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Transcript of Device World: The Basics SR and NSR Determinations Expanded Access Susie Hoffman University of...
Device World:The Basics SR and NSR DeterminationsExpanded AccessSusie HoffmanUniversity of Virginia
Margaret Foster Riley, J.D.University of Virginia, School of Law, School of Medicine, Batten School of Leadership and Public Policy
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Definition of Device §201(h)•“an instrument, apparatus, implement,
machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part or accessory, which is▫…(2)intended for use in the diagnosis of
disease or other conditions, or in the cure, mitigation, treatment or prevention of disease
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Definition of Device §201(h)•“(3)intended to affect the structure or
function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animlas and which is not dependent upon being metabolized to achieve its primary intended purposes”
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Medical Devices•Vast number
▫Tongue depressor, stethoscope, stents that hold blood vessels open
•Vary in complexity and risk as well as benefit•Characterized by “on the spot” innovation
•FDA interprets the statute broadly and claims authority over many articles that may not seem to be devices: e.g. reagents for assays, genetic tests and software (even maybe medical records)
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Line between device and drug not clear•Saline•Contrast imaging agents
▫Can be either but must treat them consistently
•Combination products▫E.g. Clot busting stents▫Office of combination products at FDA
Devices are Different
•Not just in “substance” but in regulation•Different pathways (different statutory
roots)
•Devices can be confusing because there are a number of different types of “risk assessment”—need to be clear on what question is being asked
Three Classifications based on Risk
▫I bedpans, crutches, ▫II blood pressure cuffs, catheters,
wheelchairs, heating pads, and x-ray film processing machines
▫III defibrillators, heart valves, and implanted cerebral stimulators
Marketing Pathways for New Devices
• New and novel automatically class III; go through PMA (device analog to drug NDA) process unless they are reclassified
• New and not novel—enters the market as “substantially equivalent”—inherits the classification status of the device that it emulates-- “the 510k process”
510(k) process: The new and not novel
•This is a notification process, not an approval process
•A positive response to a 510k application is a “clearance”—FDA makes no representation that the device is “safe and effective for its intended use(s).”
•98% of all post-1976 devices have entered the market through this mechanism
Substantial Equivalence
•Must have same intended use as a predicate device.
• “Piggy backing” now codified—substantially equivalent to a device that was substantially equivalent to a pre-1976 device
Investigational Devices
•IDE similar to IND for drugs, except not all IDEs require FDA approval
•If pose no significant risk, just require IRB approval—IRB makes that determination
Device World Significant Risk/Non-Significant Risk Determinations
What is Significant Risk?
• Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
• Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
• Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or
• Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject. (21 CFR 812.3(m))
Likely Significant Risk (SR) devices•Many devices that are obviously SR will be
submitted to FDA for IDE approval▫Most of those devices are submitted to IRB
review after FDA has made that determination▫An SR device must meet all FDA IDE regulations
and must have FDA approval before enrolling• IRBs do not have to make the SR or NSR
determination if FDA has already made the risk determination. ▫IRB role is then to confirm the issuance of the
IDE
Likely Non-Significant Risk (NSR) Devices•Here the sponsor does not need to submit
to FDA and FDA leaves the determination to the IRB▫In most of these cases, FDA will have no
role in the risk determination—and will not even be aware of the study
IDE Exempt
•If using an investigational device in research must first determine if the device is exempt from IDE regulations.
IDE Exempt Devices• Consumer preference testing• Testing of a device modification• Testing of two or more devices in commercial
distribution if the testing does not collect safety or effectiveness data, or put subjects at risk.
• Studies of an already cleared medical device in which the device is used or investigated in accordance with the indications in the cleared labeling ▫ If the study is looking at a new use, it is not exempt
IDE Exempt Devices
•A diagnostic device if the testing: Is noninvasive Does not require an invasive sampling
procedure that presents significant risk Does not by design or intention introduce
energy into a subject AND Is not used as a diagnostic procedure
without confirmation by another medically established diagnostic product or procedure.
Not Exempt?
•If a device is determined to NOT be exempt from an IDE, the full IRB must determine if the device meets the criteria of Significant Risk
•Exempt from IDE requirements does not mean that the device study is exempt from other IRB/FDA requirements for clinical research study
IRB Considerations of NSR Determination
• The sponsor’s description of why the study is not SR • Whether the proposed NSR research study meets
the definition of “significant risk” ▫The proposed use of the device as well as any
protocol related procedures and tests, not just the device (test article) alone. (This process is different and separate from the typical IRB review of risk)
▫Whether the subject will undergo additional procedures
• Additional information from the sponsor, if needed. •
Significant Risk Criteria (Review)
▫A device that presents a potential for serious risk to the health, safety, or welfare of a subject AND: Is intended as an implant or Is used in supporting or sustaining human life or Is for use of substantial importance in diagnosing,
curing, mitigating or treating disease, or otherwise prevents impairment of human health: or
Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.
Sometimes Examples provide the Most Insight NSR:
• http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126418.pdf
▫ Conventional Gastroenterology and Urology Endoscopes and/or Accessories
▫ Conventional General Hospital Catheters (long-term percutaneous, implanted, subcutaneous and intravascular)
▫ Conventional Implantable Vascular Access Devices (Ports) ▫ Digital Mammography ▫ Externally Worn Monitors for Insulin Reactions ▫ Urethral Occlusion Device for less than 14 days
Sometimes Examples provide the Most Insight--SR
• http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126418.pdf
▫ Catheters for General Hospital Use - except for conventional long-term percutaneous, implanted, subcutaneous and intravascular
▫ Collagen Implant Material for use in ear, nose and throat, orthopedics, plastic surgery, urological and dental applications
▫ Aortic and Mitral Valvuloplasty Catheters ▫ Organ Storage/Transport Units ▫ Cochlear Implants ▫ Biliary Stents ▫ Electrical Stimulation Devices for sperm collection ▫ Antepartum Home Monitors for Non-Stress Tests▫ Cervical Caps ▫ Condoms (for men) made from new materials (e.g., polyurethane) ▫ Contraceptive In Vitro Diagnostics (IVDs) ▫ Computer Guided Robotic Surgery
Effect of Decision
•NSR▫If the device does not meet the criteria of
Significant Risk, then is by default a Non-Significant Risk Device
▫Do not need IDE from FDA to enroll subjects
•SR▫Must have IDE from FDA prior to enrolling
subjects
Device World
Expanded Access
From FDA website: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm051345.htm#treatmentuse
Ways to Access an Investigational Device for Clinical Care
•Compassionate Use•Emergency Use•Treatment Use•Continued Access•* Humanitarian Use
Device Summary Table- see handout Clinical Care:
Compassionate Use
Clinical Care:Emergency Use
Clinical Care:Humanitarian Use
Clinical Care:Emergency or Off Label Use of an HUD
Clinical Care:Treatment Use
Clinical Care:Continued Access
Research
Background Use for patient or small group who do not meet protocol inclusion criteria. Treating physician feels device will help patient(s).Allowed before or during a clinical trial
Subject does not meet inclusion criteria, clinical trial is not open at the institution, life threatening situation and no time to get IRB approvalAllowed before or after start of clinical trial
Device that would be used in less than 4000 patients /year in the US. ( Orphan Device)
If use meets criteria for emergency use see Emergency Use column. Off label use: Follow same criteria as Humanitarian Use.
Provides access to investigational devices early in development process. Allowed during a clinical trial
Allows patients access to device after clinical trials are completed- awaiting FDA approval.
Use of an investigational device for research purposes
Other Issues Must first identify patient, then sponsor submits IDE application to FDA, then submit application to IRB.
May only use as emergency use one time at each institution- then must have a compassionate use protocol.Within 5 days of use submit notification to IRB. Sponsor cannot submit data as part of an FDA application.
Called:Humanitarian Use Device (HUD)OR Humanitarian Device Exemption (HDE) Sponsor must have HDE designation from FDA.
For Off Label Use FDA recommends patient sign a consent form and that the PI has a plan to protect the patient. PI should submit summary report to IRB following the use. Must report AE's to IRB.
For patients with serious or life threatening condition- may receive outside of a clinical trial.Sponsor must obtain a Treatment use IDE from FDA.
May use outside IRB.
IRB must determine if device is exempt from IDE regulations. If not exempt, must determine if device is significant risk.
Considered Research?
No- however FDA requires an IDE# and IRB Concurrence
No- but use must be reviewed by full board AFTER USE.
No, however IRB review required.
No, however IRB review required.
Yes Yes Yes
Protocol Yes-submit sponsors protocol only
No No, but need tosubmit Investigators Brochure
No, but for off- label use, need some type of plan of methods to protect patient.
Yes- submit sponsors protocol only
Yes-submit sponsors protocol only
Yes- may submit per local protocol template or sponsors protocol
Consent Yes-submit and use sponsors consent
Yes-use sponsors consent if patient able to consent.
No- may provide patient with product information
Yes, may use sponsors template.
YES- use local research template to develop consent
Yes-may use local research template or one approved by outside IRB.
Yes-use local research template to develop consent unless waiver approved
Training No No No No Yes Yes YesReview Type IRB Chair only Full Board- AFTER
use Initial – Full BoardContinuations- Expedited
Initial – Full BoardContinuations- Expedited
Full Board Full Board Full Board
Response Letter of Concurrence from IRB Chair
Letter of Concurrence from IRB
IRB Assurance Form
IRB Assurance Form
IRB Assurance Form
IRB Assurance Form
IRB Assurance Form
Clinical Care: Compassionate UseBackground
Other issues
Research? Protocol Consent Training Review Type
Response
Use for patient or small group who do not meet protocol inclusion criteria. Treating physician feels device will help patient(s).Allowed before or during a clinical trial.
Must first identify patient, then sponsor submits IDE application to FDA, then submit application to IRB.
No- however FDA requires an IDE# and IRB Concurrence
Yes-submit sponsors protocol only
Yes-submit and use sponsors consent
No IRB Chair only
Letter of Concurrence from IRB Chair
Clinical Care: Emergency UseBackGround
Other Issues Research? Protocol Consent
Training Review Type
Response
Subject does not meet inclusion criteria, clinical trial is not open at the institution, life threatening situation and no time to get IRB approvalAllowed before or after start of clinical trial
May only use as emergency use one time at each institution- then must have a compassionate use protocol.Within 5 days of use submit notification to IRB. Sponsor cannot submit data as part of an FDA application.
No- but use must be reviewed by full board AFTER USE.
No Yes-use sponsors consent if patient able to consent
No Full Board- AFTER use
Letter of Concurrence from IRB
Clinical Care: Treatment Use Background
Other Issues Research? Protocol Consent Training Review Type
Response
Provides access to investigational devices early in development process. Allowed during a clinical trial
For patients with serious or life threatening condition- may receive outside of a clinical trial.Sponsor must obtain a Treatment use IDE from FDA.Different from Compassionate Use: do not need to identify patient before IRB approval.
Yes Yes- submit sponsors protocol only
YES- use local research template to develop consent
Yes Full Board
IRB Assurance Form
Clinical Care: Continued AccessBackground
Other Issues
Research? Protocol Consent Training Review Type
Response
Allows patients access to device after clinical trials are completed- awaiting FDA approval.
May use outside IRB.
Difference between Treatment Use : does not have to be life threatening or serious disease.
Yes Yes-submit sponsors protocol only
Yes-may use local research template or one approved by outside IRB.
Yes Full Board
IRB Assurance Form
Clinical Care: Humanitarian UseBackground
Other Issues
Research? Protocol Consent Training Review Type
Response
Device that would be used in less than 4000 patients /year in the US. ( Orphan Device)
Called:Humanitarian Use Device (HUD)OR Humanitarian Device Exemption (HDE) Sponsor must have HDE designation from FDA.
No, however IRB review required.
No, but need tosubmit Investigators Brochure
No- may provide patient with product information
No Initial – Full BoardContinuations- Expedited
IRB Assurance Form
Clinical Care: Emergency Use or Off Label Use of an HUDBackground
Other Issues
Research?
Protocol Consent Training
Review Type
Response
If use meets criteria for emergency use- see Emergency Use column. Off label use: Follow same criteria as Humanitarian Use.
For Off Label Use FDA recommends patient sign a consent form and that the PI has a plan to protect the patient. PI should submit summary report to IRB following the use. Must report AE's to IRB.
No, however IRB review required.
No, but for off- label use, need some type of plan of methods to protect patient.
Yes, may use sponsors template.
No Initial – Full BoardContinuations- Expedited
IRB Assurance Form
ResearchBackground
Other Issues
Research?
Protocol Consent Training Review Type
Response
Use of an investigational device for research purposes
IRB must determine if device is exempt from IDE regulations. If not exempt, must determine if device is significant risk.
Yes Yes- may submit per local protocol template or sponsors protocol
Yes-use local research template to develop consent unless waiver approved
Yes Full Board
IRB Assurance Form
Device Review Decision TreeDoes this study involve the clinical investigation to
determine the safety and effectiveness of a device? ( e.g. – Are you evaluating the device for safety and
efficacy? )
Is the device a Research Use Only Device (RUO)?
Does the device being used have FDA approval for any
indication?
To Full Board for Review. As expedited criteria # 4 not applicable. DO NOT use Expedited Criteria # 1 as the device is not being evaluated therefore FDA regulations do not apply.
NOTE: FB does NOT determine SR/NSR status but may determine if protocol is minimal risk, therefore allowing future continuations to be expedited via category # 9.
Category # 9: Continuing review of research, not conducted under an
investigational new drug application or investigational device exemption where categories (2) through (8) do
not apply but the IRB has determined and documented at a convened full
IRB meeting that the research involves no greater than minimal risk
and no additional risks have been identified.
NO
NO
Will results be used to
diagnose or treat
subjects?
Yes
NO
Do all other procedures fit under
an expedited criteria?
YES
Is study minimal risk?
YesTo Full
Board for Review
NOTE: FB does NOT determine SR/NSR status
NO
Expedite under
category # 4 and any
other applicable
categories. (RUO
devices not considered a
medical device.)
Yes
NO
Is study exempt from IDE Regulations ?
Answer NO if an In-vitro diagnostic device.
Expedite under
category # 1
Yes: FDA Regs apply
Will other procedures require study to be
reviewed by full board?
(e.g all procedures do not fit under expedited criteria or study is not
minimal risk )
Yes
Send full protocol to
IRB for review.
No
Do all other procedures fit under an expedited
criteria
Is study minimal risk?
Send protocol to full board
for review and SR/NSR
Determination
Send study to full board to
make SR/NSR Determination.
YesNo
No
Yes
NoYes
Full Board determines study is SR: Full Board
to review protocol .
DO NOT expedite review of protocol.
Full Board determines study is NSR- Expedite review of protocol
under cat# 1.
NSR SR
No: FDA Regs DO NOT apply
Is the device an in-vitro diagnostic device?
No
Yes
Yes
Study Involves Device: Overall SummaryUse only/No evaluation of device: FDA regulations do NOT apply: expedited via category # 4
Evaluation of Device- FDA regulations DO apply- If device exempt from IDE regulations or NSR and protocol may otherwise be reviewed by expedited review procedures expedite via category # 1.