Medical Device Regulation: A Primer

Transcription

1 Medical Device Regulation: A Primer Frances Richmond, PhD School 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 metabolized for the achievement of its primary intended purposes F. Richmond 1

2 Code of Federal Regulations (CFR) Title 21=FDA Parts is Devices Title 21 updated every April Many devices fit together to make a system How to get a medical product to market Predicate The drawing board PMA (Class III) 510k (Class I, II) Manufacturer completes most tests & submits results to FDA for permission to conduct clinical trial (IDE) Manufacturer completes tests & submits results to FDA as premarket notification (510k) NO Clinical trial(s) Manufacturer submits all results (clinical & non-clinical) to FDA as premarket application (PMA) FDA judges if product is substantially equivalent Product goes go to market FDA judges if product is safe and effective F. Richmond 2

3 Devices are classified according to risk Class 3 High risk Class 2 Moderate risk Class 1 Low risk Class 1- General Controls Failure 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 Calipers for clinical use Cement dispenser Cement mixer for clinical use Cement monomer vapor evacuator Cement ventilation tube Depth gauge for clinical use Orthopedic manual surgical instrument Sonic surgical instrument and accessories/attachments Protractor for clinical use Template for clinical use Nonpowered orthopedic traction apparatus and accessories Noninvasive traction component Cast component Cast removal instrument Manual cast application and removal instrument F. Richmond 3

4 Sec Orthopedic 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 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 Passive tendon prosthesis Identification. A passive tendon prosthesis is a device intended to be implanted made of silicon elastomer or 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. F. Richmond 4

5 Class 3 includes life-sustaining or -supporting equipment, implantables, potentially risky devices Also includes NEW devices Sec 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 ultrahigh 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 F. Richmond 5

6 510(K) = premarket notification Identification of and comparison to substantially equivalent predicate for same application Wait for FDA acknowledgement of equivalence (90 days) 510k (Class I, II) Predicate The drawing board Manufacturer completes tests & submits results to FDA as premarket notification (510k) NO FDA judges if product is substantially equivalent Product goes go to market 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 F. Richmond 6

7 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 & 2006 Application 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 small businesses as of 2004 Areas of concern when developing Class II and III products Design controls Animal trials Clinical trials Quality systems regulations F. Richmond 7

8 Why design control requirements? Many product failures in the 1980s and 1990s were linked to flaws in the device design Design Control A systematic way to follow product design from user requirements to final product Design History File = Voluminous analysis of product development Must be in place at time of clinical trials Must be described in detail in PMA F. Richmond 8

9 Preclinical Trials Physical & Chemical testing: mechanical purity & residuals In Vitro testing: cytotoxicity genotoxicity In Vivo testing: toxicity sensitization irritation implantation hemocompatibility Testing requirements Regulatory guidelines: ISO standards Product specific considerations Common sense Clinical Trials 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 FDA application= IDE (investigational device exemption) F. Richmond 9

10 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 Premarket Approval The drawing board Manufacturer completes most tests & submits results to FDA for permission to conduct clinical trial (IDE) NO Clinical trial(s) Manufacturer submits all results (clinical & non-clinical) to FDA as premarket application (PMA) Product goes go to market FDA judges if product is safe and effective F. Richmond 10

11 Visible Results of Regulatory Efforts IDE Application Preclinical data Protocols 2-10 volumes Acknowledgment letter Approved protocol & informed consent form Rejection letter Refusal of permission to conduct study How to get a medical product to market Predicate The drawing board PMA (Class III) 510k (Class I, II) Manufacturer completes most tests & submits results to FDA for permission to conduct clinical trial (IDE) Manufacturer completes tests & submits results to FDA as premarket notification (510k) NO Clinical trial(s) Manufacturer submits all results (clinical & non-clinical) to FDA as premarket application (PMA) FDA judges if product is substantially equivalent Product goes go to market FDA judges if product is safe and effective 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 F. Richmond 11

12 Devices without predicates Consider de novo down classification Strategic Decision! Anticipate PMA route of approval System? Individual elements? Accessories? F. Richmond 12