IDE Preparation And Maintenance: Best Practices Workshop
IDE Preparation and Maintenance: BestPractices WorkshopPART 1: IDE Exemption Studies,Abbreviated IDE and IDEPART 2: IDE Maintenance and AdditionalDevice StudiesJelena P. Berglund, PhD, RACAssociate Director, Regulatory Affairs
Regulatory Affairs OfficeFront Row (L-R): Bruce Burnett, PhD, RAC; Audrey Perry, Erin O’Reilly, PhD, RAC;Amanda Parrish, PhD, RACBack Row (L-R): Preeti Chugha, PhD, PMP; Jelena Petrovic Berglund, PhD, RAC;Erika Segear Johnson, PhD
Our Website:Templates and InstructionsBest Practices Templates/Instructionshttp://tinyurl.com/axwxkmv Recorded Webcastshttp://tinyurl.com/m269l7n
PART 1: IDE Exemption Studies,Abbreviated IDE and IDE Background Clinical Investigations of a Medical Device IDE Exemptions SR/NSR Determination and Abbreviated IDE Pre-Submission Meetings with the FDA IDE Preparation and Submission
What is a Medical Device?513(a)(1) for the FD&C ActIts an instrument, apparatus, implement, machine,contrivance, implant, in vitro reagent or other similaror related article or component part or accessory which:- isintended for use in the diagnosis ofdisease or other conditions, or in thecure, mitigation, treatment, orprevention of disease- is intended to affect the structure orany function of the body- achieve it's primary intendedpurposes through physical action andNOT chemical or metabolic action
What is a Medical Device?
Medical Device RegulationMedical Device Amendments in 1976 Prior to 1976, investigational devices wereeither not reviewed or reviewed as drugs Established device classifications based on risk Established the Investigational DeviceExemption (IDE)
Medical Device Classification Devices are classified related to the:risk associated with the use of the device---Class I; lowest riskClass II; moderate riskClass III; highest riskClass I and II are non-significant risk (NSR)devicesClass III devices are significant risk (SR)devices
Medical Device Classification---Class I - e.g. dental floss, medicalscissors, dental syringeClass II – powered wheel chair, MRI,clinical mercury thermometerClass III - e.g. external defibrillator,replacement heart valves
Medical Device Classification Devices are classified related to the: medicalspecialties: 16 groups (21CFR 862-892)862 Clinical Chemistry and Clinical Toxicology864 Hematology and Pathology866 Immunology and Microbiology868 Anesthesiology870 Cardiovascular872 Dental874 Ear, Nose, and Throat876 Gastroenterology and Urology878 General and Plastic Surgery880 General Hospital and Personal Use882 Neurology884 Obstetrical and Gynecological886 Ophthalmic888 Orthopedic890 Physical Medicine892 Radiology
Medical Device Classification Devices are classified based on the time oftheir marketing- pre-Amendments device – marketed prior to1976- post-Amendments device - marketed after1976- Transitional devices - those regulated asdrugs prior to the ’76 Amendments, butsubsequently as devices
Summary of DevicesClassifications Based on the risk (Class I, II & III) NSR & SR Based on medical specialties (into 16 groups) Based on the time (pre- , post-amendment,transitional)
Commercialization Options Exempt – most Class I and a few Class II devicesare exempt from the 510(k) regulations 510(k) - device is at least as safe and effective, orsubstantially equivalent to, a legally marketeddevice (predicate) that is not subjected to a PMA 90 day FDA review http://tinyurl.com/qeh79qn PMA - premarket approval is required for all ClassIII devices. Focus on scientific and regulatoryreview of safety and effectiveness 180 day FDA review
Medical Device s/cdrh/cfdocs/cfPCD/classification.cfm
Example15
PART 1: IDE Exemption Studies,Abbreviated IDE and IDE Background Clinical Investigations of a Medical Device IDE Exemptions SR/NSR Determination and Abbreviated IDE Pre-Submission Meetings with the FDA IDE Preparation and Submission
Clinical Study of anInvestigational Device If the objective of the study is to assess the safetyand/or effectiveness of a device, the study is subjectto 21 CFR 812. Studies using devices as “tools” This is in contrast with the practice of medicine – a physiciancan use a device (or drug) without regulatory approvalOnly when used as a part of clinical investigation, a devicemight be subject to 21 CFR812
Clinical Investigation of MedicalDeviceAll Clinical Investigations of Medical Device:be exempt from the IDEregulations (21 CRF 812.2 (c))have an IDEa) abbreviated IDE (21 CRF 812.2 (b))b) IDE (21 CRF 812.20)
PART 1: IDE Exemption Studies,Abbreviated IDE and IDE Background Clinical Investigations of a Medical Device IDE Exemptions SR/NSR Determination and Abbreviated IDE Pre-Submission Meetings with the FDA IDE Preparation and Submission
Investigations Exempt fromthe IDE Regulations A legally marketed device when used inaccordance with its labelingA diagnostic device meeting 4 specified criteriaA device undergoing a consumer preferencetesting, testing of modification or testing of acombination of two or more devices in commercialdistribution if the testing is not for the purpose ofdetermining safety or effectivenessA device intended solely for veterinary useA device for research on or with laboratoryanimalsA custom device (21 CFR 812.3(b)) (http://tinyurl.com/lbxl9k8)
PART 1: IDE Exemption Studies,Abbreviated IDE and IDE Background Clinical Investigations of a Medical Device IDE Exemptions SR/NSR Determination and Abbreviated IDE Pre-Submission Meetings with the FDA IDE Preparation and Submission
Clinical Investigation of MedicalDeviceAll clinical investigation of device must:be exempt from the IDEregulations (21 CRF 812.2 (c))have an IDEa) abbreviated IDE (21 CRF 812.2 (b))b) IDE (21 CFR 812.20)
Difference between anabbreviated IDE and IDE? Who is overseeing the study:IRB (abbreviated IDE) Non-significant risk (NSR)deviceNot a banned device(21CFR 895.101) Must have informedconsentFDA and IRB Significant risk (SR) deviceInvestigation exempt from theinformed consentFDA notifies the sponsor thatIDE application is required
What are Significant Risk Devices?21 CFR 812.3 (m) Significant Risk Device is investigationaldevice that: is intended as an implant and presents a potential forserious risk to the health, safety and welfare of a subjectis used to support or sustain human lifeis substantial importance in diagnosing, curing,mitigating, or treating disease or otherwise preventingimpairment of human healthotherwise presents a potential for a serious risk to thehealth, safety or welfare of human subject
Significant Risk Device Studieshttp://tinyurl.com/48ywrw8
If the Investigational Study is NSR(21 CFR 812.2 (b))Trial can be run under an abbreviated IDE 26
Obtaining an IRB Approval Sponsor makes initial significant or nonsignificant risk study determinationSubmit to the IRB required documents:- description of the device- explanation why you believe that the device is NSR device- report of prior investigation- proposed investigational plan- other If IRB agrees with sponsor, study can beconducted under the IRB oversight only
Abbreviated IDE(21 CFR 812.2 (b)) Obtain and maintain IRB approval of theinvestigationMake sure that the device is properly labeledEnsure that informed consents are obtainedMaintain required records and reportsMonitor the study to ensure compliance with theprotocol and protect the human subjectThe promotional practices are NOT permitted
If IRB Disagrees with the NSRDetermination The Agency needs to make SR/NSRdetermination. The decision is binding
PART 1: IDE Exemption Studies,Abbreviated IDE and IDE Background Clinical Investigations of a Medical Device IDE Exemptions SR/NSR Determination and Abbreviated IDE Pre-Submission Meetings with the FDA IDE Preparation and Submission
Q-Sub Program: Requests for FDAFeedbackQ-Sub TypeMeeting as Method ofFeedback?Timeframe forMeeting/Teleconference(from receipt ofsubmission)Pre-SubmissionUpon Request75-90 daysInformational MeetingYes90 daysA pre-submissionis defined N/Aas a formalNoAgreementMeeting requestYes from an applicant30 days orforwithin timewrittenframe agreed to withfeedback from FDA to be providedin thesponsorformMeetingof a formalwritten responseor a agreedDeterminationYesDate for meetingupon within 30 days ofmeeting/teleconference.request Risk DeterminationStudySubmissionIssue Meeting Yes21 176.pdfDay 100 MeetingYes100 days (from PMA filingdate)
Q-Sub Program: Pre-Submissions A pre-submission is defined as a formalwritten request from an applicant forfeedback from FDA to be provided in theform of a formal written response or ameeting/teleconference.Guidance: http://tinyurl.com/kvbf54z
Q-Sub Program: Pre-Submissions Recommended contents for pre-sub package: Cover letterTOCDevice DescriptionProposed Intended UsePrevious Discussions or SubmissionsProduct DevelopmentSpecific QuestionsMechanism for FeedbackOther Logistical Information
Q-Sub Program: Pre-Submissions Similar to pre-IND for drugs: Mechanism to obtainfeedback from FDA on protocols and other aspectsof device developmentWritten submission of intended use, devicedescription, protocol/plan, questionsEncouraged, but not required, by FDACan be used even if no IDE will followCan be used more than once (unlike the formalmeeting schedule in drug development).
Q-Sub Program: Study RiskDetermination Informal: Email/Call Formal: Pre-Submission StudyDetermination Request Include device information and clinical protocol Recommend cover letter and highlight nature ofrequest Response usually within 60 days (bindingdetermination); no Q-Sub timing Formal: Submit full IDE Response within 30 days
Case Studies36
Scenario 1 The objective of the proposed study is to assesssafety and efficacy of a CancerSTOP drug incombination with various anti-androgens onprostate cancer. Cancer progression is assessedwith the use of a CT scan. Is this a Drug study? Is this a Device study? Is this both drug and device study?
Scenario 2 An investigator is planning on studying the safetyand effectiveness of the FDA-approved device(SLIM). The device is a PMA-approved as animplantable gastric bypass. The study is assessingthe safety and efficacy of that device incombination with specific gastric surgicalprocedure that will be performed in the same time. Q 1: Is this a device study? Q 2: Can this study be IDE exempt?
Investigations Exempt fromthe IDE Regulations A legally marketed device when used inaccordance with its labelingA diagnostic device meeting 4 specified criteriaA device undergoing a consumer preferencetesting, testing of modification or testing of acombination of two or more devices in commercialdistribution if the testing is not for the purpose ofdetermining safety or effectivenessA device intended solely for veterinary useA device for research on or with laboratoryanimalsA custom device (21 CFR 812.3(b)) (http://tinyurl.com/lbxl9k8)
Scenario 2 Q3: In your opinion is this a SR or NSRStudy? Not used per its labelIt is implant approved via PMAPotentially prolonged time of surgeryPotentially increased risks associated with thedevice itself Study required an IDE
Scenario 3 An investigator is running a multi-center trial. In 3out of 4 participating institutions, the reviewingIRBs agreed with the investigator that the devicetrial is a NSR study. The 4th IRB sees it as SRdevice study. What should investigator do?1.2.3.4.ignore the 4th IRB, since 3 others agreeddo not use the 4th siteask FDA for the opinion by sending an IDE applicationask the FDA by giving them a call
PART 1: IDE Exemption Studies,Abbreviated IDE and IDE Background Clinical Investigations of a Medical Device IDE Exemptions SR/NSR Determination and Abbreviated IDE Pre-Submission Meetings with the FDA IDE Preparation and Submission
IDE Content (21 CFR 812.20 (b))1. Cover Sheet – form 35142. Name and Address of the Sponsor3. Report of Prior Investigations4. Investigational Plan5. Manufacturing Information6. Investigators Agreement7. Investigators Certification8. IRB Information9. Name and Address of Investigators Institution10. Financial Claims11. Environmental Assessment12. Labeling13. Informed Consent14. Additional Informationhttp://tinyurl.com/axwxkmv
1. Cover Sheet – Form 3514 used voluntarilysame form is used for IDE, 510(k), PMA, meetings,513(g) etc.captures the following information:- original submission, amendment, report orsupplement- device information (name, intended use)- sponsor and manufacturer contact info- any previous discussion with the FDA
IDE Content21 CFR 812.20 (b)1. Cover Sheet – form 35142. Name and Address of the Sponsor3. Report of Prior Investigations
3. Report of Prior Investigation(21 CFR 812.27) General prior clinical, animal and laboratory testingSpecificbibliography of all publications summary of all unpublished information if laboratory studies are referenced,statement whether such a studies havebeen done according to the GLP
IDE Content21 CFR 812.20 (b)1. Cover Sheet – form 35142. Name and Address of the Sponsor3. Report of Prior Investigations4. Investigational Plan
4. Investigational Plan(21 CFR 812.25) Purpose – name and intended useProtocolRisk AnalysisDescription of the DeviceMonitoring ProceduresAdditional Records and Reports
IDE Content21 CFR 812.20 (b)1. Cover Sheet – form 35142. Name and Address of the Sponsor3. Report of Prior Investigations4. Investigational Plan5. Manufacturing Information
5. Manufacturing Information21 CFR 812.20(b)(3) FDA-Approved Device – off label and/ormodified Non-FDA Approved Device – from a company Non-FDA Approved Device – you controlmanufacturing
5. Manufacturing Information21 CFR 812.20(b)(3) Refer to its approved labelRefer to its approved label & describechanges that you makeRefer to Letter of Authorization (LoA)
What is a Letter ofAuthorization? This is a letter from a sponsor (company) to theirIDE (or IND or MF) stating that confidentialinformation from their submission can be used insupport of your submission Thus, the FDA has “permission” to reference thenamed materials in support of your IDE Get copies of the letters to include in yoursubmission
5. Manufacturing Information21 CFR 812.20(b)(3) Methods, facilities, and controls for: Manufacturing Packaging Storage Installation
IDE Content21 CFR 812.20 (b)1. Cover Sheet – form 35142. Name and Address of the Sponsor3. Report of Prior Investigations4. Investigational Plan5. Manufacturing Information6. Investigators Agreement
6. Investigators Agreement(21 CFR 812.43) Who is the investigator?-Investigator is an individual who actuallyconducts a clinical investigation, i.e., underwhose immediate direction theinvestigational device is administered,dispensed to, or used- In the event of an investigation beingconducted by a team of individuals,"investigator" refers to the responsible leaderof that team
6. Investigators Agreement(21 CFR 812.43) CV of the investigator Statement of investigator’s relevant experience If investigator was involved in the investigation that gotterminated, explain the circumstances Financial disclosure information Statement of investigators commitment to: conduct the investigation according to the agreement supervise all testing ensure that requirements for obtaining of the IC are met
IDE Content21 CFR 812.20 (b)1. Cover Sheet – form 35142. Name and Address of the Sponsor3. Report of Prior Investigations4. Investigational Plan5. Manufacturing Information6. Investigators Agreement7. Investigators Certification
IDE Content21 CFR 812.20 (b)8. IRB Information9. Name and Address of InvestigatorsInstitution10. Financial Claims11. Environmental Assessment12. Labeling13. Informed Consent14. Additional Information
IDE Content (21 CFR 812.20 (b))1. Cover Sheet – form 35142. Name and Address of the Sponsor3. Report of Prior Investigations4. Investigational Plan5. Manufacturing Information6. Investigators Agreement7. Investigators Certification8. IRB Information9. Name and Address of Investigators Institution10. Financial Claims11. Environmental Assessment12. Labeling13. Informed Consent14. Additional Informationhttp://tinyurl.com/axwxkmv
Original IDE Submission Send 3 copies of your applicationSince Dec 2012 eCopy necessary!! An exact duplicate of the paper submissionIt can be CD, DVD, or flash driveIf identical copy is not feasible, hard copy needs to have aplaceholder cross-referencing the location of certain info oneCopyCover letter must contain eCopy statementSize of the submission is irrelevantUse Adobe Acrobat 11 and belowNo security settings50MB or smaller in size
Creating an eCopy Non-Volume Based eCopy 001 G010101 Annual report 2014.pdfVolume Based eCopy VOL 001 Cover letterVOL 002 Report of Prior Investigationshttp://tinyurl.com/99jtgle
IDE SubmissionIDE should be sent to:Food and Drug AdministrationCenter for Devices and Radiological HealthDocument Mail Center - WO66-G60910903 New Hampshire AvenueSilver Spring, Maryland 20993-0002
FDA Review Process Sponsors are notified of the date thatFDA received the original application IDE number is assigned (e.g., G096000) If eCopy is missing, you will be placed on“eCopy Hold”Sand eCopy only with the appropriatestatement
FDA Review Process Within 30 calendar days of the day the application has beenreceived, FDA may grant:-IDE Approval-IDE Approval with Conditions-Staged Approval (with Conditions)-IDE DisapprovalAn IDE application is considered approved 30 days after ithas been received by FDA http://tinyurl.com/lxrmd9u
Let’s Take a Break!
IDE Preparation and Maintenance: BestPractices WorkshopPART 1: IDE Exemption Studies,Abbreviated IDE and IDEPART 2: IDE Maintenance and AdditionalDevice StudiesJelena P. Berglund, PhD, RACAssociate Director, Regulatory Affairs
PART 2: IDE Maintenance andAdditional Device Studies IDE MaintenanceIn Vitro Diagnostic (IVD) DevicesIVD Multivariate Index Assay (IVDMIA)Additional Type of Device StudiesCase Studies
Once you have an activeIDE Make sure that you also have IRBapproval(s) in place
Registering Trial onClinicalTrial.gov Introduced by FDAAA in 2007 Do not need to send a 3674 form to theFDA with your IDE submission Do need to register “applicable trial” onClinicalTrial.gov
What is the “Applicable Clinical Trial”? Defined in the 402(j) of the PHS Act- prospective study of health outcomes- compares an intervention with a device against acontrol in human subject- the studied device is subject to 510(k), 515 or520(m)- its OTHER then a small clinical trial to determine afeasibility of device, or a clinical trial to test prototypedevice when the primary outcome relates to feasibilityand not to health outcomes
Deadline(s) for Registering Trials ICMJE Policy – Study must be registeredprior to enrollment of first subjectPHS Act – No later than 21 days afterenrollment of the first subject abhttp://tinyurl.com/8xtnc7r
Requirements for IDEModifications Changes that require prior approval (30-day replyfrom FDA) Changes that DO NOT require prior approval(require 5-day notice to FDA) Changes submitted as a part of annual report http://tinyurl.com/42wvtny
IDE Modifications Changes that require prior approval (30day reply from FDA): Indication Typeor nature of study control Primary end point Statistical methods evaluation Expanding the study (number of sites orsubjects) Significant design changes Early termination
IDE MaintenanceChanges that require 5-day notice to FDA (donot usually receive reply from FDA): Emergency changeNon-significant design changesSome protocol changes----Not effecting scientific soundness,rights/safety/welfare of subjectsModification of incl/excl criteria to better definetarget populationIncreasing frequency at which information isgatheredModifying the secondary study endpoints.
IDE Maintenance Changes that notice to FDA in the annualreport include minor changes in the followingareas (do not usually receive reply from FDA): Monitoring procedures Labeling Informed Consent Materials IRB Information
Supplements/Reports to FDAFDAUnanticipated Adverse Device Effects10 working daysWithdrawal from FDA/IRB approval5 working daysInvestigator ListEvery 6 monthsProgress Report (Annual Report)At least yearlyDeviation from Investigational Plan5 working days or pre-approvalFailure to Obtain Informed Consent5 working daysRecall and Device Disposition30 working daysSignificant Risk Determination5 working daysFinal Report30 working days- notification6 months- report21 CFR 812.150
IDE Maintenance - UADEs Unanticipated Adverse Device Effect - Anyserious adverse effect on health or safety orany life-threatening problem or death causedby, or associated with, a device if that effect,problem or death was not previously identifiedin nature, severity, or degree of incidence inthe investigational plan or application (21 CFR812.3 (s)).Conduct an evaluation of the UADE and reportto the FDA within 10 working days.
Progress/Final ReportBasic information2. Study Progress- Brief summary of the study progress- Number of investigators/investigational sites- Number of subjects enrolled- Number of devices shipped- Disposition of all device shipped- Brief summary of results- Summary of anticipated and unanticipatedadverse effects- Description of any deviations from theinvestigational plan (since last progress report)1.
Progress/Final Report3. Risk Analysis- Summary of any new adverse information (since the last progressreport) that may affect the risk analysis- Reprints of any articles published from data collected from this study- New risk analysis, if necessary, based on new information and onstudy progress4. Other Changes- Summary of any changes in manufacturing practices and qualitycontrol- Summary of all changes in the investigational plan not required to besubmitted in a supplemental application5. Marketing Application or Future Plans
Submissions to the IDE Basedon Type of Information Supplements Reports Amendments http://tinyurl.comlxrmd9u
Supplements Approval for change (prior-approval, 5-day notice) Request approval for a new study under the same IDE Request study expansion (new sites, more patients) Request approval to terminate enrollment/study Notify FDA if the study been suspended Request approval for the compassionate use Request the extension of time to respond to the FDAThe FDA will usually reply. Reply is similar to the Original IDEsubmission
Reports Provide biannual investigator/IRB information Annual reports Failure to obtain ICF Notify the FDA of the Emergency Use Report the unanticipated adverse device effect Report completion of enrolment/study Provide final IDE reportThe FDA will reply within the 30 days IF they have anycomments
Amendments Any repose to deficiency letter is anamendment. Amendment may be submitted toeach of the 3 parent document types: Original IDE submissionIDE SupplementIDE Report
Terminating/Closing an IDE If IDE is not yet approved – request a withdrawal If you have an active IDE, but no subject enrolled –request a withdrawal, but state why and account for allthe device If subjects have been enrolled – you might need tocomplete follow-up of already enrolled subjects If you completed the study – notify FDA within 30-daysand send Final Report within 6 months
PART 2: IDE Maintenance andAdditional Device Studies IDE MaintenanceIn Vitro Diagnostic (IVD) DevicesIVD Multivariate Index Assay (IVDMIA)Additional Type of Device StudiesCase Studies
In Vitro Diagnostics –Why are They Devices?It is an instrument, apparatus, implement, machine,contrivance, implant, in vitro reagent, or other similar or relatedarticle or component part or accessory that: Is intended for use in the diagnosis of disease or othercondition, or in the cure, mitigation, treatment, or preventionof diseaseIs intended to affect the structure or any function of the bodyAnd does not achieve its intended purpose through chemicalaction or being metabolized for the achievement of itsprimary purpose
In Vitro Diagnostic Device StudiesAn IVD device is often different from otherdevices because most other devices function ONor IN a patient.IVDs include products used to collect specimens,or to prepare or examine specimens after theyare removed from the human body. Blood, spinal fluid, tissue samples, serum, urine
In Vitro Diagnostic Device StudiesThe FDA considers the IVD to be the entireprocess from specimen collection to resultsreporting. Specimen collection and transportSpecimen preparationSpecimen examination/analysisMethod of calculating/reporting result
In Vitro Diagnostic Device StudiesExamples: Class I- Influenza IVD Class II- Blood glucose test Class III- HIV IVD, HPV IVD
Clinical Investigation of MedicalDiagnostic DeviceAll clinical investigation of device must:be exempt from the IDE have an approved IDEregulations (21 CRF 812.2 (c)) a) abbreviated IDE (21 CRF 812.2 (b))b) IDE (21 CRF 812.20)
Investigations Exempt fromthe IDE Regulations A legally marketed device when used inaccordance with its labelingA diagnostic device meeting 4 specified criteriaA device undergoing a consumer preferencetesting, testing of modification or testing of acombination of two or more devices in commercialdistribution if the testing is not for the purpose ofdetermining safety or effectivenessA device intended solely for veterinary useA device for research on or with laboratoryanimalsA custom device (21 CFR 812.3(b)) (http://tinyurl.com/lbxl9k8)
Diagnostic & In Vitro DiagnosticDevice StudiesPer 21 CFR 812.2 (c), a diagnostic devicestudy is IDE exempt when it:---Is noninvasiveDoes not require an invasive samplingprocedure that presents a significant riskDoes not by design or intention introduce energyinto a subjectIs not used as a diagnostic procedure withoutconfirmation of the diagnosis by anothermedically established diagnostic product orprocedure
When Diagnostic Device isNoninvasive“ A noninvasive device is one that does not, bydesign or intention:- penetrate or pierce the skin or mucous membranesof the body, the ocular cavity, or the urethra; or-enter the ear beyond the external auditory canal, thenose beyond the nares, the mouth beyond thepharynx, the anal canal beyond the rectum, or thevagina beyond the cervical os.
Diagnostic & In Vitro DiagnosticDevice StudiesPer 21 CFR 812.2 (c), a diagnostic devicestudy is IDE exempt when it:-Is noninvasiveDoes not require an invasive samplingprocedure that presents a significant risk
Invasive Sampling Procedure ThatDoes Not Present a Significant Risk“ we recommend that you base your riskdetermination on the nature of the harm that mayresult from sampling. For example, FDAconsiders sampling techniques that requirebiopsy of a major organ, use of generalanesthesia, or placement of a blood access lineinto an artery or large vein (subclavian, femoral,or iliac) to present a significant risk.”
Invasive Sampling Procedure ThatDoes Not Present a Significant Risk“ Blood sampling that involves simplevenipuncture is considered noninvasive,and the use of surplus samples of bodyfluids or tissues that are left over fromsamples taken for noninvestigationalpurposes is also considered noninvasive(21 CFR 812.3(k)).“
Diagnostic & In VitroDiagnostic Device StudiesTwo step process:- Does invasive sampling presents SR(if so, study cannot be IDE exempt)- If study is not IDE exempt, thenSR/NSR determination of the whole studyneeds to be made
Diagnostic & In VitroDiagnostic Device StudiesPer 21 CFR 812.2 (c), a diagnostic devicestudy is IDE exempt when it:---Is not invasiveDoes not require an invasive samplingprocedure that presents a significant riskDoes not by design or intention introduceenergy into a subjectIs not used as a diagnostic procedurewithout confirmation of the diagnosis byanother medically established diagnosticproduct or procedure
Confirmation of Diagnostic (or IVD)Results “ test results should not influence patienttreatment or clinical management decisions beforethe diagnosis is established by a medicallyestablished product or procedure ““ If an investigational test uses a new technology orrepresents a significant technological advance,established diagnostic products or procedures maynot be adequate to confirm the diagnosis provided bythe investigational IVD.“ Therefore, the study can notbe IDE exempt
Diagnostic & In VitroDiagnostic Device StudiesPer 21 CFR 812.2 (c), a diagnostic devicestudy is IDE exempt when it:---Is noninvasiveDoes not require an invasive samplingprocedure that presents a significant riskDoes not by design or intention introduceenergy into a subjectIs not used as a diagnostic procedurewithout confirmation of the diagnosis byanother medically established diagnosticproduct or procedure
Clinical Investigation of MedicalDiagnostic DeviceAll clinical investigation of device must:be exempt from the IDEregulations (21 CRF 812.2 (c))have an approved IDEa) abbreviated IDE (21 CRF 812.2 (b))b) IDE (21 CRF 812.20)
SR vs NSR DiagnosticDevice StudiesSignificant risk IVD study is one that is for ause of substantial importance in diagnosing,curing, mitigating, or treating disease, orotherwise preventing impairment of humanhealth and presents a potential for seriousrisk to the health, safety, welfare of a subjector otherwise presents a potential for seriousrisk to health, safety, or welfare of a subject(21 CFR 812.3 (m)).
SR vs NSR DiagnosticDevice Studies FDA int
1. Cover Sheet – form 3514 2. Name and Address of the Sponsor 3. Report of Prior Investigations 4. Investigational Plan 5. Manufacturing Information 6. Investigators Agreement 7. Investigators Certification 8. IRB Information 9. Name and Address of Investigators Institution 10. Financia
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