FDA 510(k) 101The Basics

Floyd G. LarsonPresident, PaxMed International

San Diego, CA

OMTEC June 17, 2010

Chicago

Agenda

History of 510(k) processFDA’s risk-based approachFDA guidance and standardsStructure of a 510(k)Submission to FDAFollow-up with FDA

History of 510(k) ProgramBegan May 28, 1976

– Medical device amendments to Federal Food Drug & Cosmetic Act (“the Act”)

Section 510(k) of the ActInitial regulation of medical devices“Grandfathered” devices already on market, if risk low (Class I or II) – Pre-amendments devicesNew devices cleared if “substantially equivalent” to devices on market prior to May 28, 1976

– Now can be “SE” to devices that are “SE”

Section 510(k) of the Act(k) Each person who is required to register under this section and

who proposes to begin the introduction or delivery for introduction into interstate commerce for commercial distribution of a device intended for human use shall, at least ninety days before making such introduction or delivery, report to the Secretary or person who is accredited under section 523(a) (in such form and manner as the Secretary shall by regulation prescribe)(1) the class in which the device is classified under section 513 or if

such person determines that the device is not classified under such section, a statement of that determination and the basis for such person's determination that the device is or is not so classified, and

(2) action taken by such person to comply with requirements under section 514 [performance standards] or 515 [premarket approval] which are applicable to the device. . . .

Premarket “Notification”

Original 510(k) process involved sending FDA a letter indicating intent to introduce new device into interstate commerce– If no response within 90 days, OK to sell

Soon changed to require that a favorable letter from FDA be received prior to marketingReview process now much more rigorous– “Mini-PMA”

An early 510(k)

Here it is – all 6 pages

The beginning of the content

This is all there is!

How are things different now?510(k)s may have 200-500 pages (or more)Solid predicate device(s) are essentialNeed carefully considered Indications for UseNeed strong supporting data– Performance testing – bench– Performance testing – animal – Performance testing – clinical

A growing number of submissions

Need strong Substantial Equivalence argument

Risk-based Classification

Three Regulatory Classes (level of control based on risk):

Class I – General Controls (most exempt from 510(k))

Class II – General Controls & Special Controls (Guidance Documents, Standards)

Class III – General Controls & Premarket Approval

What is Class III?

FDA has determined that Special Controls are not sufficient to ensure safety and effectivenessClass III devices generally are not eligible for 510(k) clearance (need Premarket Approval)– Exception for Preamendments Class III devices for

which FDA has not yet issued a call for Premarket Approval applications

Devices Exempt from 510(k)Preamendments devicesUnfinished devicesDevices exempt by statute or by regulation– 739 Class I, 74 Class II

Finished devices not sold in U.S. Devices covered under another 510(k)– Private labeled devices

Custom devicesVeterinary devices

Is a 510(k) needed?

Is it a Medical Device?Is it exempt from 510(k) requirement?– Note that it probably is subject to QSR –

21CFR 820Is it a PMA device?

Types of 510(k)sClass II and Preamendments Class III

Traditional– 90-day review

Special– Relies on Design Controls– 30-day review

Abbreviated– Relies on conformance to standards

Special 510(k)Used to obtain clearance for a change to a manufacturers own deviceSame Indication for UseBased on conformance to Design Controls (21CFR 820.30)Submission not easier than TraditionalReview time 30 days

See FDA guidance at www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080189.pdf

Abbreviated 510(k)

Based on conformance to standards and/or FDA guidance documentsNo advantage for review timingNot commonly usedStandards are also used in Traditional 510(k)s

Role of Standards

Voluntary– Organizations such as ASTM, ISO– Voting process – ASTM by company or individual, ISO by

country

Recognized by FDA (see FDA recognition list)– www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/

search.cfm

Even when they are not performance standards, they are useful in aiding comparison to historical data or predicate devices

Substantial EquivalenceA device is substantially equivalent if, in comparison to a predicate it:

has the same intended use as the predicate; andhas the same technological characteristics as the predicate;

or has the same intended use as the predicate; andhas different technological characteristics and the information submitted to FDA; does not raise new questions of safety and effectiveness; anddemonstrates that the device is at least as safe and effective as the legally marketed device.

510(k) Review Flowchart

510(k) Review Flowchart

Reviewer Template for 510(k)

Reviewer Template for 510(k)

Reviewer Template for 510(k)

Reviewer Template for 510(k)

Reviewer Template for 510(k)

Reviewer Template for 510(k)

What does the 510(k) processaccomplish (and what not)?

Outcome of 510(k) review determines classification of a device

• If Substantially Equivalent (“SE”) takes classification of predicate• If Not Substantially Equivalent (“NSE”), device is Class III

510(k) clearance is not “approval”• That requires the Premarket Approval (PMA) process

A 510(k) is not registration or device listing

Nuts and Bolts

Beginning the SubmissionDefine intended use of deviceSearch for FDA guidance documents– FDA database of guidance documents

Determine classification– FDA database of product codes– Look at product codes of similar devices (510(k) summaries)– Read classification regulation

Search for predicate device candidates– Same intended use and product code– Similar technological characteristics– Multiple predicate devices OK

Collect key components

Key Components

Product list with part numbers for all products to be cleared, including all relevant accessoriesEngineering drawings for all components on product listDevice Description – especially characteristics not obvious from the drawings (e.g., description of surface treatment and process used) Material Certifications or Material Standards acceptable to FDA

Key Components

Labeling - copies or drafts– Instructions for Use (Package Insert) – In English– Product Labels, with text for most symbols– Surgical and/or Prosthetic Manuals– Product Brochures– List of all claims for which clearance is requested

Key Components

Packaging description and drawingsPlanned sterilization method and validation plans –including corresponding accepted FDA standardTesting completed (including protocol or standard to which the protocol is written, and final test reports)

Format of a Traditional 510(k)

FDA Guidance – August 12, 200521 sectionsSome may not applyMaintain numbering and titles

Sections of a 510(k)

Cover PageTable of Contents1. Medical Device User Fee Cover Sheet (Form FDA 3601)

2. CDRH Premarket Review Submission Cover Sheet3. 510(k) Cover Letter4. Indications for Use Statement5. 510(k) Summary or 510(k) Statement6. Truthful and Accurate Statement7. Class III Summary and Certification

Sections of a 510(k)

8. Financial Certification or Disclosure Statement9. Declarations of Conformity and Summary Reports

– Include Standards Data Reports (Form FDA 3654) for each standard referenced in submission

10. Executive Summary11. Device Description12. Substantial Equivalence Discussion13. Proposed Labeling

Sections of a 510(k)

14. Sterilization and Shelf Life15. Biocompatibility16. Software17. Electromagnetic Compatibility and Electrical Safety18. Performance Testing – Bench19. Performance Testing – Animal20. Performance Testing – Clinical21. Other

Steps in Writing a 510(k)

Write Device DescriptionSummarize bench testingSummarize animal testing (if applicable)Summarize clinical study (if applicable)Write text for other sections– Biocompatibility– Sterilization and shelf life (include packaging)

Write Substantial Equivalence section

Steps in Writing a 510(k)Complete administrative sections– FDA User Fee Cover Sheet– CDRH Cover Sheet– 510(k) Cover Letter– Indications for Use Statement– 510(k) Summary or 510(k) Statement– Truthful and Accurate Statement– Class III Summary and Certification (if applicable)– Financial Certification or Disclosure Statement (if applicable)– Declarations of Conformity and Summary Reports– Executive Summary– Certification re clinical trials databank (if applicable)

Submitting the 510(k)Submit TWO paper copies or ONE paper copy and ONE electronic (pdf) copy– If electronic copy is submitted, see for format

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/ucm134508.htm

Include MS Word file of text for reviewer useRetain an identical file copyUse 8.5 inch x 11 inch paper3-hole punch left marginYour fancy binder will be discarded – (probably used for employee children’s school projects)

Submitting the 510(k)Submit by traceable courier service to:– Food and Drug Administration

Center for Devices and Radiological HealthDocument Mail Center - WO66-G60910903 New Hampshire AvenueSilver Spring, MD 20993-0002

For 510(k)s reviewed by CBER, send to:– FDA/CBER

1401 Rockville PikeHFM-99, Room 200NRockville, MD 20852-1448

What’s Next?Administrative review for completenessFDA acknowledgement letter– Includes assigned “K” number – not a clearance

FDA has 90 calendar days to review a Traditional 510(k) Premarket Notification– Target for questions is 75 days

FDA has 30 days to review a “Special 510(k)”Reviewer may call sponsor or consultant with questions– If questions can be resolved easily, a hold might be avoided

What’s Next?Questions may come by email, FAX or letter (request for additional information – “AI” Letter)– Submission will be placed on hold

Stops FDA 90-day clockStarts sponsor 30-day clockExtensions automatically granted on request, to a total of 180 days

When sponsor submits response to questions, FDA clock starts running againFDA might ask a second round of formal questions– Submission will be placed on hold

Stops FDA 90-day clockStarts sponsor 30-day clockExtensions automatically granted on request, to a total of 180 days

What’s Next?Generally no opportunity for third round of questionsIf all questions answered satisfactorily– “Substantially Equivalent” letter – Clearance to market

If reviewer and FDA management not satisfied– “Not Substantially Equivalent” letter – Device is Class III– Some NSE letters read more like “AI” letters

Invite resubmission as 510(k) with additional informationUsually requires clinical or animal data

Questions?

Key FDA website links

Classification database– www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm

510(k) database– www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm

Guidance document databasewww.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm

Device Advicewww.fda.gov/MedicalDevices/DeviceRegulationandGuidance/default.htm

Key FDA Guidance (General)

Format for Abbreviated & Traditional 510(k)s– www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/

GuidanceDocuments/ucm084396.pdf

Certifications re clinical trials databank– www.fda.gov/RegulatoryInformation/Guidances/ucm125335.htm

User Fees and Refunds for 510(k)s– www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/

GuidanceDocuments/ucm089755.pdf

Bundling Multiple Devices or Multiple Indications in a Single Submission

– www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm089732.pdf

To contact us

Floyd Larson or Kevin ThomasPaxMed International, LLC

Office (858) 792-1235

Email flarson@paxmed.comkthomas@paxmed.com

Thank you.