USP 32
`
`General Notices
`
`1
`
`General Notices and
`Requirements
`
`Applying to Standards, Tests,
`Assays, and Other Specifications
`of the United States Pharmacopeia
`
`1. Title and Revision . . . . . . . . . . . . . . . . . . . . . . . . . . 3
`
`2. Official Status and Legal Recognition . . . . . . . .. 3
`2.10. Official Text . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
`2.20. Official Articles . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
`2.30. Legal Recognition . . . . . . . . . . . . . . . . . . . . . . . . . . 3
`
`3. Conformance and Standards . . . . . . . . . . . . . . . .. 3
`3.10. Applicability of Standards . . . . . . . . . . . . . . . . . . . . . 3
`3.20. Indicating Conformance . . . . . . . . . . . . . . . . . . . . . . 4
`
`4. Monographs and General Chapters . . . . . . . . . .. 4
`4.10. Monographs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
`4.20. General Chapters . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
`
`5. Monograph Components . . . . . . . . . . . . . . . . . . . . . 4
`5.10. Molecular Formula . . . . . . . . . . . . . . . . . . . . . . . . . . 4
`5.20. Added Substances, Excipients, and Ingredients . . . . .. 4
`5.30. Description and Solubility . . . . . . . . . . . . . . . . . . . . . 5
`5.40. Identification Test
`. . . . . . . . . . . . . . . . . . . . . . . . . . 5
`5.50. Assay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
`5.60. Impurities and Foreign Substances . . . . . . . . . . . . . .. 5
`5.70. Performance Tests . . . . . . . . . . . . . . . . . . . . . . . . . . 6
`5.80. USP Reference Standards . . . . . . . . . . . . . . . . . . . . . 6
`
`6. Testing Practices and Procedures . . . . . . . . . . . .. 6
`6.10. Safe Laboratory Practices . . . . . . . . . . . . . . . . . . . . . 6
`6.20. Automated Procedures . . . . . . . . . . . . . . . . . . . . . .. 6
`6.30. Alternative and Harmonized Methods and
`Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
`6.40. Dried, Anhydrous, Ignited, or Solvent-Free Basis . . . .. 6
`6.50. Preparation of Solutions . . . . . . . . . . . . . . . . . . . . . . 6
`6.60. Units Necessary to Complete a Test . . . . . . . . . . . . .. 7
`6.70. Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 7
`6.80. Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
`
`7. Test Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
`7.10. Interpretation of Requirements . . . . . . . . . . . . . . . . .. 7
`7.20. Rounding Rules . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
`
`8. Terms and Definitions . . . . . . . . . . . . . . . . . . . . . .. 8
`8.10. Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.20. About
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.30. Alcohol Content . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.40. Atomic Weights . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.50. Blank Determinations . . . . . . . . . . . . . . . . . . . . . .. 8
`8.60. Concomitantly . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.70. Desiccator . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.80. Logarithms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.90. Microbial Strain . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.100. Negligible . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.110. NLT/NMT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.120. Odor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.130. Percent
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 8
`8.140. Percentage Concentrations . . . . . . . . . . . . . . . . . . .. 8
`8.150. Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 8
`8.160. Reaction Time . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.170. Specific Gravity . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.180. Temperatures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.190. Time . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.200. Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 8
`8.210. Vacuum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 8
`8.220. Vacuum Desiccator . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.230. Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
`8.240. Weights and Measures . . . . . . . . . . . . . . . . . . . . . . 9
`
`9. Prescribing and Dispensing . . . . . . . . . . . . . . . . .. 9
`9.10 Use of Metric Units . . . . . . . . . . . . . . . . . . . . . . . . . 9
`9.20 Changes in Volume . . . . . . . . . . . . . . . . . . . . . . . . . . 9
`
`10. Preservation, Packaging, Storage
`and Labeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
`10.10. Storage Under Nonspecific
`Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
`
`Eye Therapies Exhibit 2025, 1 of 12
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`2 General Notices
`
`USP 32
`
`10.20. Containers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
`10.30. Storage Temperature and Humidity . . . . . . . . . . .. 10
`10.40. Labeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
`
`10.50. Guidelines for Packaging and Storage
`Statements in USP–NF Monographs . . . . . . . . . .. 12
`
`Eye Therapies Exhibit 2025, 2 of 12
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`USP 32
`
`General Notices
`
`3
`
`General Notices and
`Requirements
`
`Change to read:
`
`s The 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
`Pharmacopeia (USP) and the National Formulary (NF).
`Requirements stated in these General Notices apply to all articles
`recognized in the USP and NF (the “compendia”) and to 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 Supplement(s)
`thereto. The same titles, with no further distinction, apply equally to
`print or electronic presentation of these contents. Although USP and
`NF are 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 are 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
`Official text is text contained in USP and NF, including
`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 monograph 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 synonyms of the official 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 component of a finished device
`for which the monograph title 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 monograph is
`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 NF is 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 in the 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 acceptance cri-
`teria, whether incorporated in the monograph itself, 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 standards take on the character of statistical
`procedures, with multiple units involved and perhaps a sequential
`procedural design to allow the user to determine that 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 specimens, 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.
`
`Eye Therapies Exhibit 2025, 3 of 12
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`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 drug or as an ingredient in
`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 of official titles or transpo-
`sition in the order of the names of two or more active 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 standards if the article is a medical device, component in-
`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-
`ments if they have been shown to 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 name that is 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 does not represent assur-
`ance by USP that the article is known to comply with the relevant
`standards. USP may seek legal 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 label of 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.
`When the 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 acceptance crite-
`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, some official substances may conform to the USP or
`NF standard 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 may include several different tests, proce-
`dures, and/or acceptance criteria that reflect attributes of different
`manufacturers’ articles. Such alternatives may be presented for dif-
`ferent polymorphic forms, impurities, hydrates, and dissolution
`cases. Monographs indicate the tests, procedures, and/or acceptance
`criteria to be used and the required labeling.
`4.10.20. Acceptance Criteria
`The acceptance criteria 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 acceptance criteria does not constitute a
`basis for a claim that an official substance that more nearly ap-
`proaches 100 percent purity “exceeds” compendial 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.
`An official product shall be formulated with the intent to provide
`100 percent of the quantity of each ingredient declared on the label.
`Where the minimum amount of 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 acceptance crite-
`rion contained in the monograph may be 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 substances and 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 number that appears in angle
`brackets adjacent to the chapter name (e.g., Chromatography
`Æ621æ). 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 information for the interpretation of the compendial
`requirements,
`• Descriptions of general pharmaceutical storage, dispensing,
`and packaging practices, or
`• General guidance to manufacturers of official substances or of-
`ficial products.
`When a general chapter is referenced in a monograph, acceptance
`criteria may be presented after a colon.
`Some chapters may serve as introductory overviews of a test or
`of analytical techniques. They may reference other general chapters
`that contain techniques, details of the procedures, and, at times, ac-
`ceptance criteria.
`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 not interfere
`with the assays and tests prescribed for determining compliance
`with the compendial standards.
`
`Eye Therapies Exhibit 2025, 4 of 12
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`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).
`5.20.20. 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, unless otherwise specified in the individual monograph.
`Added substances and excipients employed solely to impart color
`may be 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 Æ1æ.)
`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.
`5.20.20.1. In Compounded Preparations
`Compounded preparations 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-
`cordance 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 finished 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 such is 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 NF Articles. 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
`for 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 Identification 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 Identifi-
`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
`dispute 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 (IU). Monographs refer 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 Æ1041æ).
`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 Æ1086æ).
`Nonmonograph tests 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 monograph includes 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 impurity
`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 of all Other Impurities combined with the mono-
`graph-detected impurities may not exceed 2.0% (see Ordinary Im-
`purities Æ466æ), unless otherwise stated in the monograph.
`The following categories of drug substances are excluded from
`Other Impurities requirements:
`
`Eye Therapies Exhibit 2025, 5 of 12
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`6 General Notices
`
`USP 32
`
`• fermentation products and semi-synthetics derived therefrom,
`• radiopharmaceuticals,
`• biologics,
`• biotechnology-derived products,
`• peptides,
`• herbals, and
`• crude products of animal or plant origin.
`Any substance known to be toxic shall not be listed under Other
`Impurities.
`5.60.20. Residual Solvents in USP and NF Articles
`All USP and NF articles are subject to relevant control of
`residual solvents, even when no test is specified in the individual
`monograph. If solvents are used during production, they must be of
`suitable quality. In addition, the toxicity and residual level of each
`solvent shall be taken into consideration, and the solvents limited
`according to the principles defined and the requirements specified
`in Residual Solvents Æ467æ, using the general methods presented
`therein or other suitable methods.
`5.70. Performance Tests
`Where content uniformity determinations have been made using
`the same analytical methodology specified in the Assay, with appro-
`priate allowances made for differences in sample preparation, the
`average of all of the individual content uniformity determinations
`may be used as the Assay value.
`5.80. USP Reference Standards
`USP Reference Standards are authentic specimens that have been
`approved by the USP Reference Standards Expert Committee as
`suitable for use as comparison standards in USP or NF tests and
`assays. (See USP Reference Standards Æ11æ.) Current official lots of
`USP Reference Standards are published in the USP Reference Stan-
`dards Catalog. Where a procedure calls for the use of a compendial
`article rather than for a USP Reference Standard as a material stan-
`dard of reference, a substance meeting all of the compendial mono-
`graph requirements for that article shall be used. No new USP or
`NF standard or procedure requiring the use of a new USP Reference
`Standard shall be official until the specified USP Reference Stan-
`dard is available.
`Unless a reference standard label bears a specific potency or con-
`tent, assume the reference standard is 100.0% pure in the official
`application. Unless otherwise directed in the procedure in the indi-
`vidual monograph or in a general chapter, USP Reference Standards
`are to be used in accordance with the instructions on the label of the
`Reference Standard.
`6. TESTING PRACTICES AND PROCEDURES
`6.10. Safe Laboratory Practices
`In performing compendial procedures, safe laboratory practices
`shall be followed, including precautionary measures, protective
`equipment, and work practices consistent with the chemicals and
`procedures used. Before undertaking any procedure described in the
`compendia, the analyst should be aware of the hazards associated
`with the chemicals and the techniques and means of protecting
`against them. These compendia are not designed to describe such
`hazards or