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`--
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`Millm . . . . . . . . . . . . . . . .
`
`MYLAN PHARMS. INC. EXHIBIT 1032 PAGE 1
`
`

`
`THE UNITED ST A TES PHARMACOPEIA
`·~
`THE NATIONAL FORMULARY.,
`
`By authority of the United States Pharmacopeial
`Convention, Inc., meeting at Washington, D. C. ~
`March 8-10, 1990. Prepared by the Committee of
`Revision and published by the Board of Trustees
`
`Official from January 1, 1995
`
`a&e
`
`---~
`
`SI N C E 1 8 20
`
`UNITED STA TES PHARMACOPEIAL CONVENTION, INC.
`12601 Twinbrook Parkway, Rockville, MD 20852
`
`MYLAN PHARMS. INC. EXHIBIT 1032 PAGE 2
`
`

`
`TX 3-871·407
`1111 ''-'-· .llmEll
`
`NOTICE AND WARNING
`
`Concerning U.S. Parelll or Trademark Rig/us
`The inclusion in the Pharmacopein or in the National Formulary of a monograph on any
`drug in respect 10 which patent or trademark rights may exis1 shall no! be deemed, and is
`not intended as, a grant of, or authority to exercise, any righ1 or privilege protected by such
`pa1en1 or trademark. All such rights and privileges arc vested in the patent or trademark
`owner, and no other person may exercise 1 he same without express permission, authority, or
`license secured from such patent or trademark owner.
`
`Concerning Use of USP or NF Texr
`Allcntion is called to the fact that USP 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.
`© 1994
`12601 Twinbrook Parkway, Rockville, MD 20852.
`All rig/us reserved
`ISSN 0195-7996
`ISB
`0-913595-76-4 (cloth)
`0-913595-81-0 (leather)
`
`Printed by Rand Mc ally, 1133 County S1rce1, Taunton. MA 02780-3795
`
`MYLAN PHARMS. INC. EXHIBIT 1032 PAGE 3
`
`

`
`p
`
`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
`Atomic Weights and Chemical
`Formulas . . . 2
`
`Abbreviations . . . 3
`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
`
`Pharmacopeial Forum .. . 4
`Pharmacopeial Previews ... 4
`I n·proccss Revision ... 4
`Stimuli to the Revision Process ... 4
`Nomenclature ... 4
`Interim Revision Announcement . . . 4
`Official Reference Standards .. . 4
`
`Reagent Standards . . . 4
`USP Reference Standards .. . 4
`
`Units of Potency . .. 5
`Ingredients and Processes . . . 5
`Water ... 5
`Alcohol ... 5
`Alcohol ... 5
`Dehydrated Alcohol ... 5
`Denatured Alcohol ... 5
`
`Added Substances ... 6
`Nutritional Supplements ... 6
`Additional Ingredients . .. 6
`Inert Headspace Gases ... 6
`Colors ... 6
`Ointments and Suppositories ... 6
`
`Tests and Assays ... 6
`Apparatus ... 6
`Steam Bath ... 6
`Water Bath ... 6
`Foreign Substances and Impurities ... 6
`Procedures ... 7
`Blank Determination ... 8
`Desiccator ... 8
`Dilution ... 8
`Drying to Constant Weight ... 8
`Filtration . . . 8
`Identification Tests ... 8
`Ignition to Constant Weight . .. 8
`Indicators ... 8
`Logarithms ... 8
`Microbial Strains ... 8
`Negligible ... 8
`Odor ... 8
`Pressure Measurements ... 9
`Solutions ... 9
`Specific Gravity ... 9
`Temperatures ... 9
`Time Limit ... 9
`Vacuum ... 9
`Water ... 9
`Water and Loss on Drying ... 9
`Test Results, St.atistics and
`Standards .. . 9
`Description . .. 9
`Solubility ... I 0
`Prescribing and Dispensing . . . l 0
`Preservation, Packaging, Storage,
`and Labeling . . . l 0
`Containers ... I 0
`Tamper-resistant Packaging ... 10
`Light-resistant Container ... 10
`
`Well-closed Container ... 10
`Tight Container ... 10
`Hermetic Container ... 11
`Single-unit Container . .. 11
`Single-dose Container ... 11
`Unit-<lose Container ... 11
`Multiple-unit Container ... I I
`Multiple-dose Container ... 11
`Storage Temperature ... 11
`Freezer ... 11
`Cold ... 11
`Cool ... 11
`Room Temperature ... I I
`Controlled Room Temperature ... 11
`Warm ... II
`Excessive Heat ... 11
`Protection from Freezing ... 11
`Storage under Nonspecific
`Conditions . . . 1 I
`Labeling . . . I I
`Amount of Ingredient per Dosage
`Unit . .. 11
`Labeling of Salts of Drugs . . . 12
`Labeling Vitamin-containing
`Products ... 12
`Labeling Parenteral and Topical
`Preparations· .. . 12
`Labeling Electrolytes ... 12
`Labeling Alcohol .. . 12
`Special Capsules and Tablets ... 12
`Expiration Date ... 12
`
`Vegetable and Animal
`Substances . . . 13
`Foreign Matter ... I 3
`Presenation . . . 13
`Weights and Measures . . . 13
`
`Concentrations . . . 13
`Percentage Measurements . . . 14
`Percent weight in weight ... 14
`Percent weight in volume ... 14
`Percent volume in volume ... 14
`
`MYLAN PHARMS. INC. EXHIBIT 1032 PAGE 4
`
`

`
`23
`
`bet
`for
`
`nd
`.g.,
`:ed
`of
`re(cid:173)
`ra-
`
`!r-
`
`ny
`·a-
`Ji(cid:173)
`be
`
`ug
`'x(cid:173)
`::>n
`al
`be
`~h
`1d
`
`II
`
`a-
`1g
`zd
`
`w
`is
`e-
`1g
`ir
`r(cid:173)
`v(cid:173)
`ID
`)(cid:173)
`Jr
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`d
`
`n
`y
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`d
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`
`usP23
`
`·nin an appropriate period of time dur-
`ln d~termi re;cription drug may be retained by a
`ing. whi~t!r ~ts dispensing, the dispenser shall take
`patient
`t in addition to any other relevant factors,
`into accounof the drug· the container in which it was
`the na~Jeb the manuf a~turer and th~ ex~iration .date
`packag. th~ characteristics of the patient s container,
`~e~e:n;rticle is re~a~kaged fo! dispensi~g; the ex(cid:173)
`if
`d torage cond1t1ons to which the article may be
`pecte J. and the expected length of time of the course
`exp~se PY Unless otherwise required, the dispenser
`oft e~~ t~king into accou.nt the f?regoing •. place on
`roayj bel of a multiple-umt container a suitable be(cid:173)
`tbe da se date to limit the patient's use of the article.
`h
`· d · 'd 1
`Yon -u
`·
`Unless otherwise specified in t e in 1v1 ua mono-
`h such beyond-use date shall be not later than
`fa}ptb'e expiration date on the manufacturer's co~­
`taioer, or (b) one ye~r fro.m the date the drug 1s
`dispensed, whichever 1s earlier.
`
`VEGETABLE AND ANIMAL SUBSTANCES
`
`The requirements for vegetable and animal sub(cid:173)
`stances apply to the articles as they enter commerce;
`however lots of such substances intended solely for
`the man~facture or isolation of volatile oils, alkaloids,
`gJycosides! or other active principles may depart from
`such requirements.
`Statements of the distinctive microscopic structural
`elements in powdered substances of animal or vege(cid:173)
`table origin may be included in the individual mono(cid:173)
`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(cid:173)
`crobiological Attributes of Nonsteri/e Pharmaceu(cid:173)
`tical Products (1111) ), and are to be as free as rea(cid:173)
`sonably practicable from microorganisms, insects, and
`other animal contamination, including animal ex(cid:173)
`creta. They shall show no -abnormal discoloration,
`abnormal odor, sliminess, or bther evidence of dete(cid:173)
`rioration.
`The amount of foreign inorganic matter in vege(cid:173)
`table or animal substances, estimated as Acid-insol(cid:173)
`uble ash, shall not exceed 2 percent of the weight of
`the substance, unless otherwise specified in the in(cid:173)
`dividual monograph.
`Before vegetable substances are ground or pow(cid:173)
`~ered, stones, dust, lumps of soil, and other foreign
`morganic matter are to be removed by mechanical or
`other suitable means.
`In commerce it is seldom possible to obtain vege(cid:173)
`table substa nces that are without some ad herent or
`admixe~, innocuous, foreign matter, which usually is
`n~t detn!11ental. No poisonous, dangerous, or other(cid:173)
`wise noxious foreign matter or residues may be pres(cid:173)
`ent. Fo~e~gn matter includes any part of the plant
`not spec1f1ed as constituting the substance.
`Preservation- Vegetable or animal substances may
`be Protected from insect infestation or microbiolog-
`
`General Notices
`
`13
`
`ical contamination by means of suitable agents or
`processes that leave no harmful residues.
`
`WEIGHTS AND MEASURES
`The International System of Units (SI) is used in
`this Pharmacopeia. The SI metric and other units,
`and the symbols commonly employed, are as follows.
`Ci - curie
`Eq = gram-equivalent
`mCi - millicurie
`weight (equivalent)
`µCi - microcurie
`mEq = mi!Jiequivaleat
`nCi - nanocurie
`mol = gram-molecular
`weight {mole)
`Mrad - megarad
`Da = dalton (relative mo(cid:173)
`lecular mass)
`mmol = millimole
`Osmol = osmole
`mOsmol = mi!Jiosmole
`Hz = hertz
`kHz = kilohertz
`MHz = megahertz
`MeV = mi!Jion electron
`volts
`ke V = kiJo-electron volt
`mV =millivolt
`psi = pounds per square
`inch
`Pa= pascal
`kPa = kilopascal
`g = gravity (in
`centrifugation)
`
`m - meter
`dm - decimeter
`cm - centimeter
`mm - millimeter
`µm - micrometer
`(0.001 mm)
`nm - nanometer•
`kg - kilogram
`g - gram••
`mg - milligram
`µg; mcg - microgramt
`ng - nanogram
`pg - picogram
`dL - deciliter
`L -
`liter
`mL - milliliter;;
`µL - microliter
`
`• Formerly the symbol mµ (for millimicron) was used.
`•• The gram is the unit of mass that is used to measure quan(cid:173)
`tities of materials. Weight, which is a measure of the gravita(cid:173)
`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(cid:173)
`ence between mass and weight is considered to be insignificant
`for compendia! assays and tests, and the term "weight" is used
`throughout USP and NF.
`t Formerly the abbreviation mcg was used in the Pharmaco(cid:173)
`peial monographs; however, the symbol µg now is more widely
`accepted and thus is used in this Pharmacopeia. The term
`"gamma," symbolized by "f, is frequently used for microgram in
`biochemical literature.
`NOTE- The abbreviation mcg is still commonly employed to
`denote microgram(s) in labeling and in prescription writing.
`Therefore, for purposes of labeling, "mcg" may be used to denote
`microgram(s).
`.
`+One milliliter (ml) is used herein as the equivalent of l cubic
`centimeter (cc).
`
`The International System of Units (SI) is also used
`in all radiopharmaceutical monographs. The symbols
`commonly employed are as follows.
`Bq - bccqucrel
`GBq = gigabecquerel
`kBq - kilobecquerel
`Gy = gray
`MBq - megabec-
`mGy = milligray
`querel
`
`CONCENTRATIONS
`Molal, molar, and normal solution concentrations
`are indicated throughout this Pharmacopeia for most
`chemical assay and test procedures (see also Volu(cid:173)
`metric Solutions in the section, Reagents, Indicators,
`and Solutions). Molality is designated by the symbol
`m preceded by a number that is the number of moles
`of the designated solute contained in one kilogram of
`
`MYLAN PHARMS. INC. EXHIBIT 1032 PAGE 5
`
`

`
`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(cid:173)
`tained in an amount of the designated solvent that is
`sufficient to prepare one liter of solution.
`Percentage Measurements- Percentage concentra(cid:173)
`tions are expressed as follows:
`Percent weight in weight-( w /w) expresses the
`number of g of a constituent in 100 g of solution or
`mixture.
`Percent weight in volume-{w / v) expresses the
`number of g of a constituent in l 00 mL of solution,
`
`and is used regardless of whether water or another
`liquid is the solvent.
`( v /v) expresses the
`Percent volume in volume-
`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(cid:173)
`solving l g of a solid or semisolid, or 1 mL of a liquid,
`in sufficient solvent to make 100 mL of the solution.
`In the dispensing of prescription medications, slight
`changes in volume owing to variations in room tem(cid:173)
`peratures may be disregarded.
`
`•
`
`A
`
`A
`
`A
`
`A
`
`A
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`c,
`Et
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`Pa
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`U5
`R.!
`
`aS!
`~,
`ld1
`
`I
`
`dis
`thi
`I
`dir
`the
`
`MYLAN PHARMS. INC. EXHIBIT 1032 PAGE 6
`
`I..