ML23157A245

From kanterella
Jump to navigation Jump to search
PRM-035-007 and PR-035 - 24FR13892 - Palladium-103 for Interstitial Treatment of Cancer
ML23157A245
Person / Time
Issue date: 04/06/1989
From:
NRC/SECY
To:
References
PRM-035-007, PR-035, 24FR13892
Download: ML23157A245 (1)
v • d • e


Text

{{#Wiki_filter:DOCUMENT DATE: TITLE: CASE

REFERENCE:

KEYWORD: ADAMS Template: SECY-067 04/06/1989 PRM-035-007 and PR-035-54FR13892 - PALLADIUM-103 FOR INTERSTITIAL TREATMENT OF CANCER PRM-035-007 and PR-035 54FR13892 RULEMAKING COMMENTS Document Sensitivity: Non-sensitive - SUNSI Review Complete

STATUS OF RULEMAKING PROPOSED RULE: PR-035 RULE NAME: PALLADIUM-103 FOR INTERSTITIAL TREATMENT OF CANCER PROPOSED RULE FED REG CITE: 54FR13892 PROPOSED RULE PUBLICATION DATE: 04/06/89 ORIGINAL DATE FOR COMMENTS: 05/08/89 NUMBER OF COMMENTS: EXTENSION DATE: I I 1 FINAL RULE FED. REG. CITE: 54FR41819 FINAL RULE PUBLICATION DATE: 10/12/89 OTES ON PROPOSED AND FINAL RULE SIGNED BY EDO. TATUS OF RULE FILE LOCATED ON Pl. TO FIND THE STAFF CONTACT OR VIEW THE RULEMAKI NG HISTORY PRESS PAGE DOWN KEY HISTORY OF THE RULE PART AFFECTED: PR-035 RULE TITLE: PALLADIUM-103 FOR INTERSTITIAL TREATMENT OF CANCER PROPOSED RULE PROPOSED RULE DATE PROPOSED RULE SECY PAPER: SRM DATE: I I SIGNED BY SECRETARY: 03/28/89 FINAL RULE FINAL RULE DATE FINAL RULE SECY PAPER: SRM DATE: I I SIGNED BY SECRETARY: 09/26/89 STAFF CONTACTS ON THE RULE CONTACTl: ANTHONY TSE MAIL STOP: NLS 129 PHONE: 492-3797 CONTACT2: MAIL STOP: PHONE:

DOCKET NO. PR-035 (54FR13892) In the Matter of PALLADIUM-103 FOR INTERSTITIAL TREATMENT OF CANCER DATE DATE OF TITLE OR DOCKETED DOCUMENT DESCRIPTION OF DOCUMENT 12/05/88 11/30/88 04/10/89 03/28/89 05/08/89 05/08/89 10/ 16/89 09/26/89 A THERAGENICS CORPORATION REQUEST TO MODIFY PART 35; IT WAS THEN ASSIGNED AS PETITION PRM 35-7. THE PROPOSED RULE WAS DEVELOPED IN RESPONSE TO THE PRM FEDERAL REGISTER NOTICE - PROPOSED RULE COMMENT OF ACR & AMER. SOC. OF THERAPEUTIC RADIOLO. (OTHA LINTON, ASSOCIATE DIRECTOR) (

1)

FEDERAL REGISTER NOTICE - FINAL RULE

DOCKET NUMBER PR. [7590-01] PROPOSED RULE ( 5 '/ ff< I 3 89 :J.) NUCIFAR RmJIA'IDRY CXl-1MISSION 10 CFR Part 35 RIN NO. 3150-ADll DOCKETED DOCXETING& SERVICE BRANCH SECY-NRC Palladium-103 for Interstitial Treatment of cancer AGENCY: Nuclear Regulatoi:y Ccmni.ssion. AcrION: Final rule.

SUMMARY

'Ihe Nuclear Regulatoi:y Ccmnission (NRC) is amerrlm;J its regulations goveminJ the medical uses of byproduct material to add palladium-103 as a sealed source in seeds to the list of bradlytherapy sources pennitted for use in the treatment of cancer. Urrler rurrent NRC regulations, users must have their licenses amemed before they use palladium-103. '!his amerment, prawlgated in response to a petitioo for rulemakinJ (PRM-35-7), will reduce the regulatoi:y burden on medical use licensees who plan to use the sealed source. An evaluation of the potential radiation hazards to hospital . pei:Sonnel arrl the plblic showed that there WCAl!d be minimal. risk if the sealed source is used in aa:::ordance with the manufacturer's radiation safety arrl harxiling instructions. EFF.EC1'IVE DM.'E: (Insert the date of plblication) FOR FURlHER INFORMATION CDNI'Acr: Or. Anthony N. Tse, Office of Nuclear Regulato:ry Research, U.S. Nuclear Regulatocy Ccmni.ssion, Washington DC 20555, telE!Eilone (301)492-3797. Pu J,},*5Ae j J" 1Ae (e J e r- <> / f<. (" ~, ~It r 01\\ /0-/J.-fq 4J fl/ Fl< l/lf 11

Pos!;;;2r'* v:>1e NJ) Cop~::; ~..... ~. ::-:----, --- _______ Add'! Co~--::: :'c,_-:*A:..~.en J ______ _ ,pedal Di:alrib;ie,;i /J h n 1) l......._ __

SUPP.IfflENI'AR INFORMATION: Petition for :Rulemak:irg On November 30, 1988, 'llleragenics Corporation sul::anitted a petition for

rulemaki:rg, PRM-35-7, whidl was dcx::keted en T'le(:PJri:)er 9, 1988.

'lbe petitioner requested that the NRC amerrl its regulations to aa3. p:tJJadi:um-103 as a sealed source in seeds for the interstitial treatment of ~ to the list of sealed sodrces an:nmt.J.y :pennitted in 10 CFR 35.400 far use in.brachytherapy. 'lbe petitioner stated that, urmr current NRC regulations, licensees vBlD are users of p:tl J adium-103 llJ.lSt go thl:a1gh the ambersane process of ha.vin;J their licenses amamed before l.lSmJ the product ani that amerx:li.rg 10 CFR 35. 400 in the ma.rmer suggested -would eliminate this cunt>ersane process. In st.:gXrl.ing the petition, the petitioner sutanitted seve:ral. doc::um:mts, inclt:rlir.g a letter fran the FDA, a safety evaluation rep:lrt frail the state of Georgia, the package insert, am product literature. 'lbe letter fran the FDA stated that, unier Section 510 (k) of the Federal Food, Drug, am Coslootic Act, as amen:led, m:rketirg the device (palladimn-103 as a sealed source in seeds) wcw.d be permitted subject to the general controls provisions of the Federal Food, Drug, ard Cosmetic Act until such tine as the device has been classified as either a Class I, II, or III device um.er Section 513. Class I devices require general controls, that is, registration am good ma.nufacturirg practices. Class II devices require perf01'.1IlaIX::e stamards in acklitian to general controls. Class III devices require prior FDA awrovaI of a Pre-Market AwrovaI. application, perfonnance sta:ooards, am general cont:rols. In Jar.uai:y 1988 (53 FR 1554), FDA classified radionuclide bradlytherapy scurces as Class II devices. 'lb.is :pennits 'lheragenics to cxntinue marketin:J the p:tl J ad]tnn-103 seeds. In March 1986, 'lllera.genics, an "Agreement state" licensee of the state of Georgia, sul:lllitted infannation on the :radiation safety properties of palladimn-103 to Georgia in order to ct>tain a "Certificate of Registration." SUch a certifica.te is necessary for 'lheragenics to ma:rufacture am distribute pal J adimn-103 seeds to specific licensees. 'lbe infacnatic:n on these safety prcperties in:::11.Xled the design am canstructic:n, prototype testin:J, ccn:litians of oorma] use, labelin;f, external radiation levels, solubility in body fluids, 2

arrl quality control an:i assurance. After reviewi.rg the infonna.tion an:i detenninirg the adequacy of the radiation safety properties of the source, the state of Geo1.'gia issued a ~ficate of Registration to T.he.ragen:ics on September 22, 1986. '1his certificate sumnari.zed the sul:mitted radiation safety infonna.tion am specified additiooal limitations and corditians on the use of the source. 'lhis certificate was amen:Jai in its entirety on June 6, 1988, to incl.ude a miD:lr design illlprovement made by T.he.ragen:ics. Fbllawin:J its detennination that the radiation safety prcperties of the source are adequate, the state of Georgi.a sent NRC a cq,y of the certificate to include in the Regisb:y of SaJrce arrl Imice Designs that is maintained by the NRC. 'Ihe NRC reviewed the certificate for CXlllSistency with other certificates in the Registry arrl. added palladh1lll-103 to the Regisb:y on October 29, 1986, arrl again in June 1988 to CXNe.r the minor design improvement. 'lhis action, in effoot, granted a pra:narketin;J awrc,vaI of the seale::i source arrl permitted the use of palladium-103, provided the user's license was ame:rrled to include that sealed source. Propose::i Anerlnelt an:i Public a:mnent After cxmsi.derinJ the petition, the NRC p.1blished a proposed a:merrlroont grantirg the petition for a 30-day p.1b].ic cnmoent period (54 FR 13892, April 6, 1989). One o:.tnne1It letter was :received. 'lhe cx:mnent letter, sul:mrl.tted by a madical professional a:tganization, SL1pJ;X)rted the petition. 'Ihe letter stated that "this would Weed alleviate burdensame current NRC regulations that :require users to ameni their licenses before usirg palladium-103." Conclusion 'lhe NRC has determined that the addition of pallad.ium-103 as a sealed source in seeds to the list of seale::i soo:rces specifie::i in § 35. 400 will not cause additional risk to hospital personnel or the public beca119e the radiation safety ar.rl ban::UinJ inst.n1ctioos to be used for pallacUum-103 are the same as the instnx::tioos used currently for the bradlytherapy sources listed in § 35.400. 'lhis action will :reduce the regulat:acy h.n:den to the 3

users of P3J J ad] i:nn-103 seeds (alx.ut 700 p:>tenti.al users) as 'Well as to the NRC staff. )Dst users will not have to follcw the pnasent requirement of sub.nittin;J inilvidual lia:mse aman:1ment awllcations in order to use palladium-103 as a sealed sa.rrce in seeds for the interstitial trea:tment of cancer (if their license pemits the use of any brachytherapy sources specified in§ 35.400). A user whlse license cmly pe:rmits the use of specified bra.dlyt:herapy sources will still be required to sub.nit a license ame.rxhnent application. But for mst llc:ensees this rule will el~te the license ane:rlnV:?nt awlicaticn pnx:::ess am the review' am approval process for the NRC. 'llllls, the NRC is am:n.:lirq § 35.400 to add ptlladium-103 as a sealed source in seeds for the interstitial trea'bnent of can:::er. Envirornrerrt:a Ilq;)act.: categorical Exclusicn 'Iha NRC has determined that this final a:men:lment is the type of action ,. -described in 10 cm 51.22(c) (2). 'Iherefore, neither an envi:ram:mtal irrpact ~ statement nor an envi:rarmental assessmerrl: bas been prepared for this ame.rxhnent. Pa.peJ:wo:rk Reductiai Act statement IJhis final a:men::iioont does not contain any new or amen:ied infonnaticn collection :requirea1elts subject to the Paperwork Reduction Act of 1980 ( 44 u.s.c. 3501 et seq.). Existirg requi.re:oont:s were approved by the Office of M:lnagaient am Budget, approval mmi:ier 3150-0010. Regulatory Analysis 'Ihe NRC has prepared a regulato:ry analysis en this a:men:lment. 'Ihe analysis examines the costs am benefits of the alternatives considered by the NRC. 'lhe analysis COJX.lu:les that the ~ of the amerrlment will not ~ the risk to the public health am safety but will redi1ce the cost to the IOO:dical use licensees wi1o plan to use P3JJadium-103 sealed sources. Interested persons :nay examine a copy of the regulatory analysis at the NRC Public Ikx:moont Roam, 2120 L street, NW. (Lower Ievel), Washir:gton, OC. 4

Sin]"le cx,pies of the regulatm:y analysis nray be ootai.ned fra:n Dr..Al1thany N. Tse (See FOR FOR.I.HER JNFOR.!ATIOO axrACl' heading")

  • Regulatory Flexibility certification As required by the Regulatm:y Flexibility Act of 1980, 5 u.s.c. 605(b),

the O:mni ssian certifies that this amemment does not have a significant ecax:mrl.c impact en a sul:stantial number of small entities. 'Ibis amemment I adds the use of pallad1~103 as a sealed san::oe in seeds in 110 CFR 35.400. 'lhis actim will reduce the regu.lat.aey birden m JOOdj cal use licensees plamti.n'.J to use the sealed san::oe by eliminatin]" the requirement of sutmittirg a license amendment ai;:plicatim. '!be NRC has adopted size stamards that classify a hospital as a small entity if its a:rn..ial gross receipts do JXJt exceed $3.5 million, an:i a private practice J;i1;ysician as a small entity if the

i;ilysician's armual gross receipts are $1.0 mill jan or less.

Alt:hol:.gh sane NRC 100d.i.caJ use licensees cx:uld be considered. "small entities," the rnnnber that woold fall into this categcn:y does JXJt constitute a substantial number for pn:p:ses of the Regulatm:y Flexibility Act. Backfit Analysis r 'Ble NRC bas detennined that a back.fit analysis is JXJt required for this amendment because the action does not constitute a back.fit as defined in 10 CFR S0.109(a) (1). List of SUbjects in 10 CFR Part 35 Byproduct material, D:ru;Js, Health facilities, Health professims, Ircorpor:atim by refenn::,e, Jte:iical. devices, Nuc.l ear materials, Occllpatimal safety an:1 health, Penalty, Radi.at:i.cm protection, ~ an:1 reco:rdkeepirq requirenents. 5

Far the reasons set out in the preamble and. uooer the authority of the Ataidc Energy Act of 1954, as an:erx:led, the Energy :Reorganization Act of 1974, as a:me:nded, and. 5 U.S.C 552 and. 553, the NRC is adopting the followirg ~ to 10 CFR Part 35. PAR!' 35 - MEDICAL USE OF ~ MAT.ERIAL

1.

'!he authority citation for Part 35 is revised to read as follows: AIJIIK>RI'IY: Secs. 81, 161, 182, 183, 68 stat. 935, 948, 953, 954, as aioorx:Jed (42 u.s.c. 2111, 2201, 2232, 2233); sec. 201, 88 stat. 1242, as amended (42 u.s.c. 5841). For the purposes of sec. 223, 68 stat. 958, as amen:ied. (42 u.s.c. 2273); §§ 35.11, 35.13, 35.20(a} an::l (b), 35.2l(a) and. (b), 35.22, 35.23, 35.25, 35.27(a), (c) an::l (d), 35.31(a), 35.49, 35.50(a)-(d), 35.5l(a)-(c), 35.53(a) an::l (b}, 35.59(a)-(c), (e)(l), (g) an::l (h), 35.60, 35.61, 35.70(a)-(f), 35.75, 35.80(a)-(e), 35.90, 35.92(a), 35.120, 35.200(b), 35.204(a) an::l (b), 35.205, 35.220, 35.310(a), 35.315, 35.320, 35.400, 35.404(a), 35.406(a} and. (c), 35.410(a}, 35.415, 35.420, 35.500, 35.520, 35.605, 35.606, 35.610(a) ani (b), 35.615, 35.620, 35.630(a) an::l (b), 35.632(a)-(f), 35.634(a)-(e), 35.636(a) and. (b), 35.64l(a} ani (b}, 35.643(a} ani (b), 35.645(a) ani (b), 35.900, 35.910, 35.920, 35.930, 35:932, 35.934, 35.940, 35.941, 35.950, 35.960, 35.961, 35.970, arrl 35.971 are jssned under sec. 161b, 68 stat. 948, as amended (42 u.s.c. 220l(b)); and. §§ 35.14, 35.2l(b), 35.22(b), 35.23 (b), 35.27(a) and. (c), 35.29(b), 35.33(a)-(d), 35.36(b), 35.50(e), 35.51(d), 35.53(c), 35.59(d) and. (e)(2), 35.59(g) and. (i), 35.70(g), 35.SO(f), 35.92(b), 35.204(c), 35.310(b), 35.315(b), 35.404(b), 35.406(b) an::l (d), 35.410(b), 35.415(b), 35.610(c), 35.615(d)(4), 35.630(0), 35.632(g), 35.634(f), 35.636(c), 35.64l(c), 35.643(c), 35.645, an::1 35.647(c} are issued under sec. 1610, 68 stat. 950 as amended (42 u.s.c. *2201(0)). 6

2.

In § 35.400, paragrai;n (g) is added to :read as follows: § 35.400 Use of sources for bradlytherapy. (g) PaJladium-103 as a sealed source in seeds for inte.rstitial treatment of cancer. Dated at Rockville, Ma.:r.yl.ard, this 2 C- -M day of-~ , 1989. For the Nuclear Regulatory o-mnj ssian. 7

DOCKET NUMBER PR :3/4&: PROPOSED RULE ~--..a..-NUCIFAR- ~ CXM'ITSSIOO ( SY ff< I 3 gq:).) (7590-01] 10 CFR Part 35 DOCIG:TED RIN ID. 3150-ADll Palladhnn-103 far Interstitial Trea:tmant of carx::er AGENCY: Nuclear Regulatory Q:mniss:lcm. ACI'IOO: Final :rule. stff.!ARY: 'Ihe Nuclear Regulatory Qmniss:lcn (NRC) is amen:lin:J its regulations gavei:n:iig the n:edical uses of byprodllct material to aai paJJadium-103 as a sealed source in seeds to the list of brachyt:herapy sources pennitted far use in the treatment of cancer. UJ'x:ier run:e1t NRC regulatims, users JIJ.lSt have their licenses amen:ied before they use palladium-103. '!his ane-rlment, pramlgated in response to a petitioo for rulenak:iDJ (:£lRtl-35-7), will reduce the regulatory burden an n:edi cal use licensees 'Who plan to use the sealed sruroe. An evaluati.cn of the potential radiation hazards to hospital persame1 am the p.1blic sba"1Erl that there wruld be minimal risk if the sealed source is used in accordance with the marufacturer's radiaticn safety am harrllirg in.structions. EFFECl'IVE CWI'E: (Insert the date of plbl.i.catial) FOR FURi.HER rnFCR'1ATIOO' cr.NrACI': Dr~ AntlDiy N. Tse, Office of Nuclear Regulatory :Researdl, U.S. Nllclear Regulatory Omn1ssian, washinfton oc 20555, telephone (301)492-3797. ' Pu J,/,*~Ae. j } " f Ae {e Jere} I R.e~ Isle. OT\\ /0-/J-fq LJ 5" l/ Fl< l/1 f 11

SUPP.I.EMENrARY INFORMATiai: Petiticn for Rll1emaki.rg On November 30, 1988, 'Ihe:rageni.cs Cocp:n:ation subnitted a petition for

  • rulemaki.rg', ::EH+-35-7, which was dcx::keted ai.cen=,,aer 9, 1988. 'lhe petitialer request:e:i that the NRC amen:1 its :cegu.l.at:ioos to aai palJacUum-103 as a sealed sa.n:ce in seeds for the interstitial t.ceatment of oana:r to the list of sealed sa:rrces cun:ently pe:cmitted in 10 CfR 35.400 for use in b.rachyt:berapy.

'lbe petitioner stated that, umer cu::a:erit NBC z:egu]..at.ia1s, licellSees 'Who a:ce users of paJJad:h:nn-103 must go tb:ca:ljb. the ambersare process of havi:rg their licenses anax1ed before usinJ the pccduct a:rd that amernin;J 10 CFR 35.400 in the manner ~ 'WCUld eliminate this a:mi'ersale process. In ~ the petition, the petitioner sutmitted several doc:uments, irci.tnin;J a letter fran the Fil\\, a safety evaluaticn zeport :fran the state of Geacgia, the package insert, ard prcduct literatm:e. 'lhe letter fran the Fil\\ stated that, mner sectim s1o(k) of the Federal Food, Ilr:\\J3', and ccsmetic Act, as amended, market:ln.;r the device (pall adi1:nn-103 as a seal ed. source in seeds) 'WtlUl.d be pe:cmitted subject to the general cxm:rols pn:wisicns of the Federal Food, Drug, a:rd ccsmetic Act until such time as the device has been classified as either a Class I, II, or III device urx:'fer Secticn 513. Class I devices r:equire general cxm:rols, that is, zegistraticn* a:rd gaxi marufacturing practices. Class II' deYices require perfonDanc:e st.arda:ros in additicn to general caxtrols. Class III deVioes requil:e prior* FDA ~ of a Pre-Hal:ket Approval ai;:plicatial, pe:rfcn:man=e st:a:rda:rds, a:rd general cart:rol.s. In Jarun:y 1988 (53 FR 1554), FDA classified radionuclide brachytherapy sairCeS as Class II devices. 'lhis pernd ts '1heragenics to continue marketir:g the pal J adinm-103 seeds. In Ma:r:dl 1986, 'lheragenics, an "Agreement state" licensee of the state of Geacgia, sul:mitted infcmnaticn on the radiaticn safety properties of paUadi.1:nn-103 to Geacgi.a in order to obtain a "cm:tificate of Registration." SUch a certificate is nea?SSaJ::Y for 'Iheragenics to manufacture arxi di.stri.bute palJadium-103 seeds to specific licensees. 'Iha infonnaticn m these safety prcperties included the design arxi c:a'lSt:cuctian, prototype testin:J, corxiltions of n::xr:naJ use, Jabelin:], extemal radiation levels, solubility in l:xxiy fluids, 2

am quality cx.11t.:ro1 am assurance. After reviewin;J the infonnatim am detenni.nin;J the adequacy of the radiaticn safety prq>erties of the sam:e, the state of Georgia issiied a Certificate of Rsgistraticn to 'lheragenic::s on September 22, 1986. 'lhis certificate sumiarized the sJtmitted radiation safety infcmnatim am specified ad:litiooal lilnitatials am caniitions on the use of the sarrce. 'lhis certificate was BIDE!m8d in its entirety en June 6, 1988, to irci.ude a minor design inprovement made by 'lberagenics. Follc:,.rln:J its datenninati.cn that the radiation safety prq>erties of the srurce are adequate, the state of Georgi.a sent NRC a cq,y of the certificate to iml.tm in the Registcy of Srurce am Device Designs that is naintained by the NRC. 'lhe NRC reviewed the certificate for consistency with other certificates in the Registcy am acxied pal 1 acUum-103 to the Registcy en Oct:cber 29, 1986, arxl again in June 1988 to CCNer the :mimr design iIIprcvement. 'llris acticn, in effect, granted a premarketin:J awroval of the sealed san:ce am permitted the use of paJJadiurn-103, provided the user's license was amerDed. to iml.we that sealed san:ce. Pl.Ofosed Amenmert: am Public O liiiirilt After coosiderinJ the petiticn, the NRC pmlished a prqxlS8d amesdnei1t grant:inJ the petiticn for a 30-day plb].ic cc11u1e1,t period (54 FR 13892, .April 6, 1989)

  • One o: a@e rt: letter was :received. 'llle o 111,ent letter, suhnitted by a madi.cal. professiooal. organizatim, Slgxnted the petitim. 'Iha letter stated that "this wall.d imeed alleviate b.Irdensane curre1rt: NRC regu1.atials that require users to arnem. their licenses before usin;J pall adi11m-103
  • 11 Ccrclusiat

'lhe NRC-has detelJnined that the additim of pal l aditnn-103 as a sealed scm:ce in seeds to the list of sealed scm:ces specified in § 35. 400 will not cause aalitialal. risk to hospital pm:san)e]. or the p.iblic because the radiaticn safety am l:larxilm3' insb:uctions to be used for paJlacUlllll-103 are the same as the instructials used arrrentl.y for the bra.chytherapy sarrces listed in § 35.400. 'Ibis acticn will reduce the regul.atm:y ru:rden to the 3

users of paJ J adirnn-103 seeds (about 700 potential users) as ~ as to the NRC staff. Most users will not have to follai, the present requirement of sumdtt:lDI inti.vi.dual. lioenge amet.dneut ai:l)l.ications in order to use paJJac:Uum-103 as a sealed soorce in seeds far the interstitial trea:bnent of carrer (if their license pennits the use of any brad1ytherapy soorces specified in§ 35.400). A user li.hose lic:ense mly pemits the use of specified brad1ytherapy san:ces will still be recpired to sul:mit a license a:memnB1t awJ.icatian. But far DDSt 1 this rule will e1ilninate the license amer-.dmeut aw].icati.cn IA' an:l the review an:l 8R)rOVal prcx:e:s far the NRC. 'llms, the NRC is ameniln;J § 35.400 to add pall ac:Jinm-103 as a seal ed. sa.m::e in seeds far the interstitial b.eal:nsnL of c::arr.er. EmTinmmental. Dipact: categorical Exclusion 'lbe NRC has detennined that this final ametdnsut is the type of actic:m

described in 10 cm 51.22(c) (2). 'lberefare, neither an erwirarm3ntal inplct statenent mr an enviramsntal. ass-asrnent bas been prepared far this I

amemnext. Papezwark Rsdootion h::t. st:atanent 'lhis final amemment does not cart:ain any. new or amemed infonnatiai collecticn requirements subject to the Papezwark Reductial h::t. of 1980 (44 u.s.c. 3501 et seq.). EKi.stm;J requirements~ approved by the Office of Management am axlget, approval rnJTOter 3l50-0010. Regulatmy Analysis 'Ihe NRC has prepared a regulatacy analysis m this amemment. 'Ihe analysis examines the costs am benefits of the altematives CCllSidered by the NRC. 'lhe analysis cx:n::l:ooes that the adoptim of the amen:lment will not irx:rease the risk to the p.lbl.ic health am safety rut will redlice the cost to the m?rlical use licensees 'Who plan to use paJJadhnn-103 sealed soorces. Interested persons may examine a ccpy of the regulatory analysis at the NRC Public Dcx::ument Reem, 2120 L Sb::et=t, NW. (I.a.te:" I.evel.), washin:Jtai, OC. 4

Sin;Jle cq;rl.es of the regul.atocy analysis may be cbtained fran Dr. Anthal;y N. Tse (see FCR FORIHER INFt:R4ATICN cnmcr headin;J)

  • Regul.atol:y Flexibility Certifi.cat.iat As required by the Regulatm:y FJex:lhility h:t of 1980, 5 U.S.C. 605(b),

the o:,mni ssian certifies that this amemment does not have a significant ecax:mic inpact ma sul:stantial. rurobe:r of small entities. 'Ibis amen:lmaut adds the use of paJJadhm-103 as a sealed san:oe in seeds in 10 CFR 35.400. 'Ihis acticm will reduce the TEgll.atm:y l::mden m merli cal use licensees p1.arm:in; to use the sealed saJrCe by eliminat:ln;J the req.rlxement of sumdttinJ a license amemment. ~- 'lbe ~ has adc.pt:ed size st:amams that classify a hospital as a small entity if its arnJal. gross receipts do not* exceed $3.5 millim, and a private practice J;iiysician as a small entity if the piysician' s annual gross receipts am $1. 0 mill i m or less. Al tbc:llJgh sane NRC medical use liceusees owl.d he considered "small entities," the rnJJDbe:r that llO.ll.d fall into this cat:eg:n:y does not c:xmstitu:te a subst:mitial. niJDi>e:r far-PJZPCSBB of the Regulatm:y FJexibi l ity }.ct. Badcfit Analysis 'Ibe NRC has deteilni.ned that a hackfit analysis is not required far this amenlme!It heauJse the act:i.cn does mt constitute a hack:fit as defined in 10 cm so.109(a) (1). List of SUbjects in 10 CFR Part 35 Byproduct naterial., Ilm;16, Health facilities, Health professims, IncoJ:poratim by refm:euce, Had.ical. devices, Nuclear materials, Occlp8.t-..ialal. safety and health, Penalty' Radi.atim protectial, Rsportirg and recordkeepiD;J

re(Jlirenents.

5

For the reascns set out in the preaniJl.e an:i unier the authority of the Atanic Energy Act of 1954, as ame:rned, the Energy :Recn:ganization Act of 1974, as anen:ied, an::i 5 U.S. C 552 an::i 553, the NRC is a.dopt.in;J the follc:Mi.n:J amerrlment to 10 CFR Part 35. PARl' 35 - MEDICAL USE OF BYIRX.OCr MATERIAL

1.

'lhe authority citation far Part 35 is revised to read as follor.,,,g: ADIJmI'IY: Secs. 81, 161, 182, 183, 68 stat. 935, 948, 953, 954, as amerrled (42 u.s.c. 2111, 2201, 2232, 2233); sec. 201, 88 stat. 1242, as amerrled (42 u.s.c. 5841). For the p..n:poses of sec. 223, 68 stat. 958, as 8lD9!'rled (42 u.s.c. 2273); §§ 35.11, 35.13, 35.20(a) am (b), 35.21(a) an::l (b), 35.22, 35.23, 35.25, 35.27(a), (c) am (d), 35.31(a), 35.49, 35.50(a)-(d), 35.51(a)-(c), 35.53(a) am (b), 35.59(a)-(c), (e)(l), (g) am (h), 35.60, 35.61, 35.70(a)-(f), 35.75, 35.80(a)-(e), 35.90, 35.92(a), 35.120, 35.200(b), 35.204(a) am (b), 35.205, 35.220, 35.310(a), 35.315, 35.320, 35.400, 35.404(a), 35.406(a) am (c), 35.410(a), 35.415, 35.420, 35.500, 35.520, 35.605, 35.606, 35.610(a) an::i (b), 35.615, 35.620, 35.630(a) am (b), 35.632(a)-(f), 35.634(a)-(e), 35.636(a) arrl (b), 35.641(a) am (b), 35.643 (a) arrl (b), 35.645(a) an:l (b), 35.900, 35.910, 35.920, 35.930, 35.932, 35.934, 35.940, 35.941, 35.950, 35.960, 35.961, 35.970, am 35.971 are issued urrler sec. 16lb, 68 stat. 948, as amerrled (42 U.S.C. 2201(b)); an:i §§ 35.14, 35.2l(b), 35.22(b), 35.23(b), 35.27(a) am (c), 35.29(b), 35.33(a)-(d), 35.36(b), 35.50(e), 35.5l(d), 35.53(c), 35.59(d) am (e) (2), 35.59(g) an:i (i), 35.70(g), 35.80(f), 35.92(b), 35.204(c), 35.310(b), 35.315(b), 35.404(b), 35.406(b) arrl (d), 35.410(b), 35.415(b), 35.610(c), 35.615(d)(4), 35.630(c), 35.632(g), 35.634(f), 35.636(c), 35.64l(c), 35.643(c), 35.645, an:i 35.647(c) are issued urrler sec. 1610, 68 stat. 950 as anezned (42 u.s.c. 2201(0)). 6

2.

In § 35.400, paragrap1 (g) is aa:led to read as folla.,.is: § 35.400 Use of scurces for bradlytherapy. (g) PaJJacUum-103 as a sealed sarrce in seeds for interstitial treatment of can::er. ll:ited at Rockville, MaJ:yl.am, this,2.t, ~day of~, 1989. For the Nuclear Regulatacy ca,,ni ssi.ai. Executive Director for q:,eratians. 7

CD Otha W. Linton Associate Executive Director

  • a9 MAY -8 P 3 :36 May 8, 1989 Secretary U.S. Nuclear Regulatory Commission One White Flint North 11555 Rockville Pil<e Rockville, Maryland 20852 Attention:

Docketing and Service Branch To Whom It May Concern: t,ft: bocKL, :,

";/'.'..N *

~The following comments are filed on behalf of the 20,000 members of the American College of Radiology (ACR) and the 3,000 members of the American Society of Therapeutic \\ Radiology and Oncology (ASTRO ) in response to the proposed rule Palladium-103 for interstitial treatment of cancer published in the April 16 Federal Register, Page 13892. The ACR and ASTRO support the proposed rule that would add Palladium-103 as a sealed source in seeds to the list of brachytherapy sources permitted for use in treatment of cancer. This would indeed alleviate burdensome current NRC regulations that require users to amend their licenses before using Palladium-103. The ACR and ASTRO agree that adding Palladium-103 to the list of sealed sources would not cause additional risk ~"~ hospital personnel or the public, as the radiation .-~afety and handling instructions for this source are similar to instructions for other brachytherapy sources. We appreciate the opportunity to be able to comment on this proposed rule. Sincerely, ~ luL-- Otha w. Linton ~ Associate Executive Director OWL/pgm MAY 2 5 f!la<J AMERICAN COLLEGE 0 F RADIOLOGY 1891 Preston White Drive, Reston, Virginia 22091 (703) 648-8900

?'~t. f, ~ (..( ' -~ 1 ! Add' I C-::~ 0 s :'.,, r &pociel D,rtribut,cn f )j f._ R.JQJ

DOCKET NUMBER PR 3J" PROPsi RULE { r I?. I 3 l2utATORY ANALYSIS 10 CFR PART 35 PALLADIOM-103 FOR INTERSTITIAL TREATMENT 6

1.

STATEMENT OF PROBLEM

2.
3.

10 CFR 35.400, "Uee of Sourcee for Brachyt specific radioactive sealed sources that ma treatment of cancer in brachytherapy. In De- --Ar NRC received a petition for rulemaking filed 6 :.-.. 1',~,i-~ Corporation dated November 30, 1988 (docketed PR~- ~ ~ amend 10 CFR 35.400. The petitioner requested that the NRC amend its regulations to add palladium-103 as a sealed source in seeds for interstitial treatment of cancer to the list of sources specified in 10 CFR 35. 400. The petitioner stated that, under the present regulation, users of palladium-103 must go through the cumbersome process of amending their licenses before they can use the product and that amending 10 CFR 35.400 would eliminate this cumbersome process. OBJECTIVES NRC's objectives are to protect the health and safety of workers and the public in the licensing of byproduct materials for medical uses. The State of Georgia, an "Agreement State" which licenses Theragenics, performed safety evaluations of the use of palladium-103 and issued a Certificate of Registration. Subsequently, the NRC reviewed the certificate for cons~stency with other certificates in the Registry of Source and Device Designs and added palladium-103 to the Registry. This action, in effect, granted a premarketing approval of the source and would permit the use of the sour~~ pr~vided -t.hat the user.' a license was amended to incl ude the source. ALTERNATIVES There are only two alternatives: (1) Maintain the status quo, i.e., a licensee seeking to use palladium-103 must first apply for and obtain a license amendment permitting the use; and

(2) Amend 10 CFR 35. 400 to include palladium-103 as a sealed source in seeds for interstitial treatment of cancer.

4.

CONSEQUENCKS

5.

In terms of the public health and safety, both alternatives would permit the use of palladium-103 as a sealed source in seeds for brachytherapy, thus, there would be essentially no difference between the two alternatives. In terms of cost, alternative 2 would be less burdensome for both the medical use licensees and the NRC. Alternative 2, if adopted, would eliminate the amendment application process for most licensees who plan to use the sealed source and the review and approval process for the NRC. DECISION RATIONALE Since Alternative 2 would result in less burden to the medical use licensees and the NRC staff while providing the same level of protection of the public health and safety, the NRC proposes to adopt this alternative. 6. IMPLEMENTATION Implementation involves adding palladium-103 as a sealed source in seeds for interstitial treatment of cancer in 10 CFR 35. 400. 2

topy to Secy- ---"""-- Original sent to the office of the Pederal Register for publication NUCLEAR REGULATORY COMMISSION [7590-01] ~ r -~. 10 CFR Part 35 RIN: 3150-AD 11 Palladium-103 for Interstitial Treatmen f g 989 AGENCY! Nuclear Regulatory Commission. ACTION: Proposed rule. ,.1;,0~fu;T!I'G & ~ *Xfc~ 1 *.r.!,c,r Y-.,,..t._ W,1;

SUMMARY

The Nuclear Regulatory Commission (NRC) is proposing to amend its regulations governing the medical uses of byproduct material. The proposed regulation would add palladium-103 as a sealed source in seeds to the list of brachytherapy sources permitted for use in treatment of cancer. Under current NRC regulations, users must have their licenses amended before they may use palladium-103. The proposed rule, developed in response to a petition for rulemaking (PRM-35-7), would reduce the regulatory burden on medical use l icensees who plan to use the sealed source. An evaluation of the potential radiation hazards to hospital personnel and the public showed that there would be minimal risk if the sealed source is used in accordance with the manufacturer's radiation safety and handling instructions. DATE: Comment period expires (30 days from the date of publication in the Federal Register). Comments received after this date will be considered if it is practical to do so, but assurance of consideration cannot be given except to comments received on*or before this date. ADDRESSES : Mail written comments to: Secretary, U.S. Nuclear Regulatory Commission, Washington, DC 20555, Attention: Docketing and Service Branch. Deliver comments to One White Flint North, 11555 Rockville Pike, Rockville, Maryland 20852, between 7:30 am and 4:15 pm weekdays.

  • l f~*lG c ;:::J( ~

1MY 0 ON ,I.:>I li l ies Postm* Iv),)) ----- Co ~ ~ Ao

  • e,:;rod c~ __,.]!.-___ _

iaf Dist ribution f.)) Y<-- {Y llf" [rlic

FOR FURTHER INFORMATION CONTACT : Dr. Anthony N. Tse, Office of Nuclear Regulatory Research, U. S. Nuclear Regulatory Commission, Washington, DC 20555, telephone : (301)492-3797. SUPPLEMENTARY INFORMATION : Petition for Rulemaking On November 30, 1988, Theragenics Corporation submitted a petition for rulemaking, PRM-35-7, which was docketed on December 9, 1988. The petitioner requests that the NRC amend its regulations to add palladium-103 as a sealed source in seeds for the interstitial treatment of cancer to the list of sealed sources currently permitted in 10 CFR 35.400 for use in brachytherapy. A copy of the petition may be obtained from the Regulatory Publications Branch, Division of Freedom of Information and Publications Services, U.S. Nuclear Regulatory Commission, Washington, DC 20555. The petitioner enclosed a document from the Food and Drug Administration (FDA) of the Department of Health and Human Services that allows the marketing of palladium-103 as a sealed source in seeds. The petitioner stated that, under current NRC regulations, licensees who are users of palladium-103 must go through the cumbersome process of having their licenses amended before using the product and that amending 10 CFR 35. 400 in the manner suggested would eliminate this cumbersome process. In supporting the petition, the petitioner submitted several documents, including a letter from the FDA, a safety evaluation report from the State of Georgia, the package insert, and product literature. The letter from the FDA stated that, under Section 510(k) of the Federal Food, Drug, and Cosmetic Act, as amended, marketing 2

the device (palladium-103 as a sealed source in seeds) would be permitted subject to the general controls provisions of the Federal Food, Drug, and Cosmetic Act until such time as the device has been classified as either a Class I, II, or III device under Section 513. In March 1986, Theragenics, an "Agreement State licensee of the state of Georgia, s ubmitted information on the radiation safety properties of palladium-103 to Georgia in order to obtain a "Certificate of Registration." Such a certific.;ate is necessary for Theragenics to manufacture and distribute palladium-103 seeds to specific licensees. The information on these sa~ety properties included the design and construction, pro~otype testing, conditions of normal use, labelling, external radiation levels, solubility in body fluids, and quality control and assurance. After reviewing the information and determining the adequacy of the radiation safety properties of the source, the State of Georgia issued a Certificate of Registration to Theragenics on September 22, 1986. This certificate summarized the submitted radiation safety information and specified additional limitations and conditions on the use of the source. This certificate was amended in its entirety on June 6, 1988 to include a minor design improvement made by Theragenics. I Following its determination that the radiation safety properties of the source are adequate, the State of Georgia sent NRC a copy of the certificate to include in the Registry of Source and Device Designs that is maintained by the NRC. The NRC reviewed the certificate for consistency with other certificates in the Registry and added pall adium-103 to the Registry on October 29, 1986, and again in June 1988 to cover the design improvement. This action, in effect, granted a premarketing approval of the seal ed source and permitted the use of palladium-103 provided that the user*s license was amended to include that sealed source. 3

Conclusion The NRC has evaluated the petition and supporting information and proposes to grant the petition. The NRC has determined that the addition of palladium-103 as a sealed source in seeds to the list of sealed sources specified in 10 CFR 35.400 would not cause additional risk to hospital personnel or the public because the radiation safety and handl ing instructions for palladium-103 are similar to the instructions for the brachytherapy sources currently listed in Section 35.400. This action would reduce the regulatory burden to the users of palladium-103 seeds (about 700 potential users) as well as to the NRC staff. Most users would not have to follow the present requirement of submitting individual license amendment applications in order to be able to use palladium-103 as a sealed source in seeds for the interstitial treatment of cancer (if their license permits the use of any brachytherapy sources specified in 10 CFR 35.400). A user whose license only permits the use of specified brachytherapy sources would still be required to submit a license amendment application. A reduction in the number of license amendment applications would reduce the expenditure of NRC staff resources in reviewing and granting or denying the requested license amendments. Environmental Impact: Categorical Exclusion The NRC has determined that this proposed regulation is the type of action described in 10 CFR 51.22(c)(2). Therefore, neither an environmental impact statement nor an environmental assessment has been prepared for this proposed regulation. Paperwork Reduction Act Statement This proposed rule does not contain a new or amended information collection requirement subject to the Paperwork 4

l Reduction Act of 1980 (44 U.S.C. 3501 et seq.). Existing requirements were approved by the Office of Management and Budget, approval number 3150-0010. Regulatory Analysis The NRC has prepared a draft regulatory analysis on this proposed regulation. The anal ysis examines the costs and benefits of the alternatives considered by the NRC. The draft regulatory analysis is available for inspection in the NRC Public Document Room, 2120 L Street, Lower Level, NW, Washington, DC. Single copies of the draft regulatory analysis may be obtained from Dr. Anthony N. Tse (See FOR FURTHER INFORMATION CONTACT heading). The NRC requests public comments on the draft regulatory analysis. Comments may be submitted to the NRC (See ADDRESSES heading). Regulatory Flexibility Certification As required by the Regulatory Flexibility Act of 1980, 5 U.S.C. 605(b), the Commission certifies that this rule, if adopted, will not have a significant economic impact on a substantial number of small entities. The proposed rule would add the use of palladium-103 as a sealed source in seeds in 10 CFR 35.400. This action would reduce the regulatory burden on medical use licensees planning to use the sealed source because most users would not have to follow the present requirement of submitting a license amendment application in order to use palladium-103 as a sealed source in seeds for the interstitial treatment of cancer (if the license permits the use of any brachytherapy sources specified in 10 CFR 35.400). 5

The NRC has adopted size standards that classify a hospital as a small entity if its annual gross receipts do not exceed $3. 5 million, and a private practice physician as a small entity if the physician ' s annual gross receipts are $1. 0 million or less. Although some NRC medical use licensees could be considered "small entities," the number is estimated to be a very small percentage of the total number of licensees and does not constitute a substantial number for purposes of the Regulatory Flexibility Act. However, the proposed rule would have a positive economic impact on about 700 licensees. Backfit Analysis The NRC has determined that a backfit analysis is not required for this proposed regulation because the amendment does not constitute a backfit as defined in 10 CFR 50.109(a)(l). List of Subjects in 10 CFR Part 35 Byproduct material, Drugs, Health facilities, Health professions, Incorporation by *reference, Medical devices, Nuclear materials, Occupational safety and health, Penalty, Radiation protection, Reporting and recordkeeping requirements. For the reasons set out in the preamble and under the authority of the Atomic Energy Act of 1954, as amended, the Energy Reorganization Act of 1974, as amended, and 5 O.S.C 553, the NRC is proposing to adopt the following amendment to 10 CFR Part 35. 6

I

1.

The authority citation for Part 35 is revised to read as follows: AUTHORITY: Secs. 81, 161, 182, 183, 68 Stat. 935, 948, 953, 954, as amended (42 0.5.C. 2111, 2201, 2232, 2233); sec. 201, 88 Stat. 1242, as amended (42 U.S. C. 5841). For the purposes of sec. 223, 68 Stat. 958, as amended (42 O.S.C. 2273); §§ 35.11, 35.13, 35. 20(a) and (b), 35.21(a) and (b), 35.22, 35. 23, 35.25, 35.27(a), (c) and (d), 35.31(a), 35.49, 35.50(a)-(d), 35.51(a)-(c), 35.53(a) and (b), 35.59(a)-(c), (e)(l), (g) and (h), 35.60, 35.61, 35.70(a)-(f), 35.75, 35.80(a)-(e), 35.90, 35.92(a), 35.120, 35. 200(b), 35.204(a) and (b), 35.205, 35.220, 35.310(a), 35.315, 35.320, 35.400, 35. 404(a), 35.406(a) and (c), 35. 410(a), 35.415, 35.420, 35. 500, 35. 520, 35.605, 35.606, 35. 610(a) and (b), 35.615, 35.620, 35.630(a) and (b), 35.632(a)-(f), 35.634(a)-(e), 35.636(a) and (b), 35.641(a) and (b), 35.643(a) and (b), 35.645(a) and (b), 35. 900, 35.910, 35.920, 35.930, 35. 932, 35.934, 35.940, 35. 941, 35.950, 35.960, 35.961, 35.970, and 35.971 are issued under sec. 161b, 68 Stat. 948, as amended (42 U.S.C. 2201(b)); and 4I §§ 35. 14, 35.21(b), 35. 22(b), 35.23(b), 35.27(a) and (c), 35.29(b), 35.33(a)-(d), 35. 36(b), 35.50(e), 35.51(d), 35.53(c), 35.59(d) and (e)(2), 35.59(g) and (1), 35.70(g), 35.80(£), 35.92(b), 35.204(c), 35.310{b), 35.315{b), 35. 404{b), 35.406(b) and {d), 35. 410(b), 35. 415(b), 35. 610(c), 35.615(d)(4), 35.630(c), 35.632(g), 35. 634(£), 35.636(c), 35.641(c), 35.643(c), 35.645, and 35.647(c) are issued under sec. 1610, 68 Stat. 950 as amended (42 ' 0.S.C. 2201(0)). 7

2. In § 35. 400, paragraph (g) is added to read as follows : § 35. 400 Use of sources for brachytherapy. (g) Palladium-103 as a sealed source in seeds for interstitial treatment of cancer. ~ ed :~Jockville, Maryland, this --LLj-L.---~~=...w:.=.......-.--------1 1989. day of For the Nuclear Regulatory Commission. Operations. 8

430 Tenth Street, N.W., Suite N 210, Atlanta, Georgia 30318 (404) 876-4531 November 30, 1988 Mr. Norman McElroy Medical and Academic Section-6H3-OWFN us Nuclear Regulatory Commission Washington, DC 20555 RE: Modifications to Title 10 Part 35.400

Dear Mr. McElroy:

C 15 P2 :37

P OJ 0

l.u Theragenics Corporation requests that Title 10 Part 35.400 be modified as follows: (g) Palladium-103 as a sealed source in seeds for interstitial treatment of cancer Theragenics manufactures and markets TheraSeed*, a sealed brachytherapy source used for interstitial treatment of cancer. In support of this request, the following documents are enclosed:

1.
2.

FDA 510K approval letter. Equivalency to Iodine-125 was the basis for approval. Georgia sealed source registration

3.

Theraseed* product literature.

4.

Package insert and Dose Rate Table.

5.

List of Theragenics Management personnel. Business cards are included. Presently, TheraSeedw users must go through the cumbersome process of having their licenses amended to use the product. Amending Part 35.400 as stated above will eliminate this cumbersome process for Qoth Theragenics and the user.

u. S.

DC" Postrn rl: Cop e Add' r: r ,...~ pec:ial Distribution ISS I,

cs N_Y

November 30, 1988 Mr. Norman McElroy Page 2 Please call me or Julie Stephens at (404) 381-8338 if you have any questions. Your efforts in expediting this request will be appreciated. I look forward to working with you. Sincerely, Howard T. Cooper Regulatory and Medical Affairs Director cc: J. Herndon

c. Jacobs J. Carden B. Kirkland J. Stephens D. Fialkowski R. Powers

.,/

DEPARTMENT Of HEALTH & HUMAN SERVICES Public Heahh Strvict Mr. John L. Russell, Jr. President ~uclear Medicine, Inc. 900 Atlantic Drive, N.W. Atlanta, Georgia 30332

Dear Mr. Russell:

Re: K852542/A Food and Drug AdmJnl1tr1t1on 8757 Georgi. Avenue Silvor Spring MO 20910 Palladium Seed Model 100 Oa ted: October 9, 1985 Received: October 10, 1985 We have reviewed your Section 510(k) notification of intent to market cha above device and we have determined the device to be substantially equivalent to d~vicea marketed in interstate corrwerce prior to May 28, 1976, the ~nactment date of the Medical Device Amendments. You may, therefore, market your device subject to the general controls provisions of the Federal Food, urug, and Cosmetic Act (Act) until such time aa your device has b~en class1f1od under Section 513. At that time, if your device is classified into either class Il (Performance Standards) or class Ill (Premarket Approvul), it would be subject to additional controls. Please note: This action doos not affect any obligation you aight have under the Radiation Control for Hualth and Safety Act of 1968, or other Federal Lawe or regulations. General controls presently include regulations on annual registration, listing of devices, good manufacturing practice, labeling, and the misbranding and adulteration provisions of the Act. VIn the future, the scope of gcn~ral controls may be broadened to include additional rogulations. All regulations and infor11.ation on meetings of the device advisory com.t.iitt~es, their -recoM~ndations, and the final decisions of the Food and Drug Administration (FDA) vill be published in the Federal Resister. We su~b~st you subscribe to this publication so you can convey your views to FDA if you d~sire and be notified of any additional requirements imposed on your d~vice, Subscriptions may be obtained from the Superintendent of Documents, U.S. Covernmcnt Printing Office, Washington, D.C. 20402. Such information also mny be Teviewed in tho Dockets Management Branch (HFA-305), Food ilnd Drug Administration, Room 4-62, 5600 Fishora Lano, Rockville, MAryland 20857. Thi, letter do~o not in any way denote official FDA opproval of your de~1~¥ or 1.ts labeling, Any representation that creates an impTession of official approval of this device because of compliance with the premarket notlf1cat1on rcgulat~ona is misleading and constitutes misbranding. If you destre advice on the labeling for your device or other information on your responsiblllties under tho Act, please contact the Office of Compliance, Division of Compliance Operations (UFZ-320), 8757 Georgia Avenue, Silver Spring, Maryland 20910. Sincerely your*, K-.;q M~ Kshitij H han, Ph.D. Director Office of Device Evaluation Center for D,v1ce1 and R.adtoloaical Health

REGISTRY OF RADIOACTIVE SEALED SOURCES AHD DEVICES SAFETY EVALUATION OF SEALED SOlfRCE (Amended in its entirety) NO: GA645S101S SEALED SOURCE TYPE: noDF.L: 200 MANUFACTURER/DISTRIBUTOR: ISOTOPE1 Palladium-103 LEAK TEST FREQUENCY: DATE: June 6, 1988 Sealed brachytherapy source (Old Model No. 100) Theragenics Corporation 900 Atlanta Drive, N.W. Atlanta, Georgia 30318 PAGEt 1 of 8 ~~XIMUM ACTIVITY: Not to exceed 10 millicuries each PRTl{CIPLF. USEs General Medical Use CUSTOM SOURCE: ___ YES X NO CUSTOM OSER,

N01 GA645Sl01S REGISTRY OF RADIOACTIVE SEALED souncES Alm DEVICES SAFETY EVALUATION OF SEALED SOURCE (Amended in its entirety) DATE1 June 6 1 1988 PAGE1 2 of 8 SEALED SOURCE TYPE1 Sealed brachytherapy source DESCRIPTION, The }!odel 200 Palladium Seed consists of a cylindrical titanium tube sealed at both ends with laser welded titanium end cups. Enclosed in the tube are two palladium-103 plated graphite cylinders and a lead rod X-ray marker to identify the position of implanted st?cds on a radiograph. The cylindrical t:ubc is 0.177 inch (4.5 r,,m) in overnll length and 0.032 inch (0.81 mm) in dia:-:eter. All of the titanium material is commercially pure ASTM B265-78, Grade

2.

The lead and graphite are both 99.99+/-1 pure. The radioactive palladium-103 is electrolytically plated upon all outer surface of the graphite substrate, LABELIHG1 The size of the Hodel 200 Palladium Seed precludes any enaraved, etched or printed labeling. The seeds will be shipped in a small vial inside a lead vial holder. The lead vial holder will be placed inside. Labeling that will be affixed to each of these containers are illustrated in Figures 1, 2, 3, .'.lnd 4. DIAGRAM1 Figure five shows the material of construction, dimensions, method of sealing, and the relationship of all major c;mponents for the Model 200 palladium Seed. it

REGISTRY OF RADIOACTI~E SEALED SOURCES Alm DEVICES SAFETY EVALUATION OF SEALED SOURCE (Amended in its entirety) NO: GA645S101S DATE1 June 6, 1988 PAGE: 3 of 8 SEALED SOURCES TYPE: Sealed brachytherapy source CO!i!H TIONS OF NORMAL USE: The ~~odel 200 Palladium Seed is intended to be used as a permanent interstitial imp 1 ant. The soft therapeutic X-ray ( 20-23kev) emitted by the Palladium Seed interact with the tissue to be treated, Palladium Seeds are indicated for tumors with the following characteristics: o Localized o Unresectable o Low to moderate radiosensitivity The tumors may be of the following 'typesz o Superficial o Intrathoracic o Intraabdominal o Lung, Pancreas, Prostrate (Stage A or B) o Residual following external radiation o Recurrent The seeds are designed to withstand temperatures and pressures up to 272°F (133°C) and 30 psig for 30 minutes. Nominal autoclaving conditions are 250°F (121 °C) at 15 psig for 15 minutes. The seeds are capable of withstanding moderate to severe challenges to their integrity. It is possible through rough handling, high temperatures or crushing that a seed could leak or be

ruptured, If such an occurence doea happen, there is little or no biological hazard due to the non-toxic nature and physical form of the internal components.

PROTOTYPE TESTING1 The Palladium Seeds were subjected to four prototype tests to demonstrate their integrity under expected stresses of use or accidents. These tests provided evaluation under the following conditions,

1) Autoclave,
2) Imp.act,
3) Percussion and 4) Bend.

The tests were conducted generally as suggested in NBS Handbook

126, ANSI N542-1977, Appendix C

and ANSI N44.l-1973. Brac~ytherapy seeds containing Pd-103 sealed in~ tube of dimensions as shown in figure 5 do not entirely fit the Classifications or Definitions in the --~fcrenced ANSI standards. Some modifications of the test conditions were ~quired. These prototype tests for the Hodel 200 Palladium Seed folJow closely he nodified ANSI prototype tests that were performed by* the 3M Company for, 1eir approved I-125 Seeds~.

REGISTRY OF RIIDIOACTIVE SEALED SOURCES AHD DEVICES SAFETY EVALUATIOH OF SEALED SOURCE (Ar:icnded in its entirety) NOr GA645S101S SEALED SOURCE TYPE: EXTERNAL RADIATION/LEVELS r Hodel 200 Seed Activity 0.5 mCi (Comp)

5. 0 mC i ( Comp QUALITY ASSURANCE AND CONTROL:

DATE: June 6, 1988 PAGEr 4 of 8 Sealed brachytherapy source Average Dose Rate (mR/hr) at 5 cm at 30 cm 25.86 258.60

o. 718 7.180 The ~ajor quality control tests that are used include the following, After Completion of Seed Assembly Visual inspection to verify proper seating of the titanium end cups in the tit~nium tubes and verify overall seed integrity.

After L.<iscr l!clding Visual optical inspection to check cleanliness and soundness of welds and verify overall seed integrity. ni~cnsional checks performed to verify that the seeds are within specifications. X-..!:!!. to verify the seed was loaded correctly. After Irradiation Autoclave leak test performed to verify no leakage of radioactive palladium. The radiation activity level of each seed is measured using a Capintec Dose Calibration apparatus or, equivalent so seeds of the same Curie level can be grouped together.

REGISTRY OF rtADIOACTIVE SEALED SOURCES AlID DEVICES SAFETY EVALUATION OF SEALED SOURCE (Amended in its entirety) NOs GA645S101S

DATE, June?* 1988 PAGEt 5 of 8 SEALED SOURCE TYPEs Sealed brachytherapy source LIMITATIONS AND/OR OTHER COHSIDERATIONS OF USE:

A. Palladium seeds are licensed by the St*ate of Georgia for distribution to persons licensed pursuant to (9)(c) and (2)(c) of Chapter 290-5*23, Schedule c, Group VI or under equivalent licenses of the U.S. Nuclear ~cgulatory Cor.unission, an Agreement State or a Licensing State. B. The seeds will be 1007. leak tested by the manufacturer prior to distribution. No further leak testing is necessary due to the 16.97 day half-life. C. 7he vial should remain in the lead pig during storage. When transporting seeds within the hospital, an appropriate carrier with adequate shielding should be used. D. Adequate radiation protection should be used during implantation procedures, however, in many instances in surgery, radiation protective barriers are not practical, thus the medical personnel must rely upon speed and distance to minimize radiation exposure. E. The titanium encapsulation provides very good biocornpatibility along with exce llcnt corrosion resistance but it is not designed to be used in a concentrated acid environment due to the chemical reaction. F. The use of Palladium Seeds, as with other brachytherapy sources, is not recommanded for the treatment of tumors in generally poor or ulcerated condition. G. The radioactive Palladium Seeds are not sterile when shipped, hence a sterilization process must be performed. Steriltzation may be accomplished by either ethylene oxide (EtO) or by steam (autoclave) prior to implantation.

REGISTRY OF RADIOAC'UYE SEALED SOURCES MID DEVICES SAFETY EVALUATION OF S!!.ALED SOURCE (Amended in its entirety) N01 GA645S101S DATE1 June 6, 1988 PAGEz 6 of 8 SEALED SOURCE TYPEi Sealed brachytherapy source SAFETY ANALYSIS SUMlfARY1 The Hodel 200 Palladium Seeds were subjected to Autoclave, Impact, Percussion, and Rend tests to verify their structural integrity under both normal and abnormal us,1ge. The seeds successfully passed these tests which generally follow ANSI N524*1977, ANSI N44.l-1973 and ANSI N44.2-1973. The Hodel 200 Palladium Seeds should not be subjected to temperatures greater than 272°F (133°C) or pressures greater than 30 psig. Under the abnornal conditions of fire or explosion, these conditions undoubtedly will be exceeded. Failure or rupture of a seed could permit release of the palladium pellets. This physical form of the radioactive content of the seed hu no tendency to pulverize into airborne rcspirable particles (see ANSI N44.l-l973, Section 5.2). Release of Pd-103 as a vapor is considered very remote. As a member of the platinum group of metals, it has a characteristically low vapor pressure of l. 6X 10*4 atm. at its melting point of 2826°F (1SS0°C). Chemically, the palladium is insoluble in water. Although not designed for a concentrated acid environment, it is only slightly attacked by sulfuric and hydrochloric acids. In the event of seed failure when implanted in the body tissue, it has been shown that palladium is biocompatible.

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF SEALED SOURCE lW: GA645S101S DATE: June 6, 1988 PAGE: 7 of 8 SEALED SOURCE TYPEz Sealed brachytherapy source

REFERENCES:

This Certificate of Registration is based on information and test data contained in the following supporting documents which are hereby incorporated by reference and r.3de a part of this registry document:

1.
Hilaria, B. S.

ed Handbook of Interstitial Brachytherapy. Publishing Sciences Group, Inc., Acton MA. 1975. 2, NCRP Report No. 37 NCRP Publication, P.O. Box 30175, Washington, DC 20014.

  • 3, NCRP Report No, 40 NCRP Publication, P.

O. Box 30175, Washington, DC 20014.

4.

NCRP Report No. 41 NCRP Publication, P. 0. Box 30175, Washington, DC 20014. 5, NCRP Report No. 48 NCRP Publication, P.O. Box 30175, Washington, DC 20014.

6.

NCRP Report No. 49 NCRP Publication, P.O. 20014. Box 30175 1 Washington, DC

7.

Ling, C. Proceedings of Fourth International Conference on Medical Physics. Ottawa, Canada, July 1976.

8.

Harper, Paul V, and Lathrop "Palladium-103 as Therapeutic Radiation Source" Nuclear Medicine, Stuttgart, F,R.G., 1965. '

9.

Theragenics Corporation application dated March 3, 1986 and enclosures thereto.

10.

Letter from Theragenics Corporation dated March 5, 1986 and enclosures thereto.

11.

Letter from Theragenics Corporation dated July 3, 1986.

12.

Letter from Theragenics Corporation dated March 15, 1988 and enclosure thereto.

13.

Letter from Theragenics Corporation dated March 21, 1988.

14.

Letter from Theragenics Corporation dated May 13, 1988 and enclosures, thereto.

REGISTRY OF RADIOi\\CTIVE SEAT.ED SOURCES Alfi DEVICES SAFETY EVALUATIO!l OF SEALED SOURCE N01 GA645S101S SEALED SOURCE TYPE 1 ISSUI!W AGENCY1 DATE1 0 88 (/u:icndcd in its entirety)

DATE, June 6, 1988 PAGR1 8 of 8 Sealed brachytherapy source Georgia Department of Human Resources Radiological Health Section REVIEHER1 tf"t/4~, rJ.* (>cwt'~

COIICURRENCE, ~M4Y /,I}, Jt(1,,,i,,

l~c:rc.c f re Broc::hy t. her*a,..;y S:x.ir--c e Cau!co: RADC4.CTIVE 1,J..A1Ef11AL 0f1.t; ~ ,na I\\C,pa1cnt k~*;

))'

t : -* ---*---caYp Tola! Ap,)Jre ! I mCi /'\\,... 0

  • L corrp

, \\.'.:)say ale. ___ ot ______ _ No. T",, r':a,~ <:I s*. -. ----- ,,...,.., \\-.us... n.,. Tt-.,.r,.c; **,...~., C:cit"r.,Jr-.*t,....o,r, ... *.J**""*At. c..~- ... -..J3, a ( 1) Seed Vial ~: :"'"\\ ~-.: =.:*.. :, ;::l"",J9 **--- *..

  • .~ :.. ;~:a*:.,:'*-:* v,,

- r,-0 C.'.."'P 1 T'* i 't'=.*...

  • :-n()

I ~-: r,p . :...,...,... :: ~*, !*..,.*-=- I ** ;1: ;_.

  • t" ', : t
  • t.,* "" ':,.0 f',:.lt*lU~t,ct \\a 1 tt')t"'t'l1';'i 1e.;i1.-;~,, ""'*-*"*""':\\. :tl')t r ** :... *)II,*:-;.-:. i:.* 1 1 a*" : :,...,..,....,.,:1,,u a*:t,l",,c, '#' c*,:.-

.. JJll $.,* 11/tC 1 :.:*,*'°~""-c-" 1*...,*,~*-:**"1g'..,,rUI ,... :*1* 0ta,,.1:--.c..:*.. u,-,.. :*"*** s.-t.rL...,*,*;s,*,

.~,i:*i,,.:1*111,.- u :-1'"'i0*****:1:,t1,o-crr*1Q~t"o-'1 F'"sl:&, *l.ll"ll"' ::., 1:1 ;*,.,**,t* *. 1:.c:1* t l.. U S...,,~ p:tCl..._"'\\Q~ *"11,.'-*'1

"~r,n11,u,1,onw..:n h '""ng f,,1C,fd#J0 ot Tl°'J'-"-~s,*\\,lc.-¥

  • .:t *;.!4,,

T!t.,_..,ft.hJtM*Ct:I Co*;.>.;.,r.* :*t*ot'I A11.,n1,1. QA.'l03 u, ( 2) Lead Vial Holder

~--------*------

I =lcJc.1icJ17L_Jcl icje l3rac:11y Cr1cr""lr.Jf_JY Source Total Apparent A9.tivity. ______ mCi comp. Surface *oose Rate --~- ___ n1R~m/hr. Assay lJate ________ _ rotc.11 No. Of Vials

  • rotal No. Of-Seeds***_--____ _

rhis r,ocJ1Jcl Made In U.S.A. Gy:

  • r11cr"'iJfJcnics <.::orporaGion

/\\1;li3n1.:.i3, (3G. :3031 8

  • c 3) Outer Container
  • ro

..,: Ir.r ~ : 1-:~ /J. ~:~ ~ : r -' ~ r:. ~~. r:. ~ J IJ ~} r1 I 'i /.. \\ *-*. ' l"' ~, t t t p

  • I l. d.; ~. '( ~ L11 t} Lr r k h ~

~.J t 1 j l.I I \\J ~Jl}D [\\*ifr111ri1: iJrive, f~.V/... P.O. 13ux 04035 r,Hanta, Gcoryia 30318 \\ I

FICl.JRE 5 't 0.032' h T1ta.ntuM End Cup <.030"L X.028'D X.002't.) Ttta.nluM Tube Pd plo. ted gra.phite pellet <.036"L X.023"D) Lo.ser weld se7 <.177'L X.032"DD X.0022"t.) Lea.d X-Ra.y Ma.rker (.039'L X :020"D) O.:i. 77' ----------------------i

500-400 300-1 -I 200 2 STEPS FORWARD... INTRODUCING TheraSeed' Alternative Permanent Implant 17 day half life provides higher dose rate - critical to the treatment of rapidly grow-ing tumors. Insoluble, non-volatile iso-tope - critical in case of capsule damage such as dur-ing subsequent procedure for removal of urethral blockage. Pallodium-103 active isotope. 21 Kev x-rays for ease of radiation protection of medical personnel and the patient. Biologically compatible titanium capsule. Sized for standard applicators. 17 day half Hfe Doo = 11,500 Rods / BiologicaRy Equivalent Doses Orton, C.G., Br. J. of Rod. 47(603-607) 60 day half fife ~ Dco = 16,000 Rods 3 4 5 6 7 Tumor RegnHsion (ca. tongue) DHEW Publication (FDA) 76-8022 8 9 10 11 12

Urology Focus Baroid P. McDonald, Jr., M.D. Prostate Cancer-Harold P. McDonald, Jr.,.'tl.D. Radioactive implant provides effective treatment A Asmcnage.probl,=msassocialed ,., ft wuh their prostate gland occur more f~ucntl). Infection. mflammauon. C)Sts. stoocs. bemgn growths-even cancer-become mcreasmgly comfll(ln m men 50 )Cars of age and older But today. the availabihty of a rad1oac11ve implant called Thera.Secd JS help-mg many men fight back. By placing this substance into the prostate. harmful tu=r llSSUC can By placing this substance Into the prostate, harmful tumor tissue can be effectively destroyed. be effectively destroyed. The new technique off en pat~nts success-ful cancer treatment \\\\ ilh less tr;u.una at a 51g111fican1 ~I ~mgs compared to tradillooal !raiment mt1hods. Enlarged prostate The pru-.late 1~ a male sel gb.nd important to semen producuoo. Approx1ma1CI} lhe size of a chcst-rdll. lhc p~IC cncJrclcs the unnc pa'\\Sage. or urethra. bel\\\\een the bladder and the ba!.e of the pcm,; Though the pros1a1t is fully devel-oped at puberty. 1t begtns to en-large in most men around lhc age of 50, causing the unne flow to fl(!' pinched off. AA tn~ pros:tatt, common among mtn 50 and oldu, ""'1 :signal Nncu in 11,i:s l'tfU'll* lmtral ') mp!otru of pm'llate en-largcment include a dC'Cl'Case in the size and force of the urine ~,ream and d1ff1CUlty in swting and S10pping the unne flow. Fre-quent urinslion ~ abo sign.al a ptmllllc prohlem. Bccau'IC an en-Facts about Prostate Cancer

  • One out of three men over 50 will get cancer of the prostate.
  • Men with prostate cancer may have no symp(omS at all.
  • A yearly cheekup Is recommended after age 40.
  • If mtm wait unlll thay have symptoms or cancer, It la often too late for curative treatment.

largcment of the prostate glapd can signal c.mcer. prompt diagnostS is important. US1ng an ultrasound 5eanner. urologtm can analyze the inlcmal ~ructure o( the prostate and deter-mine lhe weight and me of this gldnd ~ ith am:wng accuracy. Tra-d11ionall;. 1f cancer ¥.-a~ found. ~f"l!JCal relllO\\'ll or external radi* auon ~ere pl'Cl-Cnbcd. Today, using the Thcr.iSccd ra-dmacuve material. docron can dwohc the tumor far more simply. Guided by ultrasound, the urolo-gist place-. nee-sized litaruum cap-sules cootaming radioactive pal* ladium 103 into the tumor with a nced1c imened illlo the prostate. pro,tatc. release radratlO!l equ1\\,1-lent to one X-ray per second for the first 10 cta:-s and then dmunM m strength. The procedure ranks a, effectt\\e as external radiauon or ~urger). hO"'c:ver. unhle tradmonal ~ ods. the radioactive implant pro-cedure can be performed on an outpatient basis using a local ancsthet~.Theprocedure.~hich ThcraSecd, manufactured b; Thcragemcli Corp. of Atlanui. 1* only effective in treating locahze,. tumors. If the cancer has sprea, beyond the prostate gland, trad1 uonal treatment such as chemc therapy IS ncces'\\llry The availabthty of TheraSce. offers many men the cha.nee I, fight prosiau: cancer. Still. earl:, detecUon 1s one's best chance lo The procedure ranks as effective as external radiation or surgery, however, unlike traditional methods, the radioactive Implant procedure can be performed on an outpatient basis using a local anesthetic. takes approx1ma1ely one hour IO complete. costs nearly 50 percent less than remo, ing the tumor sur-gically. Overall. the technique is less traumauc 10 the patient and Is fri:e rrom Ull\\\\lll'MIXI side efkcu. In most cases. sexual functloll cure. Remember, an initial ullra-sound ewnination of'the prostate gland should be perfunncd at age

40. Men age SO and over should receive annual euminations.

is nol affected by the radioac1M! ........ A NOTE treatment. Pa!ietu also expcrienc:-c I....,...,.. c....- bl of

  • Dr. M,DoNld 1ttlt--nib rr,o,,t-

"'""' pro ems m~11.nencc ""llirs U1i&,,,. rfflltttl iopb. OIi/ lti:t and~ and/or bladder IIT!tallOO oJ/ltt., ('(HJ,Sl-1461 N-, "-"" than with Olher I} pcs of treatmenl. """ S,. **, IIIOIHM1 dur,urlt Fridtq HatvU I'. McDortril, Jr., !,In. & * """"dJt,,.. tit, ;l,l'f:dtlr-{ du: Gff,pt, l'nntttt, c.-~ d,d, !fll<<HIII:n ia ~t /lnztoMltd t<<lutif'IIU-11ot G,o,r,,,. Promttt Cniur alMI dr, \\lcDooo/11 liohtr:, Olllrr *rr ~ Ill lSSfl fflw,(, H,Q ltoM. s.., 115, ilr.\\ld/1ittM. Dr.\\lcOotu,Jd rrtn'l<td /us l/ffdJ"'1 i/rprt /"'1ff dot Ml'dicw/ Collr,r a/~, tUUI latrr comrf,:u-d"" a,tnwslnptll ~ Hosp,llll I/{ Lo,,,sJ,,n,, ia ~ ~ H, tl:t,r 'IJ:ntd

  • rnukttn "',at*~ << Sl. J-,,,. '.J laflr-r, ut Allnta IINI ntr,,,Y u.d *~,...,...,,,.,. at dw l',rf,..-, of.'lliclup,* Jltd,nl C,IIUr,

ia NIii Ar6or. Dr. JltDoltolil tlbo,-pit/ff* ""'VIJ ~ ltl IN KMait:,, 1"1~ l'mr Bntl ~ /loyil,,J,,. 8-. I Dr. McD,,,,aJ,i t11rrt1'ti1 Hf"ln ti ntt"prn:,d,lll of tJu, /111~1'fUlliMull Sontt:,, I o/~Lro"'rl;rnd,,.,.,..,.,afdttG.to,z,.r.-,c..,,., ~ls*'-nl, ,.,,.J,,,r of 11w htl,>,.,..,,.,..,,i S<<ll'tJ far n.-o,,, Mil~ sKt'f!t1Uy of I du.~-nca s<<i<<7 of o,,q.dtttl S.'l"(Ufs. Dr. Mc~ Is tlho" ~, tf-,_, *alJOMI.,_ *"" lot:.t IM'lhcal ~

  • "" -'tiffs, --r I

,,,..,_ 11w A-- AIHlal ~- A-ri<ff S<<i<<y cf,¥"""a <nttl d,~..___ 1:~ AsSOdaiM. I* oMidoa tt> Ith JNi- ~ 1k Mc""-'M.....,_,,fltl;/f ~ wtJi-"" Ion/ lwu,tw,. H~-'Aawlfe, l'rilrim. trDMM ~ M#f tluir jowffl>>llmt. The caJJS!lles. which remain in lhe Reprinted from the &at Cobb/CherOkee l;d1tlon d Health Care News, 1ml. 1, Nci. 4 © Health Care News, Inc.

  • 1 {800) 643-4351

500 400 ca -~ 'g 300 cc - UJ !ii cc UJ (J) 0 200 C 100 TheraSeed - Palladium103 Permanent Implant for Cancer Therapy Pd 103 Characteristics -Palladlum-103 17 day half life D = 11,500 Rada Energy Half-life Characteristic

21 KeV
17 days
Non-volatile, Insoluble TheraSeed Configuration Capsule : Laser welded titanium tube Size
Sized for standard applicators

' __ lodlne-125 60 day half llfe D = 16,000 Rada 1 2 3 4 5 6 7 8 9 10 11 12 TIME (Months) DECAY COMPARISON OF EQUIVALENT DOSES Blologlcalfy Equivalent Doaea Orton, C.G.,Br. J. or Rad. 47(603-607) THERAGENICS CORPORATION 900 All&ntlc 011w, N.W., ~ta.~ 30311 (<104) 873-6309 Toll tr** (800)4Jl-437l

~ x(ca) 0.000 0.500 1.000 1.500 0.000 1.030 0.518 0.356 0.500 1.271 1.020 0.549 0.358 1.000 0.946 0.869 0.587 0.396 1.500 0.697 0.677 0.545 0.388 2.000 0.510 0.497 0.443 0.334 2.500 0.372 0.353 0.328 0.262 3.000 0.272 0.249 0.235 0.196 3.500 0.200 0.180 0.174 0.147 4.000 0.148 0.136 0.139 0.116 4.500 0.112 0.106 0-.115 0.095 5.000 0.085 0.084 0.091 0.077 5.500 0.065 0.066 0.066 0.0S8 6.000 0.050 0.049 0.045 0.041 6.500 0.037 0.035 0.038 0.029 7.000 0.027 0.025 0.044 0.023 Tber&Seed - Pall.a4i.lDl103 Dose rate times distance squared around a 1 IIIICi (compensated) Pd-103 TheraSeed Model 200 in solid water, cGy c:a2 br-1 mei-1 2.000 2.S00 3.000 3.500 4.000 0.239 0.222 0.169 0.113 0.084 0.276 0.212 0.174 0.107 0.077 0.282 0.198 0.144 0.103 0.082 0.268 0.183 0.130 0.099 0.078 0.241 0.166 0.125 0.093 0.072 0.208 0.148 0.120 0.087 0.090 0.173 0.130 0.108 0.079 0.066 0.139 0.112 0.095 0.071 0.076 0.110 0.095 0.078 0.062 0.054 0.085 0.078 0.062 0.053 0.053 0.065 0.063 0.050 0.044 0.038 o.oso 0.049 0.040 0.036 0.035 0.039 0.037 0.032 0.029 0.029 0.031 0.027 0.026 0.023 0.023 0.025 0.019 0.021 0.019 0.017 >x 4.500 5.000 5.500 6.000 6.500 7.000 7.500 0.069 0.041 0.040 0.028 0.018 0.015 0.014 0.065 0.055 0.036 0.027 0.028 0.015 0.014 0.063 0.037 0.035 0.027 0.025 0.018 0.013 0.062 o.oso 0.035 0.027 0.020 0.017 0.013 0.060 0.047 0.036 0.029 0.022 0.017 0.013 0.058 0.045 0.036 0.029 0.023 0.018 0.012 0.055 0.0-42 0.035 0.028 0.023 0.018 0.012 0.050 0.040 0.033 0.027 0.022 0.017 0.012 0.045 0.037 0.031 0.025 0.020 0.016 0.012 ~-039 0.033 0.028 0.023 0.022 o.ou; 0.012 0.033 0.028 0.024 0.021 0.018 0.015 0.012 0.027 0.024 0.020 0.018 0.016 0.014 0.012 0.022 0.020 0.017 0.016 0.014 0.013 0.012 0.018 0.016 0.014 0.013 0.013 0.012 0.011 0.015 0.013 0.012 0.011 0.011 0.011 0.011 THERAGENICS CORPORATION 900 AlWltic tlri¥tl, N.W.. A11an1a. Georgia 30318 (..o4) 873-0)9 Toll fr** (800)458-4372

GENERAL INFORMATION Description Package Insert TheraseedN Implants The TheraSeedN Implant consists of a titanium tube sealed at both ends with laser welded titanium end cups. Enclosed are two Palladium-103 plated graphite pellets and an lead x-ray marker to identify the position of the implanted seeds on a radiograph (Figure 1). Ttt.i.,,o.o, £t,al o,p <.430'L X.oe:t'D X ~ T II o.oJe* 1 I. Trt-.. Tut,,. Un'\\. X nt'tll3 X.ool!r'tJ 0.177' Figure 1 Radiation Characteristics The Theraseed* Implant utilizes a Palladium-103 isotope to produce the desired therapeutic x-ray emissions. Palladium-103 (Pd-103) has a 17-day half-life and decays by electron capture with the emission of characteristic x-rays of 20-23 keV and Auger electron$. The electrons are absorbed by the titanium wall of the TheraSeed* Implant. Palladium-102 is activated to palladium-103. The Pd-103 is electroplated onto graphite pellets. Manufacturing consists of placing the activated pellets in titanium tubes and laser welding end cups on the tube. Both the pellets and Theraseed* Implants are analyzed for trace activity. Due to limitation of chemical purity, trace elements are present in the Theraseed-Implant. The total trace activity will contribute to less than 0.4% of that produced by the palladium 103 at the certification reference date. A decay chart is used to correct for physical decay of the Pd-103. The decay factors at selected days after the assay date are shown in Table 1. Page 1 of 12

f~ckage Insert Decay Chart Pd-103, Half Life 16,97 Days Decay Decay Days Factor Days Factor l 0.95998 31 0.28190 2 0.92156 32 0.27062 3 0.88467 33 0.25979 4 0.84927 34 0.24939 5 0.82528 35 0.23941 6 0.78265 36 0.22983 7 0.75132 37 0.22063 8 0.72125 38 0.21180 9 0.69239 39 0.20332 10 0.66468 40 0.19518 11 0.63807 41 0.18737 12 0.61254 42 0.17987 13 0.58802 43 0.17267 14 0.56449 44 0.16576 15 0.54190 45 0.15913 16 0.52021 46 0.15276 17 0.49939 47 0.14665 18 0.47940 48 0.14078 19 0.46180 50 0.12973 20 0.44180 50 0.12973 21 0.42411 51 0.12454 22 0.40714 52 0.11956 23 0.39084 53 0.11477 24 0.37520 54 0.11018 25 0.36019 55 0.10577 26 0.34577 56 0.10154 27 0.33193 57 0.09747 28 0.31865 58 0.09357 29 0.30589 50 0.08983 30 0.29365 60 0.08623 Table 1 B~digtiQn E~oteQtion The half-value thickness of lead for Pd-103 is.008 mm. Thus, the exposure from the TheraSeed~ Implant is reduced by> 97% by only a .06 mm lead sheet. Page 2 of_l2

Package Insert Design Therageni~s has designed the Theraseed-rmplaht -to be an alternative source for permanent interstitial implants. The soft therapeutic ionizing x-rays (20-23 keV) emitted by the TheraSeedN Inplant interact with the tissue to be treated. The use of titanium for the tube and end cups assures good tissue compatibility. The dose distribution surrounding each individual seed is moderately anisotropic which reduces the potential for low dose shadow spots in the tumor. Dose distribution calculations may need to account for this degree of anisotropy. Total attenuation resulting from titanium encapsulation, x-ray marker, and self absorption from the Pd-103 pellet is approximately 75 percent. Indications TheraSeedw Implants are indicated for tumors with the following characteristics: Localized Unresectable Low to Moderate Radiosensitivity The tumors may be of the following type: contraindications Superficial Intra thoracic Intraabdominal Lung, Pancreas, Prostate (Stage A or B) Residual Following External Radiation Recurrent The use of TheraSeed* Implants, as with other brachytherapy sources, is not recommended for the trratment of tumors in generally poor or ulcerated condition. Patient Education As with all brachytherapy sources, the patient needs to be informed of the nature of the TheraSeed* Implant and also the expected period of time during which radiation precautions will be necessary. The National Council on Radiation Protection and Measurements has detailed the guidelines for necessary radiation safety procedures which the patients, theiI ~12ss ~ssociates and medical personnel are required to follow. The patient and any close associates should be acquainted.with the procedure for handling a TheraseedN Implant which has sloughed off, and has become detached from the patient. Depending on the treated Page 3 of 12

Package Insert tu~or, bandagEs or_lin~n§.~hie~ come in contact with the site of the implant should be examined-for th-e small me-tallic seeds. -rf a -* seed is found, tweezers or a spoon should be used to pick the seed up and place it into a sealable container such as a glass jar. The container should be placed and isolated within a designated area in the house. The local radiation center should be contacted as soon as possible following the occurrence. Medical Personnel Theraseed* Implants should be used only by individuals who are trained and experienced in a safe use and handling of radionuclide& and who have been approved by the appropriate governmental agency authorized to license the use of radionuclides. DIRECTIONS FOR USE Preparation/Sterilization The radioactive Theraseed* Implants are liQ1'. sterile when shipped, hence a sterilization process must be performed. Sterilization may be accomplished by either ethylene oxide (EtO) or by steam (autoclave) prior to implantation. Both procedures require manipulation of the TheraSeedm Implant. All manipulation involving TheraSeedw Implants should be performed behind shielding of such size and thickness to shield the handler adequately. DIRECT CONTACT WITH THE THERASEEDN IMPLANTS SHOULD BE AVOIDED. THERASEED~ IMPLANTS SHOULD NOT BE PICKED UP WITH THE HANDS. Use forceps to handle TheraSeedN Implants and maintain maximum distance between handler and TheraSeedm Implants. DO NOT STERILIZE THE THERASEEDw IMPLANTS WITH GWTARALDEHYDE BASED COLD STERILIZATION SOLUTIONS BECAUSE OF THE GUMMY FILM WHICH STICKS TO THE SEEDS. sterilization - Autoclave Before using an autoclave to sterilize the TheraSeedw Implants, make sure there are drain screens, traps or some other means to prevent the loss of seeds through the drain. If sterilization is performed in the delivered dose vial, vent the cap of the vial prior to autoclaving. The Theraseed* Implants have been designed to withstand normal autoclave temperature and pressure variations, however, DO NOT exceed 138"C and 35 psi. It is necessary to autoclave the Theraseed* Implants, whether in bulk or individually, in a container of autoclavable material. The materials include glass, stainless steel, nylon and teflon. It is also possible to autoclave the TheraSeedm Implants in a few of the commercially available accessories of the implant applicators to include the seed holding nylon and teflon tubes of the Henschke and Scott or the stainless steel cartridge of the Mick applicator and gun. If Page 4 of 12

Package Insert there is any question as to the autoclavability of the material, autoclave a sample of the material with test seeds. Alternatively, use ethylene oxide (EtO) for sterilization. DO NOT AUTOCLAVE THERASEEDN IMPLANTS IN LOW MELTING POINT PLASTIC TUBING OR CONTAINERS. Precautions and Monitoring Appropriate precautions must be taken when handling Theraseed* Implants. All personnel who will be working with the TheraSeed* Implants are required to wear adequate personnel dosimetry monitors. A film badge or TLD dosimeter is worn on the body, In addition, a ring badge must be worn by personnel who are handling the TheraSeed* Implants. Advanced planning of the implant procedure is suggested to minimize radiation exposure to personnel. Radi~tion exposure should be consistent with published exposure limits. Accountability TheraseedN Implants need to be strictly controlled and stored in a locked safe. If any seeds cannot be accounted for, the appropriate regulatory agency must be contacted. cautions Theraseed~ Implants have a high structural integrity and have successfully passed the tests prescribed by the Nuclear Regulatory Commission for Sealed Brachytherapy Sources. It is possible through rough handling, high temperatures or crushing, that a seed could rupture and leak. In the event of this rare occurrence, there is little or no biological hazard due to the nontoxic nature of all the internal components. The area should be closed off immediately and the seeds put into a sealable container. Personnel movement should be limited to avoid spread of any radioactive contamination. The area should then be decontaminated. Successful decontamination is confirmed by taking "wipe" samples of the contaminated area. Dose and Administration The dose for a given implant is based on a TDF (Total Dose Factor) analysis for the specific isotope Palladium-103. From these calculations, a nomograph has been developed (Figure 2}, relating tumor volume to total activity to be implanted using dimension averaging. This information is then used to determine the number of seeds and their respective spacing (Figure 2). The decay chart is used to correct for the decay of the 17-day half-life. Palladium-103 ( Table l). The angular dose distribution of the Page 5 of 12

Package Insert -T*heraSeed 111 Implants is.mode;r::at;ely anisotropic. 1 This degree of anisotropy should be given considerat1on -in dose distributiorr* calculations. Techniques The Theraseed~ Implant and the I-1259 Seed both have the same external dimensions. This allows the Theraseedw Implant to use the same applicators as the I-1259 Seed uses. Several commercially available applicators, to include the Henschke, Mick and Scott are suitable for this purpose. The Royal Marsden Gold Grain Gun will not accept TheraSeed~ Implants. When handling the TheraSeedw Implants, radiation detection equipment capable of detecting 20-23 keV x-rays should be available. This equipment may be useful to find dropped seeds as they are very small and may be difficult to detect visually. Adequate radiation protection should be used during implantation procedures. However, in many instances in surgery, radiation protective barriers are not practical, thus the medical personnel must rely2upon speed and distance to minimize radiation exposure. warnings The titanium encapsulation provides very good biocompatibility along with excellent corrosion resistance but it is not designed to be used in a concentrated acid environment due to the chemical reaction. THERASEEDw IMPLANTS ARE li.Ql STERILE WHEN SHIPPED. Adverse Reports There have been no reports of adverse reactions from the use of The_raseed" Implants. ~ALCULATIONS Dimension Averaging The total mCi activity required to treat a given tumor, based on clinical evidence, is proportional to the tumor volume. Dimension averaging, the average of the three mutually perpendicular dimensions of the tumor, is a more practical way of determining the tumor volume and correspondingly the total activity required. A simple yet effectixe9 formula is shown below to determine the total activity required. ' 1 Page 6 of 12

rackage Insert D ~ Average Dimension a a+ b + c A= Total Activity Required A= 21.5 D1 A= 16.64 o1

  • 283 A= 11.87 o1
  • 581 seed spacing Nomograph 3

cm Where D < 2.4 cm Where 2.4 cm< D < 3.24 cm. Where D > 3.24 cm. A simple nomograph has been developed for the TheraSeedN Implant to help simplify calculations for the number of seeds and spacing required to carry out the implant (Figure 2). Example Calculation A 3 x 4 x 2 cm. tumor {average dimension is [3+4+2]/3 = 3 cm) is to be implanted with TheraseedN Implants of 2.1 mci (comp.) activity. The spacing along the needle is to be 1.0 cm. In Figure 2, a line connecting 3.0 cm on the average dimension scale with 2.1 mCi on the seed strength scale intersects at 34 for the number of seeds. A line connecting 2.1 mci on the seed strength scale with J.O cm on the average dimension scale is extended to the tie line. A second line is drawn between the tie line intersection and the 1.0 cm point on the spacing along needle scale. Extension of this line allows the needle spacing to be read at the point of intersection on the spacing between needles scale, 0.6 cm. By using the nomograph, one can determine total recommended activity, desired number of seeds and spacing between needles. The determinations made from the nomograph must be considered to*be approximations only. Page 7 of 12

""-**91' D,men;,on, t=ml I i LO u It 1.6 Aec~ jA,;l1v1ly A.vtl**Qt (mC,) O,,,,,..,r,,on IO f;ml ~, "° Ot ~ u \\!I ~ Ne-tale ~ OI PALLADIUM SEED SPACING, NOMOCRAPH Figure 2 Page 8 of 12 Si>*c,ng ~-n ~ JJ) LI If I.II

150" Angular Distribution of Radiation From Palladium Seeds Pag~_ 9 9£ 12

Package Insert SERVICES Availability TheraSeed~ Implants are available from Theragenics Corporation, Atlanta, Georgia. TheraSeed~ Implants are available with an activity between 1.5 and 2.3 mci (comp.). The seeds are shipped as a group in an screw cap vial, which is labeled to indicate the Isotope, Total Apparent Activity, Apparent Activity Range, Assay Date, Lot Number, and Number of Seeds. If there happens to be any discrepancy between the information of the vial and that which is on the certification sheet accompanying the order, Theragenics Corporation should be contacted within 24 hours of the shipment. The vial is contained in a lead pig which is labeled to provide the same information which is on the vial as well as a statement pertaining to licensing of the product. The vial should remain in the lead pig during storage. When transporting seeds within the hospital, an appropriate carrier with adequate shielding should be used. Disposal/Return A TheraSeed~ Implant disposal service is also provided by Theragenics Corporation for used or decayed seeds. If customers wish to utilize this service, they must first contact Theragenics Corporation, for approval, specific shipping containers and forms. When applicable, there will be cancellation and restock charges. Contact your Sales Representative for information. Theraseedw Implants approved for either return or disposal must comply with Department of Transportation Regulations (Title 49, U.S. Code of Federal Regulations Parts 171-177), regarding packaging and labeling. Shipments are to be directed to: Theragenics Corporation 430 Tenth Street, N.W. suite N-210 Atlanta, Georgia 30318 Phone 1-800-45 THERA Page 10 of 12

Package Insert QUALITY -CONTROL_ __ The TheraSeedN Implants have passed the prescribed tests for Sealed Brachytherapy Sources required by the Nuclear Regulatory Commission. Before the TheraSeedw Implants are shipped, they have passed an extensive series of quality control tests to include autoclave, leak, microscopic, and assay. These tests assure that the Theraseedw Implant is of superior quality. LICENSIN(i TheraSeedN Implants are licensed by the State of Georgia for distribution to persons licensed pursuant to Title 10 U.S. Code of Federal Regulations Part 35 Sections 35.14 and 35.100 Group VI or under equivalent licenses of Agreement states. Page 11 of 12

1.
2.
3.
4.
5.
6.
1.
a.

Package Insert -- References_ Hilaris, B.s., ed., Handbook of Interstitial Brachytherapy, Publishing Sciences Group, Inc., Acton, MA 1975. NCRP Report No. 37 NCRP Publication, P.O. Box 30175, Washington, DC 20014. NCRP Report No. 40 NCRP Publication, P.O. Box 30175, Washington, DC 20014. NCRP Report No. 41 NCRP Publication, P.O. Box 30175, Washington, DC 20014. NCRP Report No. 48 NCRP Publication, P.O. Box 30175, Washington, DC 20014. NCRP Report No. 49 NCRP Publication, P.O. BOX 30175, Washington, DC 20014. Ling, c., Proceedings of Fourth International Conference on Medical Physics, Ottawa, Canada, July, 1976. L. L. Anderson: Private Communication--to be published. Presented at International Endocurietherapy Meeting, LAC/USC, Los Angeles, 6/30/78 - 7/2/78.

9.

Calculated Dose from TheraSeed~ Implants, Dr. John L. Russell, Jr. Available through Theragenics Corporation, Atlanta, GA., upon request. Page 12 of 12

FIC'i.:RE 1 FIGURE 2 (1) Seed Vial ~J:tp,_ ~EAAGENICS CORPORATION TheraSeed' Palladium Seeds-(Pd-103) Radionuclide Apparent ~~ Brachytherapy Source Activity Range rnCi Model 200 -,~kt coo,p ='VC()"<" -,,..,...., ~ ~~ ~ ,...,....,.,,,..._,.""~"""'- m ofSeeds_. M',t,C~t"'ICICUC. ~~lh-:~..:t3~ ~ Assay Date----- -lunM<lbr11110-V,..~ol---tor ~.,C91(!;;)-(21)1<)olCl,opta, .'ll01>2l Sc-C i;..,,..1110,..---ol.,..US ,_.,~c.:---... -v-_o,...,__ CNJTIOII-----*-"'""""""-"'" ~---.-,~-all-(2) Lead Vial Holder C..- RADIOACTIVE ~ See package inMtt1 for 1nat,uctt0n.a on hancttl~ ato,._ of Th.....,s....,no _,,uu., The,gente& C-o<pot-atton Allan(a, GA 30318

Cb.e_raSaed~P~lt~ll:!_~§-~s. (Pd-103)

Radionuclide Brachytherapy Source Total Apparent Activity ________ mCi comp. Surface Dose Rate 1++.J;, mRem/hr. Assay Date ~~~ Total No. Of Vials ______ _ Total No. Of Seeds ______ _ This Product Made in U.S.A. By: Theragenics Corporation Atlanta, GA 30318 (3) Outer Container ~-~ A CaUbon RADIOACTIVE MMEflW.

LIST OF THERAGENICS MANAGEMENT PERSONNEL John v. Herndon Chief Operating Officer Executive Vice President John L. Carden, Jr. .Vice_ Prl?§ :i,g~nj: ______ _ Research, Development a:ria7rariufacturing

  • hristine Jacobs

,.uirector of General Sales and Marketing Roberts. Kirkland Manager of Manufacturing and Operations Julie A.K. Stephens Manager Technical and Clinical Services Diana Fialkowski Marketing Manager Rick Powers Manager of Distribution and Purchasing &-!fe_~ ~ THERAGENICS 1 CORPORATION CHRISTINE JACOBS olRECIOR Of GENERAL SAi.ES mol,IARl<ETING 900 AttanllC Drive. N.W' Atlanta. Georgta 30318 1-~ (404)873--6309 t,.g*~~ 'fl THERAGENICS V CORPORATION HOWARD T COOPER Dtl'ECTOR OF P!:0lJI.ATOflY & MEDICAi. AFFAIRS 900 Allantu: Drrve, NW. Atlanta Georg a 30318 1-800-458-4372 (404) 873-6309 +. (404JB7.l-63!>.* ~~ THERAGENICS 1' CORPORATION JULIE A.. K. STEPHENS-PROJECT :)fl'ECTOA ilADIOMICROS?t-ERE Tt1t*&Sphn. 900 Atlantic Dnve, NW, Atlanta, Georg,a 30318

~

. ~THERAGENICS 'f CORPORATION DR. JOHN L. CARDEN, JR VICE PflES/0!:NT RESEARCH AAD OE vEl.OPMENT (404) 873-63t, Res. 491-643t. 900 Allant,c Onve, N.W, Allanta, Georg,a 30318 I' THERAGENICS CORPORATION JOHN V. HERNDON CHIEF OPEJWt-lG OFFICm EXECUTIVE VlC1; P!lESlOENT (404)873-63.., 900 Atlanl!C Onve, NW, Allanta, Georgia 30318 ,~f& %,:ls?oTHERAGENICS V CORPORATroN RICK POWERS lo'NifGER[E~NCJ~ 900 Atlantic Drive, N W, Allanta. Georgia 30318 1-800-458-4372 (404)~ Res. 421-8485}}

Retrieved from "https://kanterella.com/w/index.php?title=ML23157A245&oldid=3772910"