Download Navigating the Regulatory Maze

Medical Device Bootcamp
Navigating the Regulatory
Maze
Fred Tobia
May 2012
© 2011 MDCI an Aptiv Solutions company
Navigating the Maze...
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Planning is key in the approval process
Marketing
Reimbursement
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
What is a medical device?

A medical device is an instrument,
apparatus, implement, machine,
contrivance, implant, or in vitro reagent

Intended to:
 Diagnose diseases/conditions;
 Cure, mitigate, treat, or prevent disease;
 Affect the structure/function of the human body
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
What is a medical device?

Does not achieve primary purpose through
chemical action in or on the body

Is not dependent upon being metabolized for its
primary purpose
Primary characteristics that distinguish medical devices
from drugs
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
What division do I go too?
Center for Devices and
Radiological Health (CDRH)
Primary Center & CPs
Center for Biologics
Evaluation and Research (CBER)
Designated Devices & CPs
Center for Drug
Evaluation and Research (CDER)
CPs
Center for Veterinary
Medicine (CVM)
Center for Food Safety
and Applied Nutrition (CFSAN)
FDA oversight for medical devices authorized by 1976 Medical
Device Amendments of 1976 (§513, FD&C Act, as amended)
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Medical Devices Regulated by CBER
• Collection, processing, testing, manufacture and
administration of licensed blood, blood components
and cellular products
• HIV test kits for screening/testing of donors, donor
blood, blood components and cellular products
• HIV test kits used to diagnose, treat and monitor
persons with HIV and AIDs
• Combination products (biologic/device or biologic/
drug/device with biologic primary mode of action)
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Dictated Regulation of Combination Products
• CBER Jurisdiction:
– Fibrin sealant (and delivery system)
– Intranasal flu vaccine
• CDER Jurisdiction:
– Metered dose inhalers
– Transdermal patches
• CDRH Jurisdiction:
– Fibroblast-derived dermal substitute
– Drug eluting coronary stent
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Extent of FDA oversight

Class I
 General controls sufficient for
reasonable assurance of safety /
effectiveness

Class II
 General controls insufficient
 Sufficient information for development
of standards and special controls
 Class III
 General controls insufficient
 Insufficient information for development
of standards and special controls
 Assessment of safety and effectiveness
needed for reasonable assurance of
safety and effectiveness
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Regulatory Burden
• Class I
– Exempt from premarket notification unless specifically
reserved
• Class II
– 510(k) premarket notification unless specifically
exempt - Traditional, Abbreviated, or Special
(Traditional and Abbreviated may include clinical
data)
• Class III
– Premarket approval application (PMA, PDP, or HDE)
including clinical trial data
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
510(k)s with Clinical Data
• 510(k)s cleared with clinical data (by FY):
– October 1, 2010 to September 31, 2011: 38
– October 1, 2009 to September 31, 2010: 30
– October 1, 2008 to September 31, 2009: 24
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
11
What Class is My Device?
• Formal determination
– 513(g)
– 510(k)
• Classification information sources
– Classification database
• http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm
–
Classification of competitor’s product via 510(k) or PMA databases
• http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm
• http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm
–
Keyword search of competitor’s product name in device listing
database
• http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/rl.cfm
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Classification Challenges
• No formal classification flowchart based on risk
• Device names used for clearance/approval may
not be the same in the US
• Names of companies obtaining clearance/approval
are not changed in the FDA databases
• Distributor or licensee may hold the clearance/
approval
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
De Novo Process
• Before de novo
– Devices without predicate were automatically Class III
• FDAMA 1997
– Within thirty (30) days of a “not substantially equivalent
determination,” sponsor may request risk-based
classification determination of the device
– Request to include device description and reasons for
recommended classification based on risk
– FDA “must” respond in 60 days
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Device Submissions During Development
• Request For Designation (RFD)
• 513(g)
• Pre-IDE
• IDE
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Device Submissions Marketing
Applications
• Premarket Notification (510(k))
– Content: 21 CFR 807.92
• Premarket Approval (PMA)
– Content: 21 CFR 814.20
• Product Development Protocol (PDP)
– Rarely used – Guidance outdated
• Humanitarian Device Exemption (HDE)
– Content: 21 CFR 814.104
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Device Submissions After Approval/Clearance
• IDE
• Special 510(k)
• PMA/HDE Supplements
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
FDA Review Process
• Interactive review
– By phone
– By email
• RAIs
– Requests for clarification
– Minor labeling (IFU) revision
– Response to RAI expedited to keep review active
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Additional Requirements
•
•
•
•
Establishment registration and annual renewals
Device listing
Medical device reporting
Post-market management of device
modifications
• Post-market applications for device
modifications
– Will change require a clinical study?
– Will change affect product regulatory status?
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
OUS Companies
• Registration requires designation of a US Agent (with
address in the US).
• Now eligible for Small Business designation for Medical
Device User Fees (no small business reduction for annual
registration renewals)
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Reducing Uncertainty
• Pre-IDE Process
– Informal activity
– Agreement meeting
– Determination meeting
– Does not provide an in-depth review
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Pre-IDE
• Possible pre-IDE communication
– Correspondence only (written / fax)
– Conference call
– Face-to-face meeting
• Desired results
– Establishes a cooperative relationship between
sponsor and agency counterparts
– Allows Agency to provide early input in time for early
or mid-course corrections
– Minimizes surprises
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Post Pre-IDE
• Implement recommendations provided by Agency
where appropriate
• Where recommendations were not implemented or
implemented incompletely, justify deviations from
Agency recommendations in subsequent
submissions or correspondence
• Identify pre-IDE discussions in subsequent
submissions or correspondence
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Post Pre-IDE
• IDE (or clinical study for NSR study)
• Marketing application
– 510(k)
– PMA / HDE / PDP
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
Strategies
• Have the right team
• Communicate and document frequently
• Knowing the regulations and guidance is not
always enough
• Know your potential reviewers and possible
undocumented Agency expectations
• Never submit to early
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
FDA Acronyms
FDA Acronym Database:
http://www.accessdata.fda.gov/scripts/cder/acronyms/index.cfm
•
510(k) – Premarket notification
•
513(g) – Request for Classification
•
CBER – FDA Center for Biologics Evaluation and Research
•
CDER – Center for Drug Evaluation and Research
•
CDRH – FDA Center for Devices and Radiological Health
•
CFR – Code of Federal Regulations
•
CP – Combination product
•
DSMB – Date safety monitoring board
•
FDA – Food and Drug Administration (United States)
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
FDA Acronyms…
• FDAAA – Food and Drug Administration Amendment Act of
2007
• FR – Federal Register
• GCP – Good Clinical Practices
• GLP – Good Laboratory Practices
• HDE – Humanitarian device exemption
• IDE – Investigational device exemption
• NSE – Not substantially equivalent
• PMA – Premarket approval application
• QSR – Quality System Regulations
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company
FDA Acronyms
• RAI – Request for Additional Information
• RFD – Request for Designation
• SE – Substantially equivalent
• SSE – Summary of safety and effectiveness
© 2012
2011 Aptiv
MDCISolutions
an Aptiv Solutions company