1. Andrew Harings
Scott Buchheit
MohammedHussein
RAS 621 Final Paper
Background
The ABM Medical StopLoss is a surgical hemostat productintendedtoassistwithintra-operative
hemostasis inavarietyof surgical procedures. The device hasadouble barrel syringe design,withdried
bovine collagenandthrombincontainedinone barrel andplasmaderivedfromthe patient’swhole
bloodsample inthe other. Asthe syringe barrel ispressed,the contentsof the twobarrelscombine as
the contentsare deliveredtothe injectionsite asamixture. Indicationsforuse of StopLoss include use
insurgical procedurestopromote hemostasiswhenbleedingisunable tobe controlledbyconventional
meansor isimpractical.
StopLoss includesanaccessorykit,consistingof acentrifuge vial withsterilesodiumcitrate toseparate
plasmafromwhole bloodandan extrasterile syringetodeliverthe bloodplasmatothe double barrel
syringe. StopLossand the associatedaccessorykitare packagedtogetheranddistributed sterile foruse
inthe surgical sterile field. A centrifuge forthe separationof the patient’splasmafromthe whole blood
sample isto be providedbythe healthcare provider.
Product Classificationand Market AuthorizationRequirements
StopLoss is a medical device withbiologiccomponents wherebothare requiredtoachieve the intended
use and effect,andtherefore,meetsthe definitionof acombinationproduct. ABMMedical will
appropriatelymarketStopLossinthe United State as a combinationproduct.
As establishedbythe Medical Device Amendmentsof 1976 to section513 of the Federal Food,Drug,
and CosmeticAct(FDCA),there are three regulatoryclassesformedical devices,whichare basedonthe
degree of control necessarytoassure thatthe varioustypesof devicesare safe andeffective. Itisthe

2. Andrew Harings
Scott Buchheit
MohammedHussein
intentionof ABMMedical that the StopLoss Surgical Hemostat will be indicatedforuse inpotentially
highrisksurgical situationsandmaybe of substantial importance inpreventingimpairmentof human
health. Additionally,the productutilizesbiologicalcomponents,aswell asaccessoriesthatcontributeto
the complexityof the devicethatcontribute toitsriskof use. Therefore,the StopLossSurgical
Hemostatwill have aFDA classIIIdesignationinthe UnitedStates.
StopLoss fallsunderthe FDA product code LMF, whichisfor an absorbable hemostaticagent. StopLoss
will be governedby regulationnumber878.4490. Anexistingdevice thatiscurrentlyonthe marketin
the UnitedStatesdevice similartothe StopLoss has a product code LMF, furtherdemonstratingthe
properclassificationof the StopLoss.
Under section515 of the act, all class IIIdevicesare subjecttothe PMA process and musthave proof of
safetyandeffectivenesspriorbeingmarketed. In orderto marketour StopLoss, we will submitasingle
marketingapplicationthroughthe FDA PMA process,i.e.we will notsubmitseparate marketing
applicationsforthe device andbiologiccomponentsof the product. Because of the class III designation
for StopLoss,it isnot eligiblefor 510(k) clearance,eventhoughathere are existingproduct(s)onthe
marketthat are similar.
The PublicHealthandWelfare Actpart F, establishedthe regulationsof biological productsinthe United
States. Under section503(g) of the FDCA,as addedby section16 of the Safe Medical Devices Actof
1990 and amendedbysection204 of the Medical Device UserFee andModernizationActof 2002, the
FDA will determinethe organizational componentwithinFDA designatedtohave primaryjurisdictionfor
the premarketreviewandregulationof combinationproducts. The FDA Office of CombinationProducts
(OCP) issuesclassificationandjurisdictionassignmentsformedical products. The classificationof a
productdeterminesthe type of aproduct(drug,device,biologic,orcombinationproduct). Jurisdiction

3. Andrew Harings
Scott Buchheit
MohammedHussein
determinesthe FDA CenterorLead Center(CBER,CDER,or CDRH) by which the productwill be
regulated. The ABMMedical RegulatoryAffairsDepartmentmade arequestfordesignation(RFD) tothe
OCP and confirmed thatthe StopLoss is withinthe jurisdictionof the CDRH. ABMMedical anticipated
that StopLoss wouldbe underthe jurisdictionof the CDRH,inpart,because the aforementioned
currentlymarketedproductthatissimilartoStop Lossis underthe jurisdictionof the CDRH.
In the EU, StopLoss will be classifiedasa classIII device. The rationale forclassIIIdesignation inthe EU
isthe same as the rationale forclassIIIdesignationinthe UnitedStates. Thatis,itis basedon the high
risklevel associatedwiththe use of the device. The designdossierwill be submittedforreview toa
NotifiedBodyandanISO13485 qualitysystemauditwillbe conductedbythatNotifiedBody. Upon
reviewof the designdossierand completionof the ISO13485 qualitysystemaudit,ABMMedical will
receive adeclarationof conformityandwill be able tomarketStopLossinthe EU.
In Canada,StopLoss will be a classIV device asthe consequencesare extremelyhightothe userif the
productstops workingormalfunctions. Priortomarketingthe StopLoss in Canada,ABM Medical will
obtaina medical device licensefromHealthCanada. Toobtain a medical device license,ABMMedical
musthave a qualitymanagementsystemcertifiedaccordingtoISO13485 by a CanadianMedical Device
ConformityAssessmentSystem(CMDCAS)recognizedregistrar. ABMMedical anticipatesthatthe
NotifiedBodyauditwill certifythe company’squalitysystem.
Registrationand Device Listing
Section510 of the FDCA establishesthe FDA’sauthoritytorequire medical device manufacturersto
registertheirestablishmentandlistmanufacturedproductswiththe FDA. 21 CFR 807 definesthe
regulatoryrequirementsforregistrationanddevice listingformanufacturers. ABMMedical iscurrently
registeredwiththe FDA as a medical device manufacturerandanexporter. The bovine collagenand

4. Andrew Harings
Scott Buchheit
MohammedHussein
thrombin components of StopLoss are suppliedtoABMMedical froma domesticsupplier. Therefore,it
isnot necessaryforABMMedical to registerasa biologicmanufacturer. ABM’sFDA registrationwillbe
updatedtoinclude StopLossafterthe PMA isapprovedandat least30 days prior to marketingthe
product. Since Stop Losswill be manufacturedatthe same facilityasother ABMapprovedand
marketedproducts,the addressonthe registrationandlistingwill notneedtobe updated. ABMwill
submititsannual registrationinformationagainbetweenOctober1 andDecember31 if the registration
update to listStopLossdoesnot take place duringthat time frame. Registrationinformationwill be
submittedtothe FDA electronically perthe Medical Device UserFee ModernizationAct.
Quality SystemRequirements
The FDA recognizesthatmanymanufacturingfacilitiesoperate underone type of currentgood
manufacturingpractice system(i.e.,describedbythe QSor CGMP regulation). Additionally,the FDA
recognizesthatthere isconsiderable overlapbetweenthe QSandCGMP regulations. PerCurrentGood
ManufacturingPractice forCombinationProducts(DraftGuidance),FDA considersitgenerallynot
necessaryformanufacturerswhomake combinationproductsthatare producedasa single entityorare
co-packagedtomaintaintwoseparate manufacturingsystemstoensure compliance withbothsetsof
regulationsduringandafterjoiningthe constituentstogether. FDA believesthatcompliance withboth
setsof regulationsduringandafterjoiningthesetypesof combinationproductscangenerallybe
achievedbyusingeitherthe CGMPor QS regulations,e.g.,byusingthe currentgoodmanufacturing
practice systemalreadyoperatingata manufacturingfacility. Therefore,ABMMedical will manufacture
and distribute StopLosswithinitscurrent 21 CFR 820 qualitysystem.

5. Andrew Harings
Scott Buchheit
MohammedHussein
Clinical Data Requirements
As definedinsection515 of the FDCA,clinical dataisnecessarytodemonstrate safetyandeffectiveness
inorder to obtainFDA approval of a classIIIdevice. Humanclinical trialsonStopLoss were conducted
inthe UnitedStatesinaccordance withthe FDA Good Clinical Practicesregulations(GCPs),21 CF 812.
Per21 CFR812 and 21 CFR 56, an applicationforInvestigationDevice Exemption(IDE) status wassentto
the Institutional ReviewBoard(IRB) priortothe initiationof humanclinical trials.Aspartof the clinical
trials,ABMMedical obtained informedconsentof all patientsand labeledStopLossproductwith“For
InvestigationUse Only.” All clinical trialswere appropriatelymonitoredandall requiredrecordsand
reportswere maintained.
Product Labeling
Copiesof proposedlabelingforStopLosswill be includedinthe PMA submission. The labelingwill
complywiththe regulatoryrequirementsin21 CFR 801 (Labeling) andwill includethe commonname of
the device,quantityof contents,andthe name andaddressof the manufacturer(ABMMedical). In
addition, StopLossandaccessorieswill include appropriate labelingforbloodandbloodcomponents
(plasma) per21 CFR 606.121. Furthermore, labelingwillinclude informationforuse,including
indications,effects,routes,methods,andfrequencyanddurationof administration;andanyrelevant
hazards,contraindications,side effects,precautions,instructionsforinstallationandoperation,andany
information,literature,oradvertisingthatconstituteslabelingunderPart201(m) of the FDCA.
Medical Device Tracking
The FDA’sauthorityto requiredmedical devicetrackingisestablishedinsection519 of the FDCA and
the regulationsare containedin21 CFR 821. ABM Medical RegulatoryAffairspersonnel consultedthe

6. Andrew Harings
Scott Buchheit
MohammedHussein
FDA’s“Guidance onMedical Device Tracking”and determinedStopLosswill notrequire medical device
trackingas it doesnotfitthe criteriafortrackingrequirements.
As establishedinsection522 of the FDCA,the FDA requirespostmarketsurveillance formedical
devices. StopLosswill require postmarketsurveillance (seePostMarketSurveillance sectionof this
report).
ValidationRequirements
All processesinvolvedinthe productionof StopLosswill be validatedper21 CFR 820.75, as appropriate.
Thisincludesall applicable sterilizationprocessesasStopLossisdistributedandsoldasa sterile device.
An additional keyprocessvalidationisthe productionof the doublebarrel syringewiththe driedbovine
collagenandthrombincomponents.
Special Product Testing Requirements
There isan extensivehistoryonthe safe use of bovine collagenandbovine thrombininhumans.
Therefore,standardbiocompatibilitytestsasdefinedinthe ISO10993 standardwill notbe conducted
on StopLoss.
Preclinical animalstudieswere conducted byCovance Labs,a contract researchorganization,to
evaluate the hemostaticperformance of StopLossina varietyof surgical wounds.
Special testingforStopLosswill include bioanalytical characterizationof bovine collagenandthrombin
components. Because the productisusedassterile,additional testingwill includemicrobial andviral
contaminationof bovine collagenandthrombin,aswell asall device surfaces.

7. Andrew Harings
Scott Buchheit
MohammedHussein
To establishshelflifeandstorage requirements,StopLosswill undergoforceddegradationandstability
testingwhile real-time shelf lifestudiesare conductedconcomitantly. The PMA will include the
recommendedproductshelf life basedonthe resultsof these tests.
Inspections/Audits
ABMMedical has identifiedpotential FDA inspectionsasa resultof manufacturingandmarketingStop
Loss. Inadditiontothe biannual FDA QSITinspectionsthatABMMedical iscurrentlyscheduledfor,a
preapproval inspectionforStopLossisanticipated.
As recommended,ABMMedical hasdiscussedwiththe FDA how currentGMPs will applytoStopLoss
since the producthas device andbiologiccomponents. ABMMedical has beenincommunicationwith
the FDA throughoutthe productdevelopmentprocess,seekingcommentandinputregardingthe risks
regulatoryrequirementsof StopLoss. ABMMedical’sbiologiccomponentmanufacturerhasbeen
includedinthe communicationprocesstoensure appropriate regulatoryobligationscouldbe
sufficientlyplannedforandmet. To approve the keysuppliersof bovinecollagenandthrombin
components,ABMMedical usedrigorousstandardsandcriteriaandperformedanin-depthauditof the
suppliers. Inaddition,ABMMedical will performannual auditsof the suppliersthatsupplybovine
collagenandthrombin.
ABMMedical doesnot anticipate ateam FDA inspectionasStopLossisa combinationproductthatwill
be producedas a single entityregulatedbyCDRHunder21 CFR 820.
ABMMedical will be subjecttoISO13485 auditsbya NotifiedBodyanda CMDCAS recognizedregistrar
inorder to marketandto continue tomarketStop Loss inthe EU and Canada.

8. Andrew Harings
Scott Buchheit
MohammedHussein
FDA usesCompliance ProgramGuidance Manuals(CPGM) todirectitsfieldpersonnelonthe conductof
inspectionalandinvestigational activities.The purpose of the programisto ensure the protectionof
researchsubjectsandthe integrityof datasubmittedtothe agencyinsupportof a marketing
application. ABMMedical will be conductinghumanclinical trialsinthe UnitedStatesandfully
anticipatesanassociatedBIMOaudit.
Preclinical animalstudieswere conductedbyCovance Labs,a contract researchorganization,to
evaluate the hemostaticperformance of StopLossina varietyof surgical wounds. Therefore,any
applicable FDA GLPinspectionswouldbe conductedon-site atCovance Labsandnot at ABM Medical.
Post-MarketSurveillance
The Food andDrug AdministrationModernizationActof 1997 (FDAMA) modifiedpost-market
surveillance requirementsundersection522of the FDCA. Under section522 of the FDCA,a
manufacturermustconductpost-marketsurveillance foranyclassIIIdevice forwhichfailure wouldbe
reasonablylikelytohave seriousadverse healthconsequences. Therefore, ABMMedical will be
requiredtoconductpost marketsurveillance onStopLoss. 21 CFR 822 describesthe regulatory
requirementsforpost-marketsurveillance.
Furthermore,StopLossissubjecttoMedical Device Reportingasestablishedbythe Safe Medical
DevicesActof 1990 (SMDA). Under SMDA, device userfacilitiesmustreportdevice-relateddeathsto
the FDA and the manufacturer,if known. Device userfacilitiesmustalsoreportdevice-relatedserious
injuriestothe manufacturer,orto the FDA if the manufacturerisnotknown. In addition,SMDA
requires thatdevice userfacilitiessubmittoFDA,ona semiannual basis,asummaryof all reports
submittedduringthattime period. MDR regulatory requirementsare containedin21 CFR 803.