2009
`
`THE UNITED STATES PHARMACOPEIA
`
`
`
`NE 27
`
` THE NATIONAL FORMULARY
`
`Volume 1
`
`By authority of the United States Pharmacopeial
`Convention, meeting at Washington, D.C., March 9-13,
`2005. Prepared by the Council of Experts and published
`by the Board of Trustees
`
`Official from May 1, 2009
`
`The designation on the cover of this publication, “USP NF
`2009,” is for ease of identification only. The publication
`contains two separate compendia: The United States
`Pharmacopeia, Thirty-Second Revision, and The National
`Formulary, Twenty-Seventh Edition.
`
`THE UNITED STATES PHARMACOPEIAL CONVENTION
`12601 Twinbrook Parkway, Rockville, MD 20852
`
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`SIX-MONTH IMPLEMENTATION GUIDELINE
`
`The United States Pharmacopeia—National Formulary and its Supplements becomeofficial six months after being released to the public.
`The USP-NF, which is released on November 1 of each year, becomes official on May 1 of the following year.
`’
`This change was adoptedto give users more time to bring their methods and procedures into compliance with new and revised USP-NF
`requirements.
`The table below describes the new official dates. The 2008 USP31~NF26, and the Supplements and Interim Revision Announcements
`(IRAs) to that edition, will be official until May 1, 2009, at which time the USP32—NF27 becomesofficial.
`Hd
`
`
`
`
`
`USP32-NF27
`Nov, 1, 2008
`May 1, 2009
`May 1, 2010 (except as superceded by Supplements, IRAs, and
`Revision Bulletins)
`May1, 2010 (except as superceded by Second Supplement,
`YRAs, and Revision Bulletins)
`May 1, 2010 (except as superceded by JRAs and Revision Bul-
`letins)
`May 1, 2041 (except as superceded by Supplements, IRAs, and
`Revision Bulletins)
`A
`
`First Supplement
`
`Feb. 1, 2009
`
`Aug. t, 2009
`
`Second Supplement
`
`June 1, 2009
`
`Dec. 1, 2009
`
`USP33--NF28
`
`Nov. 1, 2009
`
`May +, 2010
`2 ee fae) ee 7
`
`
`
`h
`
`IRAs will continue to becomeofficial on the first day of the second month of the Pharmacopeial Forum (PF) issue in which they are
`published as final. For instance, JRAs published as final in the May-June PF (issue 3) will becomeofficial on June 1. This table gives the
`details of the JRAs that will apply to USP31-NF26 and USP32-NF27.
`
`
`
`
`
` RA a : ».' Release Date, i ficial Dal
`
`
`
`
`an. 1; 2009 IRA, PF 35(1)
`Jan. 1, 2009
`Feb, 1, 2009
`Mar. 1, 2009 IRA, PF 35(2)
`Mar. 1, 2009
`April 1, 2009
`May 1, 2009 IRA, PF 35(3)
`May1, 2009
`June 1, 2009
`July 1, 2009 IRA, PF 35(4)
`July 1, 2009
`Aug. 1, 2009
`Sept. 1, 2009 IRA, PF 35(5)
`Sept. 1, 2009
`Oct. 1, 2009
`Nov. 1, 2009 IRA, PF 35(6)
`Nov. 1, 2009
`Dec. 1, 2009
`Jan. 1, 2010 IRA, PF 36(1)
`Jan. 1, 2010
`Feb. 1, 2010
`Mar. $,.20%0 JRA, PF 36(2)
`Mar. 1, 2010
`April 1, 2010
`
`ue
`Revises
`USP31-NF26 and its Supplements
`USP31-NF26 and its Supplements
`USP32-NF27
`USP32-—NF27and First Supplement
`USP32-NF27 and First Supplement
`USP32-NF27 and its Supplements
`USP32-NF27 and its Supplements
`USP32—NF27 and its Supplements
`
`*NOTE—Beginning January 1, 2007, USP ceased identifying JRAs numerically (First, Second, etc.) and instead now designates them by
`the date on which they are published.
`Revision Bulletins published on the USP website will continue to become official immediately upon publication, unless the Revision
`Bulletin specifies otherwise.
`'
`Revisions that contain a specific official date shall continue to becomeofficial upon such specified date, which supercedes the general
`official date for the publication.
`For more information about the change in official dates, please visit the USP website at http://www.usp.org.
`
`NOTICE AND WARNING
`Concerning U.S. Patent or Trademark Rights—The inclusion in The United States Pharmacopeia or in the National Formulary of a
`monograph on any drug in respect to which patent or trademark rights may exist shall not be deemed, and is not intended as, a grantof, or
`authority to exercise, any right or privilege protected by such patent or trademark. All such rights and privileges are vested in the patent or
`trademark owner, and no other person may exercise the same without express permission, authority, or license secured from such patent or
`trademark owner.
`
`Concerning Use of USP or NF Text—Attentionis called to the fact that USP and NFtext is fully copyrighted. Authors and others wishing
`to use portions of the text should request permission to do so from the Secretary of the USPC Board of Trustees.
`
`Copyright © 2008 The United States Pharmacopeial Convention
`12601 Twinbrook Parkway, Rockville, MD 20852
`
`All rights reserved.
`ISSN: 0195-7996
`ISBN: 1-889788-69-2
`
`Printed in the United States by United Book Press, Baltimore, Maryland
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`USP 32
`
`Contents
`
`iii
`
`
`
`Contents
`
`VOLUME1
`
`
`
`General Chapters
`
`Mission Statement and Preface ............ v
`
`See page 27 for detailed contents
`
`General Requirements for Tests and Assays....... 31
`Oficers "(2005S=201G)9a ve= oeeys eaagerpenpame eure merry, Xl
`Apparatus for Tests and Assays................ 58
`
`aa | ee i, xi
`
`Board of Trustees (2005-2010) ................. xi
`
`Microbiological Tests .............+-.--00--5- 67
`
`General Tests and Assays ...,............+... 31
`
`Council of Experts (2005-2010) ............00.. xi
`
`Council of Experts Executive Committee
`(2QOS—2ZOTO)
`. . Hoge ew cue cae cgi ences ome xii
`
`Expert Committees (2005-2010) ............... xii
`
`Information Expert Committees (2005-2010)...... xiv
`
`Ad Hoe Advisory Panels (2005-2010)........... XV
`
`Membersof the United States Pharmacopeial
`Convention as of June 30, 2008 ....... , ag xix
`
`Articles of Incorporation................ xxiii
`USP Governancetyc:.0 ou. ee. eer xxiv
`
`Biological Tests and Assays ................45 86
`
`Chemical Tests and Assays ...............40.-. 127
`
`Physical Tests and Determinations..........-... 204
`
`General Information .............. 0.000: e vue 393
`
`Dietary Supplementiimin.ch Jali. ea 767
`
`
`Reagents, Indicators, and Solutions....... 797
`
`Reagents Specifications.............. hd. Soon 801
`
`Indicators and Indicator Test Papers ............ 859
`
`Sl aea, 861
`
`Constitution and Bylaws .............00005 »» KXiV
`
`Butfer SolutionsiVA tr 0 VG). i). .8 eel DG 861
`
`Rules and Procedures .............0046, eee RLY
`
`Colorimetric Solutions. .................4.. 862
`
`USPPolicies. .......... i ee Pe a XXIV
`
`Test Solutions »..... 4... et Dee). Boe 863
`
`AQTDURSIOMIG) sev. coresesee eee on weereed + hoentnr de xxvii
`
`Articles Admitted to USP 32 by Supplement .... xxvii
`
`Changes in Official Titles .................. XXViii
`ie Ap earings in USP 32 That Were Not
`ms
`cluded
`in USP 31 Including Supplements. . . xlii
`Annotated List
`te scusse. ay cthwclecreres cane. owed xxix
`
`Notices
`
`Volumetric Solutions...................00. 870
`
`Chromatographic Reagents ..........-.....0., 877
`
`Reference Tables
`
`Containers for Dispensing Capsules and Tablets .
`. .881
`Description and Relative Solubility of USP and NF oa
`eles AM (aay, Ot Ane Se ee
`
`Approximate Solubilities of USP and NF Articles . .940
`
`ALOTWEISRISY oman:
`
`|
`
`ia
`
`sony
`
`6
`
`omar
`
`anew Kberoon a cysid ome ba:
`
`6 949
`
`General Notices and Requirements .............. 1
`
`Alcoholometric Table ............ 0.0002 ce eee 954
`
`Intrinsic Viscosity Table .................-05. 956
`
`Thermometric Equivalents................006. 959
`
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`iv Contents
`
`USP 32
`
`
`
`Dietary Supplements
`
`Notices
`
`Official Monographs ....0 20... cece eee ees 961
`
`USP General Notices and Requirements .......... ix
`
`Admissions
`
`Articles Admitted to NF 27 by Supplement...... 1140
`Revisions Appearing in NF 27 That Were Not ve
`in NF 26 Including Supplements.......... 114
`Annotated List ................ inact coca ncieit 1141
`
`USP 32
`
`Monographs
`
`Official Monographs for USP 32, AL ......... 1383
`
`Index
`
`Combined Index to USP 32 and NF 27.......... 1-1
`
`Excipients
`
`USP and NF Excipients, Listed by
`@nicsory aaa.) Sie Pe er ee 1143
`
`VOLUME3
`
`Notices
`
`Guide to General Chapters................ v
`
`NF General Notices and Requirements ......... 1148
`
`Notices
`
`Monographs
`
`USP General Notices and Requirements .......... iX
`
`Official Monographs for NF 27............00. 1150
`
`Index
`
`Combined Index to USP 32 and NF 27.......... I-1
`
`USP 32
`
`Monographs
`
`VOLUME2
`
`Official Monographs for USP 32, M-Z......... 2821
`
`Guide to General Chapters................ v
`
`Index
`Combined Index to USP 32 and NF 27.......... I-1
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`This material may be protected by Copyright law (Title 17 U.S. Code)
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`2 General Notices
`
`USP 32
`
`Paraa NT or S
`10.30. Storage Temperature and Humidity ............ 10
`10.40. Labeling ..........., Sct.» AE. 11
`
`10.50. Guidelines for Packaging and Storage
`Statements in USP-NF Monographs ........... 12
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`USP 32
`
`General Notices
`
`3
`
`
`
`General Notices and
`Requirements
`
`Changeto read:
`
`4The General Notices and Requirements section (the General
`Notices) presents the basic assumptions, definitions, and default
`conditions for the interpretation and application of the United States
`Pharmgcopeia (USP) and the National Formulary (NF).
`Requirements stated in these General Notices applyto all articles
`recognized in the USP and NF (the “compendia”) andto all general
`chapters unless specifically stated otherwise. Where the require-
`ments of an individual monograph differ from the General Notices
`or a general chapter, the monograph requirements apply and super-
`sede the requirements of the General Notices or the general chapter,
`whether or not the monograph explicitly states the difference.
`1, TITLE AND REVISION
`The full title of this publication (consisting of three volumes and
`including its Supplements),
`is The Pharmacopeia of the United
`States of America, Thirty-Second Revision and the National For-
`mulary, Twenty-Seventh Edition. These titles may be abbreviated to
`United States Pharmacopeia, Thirty-Second Revision (or to USP
`32),
`to NF 27, and to USP 32-NF 27. The United States
`Pharmacopeia, Thirty-Second Revision, and the National Formu-
`lary, Twenty-Seventh Edition, supersede all earlier revisions.
`Where the terms “USP,” “NF,” or “USP-NF”are used without fur-
`ther qualification during the period in which these compendia are
`official, they refer only to USP 32, NF 27, and any Supplements)
`thereto. The sametitles, with no further distinction, apply equally to
`print or electronic presentation of these contents. Although USP and
`NFare published under one cover and share these General Notices,
`they are separate compendia.
`This revision is official beginning May 1, 2009, unless otherwise
`indicated in specific text.
`Supplements to USP and NF are published periodically.
`Interim Revision Announcements are revisions to USP and NF
`that are published in Pharmacopeial Forum. Interim Revision An-
`nouncements contain official revisions and their effective dates, an-
`nouncements of the availability of new USP Reference Standards,
`and announcements of tests or procedures that are held in abeyance
`pending availability of required USP Reference Standards.
`Revision Bulletins are revisions to official text or postponements
`that require expedited publication. They are published on the USP
`website and generally are official immediately unless otherwise
`specified in the Revision Bulletin.
`Errata ate corrections to items erroneously published that have
`not received the approval of the Council of Experts and that do not
`reflect
`the official requirements. Errata are effective upon
`publication.
`2. OFFICIAL STATUS AND LEGAL RECOGNITION
`‘
`2.10. Official Text
`including
`Official
`text
`is text contained in USP and NF,
`monographs, general chapters, and these General Notices. Revi-
`sions to official text are provided in Supplements, Interim Revision
`Announcements, and Revision Bulletins. General chapters numbered
`from 1000 to 1999 are considered interpretive and are intended to
`provide information on, give definition to, or describe a particular
`subject. They contain no mandatory requirements applicable to any
`official article unless specifically referenced in these General No-
`tices, a monograph, or a general chapter numbered below 1000.
`General chapters numbered above 2000 apply only to articles that
`are intended for use as dietary ingredients and dietary supplements.
`2.20. Official Articles
`An official article is an article that is recognized in USP or NF.
`An article is deemed to be recognized and included in a compen-
`
`dium when a menograph for the article is published in the compen-
`dium and an official date is generally or specifically assigned to the
`monograph.
`The title specified in a monograph is the official title for such
`article. Other names considered to be synonymsoftheofficial titles
`may not be used as substitutes for official titles.
`Official articles include both official substances and official
`products. An official substance is a drug substance, excipient, diet-
`ary ingredient, other ingredient, or componentof a finished device
`for which the monographtitle includes no indication of the nature
`of the finished form.
`An official product is a drug product, dietary supplement, com-
`pounded preparation, or finished device for which a monographis
`provided.
`2.30. Legal Recognition
`The USP and NF are recognized in the laws and regulations of
`many countries throughout the world. Regulatory authorities may
`enforce the standards presented in the USP and NF, but because
`recognition of the USP and NF may vary by country, users should
`understand applicable laws and regulations. More information
`about the legal status of the USP and NFis provided in the Mission
`and Preface.
`3. CONFORMANCE TO STANDARDS
`3.10. Applicability of Standards
`Standards for an article recognized in a USP compendium are ex-
`pressed inthe article’s monograph, applicable general chapters, and
`these General Notices. Unless specifically exempted elsewhere in a
`compendium,the identity, strength, quality, and purity of an article
`are determined by the official tests, procedures, and acceptancecri-
`teria, whether incorporated in the monographitself, in the General
`Notices, or in the applicable general
`‘chapters.
`The standards in the relevant monograph, general chapter(s), and
`General Notices apply at any time in the life of the article from
`production to expiration. The manufacturer’s specifications, and
`good manufacturing practices generally, are developed and fol-
`lowed to ensure that the article will comply with compendial stan-
`dards until its expiration date, when stored as directed. Thus, any
`official article tested as directed in the relevant monograph shall
`comply. “
`At times, compendial standardstake on the characterofstatistical
`procedures, with multiple units involved and perhaps a sequential
`procedural design to allow the user to determinethat the tested arti-
`cle meets or does not meet the standard. The similarity to statistical
`procedures may seem to suggest an intent to make inference to
`some larger group of units, but in all cases, statements about
`whether the compendial standard is met apply only to the units
`tested. Repeats, replicates, statistical rejection of outliers, or extrap-
`olations of results to larger populations, as well as the necessity and
`appropriate frequency of batch testing, are neither specified nor pro-
`scribed by the compendia. First-party (manufacturer), second-party
`(buyer), or third-party (regulator) compliance testing may or may
`not require examination of additional specimeris,
`in accordance
`with predetermined guidelines or sampling strategies.
`Official products other than dietary supplements are prepared
`from ingredients that meet USP or NF standards, where standards
`for such ingredients exist.
`Official substances are prepared according to recognized princi-
`ples of good manufacturing practice and from ingredients comply-
`ing with specifications designed to ensure that the resultant sub-
`stances meet the requirements of the compendial monographs.
`
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`4 General Notices
`
`USP 32
`
`3.10.10. Applicability of Standards to Drug Products, Drug
`Substances, and Excipients
`The applicable USP or NF standard applies to any article mar-
`keted in the United States that (1) is recognized in the compendium
`and(2) is intended or labeled for use as a drugor as an ingredientin
`a drug. The applicable standard applies to such articles whether or
`not the added designation “USP” or “NF” is used. The standards
`apply equally to articles bearing the official titles or names derived
`by transposition of the definitive words ofofficial titles or transpo-
`sition in the order of the namesof two or moreactive ingredients in
`official titles.
`
`3.10.20. Applicability of Standards to Medical Devices,
`Dietary Supplements, and Their Components and Ingredients
`An article recognized in USP or NF shall comply with the com-
`pendial standardsif the article is a medical device, componentin-
`tended for a medical device, dietary supplement, dietary ingredient,
`or other ingredient that is intended for incorporation into a dietary
`supplement, and is labeled as conforming to the USP or NF.
`Generally, dietary supplements are prepared from ingredients that
`meet USP, NF, or Food Chemicals Codex standards. Where such
`standards do not exist, substances may be used in dietary supple-
`mentsif they have been shownto be of acceptable food grade qual-
`ity using other suitable procedures.
`3.20. Indicating Conformance
`A drug product, drug substance, or excipient may use the desig-
`nation “USP”or “NF” in conjunction with its official title or else-
`where on the label only when (1) a monograph is provided in the
`specified compendium and (2) the article complies with the identity
`prescribed in the specified compendium.
`When a drug product, drug substance, or excipient differs from
`the relevant USP or NF standard of strength, quality, or purity, as
`determined by the application of the tests, procedures, and accept-
`ance criteria set forth in the relevant compendium,its difference
`shall be plainly stated on its label.
`When a drug product, drug substance, or excipient fails to com-
`ply with the identity prescribed in USP or NF or contains an added
`substance that interferes with the prescribed tests and procedures,
`the article shall be designated by a namethatis clearly distinguish-
`ing and differentiating from any name recognized in USP or NF.
`A medical device, dietary supplement, or ingredient or compo-
`nent of a medical device or dietary supplement may use the desig-
`nation “USP” or “NF” in conjunction with its official title or else-
`where on the label only when (1) a monograph is provided in the
`specified compendium and (2) the article complies with the mono-
`graph standards and other applicable standards in the compendium.
`The designation “USP” or “NF” on the label may not and does
`not constitute an endorsement by USP and doesnotrepresent assur-
`ance by USPthat the article is known to comply with
`the relevant
`standards. USP mayseeklegal redress if an article purports to be or
`is represented as an official article in one of USP’s compendia and
`such claim is determined by USP not to be made in good faith.
`The designation “USP-NF” may be used on the labelof an arti-
`cle provided that the label also bears a statement such as “Meets NF
`standards as published by USP,” indicating the particular compen-
`dium to which the article purports to apply.
`Whenthe letters “USP,” “NF,” or “USP-NF”are used on the
`label of an article to indicate compliance with compendial stan-
`dards, the letters shall appear in conjunction with the official title of
`the article. The letters are not to be enclosed in any symbol such as
`a circle, square, etc., and shall appear in capital letters.
`If a dietary supplement does not comply with all applicable com-
`pendial requirements but contains one or more dietary ingredients
`or other ingredients that are recognized in USP or NF, the individ-
`ual ingredient(s) may be designated as complying with USP or NF
`standards or being of USP or NF quality provided that the designa-
`tion is limited to the individual ingredient(s) and does not suggest
`that the dietary supplement complies with USP standards.
`4, MONOGRAPHS AND GENERAL CHAPTERS
`4.10. Monographs
`Monographs set forth the article’s name, definition, specification,
`and other requirements related to packaging, storage, and labeling.
`The specification consists of tests, procedures, and acceptancecrite-
`ria that help ensure the identity, strength, quality, and purity of the
`
`article. For general requirements relating to specific monograph
`sections, see section 5, Monograph Components.
`Because monographs may not provide standards for all relevant
`characteristics, someofficial substances may conform to the USP or
`NFstandard but differ with regard to nonstandardized properties
`that are relevant to their use in specific preparations. To assure in-
`terchangeability in such instances, users may wish to ascertain func-
`tional equivalence or determine such characteristics before use.
`4.10.10. Applicability of Test Procedures
`A single monograph mayinclude several different tests, proce-
`dures, and/or acceptancecriteria that reflect attributes of different
`manufacturers’ articles. Such alternatives may be presented for dif-
`ferent polymorphic forms, impurities, hydrates, and dissolution
`cases. Monographsindicate the tests, procedures, and/or acceptance
`criteria to be used and the required labeling.
`4.10.20. Acceptance Criteria
`The acceptancecriteria allow for analytical error, for unavoidable
`variations in manufacturing and compounding,and for deterioration
`to an extent considered acceptable under practical conditions. The
`existence of compendial acceptancecriteria does not constitute a
`basis for a claim that an official substance that more nearly ap-
`proaches 100 percent purity “exceeds” compendia! quality. Simi-
`larly, the fact that an article has ‘been prepared to tighter criteria
`than those specified in the monograph does not constitute a basis
`for a claim that the article “exceeds” the compendial requirements.
`Anofficial product shall be formulated with the intent to provide
`100 percent of the quantity of each ingredient declared on the label.
`Where the minimum amountof a substance present in a dietary sup-
`plement is required by law to be higher than the lower acceptance
`criterion allowed for in the monograph, the upper acceptancecrite-
`rion contained in the monograph maybe increased by a correspond-
`ing amount.
`The acceptance criteria specified in individual monographs and
`in the general chapters for compounded preparations are based on
`such attributes of quality as might be expected to characterize an
`article compounded from suitable bulk drug substancesand ingredi-
`ents, using the procedures provided or recognized principles of
`good compounding practice, as described in these compendia.
`4.20. General Chapters
`Each general chapter is assigned a numberthat appears in angle
`brackets adjacent to the chapter name(e.g., Chromatography
`(621}). General chapters may contain the following:
`¢ Descriptions of tests and procedures for application through in-
`dividual monographs,
`° Descriptions and specifications of conditions and practices for
`pharmaceutical compounding,
`* General informatigd for the interpretation of the compendial
`requirements,
`* Descriptions of general pharmaceutical storage, dispensing,
`and packaging practices, or
`¢ General guidance to manufacturers of official substances orof-
`ficial products.
`Whena general chapteris referenced in a monograph, acceptance
`criteria may be presented after a colon.
`Sonie chapters may sérve as introductory overviewsof a test or
`of analytical téchniques. They may reference other general chapters
`that contain techniques, details of the procedures, and, at times, ac-
`ceptancecriteria.
`5. MONOGRAPH COMPONENTS
`5.10. Molecular Formula
`The use of the molecular formula for the active ingredient(s)
`named in defining the required strength of a compendial article is
`intended to designate the chemical entity or entities, as given in the
`complete chemical name of the article, having absolute (100 per-
`cent) purity.
`5.20. Added Substances, Excipients, and Ingredients
`Substances are regarded as unsuitable for inclusion in an official
`article and therefore prohibited unless: (1) they do not exceed the
`minimum quantity required for providing their intended effect; (2)
`their presence does not impair the bioavailability, therapeutic effi-
`cacy, or safety of the official article; and (3) they do notinterfere
`with the assays and tests prescribed for determining compliance
`with the compendial standards.
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`USP 32
`
`General Notices
`
`5
`
`The air in a container of an official article may, where appropri-
`ate, be evacuated or be replaced by carbon dioxide, helium, argon,
`or nitrogen, or by a mixture of these gases. The use of such gas
`need not be declared in the labeling.
`5.20.10.. Added Substances, Excipients, and Ingredients in
`Official Substances
`Official substances may contain only the specific added sub-
`stances that are permitted by the individual monograph. Where such
`addition is permitted, the label shall indicate the name(s) and
`amount(s) of any added substance(s).
`§.20.20. Added Substances, Excipients, and Ingredients in
`Official’ Products
`Suitable substances and excipients such as antimicrobial agents,
`pharmaceutical bases,carriers, coatings, flavors, preservatives, sta-
`bilizers, and vehicles may be added to an official product to en-
`hance its stability, usefulness, or elegance, or to facilitate its prepa-
`ration, urdess otherwise specified in the individual monograph.'
`Added substances and excipients employed solely to impart color
`maybe incorporated into official products other than those intended
`for parenteral or ophthalmic use, in accordance with the regulations
`pertaining to the use of colors issued by the U.S. Food and Drug
`Administration (FDA), provided such added substances or excipi-
`ents are otherwise appropriate in all respects. (See also Added Sub-
`stances under Injections (1).)
`The proportions of the substances constituting the base in oint-
`ment and suppository products and preparations may be varied to
`maintain a suitable consistency under different climatic conditions,
`provided that the concentrations of active ingredients are not varied
`and provided that the bioavailability, therapeutic efficacy, and
`safety of the preparation are not impaired.
`§.20.20.1. In Compounded Preparations
`Compoundedpreparations for which a complete composition is
`given shall contain only the ingredients named in the formulas un-
`less specifically exempted herein or in the individual monograph.
`Deviation from the specified processes or methods of com-
`pounding, although not from the ingredients or proportions thereof,
`may occur provided that the finished preparation conforms to the
`relevant standards and to preparations produced by following the
`specified process.
`‘Where a monograph for a compounded preparation calls for an
`ingredient in an amount expressed on the dried basis, the ingredient
`need not be dried before use if due'allowance is made for the water
`or other volatile substances present in the quantity taken.
`Specially denatured alcohol formulas are available for use in ac-
`cordafice with federal statutes and regulations of the Internal Reve-
`nue Service. A suitable formula of specially denatured alcohol may
`be substituted for Alcohol’ in the manufacture of official prepara-
`tions intended for internal or topical use, provided that the denatur-
`ant is volatile and does not remain in the firtished product. A prepa-
`ration that is intended for topical application to the skin may
`contain specially denatured alcohol, provided that the denaturant is
`either a usual ingredient in the preparation or a permissible added
`substance; in either case the denaturant shall be identified on the
`label of the topical preparation. Where a process is given in the in-
`dividual monograph, any preparation compounded using denatured
`alcohol shall be identical to that prepared by the monograph
`process.
`5.20.20.2. In Dietary Supplements
`Additional ingredients may be added to dietary supplement prod-
`ucts provided that the additional ingredients: (1) comply with appli-
`cable regulatory requirements; and (2) do not interfere with the as-
`says and tests prescribed for determining compliance with
`compendial standards.
`5.30. Description and Solubility
`Only where a quantitative solubility test is given in a monograph
`and is designated as suchis it a test for purity.
`A monograph may include information regarding the article’s
`description. Information about an article’s “description and solubil-
`ity” also is provided in the reference table Description and Relative
`Solubility of USP and NFArticles. The reference table merely de-
`notes the properties of articles that comply with monograph stan-
`dards. The reference table is intended primarily for those: who use,
`prepare, and dispense drugs and/or related articles. Although the in-
`formation provided in monographs and the information in the refer-
`
`ence table may indirectly assist in the preliminary evaluation of an
`article, it is not intended to serve as a standard or test for purity.
`The approximate solubility of a compendial substance is indi-
`cated by one of the following descriptive terms:
`
`Descriptive Term
`Very soluble
`Freely soluble
`Soluble
`
`Sparingly soluble
`Slightly soluble
`Very slightly soluble
`Practically insoluble, or
`Insoluble
`
`Parts of Solvent Required
`or _1
`Part
`of Solute
`=
`"Less than 1
`From 1 to 10
`From 10 to 30
`From 30 to 100
`From 100 to 1,000
`From 1,000 to 10,000
`Greater than or equal to
`10,000
`
`5.40. Identification Test
`The compendial test titled Jdentification is provided as an aid in
`verifying the identity of articles as they are purported to be, e.g.,
`those taken from labeled containers. Tests presented in the Jdentifi-
`cation section shall be used to assist in establishing the identity of
`the substance but are not necessarily sufficient to establish proof of
`identity. Other tests and specifications in the monograph often are
`necessary to establish or confirm the identity of an article. Failure
`of an article to meet the requirements of a prescribed Identification
`test may indicate that the article is mislabeled,
`5.50. Assay
`Assay tests for compounded preparations are not intended for
`evaluating a compounded preparation before dispensing, but instead
`are intended to serve as the official test in the event of a question or
`dispyte regarding the preparation’s conformance to official
`standards.
`5.50.10. Units of Potency (Biological)
`For substances that cannot be completely characterized by chemi-
`cal and physical means, it may be necessary to express quantities of
`activity in biological units of potency, each defined by an authorita-
`tive, designated reference standard.
`Units of biological potency defined by the World Health Organi-
`zation (WHO)for International Biological Standards and Interna-
`tional Biological Reference Preparations are termed International
`Units GU). Monographsrefer to the units defined.by USP Refer-
`ence Standards as “USP Units.” For biological products, units of
`potency are defined by the corresponding U.S. Standard established
`by FDA, whether or not International Units or USP Units have been
`defined (see Biologics (1041)).
`5.60. Impurities and Foreign Substances
`Tests for the presence of impurities and foreign substances are
`provided to limit such substances to amounts that are unobjection-
`able under conditions in which the article is customarily employed
`(see also Impurities in Official Articles (1086)).
`Nonmonographtests and acceptance criteria suitable for de-
`tecting and controlling impurities that may result from a change in
`the processing methods or that may be introduced from external
`sources should be employed in addition to the tests provided in the
`individual monograph, where the presence of the impurity is incon-
`sistent with applicable good manufacturing practices or good phar-
`maceutical practice.
`5.60.10. Other Impurities in USP and NF Articles
`If a USP or NF monographincludes an assay or organic impurity
`test based on chromatography, other than a test for residual sol-
`vents, and that monograph procedure does not detect an jmpurity
`present in the substance, the amount and identity of the impurity,
`where both are known, shall be stated in the labeling (certificate of
`analysis) of the official substance, under the heading Other
`Impurity(ies).
`The presence of any unlabeled other impurity in an official sub-
`stance is a variance from the standard if the content is 0.1% or
`greater. The sum ofall Other Impurities combined with the mono-
`graph-detected impurities may not exceed 2.0% (see