# Presentation: 735446

## Rockville MD 

**OIVD 510(k) Workshop**
- Rockville MD
**April 19, 2005**
**Practical Considerations In Preparing 510(k)s**
**Heather S. Rosecrans**
**Director, 510(k) Staff**
**Center for Devices and Radiological Health**
**U.S. Food and Drug Administration **
**hsr@cdrh.fda.gov**
**(301) 594-1190 x143**

## What is a 510(k)?

- Premarket Notification
- Section 510(k) of F,D, & C Act
- 21 CFR 807 Subpart E
- Marketing Clearance Application
- Allows FDA to Determine Substantial Equivalence (SE)

## What a 510(k) Is Not

-   A form
-   Establishment Registration (FDA-2891)
-   Device Listing  (FDA-2892)
-   Premarket Approval  (PMA)
-   Product Development Protocol (PDP)

## A Device is Substantially Equivalent (SE) if:

- In Comparison to a legally marketed        device, it:
- Has the same intended use, and
- Has the same technological characteristics as the predicate device, or:

## SE (cont.)

- Has the same intended use, and
- Has different technological characteristics and the information in the 510(k):
- Does not raise new questions of safety and effectiveness, and
- Demonstrates it is as safe and effective as the predicate

## May 28, 1976

- PREAMENDMENT DEVICE:				Exempted (with Conditions)			from Marketing Clearance
- POSTAMENDMENT DEVICE:			Requires Marketing Clearance unless 	 		exempt by regulation

## Establish Equivalence to:

- A legally marketed device that does not require a PMA, i.e., a:
- 		Preamendments device, or
- 		A device found by FDA to be 			Substantially Equivalent (SE)
- 		A reclassified device

## FDA finds the device Substantially Equivalent?

- NO:  PMA, PDP or HDE Application					or
- 				   De Novo
- YES:  To Market

## 510(k) Submission Required When:

- Introducing a device to the market for the first time
- Change in intended use for a marketed device
- Making significant modification to a marketed device

## Modifications - 

- Changes in Intended Use
- Modifications that significantly enhance (or decrease) Safety or Effectiveness, e.g.		-change in design, materials, chemical 	   	composition, energy source, or 		  	manufacturing process
- Guidance:  “Deciding When to Submit a 510(k) for Change to an Existing Device”

## Who Must Submit a 510(k)

- Manufacturers
- Specifications Developers
- Repackagers who change device or its labeling
- Relabelers who change the labeling, e.g., instructions for use
- Anyone who both manufactures and distributes

## Who is Not Required to Submit a 510(k)

- Private Label Distributor who _only_ adds company name and wording such as:
- “Distributed by ___________” or
- “Manufactured for _________”

## Not Required to Submit (cont.)

- Repackager who does not alter labeling
- Distributor or Importer who furthers marketing of the device and does not alter labeling or change device

## 510(k) Exempt Devices

- Preamendments Devices
- Unfinished Devices
- Devices Exempt by Statute or regulation from 510(k)
- 739 Class I (93%)
- 74 Class II (8%)
- Finished Devices not Sold in U.S.
- Devices Covered Under Another 510(k), e.g., Private Labeled Device
- Custom Devices
- General Purpose Articles
- Veterinary Devices

## 510(k) Content and Format

- 21 CFR 807.87 and 807.90
- Premarket Notification 510(k) Regulatory	Requirements for Medical Devices (FDA 95-4158, revised Aug. 1995)
- Device Specific Guidance
- 510(k) Refuse to Accept Checklist

## Information Requested in 510(k)(21 CFR 807.87)

- Submitter’s name, address, phone/fax #, contact person, rep./consultant name, establishment registration number
- Device Classification Name, CFR number, device class, procode
- Common/usual name and trade/proprietary name and model numbers

## Information Requested (cont.)(21 CFR 807.87)

- Identification of marketed device(s) to which equivalence is claimed
- Compliance with section 514 Special Controls
- Proposed labels, labeling, and advertising

## Information Requested (cont.)(21 CFR 807.87)

- Photographs, engineering drawings
- Substantially equivalent statement and comparison with predicate
- Statement of similarities and/or differences with predicate device
- Data for changes for modified devices

## Information Requested (cont.)(21 CFR 807.87)

-              510(k) MUST include either:
-   _**510(k) Statement**__**	**__**      510(k) Summary**_
-    Submitter gives		FDA provides 510(k) info to 		or     the summary to requesters			requesters via
-    within 30 days			FOI process &						Internet
- *Content and Format (21 CFR 807.92 & 807.93)

## Information Requested (cont.)(21 CFR 807.87)

- Class III 510(k) must include:
- 		Certification and literature search has 		been conducted, and
- 		Summary of adverse S&E data with 		citation to the literature
- *Content and Format (21 CFR 807.94)

## Information Requested (cont.)(21 CFR 807.87)

- Indications for Use Statement
- Truthful and Accurate Statement
- Proposed labeling
- Adherence to voluntary standard
- Financial Certification or Disclosure Statement or both

## Information Requested (cont.)(21 CFR 807.87)

- Performance Data (bench, animal, clinical)
- Sterilization, Software and Hardware Information, if any
- Address information requested in specific guidance documents

## Clinical Data in 510(k)

- 10-15% of all 510(k)s
- Important difference with the predicate device
- Must be collected under IDE
- 	(21 CFR Part 812)

## FDA Requests Additional Information for:

- Incomplete submissions (Refuse to Accept)
- When testing data is required to demonstrate equivalence

## Additional Information (cont.)

- Reviewer request by telephone, email or letter
- Clock stops by letter only
- Forward to Document Mail Center
- 30 days to submit
- May request extension of time  (180 day maximum from the date of the additional information request)
- Guidance for Industry and FDA Staff - FDA and Industry Actions on Premarket Notification (510(k)) Submissions: Effect on FDA Review Clock and Performance Assessment www.fda.gov/cdrh/mdufma/guidance/1219.html

## FDA Review Procedure

- Application Log-in
- Division Acceptance
- Assignment to Reviewer/Review Group
- ODE Review
- FDA Issues Decision letter
- SE Decision Made Public Within 30 days

## Confidentiality of Information

- 21 CFR 807.95

## Misbranding by Reference to 510(k)

- 21 CFR 807.97

##  Class I Exemptions (Section 510(l) of FD&C Act)

- All Class I Devices are Exempt* Except:
- Those Intended for a Use Which is of 		Substantial Importance in Preventing		Impairment of Human Health, or
- Those that Present a Potential Unreasonable      	Risk of Illness of Injury
- * Subject to the Limitations on Exemptions

## Class II Exemptions(Section 510(m) of the FD&C Act) 

- Class II devices that do not require 510(k)s to provide reasonable assurance of safety and effectiveness
- 75 device classifications exempt*
- Final Rule November 3, 1998
- * Subject to the Limitations on Exemptions
- (www.fda.gov/cdrh/modact/frclass2.html)

## Limitations of Exemption from 510(k) - Class I and II 

- Found in “.9” of Classification Chapters
-  Four Limitations:
- 	1) If the device has an intended use that is different from the intended use of a legally marketed device in that generic type

## Limitations of Exemptions from 510(k) Class I and II (cont.)

**2) **Operates using a different fundamental               scientific technology than that used by a legally marketed device in that generic type
- 3) Specific limitations for in vitro diagnostic devices
- 4) Device specific limitations as specified in a classification regulation

## Class II Exemption Petition Process

- Beginning 1 day after Class II exemption FR notice of Jan. 20, 1998
- Exemption of Class II devices:
- on our own initiative, or
- by an interested person
- Criteria for exemption
- 510(k) not necessary to assure the safety and effectiveness
- use exemption criteria above

## Class II Exemption Petition Process (cont.)

- Guidance	(www.fda.gov/cdrh/modact/exemii.html)
- Public notice, comment period and response
- “The Hammer” 180 days with no response

## Important 510(k) Content Points to Consider 

- Include a clearly worded Cover Sheet.
- Your 510(k) will first be seen by the Document Mail Center who open hundreds of pieces of mail a day.
- Clearly state each parties role and function e.g., consultant or expert.
- Clearly state who is the 510(k) holder (e.g., the manufacturer is not necessarily the 510(k) holder).
- The Cover Sheet or Cover Letter should be signed by the 510(k) holder.
- Note:  If at anytime during the 510(k) review this information changes, you must notify the Document Mail Center in writing.

## Can You Buy a 510(k)?

- Can you buy a 510(k)?:  YES
- What do you buy?						-Legal right to commercially distribute 	 a device with the specifications in the 	 	application on file with FDA			-In some cases, the modified 			 specifications
- Can you sell it and keep it?:  NO

## Can You Share a 510(k)?

- Can you share a 510(k)?: Sort of? How?:
- Under 21 CFR 807.85(b) as a private label distributor or re-packager of a legally marketed device
- Cannot **both** manufacture and distribute without your own 510(k)
- Labeling requirements  (see 801.1(a),(c), and (e))

## Can You Share a 510(k)? (cont.)

- How?:
- Combined devices, e.g., bed frame and cooling/heating blanket
- Labeling to file/ownership of specifications
- How?:
- Kits (Kit assembler is responsible)

## Use of Standards in Substantial Equivalence Determinations 	

**Guidance Document**
- Issued March 12, 2000
*http://www.fda.gov/cdrh/ode/guidance/1131.pdf*
- Purpose:  To clarify how standards may be used in demonstrating equivalence
- “Level 2” guidance

## Use of Standards:  3 Alternatives

- FDA-recognized standard, with a declaration
- FDA-recognized standard, without a declaration
- Non-recognized standard

## Modifications to Devices Requiring 510(k)

- When is the device new?
- When is the device modified?
- Is the proposed modification “significant?”
- “Could” it significantly affect safety or effectiveness?
- When does FDA say no 510(k) is required?

## Deciding When to Submit a 510(k) for a Change to an Existing Device

- (http://www.fda.gov/cdrh/ode/510kmod.html)
- Blue Book Memorandum #K97-1

## Hints for Using the Guidance

- Guidance Does Not Establish Regulatory Requirements, i.e., Does Not Bind FDA or Industry
- For Modification Resulting From Recalls, Refer to 510(k) Requirements for Firm-Initiated Recalls” (http://www.fda.gov/cdrh/ode/k951.html)
- Understand Roles							- Industry - Decision-maker				- FDA - Arbiter

## Hints (cont.)

- Document Does Not Supplant Device/Situation Specific Guidance
- Read the Narrative; Do Not Go Directly to the Flowcharts
- Understand the Definitions; Do Not Make Assumptions
- In Using the Guidance, Comparison Should be to Your Own “Unmodified Device, Whereas 510(k) Submission May Compare to Any Legally Marketed Device

## Hints (cont.)

- Assess Individual Changes; Consider all Reasonably Foreseeable Effects of Each Change
- Do Not Overlook the Cumulative Effect(s) of a Series of Incremental Changes
- Go All the Way Through the Flowcharts, i.e., Don’t Stop at the First Decision Point
- Establish a process for evaluation of modifications
- Document Decision-making

## What is an “Add-to-File?”

- Not required by 510(k) regulation
- What does FDA do with “it?”
- Written response to:
- send new 510(k) or
- note addition to file,
- 		based on information stated

## What is a 513(g)?

- Section 513(g) of F,D, & C Act
- Request for classification information
- Provide device description w/intended use
- Draft labeling
- Submit to Document Mail Center

## What Should You Do in the Gray Zone?

- Submit a 510(k)?
- Submit an Add-to-File?
- Submit a 513(g)?
- Document Your Files?
- Submit a Special?
- Telephone CDRH?
- Email CDRH?

## Appeal Options

-  21 CFR 10.30
- 21 CFR 10.75, includes Dispute Resolution

## 21 CFR 10.75

- For any decision
- hold letter
- not equivalent, not approvable
- policy matter
- May request a meeting
- Will receive written response
- Not on public display (other than dispute resolution process)

## What To Do When You Disagree with CDRH?

- Define the problem, what you’re willing to do, and what you want CDRH to do.
- Try to reach agreement at the lowest level possible
- Document your concerns
- Appeal through the supervisory chain before invoking a more formal process.
- Consider all the options before choosing.

## Appeals Have Their Uses

- Appeals *aren’t* a waste of time.
- Supervisors *want* feedback when you believe we’ve made an incorrect decision.
- Appeals are *routine*.  You won’t be “marked for life” if you appeal a decision.
- CDRH *does not* tolerate retribution.
- Our starting point:  *Any* dispute can be resolved when both sides keep an open mind.

## Third Party 510(k) ReviewKey Documentshttp://www.fda.gov/cdrh/thirdparty

- Procedural guidance
- List of eligible devices
- List of Accredited Persons

## MDUFMA (Medical Device User Fee and Modernization Act of 2002)

- 510(k) Performance Goals
- First action letters will issue within 75 days
- Subsequent action letters will issue within 60 days
- The above apply to:
- 70% received in FY ’05
- 80% received in FY ’06
- 90% received in FY ‘07

## MDUFMA 510(k) Performance Goals (cont.)

- 75% of 510(k)s received in fiscal years 2005 and 2006 will have an FDA decision in 90 cumulative FDA days
- 80% of 510(k)s received in fiscal year 2007 will have an FDA decision in 90 cumulative FDA days

## 510(k) MDUFMA Goals

- FY 2007 FDA Decision goal (80% within 90 days) may be re-evaluated in consultation with industry to determine whether it is appropriate for FY2007.

**Notes:**
FY 2007 FDA Decision goal (80% within 90 days) may be re-evaluated in consultation 
With industry to determine whether it is appropriate for FY2007.

## Meeting the MDUFMA goals: Review Process for Traditional 510ks

- Meeting the MDUFMA goals: Review Process for Traditional 510ks

**Preliminary determination that ****no**** additional info needed**

**FDA Initial Review**

**Interactive Review**

***Final Decision ******(***_***<***_***90 total days)***

***Scenario #1***

## Meeting the MDUFMA goals: Review Process for Traditional 510ks

**FDA Initial Review**

**Interactive Review **

**Determination that  additional info needed**

***Hold ***

***Final Decision ******(***_***<***_***90 total days)***

***Scenario #2***

**Preliminary determination that ****no**** additional info needed**

## Meeting the MDUFMA goals: Review Process for Traditional 510ks

**FDA Initial Review**

** ****Review **

**Determination that  additional info needed**

***Hold***

***Final Decision ******(***_***<***_***90 total days)***

***Scenario #3***

***Hold***

** ****Review **

**Determination that  additional info needed**

## New 510(k) Guidance

- FDA and Industry Actions on Premarket Notification (510(k)) Submissions:  Effect on FDA Review Clock and Performance Assessment
- 	**www.fda.gov/cdrh/mdufma/guidance/1219.html**
- User Fees and Refunds for Premarket Notification Submissions (510(k))
- 	**www.fda.gov/cdrh/mdufma/guidance/1511.html**

## A Strategy For Preparing Successful 510(k) Submissions

- Present information in an organized manner
- Include a table of contents
- Paginate properly
- Employ tables and graphs where appropriate
- Use visual aids whenever possible
- Highlight basic 510(k) content requirements, e.g.,  510(k) summaries

## A Strategy For Preparing Successful 510(k) Submissions (cont.)

- Understand and follow the 510(k) decision-making process
- Employ our 510(k) decision-making chart
- Use and include our “Refuse to Accept” Checklist
- Complete our documentation forms
- Follow applicable guidance documents and device specific checklist

## A Strategy For Preparing Successful 510(k) Submissions (cont.)

- Provide complete information
- Prominently display relevant data and information
- Do not confuse volume with quality when referencing          information include appropriate authorizations and reference with specificity
- Check for contradictions and inconsistencies within the document, e.g., between the indication statements in the 510(k) and the labeling/promotional materials
- Learn from your experiences and the experiences of your competitors

## Recommendations for Greater Success

- Stay abreast of regulatory changes
- 		-Preamendments strategy
- 		-Exemptions from premarket notification		-510(k) modifications document
- 		-Various proposed/final regulations

## Recommendations for Greater Success (cont.)

- Submit Quality Applications
- Understand all applicable regulations
- Become familiar with policies, precedence
-    and procedures related  to subject device
- Rely on valid scientific evidence  (21 CFR 860.7)
- Avoid premature submissions

## Recommendations for Greater Success (cont.)

- Take Advantage of Current Information
- Advisory panel meetings
- FDA sponsored workshops
- CDRH teleconferences
- Division of Small Manufacturers, International and Consumer Assistance
- Freedom of Information
- CDRH Websites
- Guidance Documents

## Average FDA Review Times for 510(k)s(Fiscal Year 2004)

- Average FDA Review Times for 510(k)s(Fiscal Year 2004)

## 510(k) StatisticsFY’s 02, 03 and O4 

**510(k)s Received:**
- FY02  -  4,322
- FY03  -  4,227
- FY04  -  3,635
**510(k)s Logged Out:**
- FY02 -  4,373
- FY03  - 4,123
- FY04  - 3,917

## 510(k) StatisticsFY’s 02, 03 & 04

**Average Review Times**
- FY 02 - FDA Days 79   Total Days 100
- FY 03 - FDA Days 76	  Total Days 96
- FY 04 – FDA Days 74   Total Days 100
**Cycles**
- FY 02 - 1.40
- FY 03 - 1.39
- FY 04 – 1.55

## 510(k) StatisticsFY’s 02, 03 & 04 

**Class I**
- FY02 – 367		FY03 – 342        FY04 - 310
**Class II**
- FY02 – 2,998	FY03 – 2,903      FY04 – 2,996
**Class III**
- FY02 – 134		FY03 – 106		FY04 - 64

## 510(k) Guidance Documents

**Guidance on the CDRH Premarket Notification Review Program**
**	****	**_**[www.fda.gov/cdrh/k863.html](http://www.fda.gov/cdrh/k863.html)**_
**The New 510(k) Paradigm ****	****	****	**_**[www.fda.gov/cdrh/ode/parad510.html](http://www.fda.gov/cdrh/ode/parad510.html)**_

## 510(k) Guidance Documents

**Frequently Asked Questions and Answers on Paradigm****	****	****	****	**_**[www.fda.gov/cdrh/ode/92_a.html](http://www.fda.gov/cdrh/ode/92_a.html)**_
**Determination of Intended Use for 510(k) Devices****	****	****	****	****	****	**_**[www.fda.gov/cdrh/ode/guidance/857.html](http://www.fda.gov/cdrh/ode/guidance/857.html)**_

## 510(k) Guidance Documents

**Deciding when to Submit a 510(k) for a Change to an Existing Device****	****	****	**_**[www.fda.gov/cdrh/ode/510kmod.html](http://www.fda.gov/cdrh/ode/510kmod.html)**_
**Use of Standards in Substantial Equivalence Determinations** _[www.fda.gov/cdrh/ode/guidance/1131.html](http://www.fda.gov/cdrh/ode/guidance/1131.html)_

## 510(k) Guidance Documents

**Convenience Kit Interim Regulatory Guidance****	**_**[www.fda.gov/cdrh/ode/convkit.html](http://www.fda.gov/cdrh/ode/convkit.html)**_
**	**
**Evaluation of Automatic Class III Designation****	**_**[www.fda.gov/cdrh/modact/classiii.html](http://www.fda.gov/cdrh/modact/classiii.html)**_

## 510(k) Guidance Documents

**Expedited Review****	**
- 		_[www.fda.gov/cdrh/modact/expedite.html](http://www.fda.gov/cdrh/modact/expedite.html)_
**Procedures for Class II Device Exemptions from 510(k)****	****	****	****	****	**_**[www.fda.gov/cdrh/modact/exemii.html](http://www.fda.gov/cdrh/modact/exemii.html)**_

## 510(k) Guidance Documents

**Updated Sterility Review Guidance**
- 	_[www.fda.gov/cdrh/ode/guidance/361.html](http://www.fda.gov/cdrh/ode/guidance/361.html)_
**Resolving Scientific Disputes Concerning the Regulation of Medical Devices****	**
- 	_[www.fda.gov/cdrh/resolvingdisputes/1121.html](http://www.fda.gov/cdrh/resolvingdisputes/1121.html)_

## 510(k) Guidance Documents

**Medical Device Appeals and Complaints**
- 		_[www.fda.gov/cdrh/modact/dispresl.pdf](http://www.fda.gov/cdrh/modact/dispresl.pdf)_
**General/Specific Intended Use****	****	****	**_**[www.fda.gov/cdrh/modact/genspec.html](http://www.fda.gov/cdrh/modact/genspec.html)**_
**	**

## New 510(k) Guidance Documents

**FDA and Industry Actions on Premarket Notification (510(k)) Submissions:  Effect on FDA Review Clock and Performance Assessment**
- _[www.fda.gov/cdrh/mdufma/guidance/1219.html](http://www.fda.gov/cdrh/mdufma/guidance/1219.html)_
**User Fees and Refunds for Premarket Notification Submissions (510(k))**
**www.fda.gov/cdrh/mdufma/guidance/1511.html**

## Related Websites 

**Medical Device User Fee Modernization Act****	**_**[www.fda.gov/cdrh/mdufma/index.html](http://www.fda.gov/cdrh/mdufma/index.html)**_
**Combination Products**					_[www.fda.gov/oc/combination.htm](http://www.fda.gov/oc/combination.htm)_l
**Preamendment Status Determination**
- 	       _[www.fda.gov/cdrh/comp/preamend.html](http://www.fda.gov/cdrh/comp/preamend.html)_

## More Related Websites

**Office of In Vitro Diagnostic Devices**
**	****	**_**[http://www.fda.gov/cdrh/oivd](http://www.fda.gov/cdrh/oivd)**_
**CDRH Device Advice**					_[www.fda.gov/cdrh/devadvice](http://www.fda.gov/cdrh/devadvice)_
**CDRH Standards Program**
- 		_[www.fda.gov/cdrh/stdsprog.html](http://www.fda.gov/cdrh/stdsprog.html)_
**Good Guidance Practices****	**			_[www.fda.gov/cdrh/ggpmain.html](http://www.fda.gov/cdrh/ggpmain.html)_

## Additional Resources

- Facts-on-Demand:						1-800-899-0381 (Index is #919)			301-827-0111
- Division of Small Manufacturers, International and Consumer Assistance (DSMICA)
- 		1-800-638-2041 or 301-443-6597

## Additional Resources

**Blue Book Memo: Fax & E-mail Communication** _[http://www.fda.gov/cdrh/ode/a02-01.html](http://www.fda.gov/cdrh/ode/a02-01.html)_
**CDRH website**
- 	_[http://www.fda.gov/cdrh](http://www.fda.gov/cdrh)_

## Additional Resources

**You can subscribe to the CDRHNEW list by going to:**
- _[http://list.nih.gov/archives/cdrhnew.html](http://list.nih.gov/archives/cdrhnew.html)_

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