How to Manage Regulatory Issues
and get FDA Approvals
Maureen Garner, President
Glenn Neuman, Director of Scientific Affairs
New World Regulatory Solutions, Inc.
www.NewWorldReg.com
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About NWRS
New World Regulatory Solutions, Inc. (NWRS)
was founded in 2002 with the mission of helping
domestic and international companies
gain regulatory approval
for innovative medical devices.
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What % of Medical Devices
sold in the US
are manufactured off-shore?
50% !
I s yours one of them ?
3
US FDA is the Gatekeeper to
the US Medical Device Market
Company Team
MANAGEMENT
REGULATORY
US FDA
QUALITY
MARKETING
R&D
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Good Regulatory Practices
Lead to FDA Clearance
MANAGEMENT
REGULATORY
US FDA
QUALITY SYSTEMS
MARKETING
R&D
Strategy, compliance
and know-how are critical!
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Overseas
Manufacturers
US
Partner
USA
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Regulatory Submissions to US FDA
FAQs about FDA Submissions
• What % of submissions require clinical data?
10%
• Can clinical data from foreign studies be used?
Yes, provided that:
• Similar practice of medicine
• Similar protocols
• Ethics approval
• Sample availability issues
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Regulatory Submissions to US FDA
FAQs about FDA Submissions
• Does conformance with International Consensus
Standards help?
Yes
• FDA has a list of “recognized standards”
• Basis for Abbreviated 510(k)
• Must submit FDA Form 3654 for each
recognized standard cited
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Regulatory Submissions to US FDA
FAQs about FDA Submissions
• How similar are the FDA quality system
requirements and ISO 13485?
Pretty Close!
• ISO-compliant companies need only a few
Quality System adjustments to meet FDA
regulation
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Regulatory Submissions to US FDA
FAQs about FDA Submissions
• FDA refers to a “least burdensome” approach –
what is that?
 Good question! We find that it’s a case-by-case
negotiation, often with frustrating outcomes.
• Will FDA review requirements get more stringent?
 Yes! Upcoming public meeting on February 18
 But so is the EU -- 2007/47/EC amendment to MDD
• FDA Approvals are based on two key issues:
1. Good Science
2. Public Health Safety
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New MDD Requirements
(2007/47/EC)
• Clinical evaluation required in Technical File
• Actively updated; post-market surveillance
• Clinical investigation can be required
• CNS surgical devices: Class IIa  Class III
• Class IIa disinfecting devices  Class IIb
• Software becomes a stand alone medical device
• Classification via Primary Mode of Action, not
Intended Use
• New labeling requirements for high-risk devices
• March 21, 2010
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Regulatory Submissions to US FDA
Review occurs in one or more FDA Centers
FDA
CDRH
CBER
CDER
OCP
Devices,
IVDs
Biologicals,
Blood
Banking
Drugs
Combination
Products
HIV
diagnostics
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Regulatory Submissions to US FDA
FDA conducts either:
• Pre-Market Review, known as a “510(k)”
 New product is “substantially equivalent” to existing
legally marketed product
 Product is “cleared” for market through a 510(k)
Notification
• Pre-Market Approval, known as a “PMA”
 New product is tested directly against a clinical
reference to demonstrate safety and efficacy
 Product is “approved” for market
• Which route should you choose?
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Device Submissions to US FDA
• Type of FDA submission required
depends on Device Classification
• Device Classification depends on Risk

Class 1
Class 2

Class 3

- lowest risk, most are exempt*:
- moderate risk, some exempt*,
remainder are 510(k)
- highest risk, mostly PMA,
some (<50) 510(k)
* “Exempt” does not apply for point of care, automated
or home use.
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Device Submissions to US FDA
• Are FDA Classes the same as CE
classes?




No
FDA classes are based on RISK and
INTENDED USE
CE classes are based on PRIMARY MODE
OF ACTION
But, there is plenty of similarity when these
methods are applied
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Device Submissions to US FDA
Types of FDA Submissions
• 510(k) Premarket Notification


~3,500/year, >95% approved
Clinical performance data needed for
IVDs, but some can be done “in-house.”
• PMA Premarket Approval


~35 submissions/year, ~80% approved
Most stringent -- Clinical safety and
effectiveness data required
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Device Submissions to US FDA
• 510(k) Demonstrates “substantial
equivalence” with predicate




Traditional -- new device
Abbreviated -- conformance to
guidance, special control, or recognized
standard
Special -- minor changes to device or
reagents or sample treatment with
review of design control
De Novo -- lower risk device with no
predicate
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Device Submissions to US FDA
Types of FDA Submissions
• CLIA Waiver
IVDs only,
• Market Access > 170,000 POC sites in US
• Must be simple, fool-proof:
• “So easy even a doctor can do it!”
• 11 Submission in 2008, 5 approved
• 6 Submissions in 2009, 1 approved
• New FDA Guidance -- harder than 510(k)s
• The test has to be easy, but the approval
is not!
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Device Submissions to US FDA
How Long Does It Take (excluding studies)?
• PMA FDA

Average Real Days = ~ one year
• 510(k)


FDA review time goal is 180 days
FDA review time goal is 90 days
Average Real Days = ~ 100 (Traditional)
IVDs take longer (statistical review of
performance data)
• CLIA Waiver


no official Goal
69 - 398 Real Days for 5 approvals in 2008
56 - 217 Real Days for 6 denials in 2008
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Realistic 510(k) Time Scenario
100 %
PostProduct Market
Cleared Activities
90 %
% Project Completion
80 %
70 %
Negotiations
60 %
FDA Review
50 %
40 %
Conduct
Clinical
Studies
30 %
20 %
10 %
Submit
Initiation Pre-IDE
Submit
510(k)
Pre-IDE
Approved
Conduct Non-Clinical Studies
0%
0
1
3
6
9
Time, Months
12
15
18
24
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Device Submissions to US FDA
How Much Does It Cost?
• PMA




Most expensive
FDA Application fee
• $0 for first if under $30MM
• $50,181 < $100MM
• $200,000 > $100MM
Clinical Costs
• $1MM for IVD, can be less for Devices
Non-clinical studies
$1-2MM Total Costs (Rule of Thumb)
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Device Submissions to US FDA
How Much Does It Cost?
• 510(k)



FDA Application Fee
• $1,847 < $100MM
• $3,693 > $100MM
Total Costs are Extremely Varied
• Depends on Device
• Depends on type of 510(k)
$20,000 - $250,000 Total Costs
• Clinical Studies increase costs
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Device Submissions to US FDA
How Much Does It Cost?
• CLIA Waiver





(IVDs Only)
No FDA Application Fee
Clinical “Intended User” Data are required
240 or 360 prospective patients
Comparison to reference method
$80,000 - $120,000 Total Costs
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Where to Begin
Does FDA help?







Guidance Documents
513(g) Request classification
Pre-IDE FDA informal review of study plan
IDE (Devices or reporting IVD results)
DSMICA
Meetings phone or face-to-face, can be
binding or non-binding
Quality System Regulations (“GMPs”)
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Quality Systems Regulations
Manufacturers must conform with “GMPs”
• GMPs -- Devices and IVDs


21CFR820
Same for Devices and IVDs
• cGMPs -- Drugs

21CFR211
• Similar to ISO
• GLPs and GCPs also required
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Device Submissions to US FDA
AVOID COSTLY MISTAKES
• Submission poorly written
• Lack of statistical support
• Studies not designed to support claims
• Poor oversight of clinical studies
• Product not designed for target market


High, Moderate and Waived complexity
Human factors not considered
• Quality Systems not compliant
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Labeling and Instructions
Labeling and Instructions must follow
regulations and guidelines


Special considerations for CLIA Waiver and
Home Use
Marketing materials and website are
considered labeling
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Quality System Inspections by US FDA
• Occur BEFORE your PMA Approval



Study sites, investigator files
Manufacturing facilities
Company Quality System
• Occur AFTER your 510(k) Clearance



Manufacturing facilities
Company Quality System
Will occur, FDA priorities and resources
dictate schedule
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Regulatory Strategy in Business Plans
Phase 1
Strategic
Development
•
•
•
•
•
•
•
Target Market
Intended Use
Protocols
Study Forms
Draft Labeling
Pre-IDE
FDA Meeting
Seed
Money
Phase 2
Project
Initiation
• Qualify/Contract
Study Sites
• Ethics Approval
• Train/Initiate
Sites
• Non-Clinical
Studies
Milestone
payment
Phase 3
Execute
Studies
Phase 4
FDA Submission
and Clearance
• Prepare
• Monitor Sites
Submission
• Collect/Compile
• Follow-up with
Data
FDA
• Close Sites
• Prepare Reports • Finalize Labeling
• FDA Approval
Milestone
payment
P R ODUCT LAUN CH
Milestone
payment
R OI
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Good Regulatory Strategy
Ensures Success
Market
Goals
Regulatory
Strategy
Product
Design
Funding
Milestones
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Thank you!
Looking forward to seeing YOUR product in the US!
Maureen Garner, President
Glenn Neuman, Director of Scientific Affairs
New World Regulatory Solutions, Inc.
www.NewWorldReg.com
[email protected]
001-267-980-2414 (Glenn)
001-732-779-7422 (Maureen)
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