FDA Regulatory Process and Issues

Understanding the Regulatory Landscape.

Presentation OutlinePresentation Outline

FDA Overview

Device Classifications / Submission Types

Approval / Clearance Requirements

Investigational Devices

Combination Products

FDA Structure / OrganizationCenter for Veterinary DevicesFood and Drug AdministrationCenter for Biologics Evaluation and ResearchCenter for Devices and Radiological HealthNational Center for Toxicological ResearchCenter for Food Safety and Applied NutritionCenter for Drug Evaluation and Research

FDA Structure / Organization

Office of Combination Products

Office of Device EvaluationOffice of In-Vitro Diagnostic Devices & SafetyOffice of Health & Industry ProgramsOffice of Science & TechnologyOffice of ComplianceOffice of Surveillance & BiometricsCenter for Devices and Radiological HealthCDRH Offices

FDA Regulatory Framework

Federal Food, Drug and Cosmetic Act
(FDC Act)

Issued regulation classifying most types of medical devices

Entering the US Device Market

Exempt medical devices

Established two primary routes for obtaining authorization to market medical devices

510(k) premarket clearance

Premarket approval (PMA)

Vast majority of nonexempt cleared via a 510(k) or approved via the PMA process

FDA Premarket Submissions

Type of SubmissionFY02FY03FY04

Original PMA495451

510(k)4,3204,2473,635

PMA Supplement645666635

Original HDE5109

HDE Supplement162929

Original IDE312242226

IDE amendment252216167

IDE supplement4,7244,4154,312

Total10,3239,8799,064

FDA FeesFDA Medical Device User Fees

FY2008Standard Fee
(U.S. Dollars)Small
Business Fee

510(k) Submission

$3,404

$1,702

PMA Submission

$185,000

$46,250

FY2008 (Oct. 1, 2007 - Sept. 30, 2008)

FDA Classification

Three classes based on the levels of controls

Necessary to reasonably assure device safety and effectiveness

Class I Devices

Subject to general controls

Device listing

510(k) premarket notification

Labeling

FDA quality system regulations (QSR) compliance

Most Class I

Exempt from 510(k) premarket notification

In some cases, exempt from QSR compliance, other than minimal record keeping and reporting

Class II Devices

Subject to general and special controls

Performance standards

Postmarket surveillance

FDA guidelines

Most Class II

Require 510(k) submission

Labeling

QSR Compliance

Device Listing

Class III Devices

Subject to general and special controls

Life sustaining

Life supporting

Implantable devices

New devices not found to be substantially equivalent to legally marketed devices

Most Class III

Require approval of a PMA

Unless marketed prior to May 28, 1976 (Preamendment devices)

Most stringently regulated

Approval / Clearance Criteria

Before a company can market a new device, manufacturer must obtain from the FDA

510(k) premarket clearance, or

premarket approval (PMA)

Unless the device is exempt

Candidate for alternate submission

510(k) Requirements

Description of the new device

Photographs

Engineering drawing

Labeling

Draft promotional materials

Identification of predicate device(s)

Narrative and tabular comparisons

Predicate devices intended use, indications

Technological characteristics

Principles of operation

Software documentation

Sterility information

Biocompatibility information

Statement or declarations of conformance to applicable standards and guidance documents

Summaries of any performance testing

Administrative requirements

Truthfulness and accuracy statement

510(k) summary

Payment of a user fee

Some Cases to Support 510(k)

Laboratory Testing

Clinical Testing

Substantial Equivalence

A device is substantially equivalent to a legally marketed predicate device

Both have the same intended use

Same technological characteristics or;

Different technological characteristics do not raise any new questions of safety or effectiveness and performance data that demonstrates the new device is as safe and effective as the predicate deviceBench

Animal

Clinical data

Substantial Equivalence Analysis

Intended use / indication for use

Technological characteristic

Clinical trials

Conclusions

Substantial Equivalence

If the FDA concludes substantially equivalent

Issue an order granting 510(k) clearance

If the FDA concludes not substantially equivalent

The device is a Class III, requires PMA approval

Unless the FDA reclassifies into Class I or II

De Novo Down Classification

FDA issues a not substantially equivalent

Two options

Proceed with submission of a PMA

Petition the agency in writing for
De Novo down classification within 30 days of receipt of the letter

De Novo Down Classification

To qualify, the device must be both novel and low risk

Novel

Limits to not previously classified FDC Act and classified by written notice

Low Risk

Application to lower-risk devices the agency has found not substantially equivalent for the lack of a predicate device

De Novo Requirements

Within 30 days

Description of the device

Labeling

Justification for recommendation classification

Information to support the recommendation

bench, animal, human clinical data

Usually clinical data is required

De Novo Review

FDA has 60 days to review the petition

If FDA classifies the device into Class I or II

Special control guidance issues

Device that can be used a predicate

If FDA determines that the device remains Class III

PMA approval required to market

PMAPMA Requirements

Must demonstrate safety and effectiveness of a new device, supported by valid scientific evidence

Convenes an advisory committee

Nonbinding recommendation to FDA

FDA inspects manufacturers facilities to QSR

FDA issues

Approval letter, or

Non approvable (identifies major deficiencies)

PMA Requirements

Complete description of the device

Complete description of the components

Photographs

Engineering drawings of the device

Detailed description of the methods, facilities and controls used to manufacture

Prepared labeling, advertising literature, any training material

Software documentation

Sterility information

Biocompatibility information

Extensive clinical trials

Animal studies

Bench tests

Published and unpublished literature

Bibliography of all published reports known concerning the devices safety or effectiveness

Investigational Device Exemptions

Devices that are not approved or cleared and are used in clinical trials must be labeled asInvestigational Devices IDE

Investigational Device Exemptions

The FDA may request

Submission of animal or human clinical data to demonstrate equivalence or safety and effectiveness of a device

Significant risk

Prior approval by an Institutional Review Board (IRB)

Informed consent of patients

FDA approval of an IDE application

IDE Application

21 CFR Part 812

Clinical study protocol

A significant risk device study

Potential for serious risk to health, safety or welfare to the subjects

Intended as an implant

Used in supporting or sustaining human life

Substantial importance inDiagnosing

Curing

Mitigating or treating a disease

Prevents impairment of human health

Potential for serious risk to health, safety or welfare of a subject

IDE Application

Non significant risk (NSR) investigated device

Requires IRB approval

Informed consent

Need not obtain FDA approval before study begins

What is a Combination Product?

Safe Medical Device Act (1990)

503(g)(1) Products that constitute a combination of a drug, device or biologic

Drug Device

Device Biologic

Biologic Drug

Drug Device Biologic

Note: Drug Drug, or Device - Device combination not included here

What is a Combination Product?

StentDrugStent Delivery SystemPolymerSlide courtesy of Nadine Ding, Guidant Corporation

Challenge of Combination Products

CDRHCDERCBERNDA, BLAPMA, 510(K)IND, IDEDeviceDrugBiologic

IND, NDAIDE, PMA, 510(k)IND, BLA

CDERCDRHCBER

DrugDeviceBiologicDifferent FrameworksDifferent Product TypesDifferent FDA Reviews

Challenge of Combination Products

ProductPre-Market FrameworkApprovalFDA
Reviewing
CenterQuality
SystemSafety
Reporting

DeviceIDEPMA, 510(k)CDRHQSRMDR

DrugINDNDACDERGMPAERS

BiologicINDBLACBER /
CDERGMPAERS

Regulatory Complexity

DrugMatrix

Drug polymer
compatibilityLoading capacityRelease kineticsPharmacologyPolymer Chemistry

StentTissue

Mechanical scaffolding

MechanicalEngineeringVascular Biology

Coating integrity

Vascular biologyTissue pharmacokineticsPreclinical models

Vascular biologyDrug Eluting Stent System Design

Slide courtesy of Nadine Ding, Guidant Corporation

Real World Examples

Drug-eluting stentCDRH

Drug-eluting disc (oncology)CDER

Contact lens/glaucoma drugCDER

Contact lens/glaucoma drug (new submission)CDER

Spinal fusion device/therapeutic proteinCDRH

Chemo drug/monoclonal antibodyCDER

Scaffold seeded with autologous cellsCBER

Interferon/Ribivarin therapyCDER

Embolization implant device/chemo drugCDRH

Vertobroplasty device/analgesicCDRH

Links and Resources

FDA Center for Devices and Radiological Health (CDRH) http://www.fda.gov/cdrh/index.html

FDA Office of Combination Products http://www.fda.gov/oc/combination/

FDA US Agent
http://www.fda.gov/cdrh/usagent/index.html

FDA Establishment and Device Listing Forms
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/printforms.cfm

Thank you

For additional information contact:

Medical Device Launchpad800.525.0975