`

`

`

`
`
`NOTICE AND WARNING
`
`Concerning US. Patent or Trademark Rights
`
`The inclusion in the Pharmacopeizt or in the National Formulary of it monograph on any
`drug in respect to which patent or trademark rights may exist shall nut be deemed. and is
`not intended us. at grant of. 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. ttutherity. or
`iieense secured from such patent or trademark owner.
`
`Concerning Use of USP or NF Text
`Attention is called to the fttct that US? and NF text 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.
`
`The United States Pharmacopeial Convention. Inc.
`I994
`ta
`I260] Twitthroolt Parkway. Rotkville. MD 20352.
`AN rigklx reserved
`ISSN 0195-7996
`ISBN 0-91359546-4 [cloth]
`0~9l359$-SI-0 (leather)
`
`Printed by Rand McNally.
`
`1 I33 County Street. Taunton. MA 02780-3795
`
`|nnoPharma Exhibit 1113.0003
`
`

`

`
`
`General Notices
`and Requirements
`
`Applying to Standards, Tests,
`Assays, and Other Specifications
`of the United States Pharmacopeia
`
`Guide to GENERAL NOTICES AND REQUIREMENTS
`
`Title .
`
`.
`
`. 2
`
`“Official” and “Official
`Articles” .
`.
`. 2
`
`Nutritional Supplements .
`
`.
`
`. 2
`
`Montic Weights and Chemical
`Formulas .
`.
`. 2
`
`. 3
`.
`Abbreviations .
`Abbreviated Statements in
`Monographs... 3
`
`Significant Figures and
`Tolerances .
`.
`. 3
`
`Equivalence Statements in Titrimetric
`Procedures .. . 3
`Tolerances .. . 3
`Interpretation of Requirements .
`
`. 3
`
`.
`
`General Chapters .
`
`.
`
`. 4
`
`. 4
`
`.
`Pliarmacopeial Forum .
`Pltarmacopeial Previews .
`.
`. 4
`lnjprocess Revision .
`.
`. 4
`Stimuli to the Revision Process .
`Nomenclature .
`.
`. 4
`3‘r‘F’aEi‘!.i {'i§lii§.§‘c;"§i‘§.?鑧?é'£“.".‘.‘4“ 4
`
`.
`
`. 4
`
`Reagent Standards .
`
`.
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`. 4
`
`USP Reference Standards .
`
`.
`
`. 4
`
`Units of Potency .
`
`.
`
`. 5
`
`Ingredients and Processes .
`Water . ._ 5
`Alcohol .
`.
`. 5
`Alcohol 5
`D"hi'dratcd Alcohoi .
`Denatured Alcohol .
`.
`
`. 5
`.
`. 5
`
`.
`
`. 5
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`. 6
`.
`Added Substances .
`. 6
`.
`Nutritional Supplements .
`Additional Ingredients .
`.
`. 6
`Inert Headspace Gases .
`. 6
`_
`Colors .
`.
`. 6
`Ointments and Suppositortes .
`
`.
`
`.
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`. 6
`
`Tests and Assays .
`
`. . 6
`
`.
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`.
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`.
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`. 8
`
`.,
`
`. 8
`
`.
`
`. B
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`. 6
`.
`Apparatus .
`.
`. 6
`Steam Bath .
`Water Bath . .. 6
`Foreign Substances and Impurities .
`Procedures .
`.
`. 7
`Blank Determination .
`Desiccator .
`.
`. 8
`Dilution .
`.
`. 8
`Drying to Constant Weight .
`Filtration .
`.
`. 8
`. 8
`.
`Identification Tests .
`Ignition to Constant Weight .
`Indicators .
`.
`. 8
`Logaritlirns .
`.
`. B
`Microbial Strains
`Negligible... 3
`Odor... 3
`Pressure Measurements .
`Solutions .
`.
`. 9
`.
`Specific Gravity .
`Temperatures .
`.
`. 9
`Time Limit .
`.
`. 9
`Vacuum .
`.
`. 9
`Water .
`.
`. 9
`Water and Loss on Drying .. . 9
`Test Results, Statistics and
`Standards .
`.
`. 9
`Description .
`.
`. 9
`Solubility .
`.
`. 10
`Prescribing and Dispensing . ..I0
`
`. S
`
`. 9
`
`.
`
`. 9
`
`Preservation, Packaging, Storage,
`and Labeling .
`.
`. 10
`
`4
`. 10
`.
`Containers .
`. I0
`.
`Tamper-resistant Packaging .
`Light-resistant Container .
`.
`. I0
`
`.
`
`. I0
`
`.
`
`Well-closed Container .
`Tight Container .
`.
`. I0
`Hermetic Container . .. ll
`Single-unit Container .
`.
`. ll
`Single-close Container .
`. ll
`.
`Unit-dose Container .
`.
`. ll
`I I
`Multiple-unit Container .
`.
`. ll
`.
`Multiple-dose Container .
`Storage Temperature .. . ll
`Freezer .. . 11
`Cold...ll
`Cool...ll
`Room Temperature .. . ll
`Controlled Room Temperature .
`Warm .
`.
`. 1]
`. ll
`.
`Excessive Heat .
`Protection from Freezing .
`Storage under Nonspecific
`Conditions . .. Ii
`Labeling... I1
`Amount of Ingredient per Dosage
`Unit... 11
`Labeling of Salts of Drugs .
`Labeiing Vitamin-containing
`Products . .. 12
`Labeling Parenteral and Topical
`Preparations . .. [2
`Labeling Electrolytes .
`.
`Labeling Alcohol .
`.
`. [2
`Special Capsules and Tablets
`Expiration Date .
`.
`. 12
`
`.
`
`.
`
`. 11
`
`.
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`. 12
`
`. 12
`
`. ll
`
`I2
`
`Vegetable and Animal
`Substances .
`.
`. 13
`
`. 13
`.
`Foreign Matter .
`Preservation .
`.
`. 13
`
`Weights and Measures .
`
`.
`
`. 13
`
`Concentrations . .
`
`. 13
`
`. 14
`.
`Percentage Measurements .
`. 14
`Percent weight in weight .
`.
`Percent weight in volume .. . 14
`Percent volume in volume .
`.
`.
`I-3
`
`|nnoPharma Exhibit 1113.0004
`
`

`

`-“in an appropriate period of time dur-
`Inwctllggplngllpresgcripytioq drug may be retained by :1
`its dispensing, the dispenser shall take
`aunt in addition to any other relevant factors.
`into acc 6 0} the drug; the container in which it was
`the until; 1”, the manufacturer and the expiration date
`P§'°kagc.t1;e characteristics of the patient’s container.
`therwmriicle is repackaged for dispensing; the ex-
`it mi-3 image conditions to which the article may be
`13°“: ed. and the expected length of time of the course
`a thcrfli,y_ Unless otherwise required. the dispenser
`of
`on taking into account the foregoing, place on
`$?fabe| of a multiple-unit container at suitable be-
`*nd-use date to limit the patient’s 1.158" of the article.
`gjonlcss otherwise specified in the individual mono-
`ph, such beyond-use date shall be not later than
`53 the expiration date on the manufacturer’s con-
`tainer’ 01- (b) one year from the date the drug 15
`dispensed, whichever is earlier.
`
`VEGETABLE AND rliNll'v‘lAL SUBST.-U'*~'CES
`
`The requirements for vegetable and animal sub-
`stances apply to the articles as they enter commerce;
`however, lots of such substances intended solely _for
`the manufacture or isol'ation_ol' volatile oils, alkaloids.
`glycosides, or other active principles may depart from
`such requirements.
`Statements of the distinctive microscopic structural
`elements in powdered substances of animal or vege-
`table origin may be included in the individual mono-
`graph as a means of determining identity, quality, or
`purity.
`
`Foreign Matter—Vegetable and animal substances
`are to be free from pathogenic organisms (see Mi‘-
`crobioiogical Attributes of Nonsterile Pharmaceu-
`tical Products (I l
`1 1)). and are to be as free as rea-
`sonably practicable from microorganisms, insects, and
`other animal contamination,
`including animal ex-
`creta. They shall show no abnormal discoloration,
`a_bnor_mal odor, sliminess, or other evidence of dete-
`rioration.
`The amount of foreign inorganic matter in vege-
`table or animal substances, estimated as Aci'd—i’n.rol‘-
`uble ash, shall not exceed 2 percent of the weight of
`the substance. unless otherwise specified in the in-
`dividual monograph.
`Bclore vegetable substances are ground or pow-
`?:;:§é:il;)neS, dust. lumps of soil, and other foreign
`matter are to be removed by mechanical or
`other suitable means.
`Edit‘; étirlraisiiiaelrce it
`is seldompossible to obtain vege-
`d
`.
`M
`_
`ces that are without some adherent or
`3 mixed. innocuous, foreign matter, which usually is
`agfiedggggfintfal.
`'No poisonous, diiggerous, 01;‘ other-
`_ 5 oreign matter or resi
`ties may e pres-
`;=1nt. Foreign matter includes any part of the plant
`‘“ Speciiled as constituting the substance.
`P|'eservation——VegetabIe or animal substances may
`bl’-‘ protected from insect infestation or microbiolog-
`
`Genern! Notices
`
`13
`
`ical contamination by means of suitable agents or
`processes that leave no harmful residues.
`
`wcioirrs AND MEASURES
`
`The international System of Units (Si) is used in
`this Pharrnacopeia. The S1 metric and other units,
`and the symbols commonly employed, are as follows.
`Ci = curie
`Eq = grant-equivalent
`mCi == millicuric
`weight (equivalent)
`uCi = rnicrocurie
`mE = milliequivalent
`nCi = nanociiric
`mo = gram-molecular
`vv
`Mmd = mcsarnd
`Da = daltcinlgh mo-
`lecular mass)
`in = mctcr
`mmol = niillimole
`din =- dcciincter
`Osmol = osrnole
`em = centimeter
`mDsmol = rnilliosrnolc
`mm = millimeter
`Hz = hertz
`um = micrometer
`lcl-iz = liiiohertz
`(0.001 mm)
`Ml-lz = megahertz
`Mo =- nanometer‘
`MeV = million electron
`kg =' kilogram
`volts
`= gram "
`keV = kilo-electron volt
`mg -== milligram
`rnV = millivolt
`rig: meg == microgrami
`psi = pounds per square
`rig = nanogram
`inch
`pg ==- picogriim
`Pa = pascal
`dL E deciliter
`kl"-‘a = kilopascal
`L = liter
`g = gravity (in
`mL = milliliter: i
`centrifugatiori)
`uL = microliter
`
`' Formerly the symbol min (for millimicronj was used.
`“ The grain is the unit of mass that is used to measure quan-
`tities of rniiicrials. Weight. which is a measure of the gravita-
`tional force acting on the mass of a material, is proportional to.
`and may differ slightly from. its mass due to the effects of factors
`such as gravity. temperature. latitude, and altitude. The differ-
`ence between mass and weight is considered to be insignificant
`for compendial assa '5 and tests, and the term “wcight" is used
`throughout USP an NF.
`'l“Formcrly the abbreviation meg was used in the Pharmaco-
`pcinl monographs: however. the symbol pig now is more widely
`accepted and thus is used in this Pharmaco eia. The term
`"gamma," symbolized by 7, is frequently used or n-iicrogram in
`biochemical literature.
`l"~l0'rt3—Thc abbreviation meg is still commonly employed to
`denote microgramis) in labeling and in prescription writing.
`Tiiercforc. for purposes of labeling, “mcg" may be used to denote
`micrograms).
`It One milliliter (mL) is used herein as the equivalent of 1 cubic
`centimeter (cc).
`
`The International System of Units (S1) is also used
`in all radiopharmaceutical monographs. The symbols
`commonly employed are as follows.
`Bq = bccqucrcl
`GBq = gigabccquerel
`kBq = ltilobccquerel
`Gy = gray
`MBq = megabec-
`trtGy = milligray
`qucrel
`
`CONCENTRATIONS
`
`Molal, molar. and normal solution concentrations
`are indicated throu bout this Pharinacopeia for most
`chemical assay ant? test procedures (see also Volu-
`metric Solimoris in the section, Reagents, Indicators,
`and Soliiiions). Molality is designated by the symbol
`in preceded by a number that is the number of moles
`of the designated solute contained in one kilogram of
`
`l l 3
`
`|nnoPharma Exhibit 1113.0005
`
`
`
`
`
`!—!—u-n-—--iii--11117:!‘-I.-I’-'..'-I‘-ct:D.-'-'ul:‘l'?-ii
`
`

`

`14
`
`General’ Notices
`
`USP 23
`
`
`
`the designated solvent. Molarity is designated by the
`symbol M preceded by a number that is the number
`of moles of the designated solute contained in an
`amount of the designated solvent that is sufficient to
`prepare one liter of solution. Normality is designated
`by the symbol N preceded by a number that is the
`number of equivalents of the designated solute con-
`tained in an amount of the designated solvent that is
`sufficient to prepare one liter of solution.
`
`Percentage Measurements—Percentage concentra—
`tions are expressed as follows:
`Percent weight
`in wet'g}zt~(w/w) expresses the
`number of g of a constituent in 100 g of solution or
`mixture.
`
`in voIume—(w/v) expresses the
`Percent weight
`number of g of a constituent in 100 ml. of solution.
`
`and is used regardless of whether water or another
`liquid is the solvent.
`Percent volume in vo!ume—(v/vi) expresses the,
`number of mL of a constituent in 100 mL of solution,
`The term percent used without qualification means_
`for mixtures of solids and semisolids, percent ‘Weight
`in weight; for solutions or suspensions of solids in
`liquids, percent weight
`in volume; for solutions of
`liquids in liquids, percent volume in volume; and for
`solutions of gases in liquids, percent weight in volume,
`For example, a 1 percent solution is prepared by dis.
`solving 1 g of a solid or semisolid, or 1 mL of a liquid,
`in sufficient solvent to make I00 ml. of the solution.
`In the dispensing of prescription medications. slight
`changes in volume owing to variations in room tem-
`peratures may be disregarded.
`
`>i>>->-:I~:h-
`
`
`
`4t——m:%:jé: pl-I—p«q¢:u
`
`|nnoPharma Exhibit 1113.0006
`
`