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)

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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)




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510k (Class I, II)



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


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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…


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510k(Class I, II)

PMA(Class III)








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


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Devices without predicates

• Consider de novo down classification

• Anticipate PMA route of approval

Strategic Decision!

System?Individual elements?Accessories?

medical device regulation: a primer - nakfi device regulation: a primer frances richmond, phd ......

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