Slide 1

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 2

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 3

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 4

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 5

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 6

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 7

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 8

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 9

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 10

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 11

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 12

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 13

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 14

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 15

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 16

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 17

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 18

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 19

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 20

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 21

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 22

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 23

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 24

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 25

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 26

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27


Slide 27

Regulation of Medical Devices
Celia M. Witten, Ph.D., M.D.
Director
Division of General, Restorative and
Neurological Devices
Office of Device Evaluation
Food and Drug Administration
RHAIR
Society for Academic Emergency
Medicine
Boston, Massachusetts
May 31, 2003

Outline







Who we are
Device types
Paths to market
Temperature control devices
Clinical study regulation

2

Who We Are

FDA
CVM

CFSCAN

OST

OSM

OSB

CDRH

CBER

CDER

ODE

OHIP

OC

OIVD

DAGID
DCD
*DGRND
DOED
DRARD
3

Device Examples








Neuroembolization devices
Deep brain stimulators
Neurodiagnostic devices (EEG, EMG)
Neurosurgical shunts
Muscle stimulators
Neurovascular stents
4

Regulatory Review:
Pathways to Market








Premarket Notification 510(k)
Premarket Approval Application
(PMA)
Product Development Protocol (PDP)
Humanitarian Device Exemption
(HDE)
De Novo Classification
5

Premarket Notification 510(k)




Substantial Equivalence
Predicate Device (legally marketed,
not subject to PMA)
Comparison
–
–
–
–

same intended use and
same technological characteristics or
different technological characteristics and
as safe and effective as predicate
6

Premarket Application (PMA)

…”reasonable assurance of safety and
effectiveness”…

7

Regulatory Path Examples

8

Hydrocephalus Shunts




510(k) (substantial equivalence)
Comparison to predicate
Standards:
– ASTM F647
– ISO 7197




Materials/biocompatibility
For new/unusual designs, may need a
clinical study for
– Infection
– Revision/causes
– Failures/failure modes
9

Intracranial Neurovascular Stents



Class III (PMA/HDE/PDP)
2 HDE’s approved

10

Deep Brain Stimulation





Class III
PMA approval for essential tremor and
Parkinson’s disease symptoms

11

Clinical Study Regulation
FFD&C Act gives FDA the authority to
regulate investigational devices:
 To encourage the discovery and
development of new devices
 Maintain optimum freedom for
scientific investigations
12

Section 520(g)
of the Act




Requires IRB approval for all clinical
investigations
Requires informed consent from all
subjects unless emergency use

13

IDE Regulation
(Part 812)
Allows an unapproved device to be
shipped for clinical evaluation:
 Identifies sections of the Act from
which IDEs are exempt
 Identifies exempted investigations
(e.g. cleared devices, IVDs)
 Defines SR and NSR investigations
14

Significant Risk (SR) Study


Presents a potential serious risk to the
health, safety, and welfare of a subject and
is:
– an implant; or
– life supporting or sustaining; or
– of substantial importance in diagnosing,
curing, mitigating, or treating disease or
preventing impairment of human health



FDA approval required
15

Non-significant Risk
Studies



FDA approval not needed
Examples:
–
–
–
–



MRI < 4 Tesla
Urologic catheters
Low level biostimulation lasers
Laparoscopes

NSR devices can be SR studies
16

Informed Consent:
Emergency Use



Must be reviewed and approved by
the IRB and the FDA prior to use
May be waived when there is a lifethreatening situation
–
–
–
–

the subject cannot communicate
time is not sufficient
no available alternative
two physicians certify in writing
17

Informed Consent:
Emergency Research


Certain studies may not require informed
consent when IRB agrees that
– there is a life-threatening situation and current
treatments are unsatisfactory
– no time
– can’t identify subjects prospectively
– community consultation
– public disclosure

18

When Are Clinical Data
Needed?
To support:
 PMA, PDP or HDE (almost always)
 510(k) (<10%)
 New indication for an approved
device (e.g., BPH for a urologic laser)
 Significant change to device,
especially Class III devices
19

Types of Studies
Sponsor-investigator
 Manufacturer-sponsored


– Feasibility
– Pivotal, including sites outside the US
– Post-approval

20

Feasibility Trial








Answer design-related questions that
cannot be addressed by bench/animal
testing
Modify device design &/or instructions for
use
Preliminary safety data
No control
Limited # pts/limited follow-up
21

Pivotal Trial









Final design, indication for use, and
protocol
Controlled
Masked, if possible
Primary/secondary endpoints
Develop information for labeling
Statistical validity to show S & E
22

Post-Approval
May be required for PMA approval
 Designed to address specific
question
 # of patients and duration
specified by FDA


23

Cooling Devices:
Clinical Study Questions









How soon?
How cold?
How fast?
How long?
How measured?
Speed of rewarming?
Other treatments provided?
Local versus systemic?
24

Temperature Control
Devices



Tool?
Treatment?

25

Temperature Control
Devices



Cooling Blankets
Endovascular Devices

26

27