Medical Device Development

The Framework for Regulation of Medical Devices
The Impetus for Premarket Clearance of Medical Devices
The Medical Device Amendments of 1976
Definition of a Medical Device
The Medical Device Classification Process
The Classification System
Classification of "Preamendment" Devices
FDA's Device Classification, 1973-1988
Continuing Classification of Devices
Marketing a Medical Device: Routes to Market
510(k) Notification Process
PMA Process
PDP Process
Reclassification
De Novo Review
General Principles of Market Clearance/Approval
Reasonable Safety and Effectiveness
Substantial Equivalence
Considering Whether to File a 510(k) or PMA
The Safe Medical Devices Act of 1990 and the Medical Device Amendments of 1992
The SMDA
User Reports
Distributor Reports
Device Tracking
Substantial Equivalence to Preamendment Class III Devices
Reclassification of Preamendment Class III Devices
Transitional Devices
Special Controls
Performance Standards
Reports of Removals and Corrections
Recall Authority
Temporary PMA Suspension
Postmarketing Surveillance
Use of Premarketing Approval Data
Determining Substantial Equivalence
Humanitarian Use Devices
Office of International Relations
Combination Products
Civil Penalties
Design Validation
MDA 1992
The Impact of the Food and Drug Administration Modernization Act of 1997 on the Approval Process
CDRH Organizational Structure

The 510(k) Premarket Notification Process
Premarket Notification: The Original Intent
When Is a 510(k) Required?
Misbranded/Adulterated Devices
Definition of Commercial Distribution
Determination of Preamendment Status
Exemptions from Premarket Notification
Exemptions of Generic Types of Class I Devices
Exemptions of Generic Types of Class II Devices
Other Exempt Devices
Determination of Substantial Equivalence
Congress Defines "Substantial Equivalence"
Data Requirements for Substantial Equivalence
Clinical Trials
Biocompatibility Issues
Preclinical Testing
Device Standards
Determination of Intended Use: Implied Intended Use and General/Specific Intended Use
Regulatory Strategy Considerations
The Format and Content of a 510(k) Notice
Basic Content Requirements for 510(k) Notices
Certain Elements of a 510(k) Notice
Comparison Table
The 510(k) Summary vs. 510(k) Statement
510(k) Summary
510(k) Statement
The Choice Between a 510(k) Summary or a 510(k) Statement
Class III Summary, Citation, and Certification
Indications for Use Statement
Certification of the Truthfulness and Accuracy of the 510(k) Notice
Separate Report Presenting the Data on Each Major Study or Test Program
Alternative Methods of Demonstrating Substantial Equivalence
Guidance on Abbreviated 510(k) Notices
Special Requirements for Kit 510(k)s
FDA Review of 510(k) Notices
FDA's Refuse to Accept 510(k) Notifications Policy
FDA Requests for Additional Information
Written Requests for Additional Information
Telephone Requests for Additional Information
Third Party Review of 510(k)s
Advertising and Promotion of a Device Pending FDA Clearance
FDA Actions Regarding Premarket Notifications
The Implications of a Finding of Substantial Equivalence
The Implications of a Not Substantially Equivalent Finding
Dispute Resolution
Judicial Review of a Substantial Equivalence Determination
510(k) Notice Review Times
Expedited Review
Determining the Status of the 510(k) Review
Linking GMP Inspections to Product Clearances

Device Modifications Requiring a 510(k) Notice
CDRH Device Modification Policy
The 510(k) Decision Flowchart
Types of Device Modifications
Design Creep/Changes
Labeling Changes
Technology/Manufacturing Changes
Materials Changes
Implantable Devices
Non-Implantable Devices
Changes to In Vitro Diagnostic Devices
Changes to Recalled or Corrected Devices
Impact of a Decision Not to File a New 510(k)
The Special 510(k) Notice

510(k) Notifications for Medical Device Software
Classification of Medical Device Software
Software as a Component
Stand-Alone Information Management Software Devices
Exempt Categories of Software
Review of Software Premarket Submissions
Reviewer Guidelines
Establishing the Level of Concern
Device Risk
Device Function
Documentation of the Level of Concern
Results of Testing and Analysis
Labeling
Off-the-Shelf Software (OTS)
Software Changes
Telemedicine and PACS Devices
Year 2000 Computer Problem
Medical Device Software: The Future

The Investigational Device Exemption Application: Overview of the IDE Process and Humanitarian Devices
Exempted Investigations: Devices Exempted from IDE Requirements
Determination of Device Risk
Significant vs. Nonsignificant Risk Devices
Selection of the IRB
Planning for the IDE Application
CDRH Guidances Applicable to IDEs
Pre-IDE Filing Meeting
FDAMA Early Collaboration Meetings
Content of an IDE Application
ODE Review of the IDE Application
FDA's Refuse to Accept Policy
FDA Requests for Additional Information
FDA Actions Regarding IDE Applications
Confidentiality
Reimbursement for Investigational Drugs
IDE Supplements
IDE Applications for Feasibility Studies
Humanitarian Devices
Expanded Access to Investigational Devices
Summary

Medical Device Clinical Studies
Impact of the Temple Report on Clinical Study Design
Clinical Trial Design Considerations
Study Hypothesis
Control Group
Eligibility Criteria
Assignment of Intervention
Sample Size
Endpoints
Blinding (Masking)
Comparability of Patients in Study Groups
Other Design Considerations
Study Conduct
Study Data Analysis
The Aftermath of the Temple Report and the Dawn of FDAMA
Responsibilities of Clinical Trial Participants
Sponsor Obligations
Requirements for an NSR Device
Requirements Prior to Clinical Trial
Requirements During Clinical Trial
Requirements After Clinical Phase
Recordkeeping Requirements
Reporting Requirements
Investigator Obligations
Requirements Prior to Clinical Trial
Requirements During Clinical Trial
Requirements After Clinical Phase
Recordkeeping Requirements
Reporting Requirements
Financial Disclosure by Clinical Investigators
IRB Obligations
Monitoring of Clinical Studies
Qualifications of a Study Monitor
Monitoring Procedures
Result of Monitoring or Failure to Monitor
International Clinical Studies
Data from International Feasibility Studies
Reliance on International Data as the Sole Basis for Approval
Pooling International Data with U.S. Data
International Data in Support of 510(k) Notices or PMA Applications
Issues for IVD Studies
Promotion and Commercialization of Investigational Devices
The Impact of FDAMA on Clinical Studies
Number of Clinical Investigations Required for Approval
"Least Burdensome" Data Requirements

The Premarket Approval Application
Medical Devices Subject to the PMA Process
Early Collaboration Meetings Under FDAMA
Structure of the PMA Application
Section 1: Cover Page
Section 2: Table of Contents
Section 3: Summary of Safety and Effectiveness
Section 4: Device Description and Manufacturing
Device Description
Manufacturing
Section 5: Performance Standards
Section 6: Technical Data
Preclinical Studies
Clinical Studies
Section 7: Justification for One Investigator
Section 8: Bibliography, References, and Other Reports
Section 9: Samples
Section 10: Labeling
Section 11: Environmental Assessment
Section 12: Financial Certification or Disclosure Statement
Common Flaws in Drafting PMAs
Biostatistical Methodologies and Analyses Supporting PMA Approval
The Modular PMA Review Initiative

Review of a Premarket Approval Application
Overview of the PMA Review Process
The Filing Decision
FDA Review of the PMA
The 100-Day Meeting and Other Mid-Review Communications
A Modular Approach to PMA Review
The Panel Review Process
Advisory Panel Procedures
Preparing for Advisory Panel Presentations
Providing New Information During the PMA Review Process: Amendments to Pending PMAs
PMA Amendments and Resubmitted PMAs
Abandonment of a PMA
Voluntary Withdrawal of a PMA
FDA Action on a PMA
PMA Submission and Approval Times
PMA Confidentiality During the Review Process
Conditions of PMA Approval: GMP Inspections and Bioresearch Monitoring
QSR Inspections
Preapproval Inspections
Postapproval Inspections
Bioresearch Monitoring Inspections
Postapproval Requirements
Postmarket Surveillance Studies
Withdrawal of Approval of a PMA
Change of PMA Ownership
The Impact of FDAMA on the PMA Review Process

PMA Supplements
When Is a PMA Supplement Necessary and What Type Should be Submitted?
The 180-Day PMA Supplement
The 30-Day Notice and 135-Day Supplement
The 30-Day Supplement
Special PMA Supplement-Changes Being Effected
Annual Report
FDA's Modifications Guidance
Changes Due to Recalls and Corrective Field Actions
Labeling Changes
Technology or Performance Changes
Packaging/Sterilization Changes
Materials Changes
The PMA Supplement Application
Review of the PMA Supplement
PMA Supplement Strategies

Medical Device Reclassification
Reclassification Standard
The Statutory Framework
Reclassification Based on New Information
Reclassification Based on FDA's Requirement for Performance Standards/Premarket Approval
Reclassification of New Devices
Reclassification of Transitional Devices Under the 1976 Amendments
The Reclassification of Preamendment Class III Devices
Data Requirements for a Reclassification Petition
FDA's Reclassification Record, 1976-1998
Contact Lenses
Sutures
Drionic Device
Inductive Nasal Device
Magnetic Resonance Imaging
Ophthalmic Nd:Yag Lasers
Hip Prostheses
Bilirubin Test Systems
Cardiopulmonary Bypass Oxygenator
Automated Differential Cell Counter
Obstetrics and Gynecology Devices
Infant Radiant Warmers
Cardiovascular Cardiopulmonary Bypass Pumps
Electroconvulsive Therapy (ECT) Devices
Endosseous Dental Implants
Pedicle Screw Spinal Systems
De Novo Classification
Conclusion

The Product Development Protocol
Statutory Requirements
The PDP Concept
PDP Reengineering
PDP Draft Guidance
The PDP Process
Initial Consultation with FDA
PDP Proposal
The Full PDP Submission
PDP Modifications

The Regulation of Combination Products
Determining Primary Jurisdiction for a Combination Product
FDA Intercenter Agreements
Request for Primary Jurisdiction Designation
Strategies for Combination Product Approval

Medical Device Exports
Statutory Background
The Export Reform and Enhancement Act of 1996
Medical Device Export Decision Tree
Export of Legally Marketed Devices
Export Procedures for Unapproved Devices
Exporting Devices via Section 801(e)(1)
Exporting Devices via Section 801(e)(2)
Exporting Devices via Section 802
Exporting for Marketing or In Anticipation of Foreign Marketing Approval
Importing for Export
Certificates for Export

Medical Device Reporting Requirements
Manufacturers and MDR Reporting Requirements
Device Manufacturers and MDR-Reportable Events
Time and Knowledge Requirements
Importers and MDR Reporting Requirements
Importers and MDR-Reportable Events
Time and Knowledge Requirements
User Facilities and MDR Reporting Requirements
MDR-Reportable Events
Time and Knowledge Requirements
Sentinel Reporting System
The Practical Application of the MDR
Internal MDR Procedures
Record Requirements
How and Where to File
When Not to File

Working Well with FDA
Frequent Communication
Internal Planning for the Product Submission
Meeting with CDRH
Review Status Reports
Disagreements Between CDRH and the Sponsor
Strategies for Successful Product Submissions
Glossary