THE UNITED STATES 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
`
`lUSI
`---(cid:173)
`
`SINCE 1820
`
`UNITED STATES PHARMACOPEIAL CONVENTION, INC.
`12601 Twinbrook Parkway, Rockville, MD 20852
`
`JUBILANT EXHIBIT 1019
`Jubilant v. Bracco, IPR2018-01449
`
`1 of 5
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`

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`Continuous Revision of the USP and the NF
`
`The need for continuously refining specifications
`and updating standards is a natural consequence of
`the introduction of new drugs and the accelerated
`growth of knowledge in the pharmaceutical sci(cid:173)
`ences.
`In order to keep the Cni1ed S1a1es Pharmacopeia
`and the Sarional Formularr abreast of these de(cid:173)
`velopments and to maintain the official standards
`accordingly. the main rnlume is revised regularly
`by Supplemenrs. /nrerim Revision Announcemenrs
`are issued between Supplemenrs as necessary.
`
`Interim Re~ision Announcements pertaining to this
`volume of l SP and SF are published in the journal.
`Pharmacopeial Forum. Reprints of lnrerim Re(cid:173)
`vision Announcemenrs are available on order. A
`single copy of each lnrerim Revision Announcemenr
`is available without charge for each subscription to
`CSP-SF. Each request should be sent to CSPC at
`the address shown below. Corrections and revisions
`included in /nrerim Revision Announcemenrs are
`incorporated in the next regular Supp/emenr.
`
`Supplements to USP 23-NF 18 are issued seri(cid:173)
`ally as necessary, with the Index in the latest Sup(cid:173)
`plemenr being fully cumulative with respect to all
`Supplemenrs issued previously. Thus, in order to
`keep the compendia up to date, the user needs to
`keep all of the Supplements. Cumulation of the
`Supplemenrs into a new main volume will occur
`whenever the amount of text in the Supplements
`becomes unwieldy for the user, or the logistics of
`publication so dictate. The publication cycle of main
`volumes may therefore vary from the five-year in(cid:173)
`terval characteristic of new main volumes published
`since 1950.
`
`Electronic publication of the USP-NF first oc(cid:173)
`curred in ~ovember 1992. The complete text of
`CSP is available in a fully searchable electronic
`format for ease of use. It allows the user to conduct
`searches that would not have been cost effective or
`possible with the printed format, and provides fully
`integrated up-to-date text as it is updated with each
`Supp/emenr.
`
`Inquiries, Comments, and Suggestions
`
`for revisions in the CSP or SF text should be addressed to the Drug Standards Division:
`
`USPC, Inc.
`12601 Twinbrook Parkway
`Rockville, MD 20852 CSA
`
`Telephone: 1-301-881-0666
`FAX: 1-301-816-8373
`Telex: 710828-9787
`Ordering Dept.: 1-800-227-8772
`
`USP-NF Continuous Revision Process
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`Requests/ comments submitted
`
`DSD Subcommittee reviews requests/comments
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`Publish in Pharmacopeial Forum for public review
`(In-process Revision or Pharmacopeial Previews)
`
`..
`..
`..
`..
`..
`..
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`Subcommittee approves
`
`DSD Executive Committee approves
`
`Executive Committee of Revision approves
`
`Board of Trustees approves publication in USP-NF
`
`2 of 5
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`BIOMEDICAL LIBRARY
`APR O 8 'i996
`
`University of California'
`Los Angeles
`
`3 of 5
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`NOTICE AND WARNING
`
`Concerning U.S. Patent or Trademark Rights
`The inclusion in the 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 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, authority, or
`license secured from such patent or trademark owner.
`
`Concerning Use of USP of NF Text
`Attention 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 rights reserved
`ISSN 0195-7996
`ISBN 0-913595-76-4 (cloth)
`0-913595-81-0 (leather)
`
`Printed by Rand McNally, 1133 County Street, Taunton, MA 02780-3795
`
`4 of 5
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`1392
`
`Rubidium / Official Monographs
`
`USP 23
`
`or for use by either jet or syringe injection, whichever is appli(cid:173)
`cable. Label the Vaccine in single-dose containers, if such con(cid:173)
`tainers are not light-resistant, to state that it should be protected
`from sunlight. Label it also to state that constituted Vaccine
`should be discarded if not used within 8 hours.
`
`Rubidium Chloride Rb 82 Injection
`
`» Rubidium Chloride Rb 82 Injection is a sterile
`solution, suitable for intravenous administration. It
`contains not less than 90.0 percent and not more than
`110.0 percent of the labeled amount of 82Rb expressed
`in megabecquerels ( or in millicuries) per mL at the
`time indicated in the labeling. It is obtained by elu(cid:173)
`tion from a strontium 82-rubidium 82 generator sys(cid:173)
`tem. 82Rb, with a half-life of 76 seconds, is a short(cid:173)
`lived positron-emitting radionuclide formed by the
`radioactive decay of the parent nuclide 82Sr. Stron(cid:173)
`tium Sr 82 with a half-life of 25.5 days is produced
`by the proton irradiation of rubidium or spallation of
`molybdenum. The chemical form of the Injection is
`82RbCl. [NOTE-Elute with additive-free Sodium
`Chloride Injection only. Discard the first 50 mL of
`the eluate each day the generator is eluted.]
`
`Packaging, storage, and labeling-Requirements for packaging,
`storage, and labeling do not apply; Rubidium Chloride Rb 82
`Injection is obtained by elution from the generator and is ad(cid:173)
`ministered by direct infusion.
`USP Reference standards ( 11 )-USP Endotoxin RS.
`Bacterial endotoxins (85 )-It contains not more than 175 / V USP
`Endotoxin Unit per mL of the Injection, when compared with
`the USP Endotoxin RS, in which V is the maximum recom(cid:173)
`mended total dose, in mL, at the expiration date or time.
`Radionuclide identification (see Radioactivity ( 821) )-[NOTE(cid:173)
`Perform this test quickly, because of the rapid decay of the 82Rb.]
`The gamma-ray spectrum of eluted 82Rb exhibits photopeaks at
`511 and 777 keV.
`pH ( 791): between 4.0 and 8.0.
`Radionuclidic purity-Using a suitable counting assembly (see
`Selection of a Counting Assembly under Radioactivity ( 821) ),
`determine the radioactivity of each radionuclidic impurity, in kBq
`per MBq (or µCi per mCi), of Rb 82 in the generator eluate by
`use of a calibrated system as directed under Radioactivity (821 ).
`[NOTE-For the following tests, use the generator eluate con(cid:173)
`taining 82Rb that has been allowed to decay for I hour after the
`end of elution.]
`Sr 82 and Rb 83-0btain a gamma-ray spectrum of the hour(cid:173)
`old eluate, and measure the activities of the radionuclidic im(cid:173)
`purities directly from the spectrum. Sr 82 exhibits photopeaks
`at 511 and 777 keV and decays with a radioactive half-life of
`25.5 days. Rb 83 exhibits a photopeak at 530 keV and decays
`with a radioactive half-life of 86.2 days. The activity levels of
`Sr 82 and Rb 83 are not more than 0.02 kBq per MBq (0.02 µCi
`per mCi) and not more than 0.05 kBq per MBq (0.05 µCi per
`mCi) of Rb 82 at the end of elution, respectively.
`Sr 85-0btain a gamma spectrum of the hour-old eluate, and,
`using the same system and geometry, obtain a gamma spectrum
`of a pure Rb 82 specimen (generator eluate containing 82Rb taken
`within IO minutes of elution). Sr 85 exhibits a major photopeak
`at 514 keV and decays with a radioactive half-life of 64.8 days.
`Sr 85 may be determined by subtraction of the 511 and 777 ke V
`peaks in the pure Rb 82, from the 511-514 keV and 777 keV
`peaks in the hour-old eluate. The activity level of Sr 85 is not
`more than 0.2 kBq per MBq (0.2 µCi per mCi) of Rb 82 at the
`end of elution.
`
`Other gamma-ray emitters-The total of other gamma-ray
`emitting radionuclidic impurities does not exceed 0.005 kBq per
`MBq (0.005 µCi per mCi) of Rb 82 at the end of elution.
`Chemical purity-
`Electrolyte solution-Transfer 107 g of ammonium chloride,
`25 g of gelatin, and 42 mL of hydrochloric acid to a 500-mL
`volumetric flask. Add about 450 mL of water, and sonicate until
`a clear solution is obtained. Dilute with water to volume, and
`mix.
`Tin stock standard solution-Dissolve 100 mg of metallic tin
`(Sn), accurately weighed, in 10 mL of dilute hydrochloric acid
`(I in 2), and dilute with water to 100 mL.
`Tin standard solution A-Transfer 0.5 mL of Tin stock stan(cid:173)
`dard solution to a 50-mL volumetric flask and dilute with 0.1 N
`hydrochloric acid to volume.
`Tin standard solution B-Transfer 1.0 mL of Tin standard
`solution A to a 50-mL volumetric flask. Add 10.0 mL of 0.9%
`sodium chloride solution, dilute with Electrolyte solution to vol(cid:173)
`ume, and mix.
`Test solution-Obtain a 50-mL eluate from the generator, and
`allow to stand for at least 1 hour to allow for the complete decay
`of 82Rb. Transfer 10.0 mL of the eluate to a 50-mL volumetric
`flask, dilute with the Electrolyte solution to volume, and mix.
`Procedure-Transfer a portion of the Test solution to a po(cid:173)
`larographic cell, and deaerate by bubbling nitrogen through the
`solution for 5 minutes. Insert the dropping mercury electrode of
`a suitable polarograph, and obtain the differential pulse polaro(cid:173)
`gram from -0.15 to -0.75 volts, at a current range of 0.5 µA,
`using a saturated calomel electrode as the reference electrode
`and a platinum wire as the auxiliary electrode (see Polarography
`( 801) ). Similarly, transfer a portion of the Tin standard solution
`B to a polarographic cell and obtain the polarogram. A peak at
`-0.52 volts indicates the presence of tin. The peak height of
`the Test solution is not greater than that of the Tin standard
`solution B ( I µg per mL).
`Other requirements-It meets the requirements under Injections
`(1 ), except that the Injection may be distributed or dispensed
`prior to completion of the test for Sterility, the latter test being
`started on the day of final manufacture, and except that it is not
`subject to the recommendation for Volume in Container under
`Injections (1 ) .
`Assay for radioactivity-Using a suitable counting assembly (see
`Selection of Counting Assembly under Radioactivity (821) ), de(cid:173)
`termine the radioactivity, in MBq (or in µCi) per mL, of the
`Injection by use of a calibrated system as directed under Radio(cid:173)
`activity ( 821).
`
`Saccharin-see Saccharin NF
`
`Saccharin Calcium
`
`467.49
`C 14H 8CaN 20 6S2·3½Hp
`l ,2-Benzisothiazol-3(2H)-one, 1, I-dioxide, calcium salt, hydrate
`(2: 7).
`1,2-Benzisothiazolin-3-one 1,1-dioxide calcium salt hydrate
`(2:7)
`[6381-91-5].
`Anhydrous
`404.44
`[6485-34-3].
`
`» Saccharin Calcium contains not less than 98.0 per(cid:173)
`cent and not more than 101.0 percent of C14H8-
`CaN206S2, calculated on the anhydrous basis.
`Packaging and storage--Preserve in well-closed containers.
`
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