how to manage regulatory issues and get fda approvals how to manage regulatory issues and get fda...

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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 Devicessold in the US

are manufactured off-shore?

50% !Is yours one of them?

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US FDA is the Gatekeeper to the US Medical Device Market

US FDA

R & D

MARKETING

REGULATORY

MANAGEMENT

QUALITY

Company Team

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Good Regulatory Practices Lead to FDA Clearance

US FDA

R & D

MARKETING

REGULATORY

MANAGEMENT

QUALITY SYSTEMS

Strategy, complianceand know-how are critical!

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Overseas Manufacturers

USA

US Partner

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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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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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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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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 Science2. 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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FDA

CDRH

Devices, IVDs

CBER

Biologicals,Blood

Banking

HIV diagnostics

CDER

Drugs

OCP

Combination Products

Review occurs in one or more FDA Centers

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Regulatory Submissions to US FDAFDA 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 - lowest risk, most are exempt*: Class 2 - moderate risk, some exempt*,

remainder are 510(k) Class 3 - highest risk, mostly PMA,

some (<50) 510(k)

* “Exempt” does not apply for point of care, automated or home use.

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• 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 FDATypes 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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•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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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 FDAHow Long Does It Take (excluding studies)?•PMA FDA FDA review time goal is 180 days

Average Real Days = ~ one year

•510(k) 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

Realistic 510(k) Time Scenario

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0 %

10 %

20 %

30 %

40 %

50 %

60 %

70 %

80 %

90 %

100 %

0 1 3 6 9 12 15 18 24

% P

roje

ct C

ompl

etio

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Time, Months

Pre-IDEApproved

InitiationSubmitPre-IDE

Conduct ClinicalStudies

Submit 510(k)

FDA Review

Negotiations

Product Cleared

Post-Market

Activities

Conduct Non-Clinical Studies

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Device Submissions to US FDAHow 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 FDAHow 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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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 BeginDoes 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 FDAAVOID 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

Regulatory Strategy in Business Plans

Phase 1 Phase 2 Phase 3 Phase 4

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StrategicDevelopment• Target Market• Intended Use• Protocols• Study Forms• Draft Labeling• Pre-IDE• FDA Meeting

Project Initiation• Qualify/Contract

Study Sites• Ethics Approval• Train/Initiate

Sites• Non-Clinical

Studies

Execute Studies• Monitor Sites• Collect/Compile

Data • Close Sites• Prepare Reports

FDA Submission and Clearance• Prepare

Submission• Follow-up with

FDA• Finalize Labeling• FDA ApprovalPRODUCT LAUNCH

Seed Money

Milestone payment

Milestone payment

Milestone payment

ROI

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Good Regulatory StrategyEnsures Success

Product Design

Market Goals

Funding Milestones

Regulatory Strategy

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Thank you!

Maureen Garner, PresidentGlenn Neuman, Director of Scientific AffairsNew World Regulatory Solutions, Inc.

[email protected]

001-267-980-2414 (Glenn)001-732-779-7422 (Maureen)

Looking forward to seeing YOUR product in the US!