Understanding the Regulatory Landscape.

Presentation OutlinePresentation Outline FDA Overview Device Classifications / Submission Types Approval / Clearance Requirements Investigational Devices Combination Products

FDA Structure / Organization

Center for Veterinary Center for Veterinary DevicesDevices

Food and Drug Food and Drug AdministrationAdministration

Center for Biologics Center for Biologics Evaluation and ResearchEvaluation and Research

Center for Devices and Center for Devices and Radiological HealthRadiological Health

National Center for National Center for Toxicological ResearchToxicological Research

Center for Food Safety and Center for Food Safety and Applied NutritionApplied Nutrition

Center for Drug Evaluation Center for Drug Evaluation and Researchand Research

FDA Structure / Organization

Office of Office of Combination Combination

ProductsProducts

Office of Device Office of Device EvaluationEvaluation

Office of In-Vitro Office of In-Vitro Diagnostic Diagnostic

Devices & SafetyDevices & Safety

Office of Health Office of Health & Industry & Industry ProgramsPrograms

Office of Office of Science & Science & TechnologyTechnology

Office Office of of

ComplianceCompliance

Office of Office of Surveillance Surveillance & Biometrics& Biometrics

Center for Devices and Center for Devices and Radiological HealthRadiological Health

CDRH 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 SubmissionsType of

SubmissionFY02 FY03 FY04

Original PMA 49 54 51

510(k) 4,320 4,247 3,635

PMA Supplement 645 666 635

Original HDE 5 10 9

HDE Supplement 16 29 29

Original IDE 312 242 226

IDE amendment 252 216 167

IDE supplement 4,724 4,415 4,312

Total 10,323 9,879 9,064

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 device’s 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 device Bench 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 manufacturer’s 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 device’s safety or effectiveness

Investigational Device ExemptionsDevices that are not approved or cleared and are used in clinical trials must be labeled as

Investigational 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 in

Diagnosing 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?

Stent

Drug

Stent Delivery System

Polymer

Slide courtesy of Nadine Ding, Guidant Corporation

Challenge of Combination Products

CDRHCDERCBER

NDA, BLAPMA, 510(K)IND, IDE

DeviceDrugBiologic

IND, NDA

IDE, PMA, 510(k)

IND, BLA

CDER

CDRH

CBER

Drug

Device

Biologic

Different Frameworks

Different Product Types

Different FDA Reviews

Challenge of Combination Products

ProductPre-Market Framework Approval

FDA Reviewing Center

Quality System

Safety Reporting

Device IDEPMA, 510(k) CDRH QSR MDR

Drug IND NDA CDER GMP AERS

Biologic IND BLACBER /

CDER GMP AERS

Regulatory Complexity

Drug

Matrix

Drug – polymer compatibility

Loading capacityRelease kinetics

PharmacologyPharmacology

Polymer ChemistryPolymer

ChemistryStent

Tissue

Mechanical scaffolding

MechanicalEngineeringMechanicalEngineering

Vascular Biology

Vascular Biology

Coating integrity

Vascular biologyTissue pharmacokineticsPreclinical models

Vascu

lar b

iolo

gy

Drug Eluting Stent System Design

Slide courtesy of Nadine Ding, Guidant Corporation

Real World Examples Drug-eluting stent CDRH Drug-eluting disc (oncology) CDER Contact lens/glaucoma drug CDER Contact lens/glaucoma drug (new submission)

CDER Spinal fusion device/therapeutic protein CDRH Chemo drug/monoclonal antibody CDER Scaffold seeded with autologous cells CBER Interferon/Ribivarin therapy CDER Embolization implant device/chemo drug CDRH Vertobroplasty device/analgesic CDRH

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 Agenthttp://www.fda.gov/cdrh/usagent/index.html

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

Thank you

For additional information contact:

Medical Device Launchpad800.525.0975