MassMassachachuusesettstts InInssttiittuutte of Technole of TechnoloogygyHaHarvarvarrd Md Meedicadicall SScchohoololBrBrigighaham am annddWWoomemenn’’s Hs HoossppitalitalVA BVA Boossttonon HeHealalthcthcaare Sre Syysstteemm22..7782J82J//33.9.961J61J//BEH.45BEH.4511JJ//HST5HST52424JJFEDERAL REGULATORY ISSUES:FEDERAL REGULATORY ISSUES:RECOMRECOMMMENDED BIOCOMPATIILITY TESENDED BIOCOMPATIILITY TESTTINGING AND REGULTIOAND REGULTIONN OOFF TISSUE ENGTISSUE ENGIINEEREDNEERED PRODUCTSPRODUCTSM. SpecM. Specttor,or, PPhh.D..D.Required Biocompatibility Training andRequired Biocompatibility Training and ToxiToxicolcoloogy Profilgy Profiles fes foor Er Evvaluatialuation of Mon of Meedicaldical DeviDevicesceshttp://www.fda.gov/cdrh/g951.htmlhttp://www.fda.gov/cdrh/g951.html••FDAFDA--modified matrix that designates the type of testingmodified matrix that designates the type of testingneeded for variousneeded for various medical devices.medical devices.••It also incluIt also includdes a flowes a flow chart entitled "Biocompatibilitychart entitled "BiocompatibilityFlowFlow Chart for the SeChart for the Selelectioction of Toxicity Tn of Toxicity Teests forsts for 510(k)s.510(k)s.““••The guidance wThe guidance wiill be efll be effecfecttivive foe for ar alll submissiol submissionns that ws that willill be received on or after July 1, 1995. The former guidance,be received on or after July 1, 1995. The former guidance,#G87#G87--1 entitled "Trip1 entitled "Tripaartite Brtite Biiocompatibility Guidance,ocompatibility Guidance,"may continue to be applied until a final decision is reachedmay continue to be applied until a final decision is reachedon each submission receivon each submission received prior to July 1, 1995.ed prior to July 1, 1995. Page 1–––••– -––––––•–•Required Biocompatibility Training andRequired Biocompatibility Training and ToxiToxicolcoloogy Profilgy Profiles fes foor Er Evvaluatialuation of Mon of Meedicaldical DeviDevicesces••Biological evaluation of mediBiological evaluation of medical devices is performed tocal devices is performed todeterdetermmine the potentiaine the potential toxicityl toxicity resulting from contact ofresulting from contact ofthe component matethe component materriiaalls of the devs of the deviiccee wwiith the body.th the body.••The device materiaThe device materialls ss shhould not,ould not, either directly or througheither directly or throughthe release of their mathe release of their materiateriall constituents:constituents:– ((ii)) pprroodduucceeaaddvveerrsse loe locacal ol orrssyyssttememicic effeffeectcts;s;– (ii(ii)) bebe ccaarcinrcinoogenicgenic;; oror– (iii(iii) produce advers) produce adversee reprreprooductiductivve ande and dedevelveloopmepmenntaltaleefffects.fects.••Therefore, evaluation of anTherefore, evaluation of any newy new device intended fordevice intended for human use requires data from systematic testing to ensurehuman use requires data from systematic testing to ensurethat the benefits provided by the final product wiill exceethat the benefits provided by the final product w ll exceed any potential risks produced by deany potential risks produced by device materials.vice materials.Required Biocompatibility Training andRequired Biocompatibility Training and ToxiToxicolcoloogy Profilgy Profiles fes foor Er Evvaluatialuation of Mon of Meedicaldical DeviDevicesces• When selWhen seleeccttiinng the apg the appropropprriiaatte tese testtss forforbbiiolologogiiccalalevevalaluuaattiioonn oof a mef a medicaldical devicedevice, one m, one muussttccoonsinsidder theer the chechemmicalical cchhararacacteristeristticics ofs of dedevicevicemmaateterialsrials andand the nature, dethe nature, degree, fregree, frequencquency any and durd duratiatioon ofn of its eits exxposposuure tore to ththe boe body.dy.• InIn genergeneraal, thl, the tee tests ists inncludeclude::– acute, subacute, sub- chchroronniic anc andd chchronroniicc toxictoxiciittyy;;– irritatirritatiionon to sto skkiinn, e, eyyeses anandd mumucoscosaal sl suurfacesrfaces;;– sensitisensitizzation;ation;– hemocompatibilithemocompatibilityy;;– genotoxicitgenotoxicityy;;– carcincarcinogenogeniicitcityy; an; andd– effectseffects ononrepreprorodduucctiontion ininclucluddiinngg ddeevelopvelopmmenenttaal effl effectsects..• AddiAddititiononal tesal testtssffoor specir specificfic tatargergett ororgan toxicigan toxicity,ty, ssuuch asch as neurneurotoxicotoxiciitytyanandimmunotoxiciimmunotoxicitytymmaay bey be necneceessssary forary for ssoome deme devicevices.s.– For example,For example, a neurologicala neurological devicedevice withwithddiirerect conct conttact withact withbbrraiain parn pareenncchhyymma anda and cerebcerebrosrosppininalal flfluuiidd (CS(CSFF) may) may reqrequuiirere anan ananiimmal impal impllanant tt teesstt toto evaevalluuaate itste its effecteffectson the brain paon the brain parenchymarenchyma,, suscsusceptieptibilitbility to seizy to seizure, andure, and effectseffects on the functionalon the functional mechanism ofmechanism of choroidchoroidpleplexxus andus and arachnoidarachnoidvilli to secrete anvilli to secrete and absorb (CSF).d absorb (CSF).• The speciThe specific clfic clinicalinical aapplicatiopplicationn andand thethe mmaaterialsterials used iused inn thethe manumanufacfacttureure ofof thethe new devinew deviccee dedetermiterminesnes which tewhich testssts arare approprie appropriateate..Page 2InteInterrnnaattioionanal Ol Orrgaganizanizatition fon foor Sr Sttandards, ISOandards, ISO htthttpp:://www.//www.isoiso..ch/isoch/iso//en/Cen/CatatalogalogueListueListPagPagee..CCatatalogalogueList?ueList?IICCSS11==1111&ICS2=&ICS2=100100&ICS3=&ICS3=ISO 10993ISO 10993--1:19971:1997BiBiolologiogiccalal eevalvaluatuatiionon of medical devof medical deviicesces ----Part 1: Evaluation and testingPart 1: Evaluation and testingISO 10993ISO 10993--2:19922:1992BiBiolologiogiccalal eevalvaluatuatiionon of medical devof medical deviicesces ----Part 2: Animal wPart 2: Animal weellffare requiare requirementrementssISO 10993ISO 10993--3:19923:1992BiBiolologiogiccalal eevalvaluatuatiionon of medical devof medical deviicesces ----Part 3: Tests forPart 3: Tests for genotoxicitygenotoxicity, carcinogenicity and, carcinogenicity andreproductivreproductivee toxtoxiicitycityISO 10993ISO 10993--4:20024:2002BiBiolologiogiccalal eevalvaluatuatiionon of medical devof medical deviicesces ----Part 4: Selection of