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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 1
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 1
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`National Formulary XII
`
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 2
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`
`
`1
`J\v. 1
`
`11
`
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`
`:,JlTlnNlll
`l:'nD111111._"n 10,v1
`I 1v11n1. I Vl\IJI u
`n
`
`The National Formulary - Twelfth Edition
`(N.F. XII).
`
`Prt:an~rllri hu tho f'nmmif+"" nn
`• 1 upu1vu JJJ UP.,• VVlllllllLl!Jtt Ull
`National Formulary under the Supervision
`of the Council, by authority of the
`American Pharmaceutical Association
`
`OFFiCiAL FROM SEPTEMBER l, 1965
`
`Published by the
`
`AMERICAN PHARMACEUTICAL ASSOCIATION
`
`WASHINGTON, D. C. 20037
`
`1965
`
`PRINTED IN THE UNITED STATES OF AMERICA
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 3
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`

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`OFFICIAL COUPON-DO NOT REMOVE
`
`Notice and Warning
`
`Patent or Trade-Mark Rights-The inclusion in this National Formulary of any
`d111g in respecL to which patent or trade-mark rights may exist shall not
`be deemed, and is not intended W''li a grant of, or authority to exercisCi any
`right or privilege protected by such patent or trade-1nark. All such rights
`and privilege.s are versted in the patent or trade-;nark o>vner, and no other
`person tnay exercise the same without express permission, authority, or
`license set.'Ured fnun such patent or trade-mark owner.
`
`Compliance with 1'~ederal Statutes-The fact that an article appears in this Na(cid:173)
`tional Fonnul:iry does not exe1npt it from compliance with require1nonLs of
`Acts of Congress or with regulations issued by agencies of the United
`States Government under authority of these Act,s. Revisions of the
`Federal requirements which aiiect the National Formulary standards will
`be made the subject of N . .F. !ntoriin Revision Announcements nr Supple(cid:173)
`ments as promptly as practicable.
`
`Use of N. F. Text-The National Formulary text is fully copyrighLed. Authors
`and others wishing to use portions of the text must obtain pennission to do
`so through the Director of National Formulary Revli!ion (see page xx).
`
`© Copyright, 1965, by the American Pharmaceutical Association
`All rights reserved
`Library of Congress Catalog Card No. 55·4116
`
`Plated and printed by
`MAGI< PR!NTINC COMPANY, Easton, Pa.
`Distributed for the Association by
`MACK PUBLISHING COMPANY, Easton, Pa.
`
`ii
`
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 4
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`

`

`PREFACE
`
`outstanding scientific and
`:·;.The
`1111:111 t
`'iechnical discoveries and advancr~·-as
`'.~,.,11 as the sweeping and radical changes in
`£;;sonal philosOphJ, public attiLude, and
`llationa1 logislation--1vhich have occurred
`during the past five years, have inade the
`revision period leading to this edition of the
`:t~u.tional Formu!ary unpara!!eled in phar(cid:173)
`macentical and medical history.
`In
`meeting these cha.llenges, the preparation
`and coDtcnt of this volurne attest to the
`unlimited patience and exceptional efforts
`which were required from the Committee
`on National Formulary, along with its
`many collaborating curnL."'.ittees and in(cid:173)
`dividual advisors.
`The careful consideration exercised in
`selecting the drugs to be recognized in
`N .F. XII, coupled \vith the vigorous effort
`on the part of the revision Con1mitLec to
`1nove for\vard in adopting the benefits of
`inodern analytical science and technology,
`has resulted in the tests, standards, and
`specifications which are herewith presented
`for 783 important and valuable drugs and
`l\1oreover, it is expected
`dosage form8.
`that Lhesc dctern1incd efforts \vill bring Lhe
`National Forn1ulary again to the forefront
`as a wol'ld-lefl.rlin11 inf111An1'P in th_P: rlP:VP.lon-
`mcnt and uf:ili~:,t,i~~~-~f--~~;- P~hi~iPI~s. ~f
`drug standardization.
`Admissions Policy
`As its firsL ruajor action, the Con1n1ittee
`on National _Fonnulary struck down the
`pl~ilu:::;ophy of e:r,f.Bnt of u:ie a,R a Rignificant
`criterion in deterrnining; the drugs to be
`to
`this National Fonnulary.
`adn1itted
`The Committee instructed the N .. 1:1'. Ad(cid:173)
`visory Com1nittee on Adrnission:s to base
`its recom111endations for a.dmission solely
`therapeutic value.
`on
`This marked a
`significant denarture in N.F. oolicv. since
`extent Of use had historically been a-major
`criterion for admission t.o the cornpendium,
`as evidenced by the grp,a.t reliance pre(cid:173)
`viously µlaced upon prescription ingredient
`~L1rvcys.
`
`Tt. ii:.i int.Pw=>.<d.inO" t.o not8 t.hnt, hv adontinu:
`
`thi~- ~e;-~~c~li~J0 th-c :t-.~ational Form~larY
`anticipated the concern and subsequent
`action of the United States Congress w11en
`it introduced efficacy as a ne"\v requirement
`under the Federal Food, Drug, and Cos(cid:173)
`metic A.ct through the Drug Amendments
`of 1962.
`N.F. XII Content
`Following very closely the recon1menda(cid:173)
`tions of the N,F, Advisory Coinmittee on
`AdnllS1:1iuns, 248 new drugs and dosage
`forms were admitted to the twelfth edition,
`w·hilc 280 nrticlf!R which had been in the
`previous edition are no longer accorded
`N .Ii~. recognition. This virtually completes
`a full transition in the character of the
`National Formulary during the last decade,
`::;inl!e a Lota.I of 729 articles ha.ve been
`the
`last
`dropped from
`three editions,
`hPflinnin!rwit.h N.F. X which was uublished
`i;;J 955. '-'
`.
`The charact,er of the new adrnissions
`particularly reflects the critical medical
`judgment that attended the selection of
`these iten1s 1 which cover the full range of
`modern therapy.
`Tests and Assays
`Since the principle purpose of the Na-(cid:173)
`l?ormulary continues to be the
`tional
`establishment a.nd publication of official
`standards for drugs deemed ~vorthy of
`admission, the tests and assays presented
`for
`those articles are of considerable
`It is in this area that the
`cig;nificancc.
`greatest attention must Lo devoted by
`those responsible for the N.F. revision,
`because of the recognition accorded to the
`compendium standards under provisions
`·of the Federal Foodi Drug, and Cosrnetic
`Act and comparable laws of the individual
`states.
`Not unexpoctedlyi therefore, it will be
`noted
`that many modern
`i:tiul useful
`instrumental 1nethods of analysis have
`been newly introdu~ed1 and several of
`
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 5
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`been adopted fol' thr..se dosage funn~. The
`forrner weight va.riat,ion standard
`for
`stcriie solids has been cun1p1~tely revised
`and materially tightened.
`
`General Information
`\Vhlle the prirr1ary purpose of t,he Na(cid:173)
`tional Fonnulary is to provide drug ~~a.nd­
`ards and specifications, the value of the
`cornpendiurn as a convenient sou1·ce of
`reference t.o pharmacists 1 phyi)icians, and
`others, has not h(~en overlooked. Con(cid:173)
`sequently, sulJstantial a.dditi.onal informa(cid:173)
`tion has been incorporated in N .F. Xll
`to further its value in this rc~Jxd. ~\..
`chapter on federal regulat.ions pertaining to
`narcotic drugs anrl. a cross listing of drug
`names have been included in the General
`Information section. Discussions relating
`to various dosage fonns have been brought
`together in a new chapter on pharn1aceuti(cid:173)
`,vhich appears in the
`cal preparations,
`General Tests sr.ction. The index has
`been expanded to rrbout t,-1.vicc its former
`eizc to provide for easier reference and
`cross-reference of pertinent subjects. For
`the convenience of those using the I\J".F.,
`the follo~·ing table:-; ha.ve b<oen added:
`a1coholometric,
`aton1ic
`'.v1:;ights,
`exact
`equivalents of ,veig;ht,s and measureR, and
`t.hermornet.ric. equivalents.
`
`those i.vhich were employed for the first
`time in the previoui::. N .F. have nov.' been
`applied much inure widely. Gas-liquid
`f'.hromatography, flame speclrophoto1netry,
`thin-layer- chro1nato~raphy, polaro;.i;.raphy,
`and dclta-pll titrirnctry arc a.1nong the
`techniques inch1tled inltitotlly in N ~11'. XII.
`Many more procedures now call for the
`u;;;c of non~_qoeous titrirnctry! cornplcx(cid:173)
`ometry1 ultraviolet and infrared spect.ro(cid:173)
`photometry, radioisotope tracer dilution,
`and colu1nn and paper chron1fitography.
`~rhc General 'fcRts section is replete \YiLh
`new· geut:ra.1 procedures, inel11(lin~ new
`assays for alcohol, a1nphetamines, bar(cid:173)
`biturt1,te:-1i epinephrine cornpoundB, steroids,
`and several vitamins. 1'1any of the iong(cid:173)
`-accepted monographs no-..v have been pro(cid:173)
`vided with assays for the Ur-st time, and in
`the case of numerous other rnonograph1',
`a~~sr~ys h1-1vr: heen adopted.
`in1ptoved
`'Examination of the individual n1onographs
`wi11 reveal that attention has also been
`directed to other specifications ,vith the
`resu1t that improved identity tests a.nd
`purity tests are now provided for many
`articles. For example, one n1onugraph
`presently includes a limit test using thin(cid:173)
`Jayer chro1natography and a
`reference
`standard to eRtablish the absence of a
`possib1c irnpurity. Rven the long stanci.iug,
`paper-stain test proccdurc for arsenic has
`been replaced w·ith a. inore precise col(cid:173)
`orimetric method. •rhe ti1ne disintegration
`lirr1its for tablets h::i.vc: been drastically
`revised; over one-half of the tablets a<l(cid:173)
`mittc:d from N.F. X[ have had
`their
`disintegration tirnc limits reduced, and ln
`1nost cases the time limit, has been reduced
`by at least 50 per cent.
`Test Specifications
`Equally as important as the iniprovc-
`1ncntH in conducting the various te!:'!ts, has
`been the inLroduction of many n0w types
`of specifications in N .F, XII. Adoption of
`the nc"\-1/
`sper,ificat,i.on
`for
`the content
`uniformity of tahlets 1 and its application to
`a selected numb0r of highly potent drugs,
`is the result of evidence indicating the
`need for a requirement to de1nonstrate
`acceptable homogc:neity ·uf t,t1,blct fonnula(cid:173)
`'fhe need for standards l'Overing
`tions.
`the fill tolerances of creams, oinlments,
`and po\vders is recognized by the nev.·
`weight variation ::specification which luts
`
`NATiOl-..IAl FOR/-,A;ULA.RY Xii
`
`Formal and Style
`The two-column format adopted in N .F.
`XI was well received and it, has been con(cid:173)
`IIowevcr 1 Ll1e width
`tinued in N.F. Xll.
`of the individual columns l1as been nar(cid:173)
`rowed to provide for somew"lwJ. wider
`marg1ns. The flystematic chernical names
`have been plti.('.P,d below
`the graphic
`formulas to err1plw .. size their relationship to
`the structures illustrated, as well as to the
`empi.ri.cal fonnulas and rnolecular weights.
`spoctrophotornctric assay
`Ultraviolet
`ca1cuiations iu ·N .F. XI \yere Rbont. equally
`divided between those based upon ab-(cid:173)
`sorbance v~Jnes and those has<"..d upon
`absorptivity values. In the interest of ease
`of ca.lculatiou, virtually all of these mathc(cid:173)
`matica.1 formulas have been converted to
`calculations based upon absorhance values.
`
`Antibiotics Monographs
`One provi10ion 0£ Lhc Dru~ A.mend1nents
`of 1962 served to extend batch certification
`
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 6
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`NATIONAL FORMULARY XII
`
`of rrntibiotics by the FDA to a.U antibiotics
`and all antibiotic dosage forms. 1'he Com(cid:173)
`mittee on Xntional Forrnulary was deeply
`di::;lurbed by this unv.rarranied cncroach(cid:173)
`;nent upon 1.he Rt.andard s_etting rm:ipon(cid:173)
`sibilities ¥.rhich had been -~entrusted by
`Congress to private parties under the 1906
`and J !)38 food a.nd drug la,vs.
`Rather than risk the confusion which
`would unduubtedly result fro1n dual and
`possibly even conflicting standards, it was
`decided tn dis<'.ontinue snecifications and
`standards for antibiotics i in the National
`Formulary,
`l\:Ionographs, in abbreviated
`fonn, do appear in N.F. Xll for so1ne anti(cid:173)
`biotics in order to provide official recogni(cid:173)
`tion for them, to indicate their accepted
`therapeutic value as determined by the
`N.F. Advisory Committee on Admissions,
`and to give related information of interest
`to pharmaceutical and medical practi(cid:173)
`tioners.
`
`Nome!'!C!(!ture
`In recent years, probably no othf!r single
`subjeet pertaining to drugs has received
`mow~ attention fro1n Congress, enforcement
`agencies, purchasing departments, hospi(cid:173)
`tals, manufacturers, physicians, pharma(cid:173)
`cists, and the general public, than has drug
`It is not. surprising, then,
`non1enclaturc.
`that the National Formulary also has been
`deeply concerned ... :ith the mutter of drug
`name~'>.
`Most signifieantly, the Drug; Amend(cid:173)
`ments of 1962 specifically prohibit the
`official con1pendia from including more
`than one nan1e for any drug; furLherrnore,
`the law states that the na1no provided
`muHt ha:ve the attributes of u1:;efuh1~RR a.nrl
`'fhis required the N.F. Com~
`sin1plicity.
`mittee to eliminate all synonyms and to
`rcv1cv.· in dr.tail all monograph titles to
`ensure that the
`titles provided
`\\rould
`reflect
`t.ho elerucnts of ut>efulncss and
`simplicity specified in the law. Based
`Upon thiR review. it. will he noted tha.t a
`nu~ber of mon~gi·-aph titles have been
`rev1sctl from those \vhich '.verc previou::ily
`1Jrovidcd as the main titles. Furthermore,
`only one title or name appettirs with each
`~~~:;~~I.ap~i'c~i~~c~ilt~i:0f;?:~~~n1~av:rt~~r~
`Under the titlP-R anoearin(! in N.Ii'. XII,
`a cross-1·efcrenced li;t of 11Former Name;;';
`
`is provided 1n the ueneral intormation
`section. It should be noted that in addition
`to adopting n.. nurnber of simplified titles,
`the Committee on National Formulary
`has aL'3o established a policy of nan1ing
`salts by specifying thfl cation portion first
`and then the anion. This has resulted in
`the transpoRition of the tities for about ten
`salts.
`'l'he revie'.v and consider~.J.tion devoted
`to the tit.les of N.F. articles during the
`past five years has further pointed to the
`need for selecting a simple and useful
`nonproprietary naffie early in the history
`of each dru!!;iS introduction. Such a v1u(cid:173)
`ccdurc would elin1inate the undesirable
`choice of either admitting the drug under fl,
`grossly objectionable title or subjecting the
`article to the traumatic ordeal involved in
`changing the na1ne to a more acceptable
`title when it is admitted to the corn(cid:173)
`pendium.
`\.Vhile the National Formnlary has long
`participated informally in the selection of
`nonproprietary names for new drugs, this
`participation ~'as greatly intensified with
`the formation of the A1\1A.-USP Nomen(cid:173)
`clature Comn1ittee in 1961. As of ,Janua.ry
`2, 1964,
`the A_meriean PhannucL~l1Lioal
`Association, as publisher of the Xational
`Formulary t
`joined with
`the Americfl.n
`Tvicdical Association and the lJnited States
`Pharmacopeia in full cosponsorship of the
`nomenclature prograrn. Therefore,
`the
`National Formulary now participates
`formally in the t:>clceLio1:i oI appropriate
`nonproprietary drug names long before
`most of those article:-: 9_.r('; consirlerecl for
`admission to the N .F.
`Each of the three sponsoring organiza(cid:173)
`tions appoints mutually o..cceptablc mem(cid:173)
`bers to a committee known as the USAN
`Cou1u.:il, m1d the narcies adopted by that
`body are termed United States Adopted
`N8 .. mes (T_TSAN).
`
`Reference Standards
`Under the policy previously adopted,
`N .F. spectrophotometric assay procedures
`require the use of a reference substnnce.
`On this basis it has been necessu.ry to
`provide many ne,•1 reference st.andards
`becau::ie of the much greater applicat.ion of
`spectrophoton1ctric procedures in this edi~
`tion. Thus, the number of N.Ji'. Reference
`
`.~ ..
`
`
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 7
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`

`

`xviii-Preface
`
`NATIONAL fORMULARY XII
`
`Standards has been inf~reascd from forty(cid:173)
`two in N.F. XI to ninety-one in N.F. Xll,
`of which fifty-nine are being provided for
`the firsL time.
`Atnmic Weights
`The greatly revised l 961 list of Inter(cid:173)
`nationflJ _Atnrnic 'Veights, which is based
`upon carbon-12 rather than oxygen-16
`as t.he element of reference, has been used
`in preparing this edition of the I'{ational
`J!'ormulary'
`rrhi::i results in changes in
`n1ost of the molecular vi:ei~hts, as \vell as
`the factor employed in assay calculations
`9.nrl fllscwhere.
`Graphic Formulas
`the
`The graphic iormulas proviaea w
`monographs for organic compounds have
`been completely rev:orked to present them
`uniformly and systematically. Practically
`without exception 1 the graphic or structural
`formulas have been constructed around the
`nucleus dra\vU in accord with the style and
`numbering adopted by the Tnterna:Lional
`Union of Pure and Applied Chemistry
`(IUP .._A ... C) \>:hich is also the style a,dopted by
`Chemical Abstracts.
`Chemicai Names
`The chemical names of all organic cornM
`pounds ha vc also been exan1ined with a
`view to presenting them in a 1nore syR(cid:173)
`tcmatic fa-shion, in order th:tt. the relation(cid:173)
`ship between various 0drugs might be 1nore
`readily apparent. On this basis all chemi(cid:173)
`cal names ha\'C been replaced with the
`systematic chem.ical narne employed most
`recentiy by Chemical Abstracts as the
`niain entry for index purposes.
`
`Indication of Patent Status
`National Formulal'y drugs covered by
`patents are indicated by footnotes to the
`monographs concerned.
`'rhis designation,
`as far as it was possible to detcunine, ap(cid:173)
`plies to patents in effect at the time of
`publicntion of N .F. XII.
`
`Revision Processes
`Revision activities rclat,ing to the prep(cid:173)
`aration of N .F. XII were materially ex(cid:173)
`pa.nded. Subsequent to the co1npilation
`period--·which constitutes selection of the
`articles for admission and the drafting of
`
`suitable monographs- -the proposed con(cid:173)
`tent for K.F. XIT was distributed in ga.lley
`proof form to over 2.i=iO inlcrested persons
`for co1nn1cnt and correction. After in~
`corporating appropriate changes and cor(cid:173)
`rections, the text 'v::is t.hen circulated in
`page proof form to over 150 proofreaders.
`In each category this represented
`the
`largest number of N.F. proofreaders ever
`employed. A_n open conference or public
`hearing-the first conducted solely to con(cid:173)
`sider N.F. pag-e proof-wa,s then held on
`to vrovide a final op(cid:173)
`A nriJ 2:l. 106,1.
`p-~;t~nitY for ~ll interrn;;tcd persons to
`present theil· viCVi-'S on the proposed content
`of the new edition.
`
`Drug. Standards laboratory
`For many years the official compendia
`have re1_·ogni:r.cd the need for some direct
`laboratory facilities in spite of the in(cid:173)
`estirnable
`tirne and
`talent generously
`contributed by the many cornmittce mem(cid:173)
`bers as well as manufact.uring and govern(cid:173)
`rnent laboratories. Beginning in Janua.ry,
`1962, the American Th-fedical Association
`the Gnit-ed States Pharmacopeia
`fl_.nd
`therefore joined with the American Phar(cid:173)
`maceutival A.ssociation in sponsorship of
`faciliiies
`certain analytical
`iaboratory
`through the A.Ph.A. Foundation. The
`resulting laboratory is designated as the
`Drug Standards Laboratory and is housed
`in the Arnerican Institute of Pharmacy
`building in V1i'ashington, D.C. The pri(cid:173)
`mary purpose of this relatively modest
`facility is to provide direct, convenient
`la.boratory services to the N.l( and U.S.P.,
`a.s an aid
`in
`their re::ipective revision
`programs, and to supplement the sources of
`infonnation and assistance otherwise avail(cid:173)
`able to t,he1n.
`
`Interim Revision
`During the periods covered by the past
`seven editions of the i'~ational Formula.ry,
`it has been nece:-isary to issue interim re~
`visions fron1 time to time,
`:B'or example,
`four Interim Revision Announcement$ to
`N .F. XI \\'r,rc issued and became official
`January 1, 1961, May li l\J62 1 F'0b111ary 1,
`196:~, and M a.y 11 1963, respectively.
`to
`Interim Itevision 1\nnouncements
`this edition of the National Forn1ulary
`may be issued from time to time iu thE
`
`
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 8
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`

`

`'rm of releases to the pharn1accuticai
`reSs \vhich also 'Nill be published in one or
`ore of the periodicals of the A1nerican
`'l'het1e An-
`1armaccutical Association.
`'uncernents are designed
`to publicize
`omptly minor co1Tections and other
`visions of limited scope. Reprints of
`nterim Revision A.nnouncements will be
`T;11nade available only upon request ac-
`·bornµanied by an addressed and starriped
`'envelope.
`· 811nnlen1ents t,o N.F. XII, covering a
`wid~; ~scope than ctu1 be i~cluded ade(cid:173)
`quately in Interin1 _Revision Announce(cid:173)
`ments, may also be issued when necessary.
`Interim Revision Announcements pub(cid:173)
`lished prior to the issuance of a Supplement
`~·ill be incorporated in it. Supplements, if
`issued. will be published and publicized as
`described in the p1'eceding paragra.ph and
`copies will be mailed, \Vithout cost, to
`every o'Vi·ner of a J:\f ational Forroulary Xil
`who takes the µrecant.ion to fill in and mail
`'the "official order for:n" postal card 1.vhich
`is included inside the back cover of each
`book.
`
`Authority
`The National Formulary is revised by
`the Cornmittee on National Formulary
`under the direct authority and supervision
`of the Council of the American Phar-
`rrtaceutical }~ssocia.tion. The orgunization
`plan of the N.F. Committee, as revised in
`1961, is det1cribed in Chapter IX, Article V 1
`of the l3y-La.Vi'S of the A.ssociation as fol(cid:173)
`lows:
`'jThe Committee on National
`.Fonnulary shail consist of a Chairn1a.n m1J
`ten n1embers, each elected by the Council to
`serve fnr"' l orm nf fi~ro voi:11'>1 A nv vn1•.fl.ncv
`·~• ~ v~••••v• •••-J--·-• ----J ·--------,,
`occurring prior to t.he expiration of a ter1n
`may be filled by election for the unexpired
`period of that term. The Cornmittec shall
`elect a Vice-Chairman and a. Secretary
`fro111 its own me1nbers11ip. The Conunittcc
`shall serve as an executjve corrnnittee of
`revision of the Nntionn.1 Fnrmnlarv. 1'he
`Chairn1an of the Con1mittee on National
`:F'ormulary, \Yith the advice and consent
`of the members of the executive com1nittf',(\
`shall nominate to the Council additional
`participr~Ung rn.ernbers t(J the nurnber of
`not more than fiftyi
`to constitute an
`adviRorv nri,ni>:l on National Formularv.
`Subc~r~~rni't.-t.ee~ may be organized
`f0r
`
`generai or specific projects as required hy
`the executive committee. The Committee
`on !"-~ ati0nal Formulary shall rf!port an(cid:173)
`nually1 or as oft.en as ,required, to the
`Council. The Chair1nan will be designated
`as t.he Director of Revision of the National
`Formula.ry.''
`
`Significance and Functio.n
`l ne 1~ar;iona1 l' orrnuh-uy serves phar(cid:173)
`macists and pharmaceutical manufa.cturers
`hv 11r11vidinu· >it.HnrlRrrl!'! fnr thP. nrof'.nrRmflnt
`-J 1~•-••~•~·~o~v---··~--------- •----,-----
`of drul!,'S u8ed in dispensing, prescription
`coinponnding, and 1nanufacturing, and
`supplying formulas and working directions
`for the preparation of some dosage forms.
`lt provides 8ta.uJarJs for use by i:>tate r~nd
`federal food and drug law administration
`officials in their enforcernent nro!!fams.
`thus sirnplifying legal procedu;es.'""' Th{;
`activities and functions of the National
`Formulary also constitute an important
`service to the n1edical profession and to the
`public. The firsL
`three editions of the
`National Formulary served mainly as a
`convenience to pract.icing phn.rmacists by
`providing uniform names 1 uniforn1 formu(cid:173)
`las, ·and working directions fof the s1nall(cid:173)
`scale manufacture of pharmaceutical prep(cid:173)
`arations frequently prescribed by physi(cid:173)
`cittnti.
`Under the new criterion of therapeutic
`val·ue; a.f'! rleRr.rihP-rl in the paragraph on
`Admissions Policy, lhc National Fonnulary
`has also assumed added importance as a
`therapeutic guide for pharmacists and
`physicians. Taken together, those articles
`in the concurrent
`... vhich now· appear
`editions of the Nationa.l l~'ormula.ry and
`the United States Pharmacopeia, constitute
`the drugs of the greatest established incrit
`and the most generally accepted usefulness.
`Until 11106, when it was designated as
`one of the two official compendia by the
`-1-~"~•C• .... ~l-,,-,. li',,,.I,,,,,,] 1'',,,.,.I anrl n,.,,N T <>=
`VC:lUl•".I VI UUV .1..· VU.'-'''-"' .J. vvu. .__.u._. _.___,.'-'!ti ~·~••'
`the function and significance of Lhe Na(cid:173)
`t.ional Formulary remained unchanged.
`The provisions inherent in the 1906 law
`and the Federal Food, Drug, and Co~n1etic
`Act of 1938 and it.s amend1nents-par(cid:173)
`ticularly those enacted in 1962·" ·have in(cid:173)
`creased t.he obligation of those responsible
`for the revision of the National Formulary,
`and have added greatly to. its significance.
`'fhe position of the National Formulary
`
`t
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`
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`
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 9
`
`

`

`xx-Preface
`
`as a book of legal si.[l,ndnrrhi for drugs ls
`made clear by the references to it in the
`1938 Federal· Food, Drug, and Cos1neiic
`Act. Section 501(b) of this sLatute requires
`that drugs purporting to be those listed in
`the i-J ational Fonuu1ar-y 1nust conform to
`the standards of strength, quality, and
`n111~tv nrP.<::~rihPr:I. therein. All dctcrmina(cid:173)
`t"i~~~_, of-ti~~·se -standards must be made in
`accordance with the n1ethods preseribcd in
`the text. Variations from these standards
`arc permitted only \Yhen certain labeling
`requiren1ents of the /tct in<licatin~ the
`nature of the deviation are 1net.
`The same section of the . .\ct authorizes
`the U. S. Secretary of I-lealth, Education,
`and Welfare to prescribe tests where none
`have been provided or where those de(cid:173)
`scribed arc believed to be inadequate.
`13efore the Secretary can take such act.ion,
`however, he must first call to the attention
`of those responsible for the revision of the
`National _Formulary the need for additional
`or more adequate tests. He may then
`proceed only atter a reasona,01e 1,1111e u1:1.1:>
`clap::1ed, and the Committee on National
`Formula.ry has failed t-0 provide 3,d_eq11atc
`tests or rr1ethods of assay. Thus, 'vhile
`considerable recognition of N.F. standards
`is sho\vn in the Act, adequate checks and
`safeguards against omissions a.nd arbitrary
`or scientiiicaliy unHouncl spooifioations are
`also provided.
`
`1 1 -
`
`''--- -
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`'- .,.
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`Copyright Use
`The partial reproduction of the text of
`the National Formulary by periodicals 1
`textbooks and works of reference, for the
`purpose of con1u1en~, such as cannot be
`used as a subt:ititutc for the National
`Fonnulary, will be permit.t.cd, provided
`the for1n of reproduction is first approved
`hy the Comn1ittcc on Publications of the
`American Pharmaceutical AsRociation.
`The substantial reproduction of the text of
`the National Formulary in sueh a way as
`to permit of such reproduction heing used
`in lieu of the National Formulary is pro(cid:173)
`hibited, except after approval of the form
`and under agreement for co1npensation to
`be determined in each case by t.he Co1n-
`1nittee on .Publications and appruved by
`the (;ouncil of the An1erican Pharmaceuti(cid:173)
`cal A .. t1t:1ociation. Applications for use of
`
`t.:ATIONAL FORMULARY X!!
`
`coDvria:ht should be made to the Dir0ctor
`of .Revision of the .'..\ational Formulary.
`
`Coupon
`A coupon Vi'ill be founJ on the back of
`the title pf1g,'\ bearing the nurnbor of the
`copy and the following words: "National
`~01·m11litrv. 'rwelfth Edition. Officia.l Copy.
`C~-py;ight,' 1965, by the American Pha-r(cid:173)
`maceutical Association.i'
`1-~his coupon
`serves to identify an oHlcial copy of the
`National For1nulary and should not be
`rernoved.
`
`Assistance
`As specified in the By-Laws of the A.s(cid:173)
`sociation,
`the Com1nittee on National
`Fonnulary is charged with the primary
`re::;ponsibility for revising this L'.Otnpendium.
`1~here1'ore, Lhc greatest credit for the re(cid:173)
`vision of each edition of the N Ji'. naturally
`to tlu::i rf!spcr:tive N.F. Cornrnittcc
`C:OP.R
`responsible. The history of the National
`Formulary includes many competent and
`highly qualified conunittees, each of which
`made an admirable contribution. HowR
`ever, the revision cornmittee ;.vhich par~
`ticipated in the preparation of N.F. XII
`was csueciallv uniaue in that it was corn(cid:173)
`posed ~f a Woup (;f unusually knoVi•ledge(cid:173)
`able a.nd dedicated individuals, who gave
`generously of their time and efforts \vith
`but one purpose in mind-the con1pilation
`of the best possible }~ u tional Forrnulary.
`An undertaking as vast as the revision
`nro!!'.ram of the N.F. also requires the
`ina.~hRlling of numerous
`in(cid:173)
`talented
`dividuals and the organization of many
`::;pecial advisory bodies, in order that ail
`of
`the various areas of responsibility
`touched by this ofiicirtl compendium might
`be discharged in the 1nost knowledgeable,
`efficient. and appropriate n1annor. This
`~ation~l Form1llfiry-has been 1nost fortu(cid:173)
`nate in having the benefit of valuable
`advice and cooperation from many person,,;.
`The names of members of the NJ!'. A.d(cid:173)
`visory P11n~l and the various other special
`cornrnittees and panels are provided on
`()n pages xii and
`pages vi through xi.
`~iii, there is a list of those whose nt-tines do
`not appear as 1nen1bers of either the
`Advisory Panei or one oi Lhc spcciai curn(cid:173)
`mittees and pancfa 1 hut who voluntarily
`contributed tirne and knovi'ledge Ly furnish-
`
`
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1019 - Page 10
`
`

`

`· ATIONAl FORMULARY Xii
`
`Prefo1;e-xxi
`
`::-_:<_fi,iig informati~r~ and advic.e which was conR
`:--fSider-ed in rev1s1ng the various monographs.
`' -- Special a pprecia ti on is hereby expressed
`;io all of these individuals, since limitations
`,:,0f :~pace 1nake it impractical to recognize
`-it.heir specific contributions.
`As every administrator iti keenly av\rare,
`,-.ifficcess in any undertaking ultimately is
`:;-dependent upon the abilities and assistance
`rendered Uy his im1nediatc st.a.ff. 1'he
`Director of Revision had the benefit of a
`very dedica.t.P.d and loyal staff, the rnember::;
`of which compensated for their lirnited
`number by extending; them,selves on n1any
`occasions far beyond the ca.ii of duty.
`The considerable assistance of Dr.
`Samuel \V. (}uldstoin in a.11 phases of the
`revision program is kno\Vll to inany. Ho~r­
`ever, few fl.re a.v.·are of the rnajor role he
`has played in the N.F. Xll publication
`progra1n, which included his drafting and
`revising 1nuch of the manuscript vopy,
`reviewing and processing all of the proof1
`and con1piling and editing the entire index.
`AR the immedintc associate of the Director
`of R.r:viRion, Dr. Goldstein also was most
`instru1nental in assiBting to effect a l:l1nooth
`transition in the Office of the Director of
`1\evisioni a.fter the Director aSBumr,rl his
`position in 1960. The highest prai8C is
`due Dr. Goldotein for this and his Inany
`other contributions.
`}~.s sc~rc:;tary to the Director of llevision,
`IVIiss Beatrice Lyons a.gain assiRted most
`co1npeiently·-·making five editions of the
`:National l 1'unnulary on \vhich she has ieft
`her i1nµressiun. Rhe has had rel::iponsibility
`for preparing; all the rnanuscript and cor(cid:173)
`relating all corrections in proof.
`It has
`been through her faithful assistance and
`devotion to duty that publication i:ichcdules
`\Vere rnet and ~hat the volume is sub(cid:173)
`stantiaiiy free fron1 errors.
`1Jeeµ a1J(cid:173)
`prceiation is also -expreRsed tu J\ifrs. Niaria
`E. Cu.ssidy '.Yho contributed prominently
`in processing correspondence and syc(cid:173)
`teinatically 1naintaining records of
`the
`revision prograrn progress. T'ha.nks
`is
`likewise due l\irs. Clare H. Gee for as(cid:173)
`sisting in the preparation of 1nonograph
`copy and the index.
`'l'hc contribution of JYir. R.obert F.
`Steeves to various phases of the N .F.
`He-fcrcncc Standards program ic ackno\vl(cid:173)
`edgeJ. Particular recog;nition ir-; due to
`
`hirn for Ju:-; prepan1tion of the new chn.pter
`-on narcotic drug regulations ,vhich appears
`in the ()enet'.fl.i Infor1nat.ion section.
`'l'hc confidence in the Cornn1ittec on
`National Formulary v.rhich was demon(cid:173)
`stra.ted during this pa.st revision period by
`the A.Ph.A. Council and its Secretary, Dr.
`·was ;nost gra.tifyin~.
`\Vil1i~1u1 S. Apple 1
`In addition) the constructive interest sho,vn
`hy the Commit.tee on Public.;aLions and its
`chairman, Dean Linw-ood Ii'. Tice, pro(cid:173)
`vided a source of deep satisfaction.
`Staff rnembers of the federai Foo<l and
`Drug 1\d1ninistration have been a source