Medical Device Regulation: A Primer - NAKFI Device Regulation: A Primer Frances Richmond, PhD ......
Transcript of Medical Device Regulation: A Primer - NAKFI Device Regulation: A Primer Frances Richmond, PhD ......
Medical Device Regulations
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Medical Device Regulation: A Primer
Frances Richmond, PhDSchool of Pharmacy
A E Mann Institute of Biomedical Engineering
FDA is a big place, so products must go through
channels…
A device is: An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent or other similar or related article, .. which is …
• intended for use in the diagnosis, treatment or prevention of disease, in man or other animals; or
• intended to affect the structure or function of the body of man or other animals,
and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals
and which is not dependent upon being metabolizedfor the achievement of its primary intended purposes
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Code of Federal Regulations (CFR)
• Title 21=FDA • Parts 800-1299 is
Devices• Title 21 updated every
April
Many devices fit together to make a system
How to get a medical product to market…
FDA judges if product is “safe
and effective”
Product goes go to market
Manufacturer completes tests & submits results to FDA
as premarket notification (510k)
“The
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ard”
510k(Class I, II)
PMA(Class III)
FDA judges if product is
“substantially equivalent”
Manufacturer submits all results (clinical & non-clinical) to FDA
as premarket application (PMA)
Manufacturer completes most tests & submits
results to FDA for permission to conduct
clinical trial (IDE)
Clinical trial(s)
Predicate
NO
YES
YES
YES
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http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm
Devices are classified according to risk
Class 1
Class 2
Class 3
Low risk
High risk
Moderate risk
Class 1- General ControlsFailure poses no risk to life
– no performance standards– requires no clinical testing
• Must not be adulterated or misbranded
• Requires:– Establishment registration– Device listing– Labeling
• Requires (but may be waived):– premarket notification– GMP – Design control
Subpart E--Surgical Devices
§ 888.4150 - Calipers for clinical use. § 888.4200 - Cement dispenser. § 888.4210 - Cement mixer for clinical use. § 888.4220 - Cement monomer vapor evacuator. § 888.4230 - Cement ventilation tube. § 888.4300 - Depth gauge for clinical use. § 888.4540 - Orthopedic manual surgical instrument. § 888.4580 - Sonic surgical instrument and accessories/attachments. § 888.4600 - Protractor for clinical use. § 888.4800 - Template for clinical use. § 888.5850 - Nonpowered orthopedic traction apparatus and accessories. § 888.5890 - Noninvasive traction component. § 888.5940 - Cast component. § 888.5960 - Cast removal instrument. § 888.5980 - Manual cast application and removal instrument
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Sec. 888.4540Orthopedic manual surgical instrument
Identification. An orthopedic manual surgical instrument is a nonpowered hand-held device intended for medical purposes to manipulate tissue, or for use with other devices in orthopedic surgery. This generic type of device includes the cerclage applier, awl, bender, drill brace, broach, burr…. bending or contouring instrument, compression instrument, passer, socket positioner, probe, femoral neck punch, socket pusher, reamer, rongeur, scissors, screwdriver, bone skid, staple driver, bone screw starter, surgical stripper, tamp, bone tap, trephine, wire twister, and wrench.
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter, subject to the limitations in 888.9.
Class II- Special Controls
• Additional rules to ensure that a product is and stays safe– e.g.”mandatory” performance standards– usually established for device class
Sec. 888.3025
Passive tendon prosthesisIdentification. A passive tendon prosthesis is a device
intended to be implanted made of silicon elastomeror a polyester reinforced medical grade silicone elastomer intended for use in the surgical reconstruction of a flexor tendon of the hand. The device is implanted for a period of 2 to 6 months to aid growth of a new tendon sheath. The device is not intended as a permanent implant nor to function as a replacement for the ligament or tendon nor to function as a scaffold for soft tissue ingrowth
Classification. Class II.
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Class 3
• includes life-sustaining or -supporting equipment, implantables, potentially risky devices
• Also includes NEW devices
Sec. 888.3680
Shoulder joint glenoid (hemi-shoulder) metallic cemented prosthesis
Identification. A shoulder joint glenoid (hemi-shoulder) metallic cemented prosthesis is a device that has a glenoid (socket) component made of alloys, such as cobalt-chromium-molybdenum, or alloys with ultra-high molecular weight polyethylene and intended to be implanted to replace part of a shoulder joint. This generic type of device is limited to those prostheses intended for use with bone cement
Classification. Class III. …PMA or notice of completion of a PDP is required.
Medical Device Amendments of 1976
Comprehensive classification of devices by risk
Premarket review of devices through 510K and PMA routes
This was H U G E
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510(K) = premarket notification
Identification of and comparison to substantially equivalent predicate for same application
Wait forFDA acknowledgement
of equivalence(90 days)
Product goes go to market
Manufacturer completes tests & submits results to FDA
as premarket notification (510k)
“The
dra
win
g bo
ard”
510k (Class I, II)
FDA judges if product is
“substantially equivalent”
Predicate
NO
YES
FDA cleared not FDA approved!
Things to know about the 510(k) route….
• Mostly used for class II devices• Not used for novel devices even if relatively
safe without de novo classification• Usually requires no clinical trials
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Novel, invasive products are approved by PMA (premarket approval)
Data concerning• design controls• pre-clinical testing (GLPs)• human testing (GCPs)• risk analysis etc.
Outcomes:
•Approval order•Approval letter
•Not approvable letter•Order denying approval
(180+ days)
User Fees: 2003 & 2006Application Standard Fee Small Business Fee
(<$100 million in sales)
• PMA, PDP, BLA, $154,000 ($259,600) $58,520 ($98,648)Premarket report,Panel-track supplement,BLA efficacy supplement
• 180-day supplement $33,100 ($55,814) $12,582 ($21,209)
• Real-time supplement $11,088 ($18,691) $4,213 ($7,103)
• 510(k) $2,187 ($3,833) $2,187† ($3,066)
†Reduced fee for smallbusinesses as of 2004
Areas of concern when developing Class II and III products
• Design controls• Animal trials• Clinical trials• Quality systems regulations
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Why design control requirements?
Many product failures in the 1980s and 1990s were linked to flaws in the device design
Design ControlA systematic way to follow product design from
user requirements to final product
• Must be in place at time of clinical trials
• Must be described in detail in PMA
Design History File =Voluminous analysis of product development
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Preclinical TrialsPhysical & Chemical testing:
mechanicalpurity & residuals
In Vivo testing: toxicitysensitizationirritationimplantationhemocompatibility
In Vitro testing: cytotoxicitygenotoxicity
Testing requirements • Regulatory guidelines: ISO standards• Product specific considerations• Common sense
• If the device poses no significant risk, it must be approved by an investigational review board (IRB)
(IRB role: protect patients from undue risk)
• If the device poses a significant risk, it must be approved by an IRB and the FDA
Clinical Trials
FDA application= IDE (investigational device exemption)
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Significant Risk Device• Use of device presents a potential serious risk
to the health and safety of a subject
• Device may be:– an implant– used in supporting or sustaining human life– of substantial importance in diagnosing, curing,
mitigating or treating disease or preventing impairment of human health
Clinical Trial permission should be sought for all trials with
significant risk devices! • US----Investigational Device Exemption• Canada----Authorization for Investigational
Testing---HealthCanada• Europe---- Authorization from Competent
Authority may be needed
Clinical Trials need authorization from a human ethics review board before proceeding
FDA judges if product is “safe
and effective”
Product goes go to market
“The
dra
win
g bo
ard”
Manufacturer submits all results (clinical & non-clinical) to FDA
as premarket application (PMA)
Manufacturer completes most tests & submits
results to FDA for permission to conduct
clinical trial (IDE)
Clinical trial(s)
NO
YESYES
Premarket Approval
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Preclinical data
Protocols
2-10volumes
• Acknowledgment letter• Approved protocol &
informed consent form
• Rejection letter• Refusal of permission
to conduct study
IDE Application
Visible Results of Regulatory Efforts
How to get a medical product to market…
FDA judges if product is “safe
and effective”
Product goes go to market
Manufacturer completes tests & submits results to FDA
as premarket notification (510k)
“The
dra
win
g bo
ard”
510k(Class I, II)
PMA(Class III)
FDA judges if product is
“substantially equivalent”
Manufacturer submits all results (clinical & non-clinical) to FDA
as premarket application (PMA)
Manufacturer completes most tests & submits
results to FDA for permission to conduct
clinical trial (IDE)
Clinical trial(s)
Predicate
NO
YES
YES
YES
Current rules when seeking permission to market in the US
• Devices with predicates– Identify classification and predicate– Check rules for submission:
• 510(k) exempt• 510(k)• PMA