Understanding the Regulatory Landscape'

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Understanding the Regulatory Landscape.

• MassMEDIC Regulatory Boot Camp
• December 13, 2007

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Presentation Outline
Presentation Outline

• FDA Overview
• Device Classifications / Submission Types
• Approval / Clearance Requirements
• Investigational Devices
• Combination Products

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FDA Structure / Organization
FDA Structure / Organization
Office of Combination Products
Food and Drug Administration
Center for Veterinary Devices
National Center for Toxicological Research
Center for Biologics Evaluation and Research
Center for Food Safety and Applied Nutrition
Center for Devices and Radiological Health
Center for Drug Evaluation and Research
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CDRH Offices
Office of Device Evaluation
Office of In-Vitro Diagnostic Devices Safety
Center for Devices and Radiological Health
Office of Science Technology
Office of Surveillance Biometrics
Office of Health Industry Programs
Office of Compliance
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FDA Regulatory Framework

• Federal Food, Drug and Cosmetic Act (FDC Act)
• Issued regulation classifying most types of
  medical devices

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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

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FDA Premarket Submissions
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FDA Medical Device User Fees
FDA Fees
FY2008 (Oct. 1, 2007 - Sept. 30, 2008)
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FDA Classification

• Three classes based on the levels of controls
• Necessary to reasonably assure device safety and
  effectiveness

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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

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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

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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

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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

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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

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Some Cases to Support 510(k)

• Laboratory Testing
• Clinical Testing

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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

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Substantial Equivalence Analysis

• Intended use / indication for use
• Technological characteristic
• Clinical trials
• Conclusions

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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

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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

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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

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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

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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

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PMA Requirements
PMA

• 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)

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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

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Investigational Device Exemptions

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

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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

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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

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IDE Application

• Non significant risk (NSR) investigated device
• Requires IRB approval
• Informed consent
• Need not obtain FDA approval before study begins

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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

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What is a Combination Product?
Stent
Stent Delivery System
Drug
Polymer
Slide courtesy of Nadine Ding, Guidant Corporation
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Challenge of Combination Products
Different Product Types
NDA, BLA PMA, 510(K) IND, IDE
CDRH CDER CBER
Device Drug Biologic
Different Frameworks
Different FDA Reviews
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Challenge of Combination Products
Regulatory Complexity
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Drug Eluting Stent System Design
Slide courtesy of Nadine Ding, Guidant Corporation
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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

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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/c
  fdocs/cfRL/printforms.cfm

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Thank you

• For additional information contactJames Wason,
  Ph.D.T 603-672-4678EJWason_at_Maelor-Group.com