purity of an official article” are
`determined by the definition, physical properties, tests, assays, and
`other specificationsrelating to-thearticle, whetiier incdrporatedinithe
`monograph itself, in the General Notices, or in the’section General
`Chapters.
`—
`.
`CH ae
`Water —Water used asaningredientofofficial préparations mee