how to prepare a 510(k) submission for the fda june 4, · pdf filehow to prepare a 510(k)...

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Rob Packard, President

www.MedicalDeviceAcademy.com

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How to prepare a 510(k) Submission for the FDA

June 4, 2015

http://www.medicaldeviceacademy.com/

mailto:[email protected]

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Agenda

• Introduction

• Step-by-Step Predicate Selection

• Strategic Considerations

• When You Can’t Identify a Predicate Device

• Substantial Equivalence & New Flow Chart

• 510(k) Project Management

• Q&A



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510(k) Target Timeline



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RTA Checklist

4

http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm315014.pdf






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Acceptance Review & RTA Common Issues

• Results in 1 of 3 paths w/in 15 days of receipt:

– 510(k) is accepted for substantive review or

– 510(k) isn’t accepted for review = RTA or

– 510(k) is under substantive review FDA didn’t complete acceptance review w/in 15 days (Does not happen often, if at all)

• Rate of submissions not accepted (based on RTA)

– FY 2013 – 58%; FY 2014 – 56%

5

Top 15 Criteria most frequently missed by industry

Shelf life (purple) and biocompatibility (peach) are problematic sections

Outcome: increase training to industry to address all criteria, even if not applicable Checklist: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM315014.pdf

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Criteria # Rate

28 – shelf life 54%

9 – prior submissions 47%

36 – performance data 33%

4a – 510(k) summary 32%

17a - labeling 32%

26 – expiration date 32%

30 - biocompatibility 30%

16–comparison to predicate 29%

29 - biocompatibility 29%

8 – Form 3654 28%

18 – prescription use 22%

12- engineering drawings 21%

31- biocompatibility 21%

13c- components/accessory 20%

15a - comparison to

predicate 20%

Results Top 15 Mistakes



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Product Classification

1. Identify a device similar to yours

2. Use the registration and listing database http://bit.ly/CDRH-Registration-Listing-Database

3. Identify the 3-letter product code

4. Click on the code to go to the product

classification page

5. Click on the TPLC link http://bit.ly/FDATPLC

http://medicaldeviceacademy.com/fda-device-classification/



http://bit.ly/CDRH-Registration-Listing-Database









http://bit.ly/FDATPLC

http://bit.ly/FDATPLC







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Find Classification Other Ways http://bit.ly/ProductClassification



http://bit.ly/ProductClassification

http://bit.ly/ProductClassification

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Case Study Example #1

• Topical skin adhesive

• Special controls guidance

• Multiple predicates to choose within the MPN product code

http://medicaldeviceacademy.com/510k-submission-fda-case-study/













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Case Study Example #2

• Pedicle Screw Spinal System, Adolescent Idiopathic Scoliosis

• Specific Labeling Requirements

• 90 predicates to choose within the OSH product code, but most people only find 3

http://medicaldeviceacademy.com/indications-for-use-case-study/













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Strategic Considerations

• Is It Legally Marketed

• History of Adverse Events

• Intended Use Breadth

• Technological Characteristics & Associated Risks

• Version 1.0, 2.0, 3.0…



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Version 1.0, 2.0, 3.0…

• Establish History of Company with FDA

• Many Small Leaps of Logic vs. One Big Leap

• Clinical Studies in Parallel with 1st Submission

• Earlier Cash Flow



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When You Can’t Identify a Predicate

1. Clinical Study & PMA

2. De Novo Submission

3. 510(k) Submission

4. Pre-Sub Meeting

5. 513(g) Submission



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Most Critical Sections

• 4 – Indications for Use (1st)

• 5 - 510(k) Summary (4th)

• 10 – Executive Summary (my last)

• 11 - Device Description (2nd)

• 12 – Substantial Equivalence (3rd)

• RTA Checklist is a great quality



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How FDA Evaluates SE? http://bit.ly/Substantial-Equiv-Guidance



http://bit.ly/Substantial-Equiv-Guidance






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Predicate Selection

1. Is the predicate device legally marketed?

2. Do the devices have the same intended use?

3. Do the devices have the same technological

characteristics?

4. Do the different technological characteristics raise

different questions of safety and effectiveness?

5. Are the methods of evaluating new/different

characteristics acceptable?

6. Does the data demonstrate substantial

equivalence?



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Legally Marketed?

Registration and listing database


A 510(k) is not enough!










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Technological Characteristics?

• Materials

• Design

• Energy Source

• Other Features

• Same ≠ Equivalent

– Does not raise DIFFERENT issues of safety or effectiveness

– Must be as safe and effective as predicate



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Split Predicates

• 1st Predicate has same intended use

• 2nd Predicate has same technological characteristics

This is not allowed.



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Multiple Predicates Allowed…

• Option 1:

– Two predicates with different technological characteristics, but the same intended use

• Option 2:

– A device with more than one intended use

• Options 3:

– More than one indication under the same intended use



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Examples

• Example 1 – Hemodialysis catheter – Predicate A has same extension design

– Predicate B has same tip design

– Both A & B predicates have the same intended use

• Example 2 – Fracture fixation plate – Predicate A is indicated for middle bone fractures

– Predicate B is indicated for bone tip fractures

– Both A & B predicates are intended for long bone fractures

– New performance testing may be required



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Examples (continued)

• Example 3 – Laser hand piece – Predicate A Er:YAG laser hand piece

– Predicate B Q-Switch Nd:YAG laser hand piece

– Both A & B predicates have the same general intended use of lasers: “incision, excision, ablation, vaporization of soft tissue.”


– A single predicate could have been used, but the inclusion of a second predicate is helpful in establishing substantial equivalence with regard to specific indications and technological characteristics.



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• Example 4 – Multi-parameter monitor

– New monitor includes different technologies

– Predicate for each parameter

– Monitoring of each parameter cannot interfere with the others




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• Example 5 – Temperature measuring urinary catheter

– Urinary catheter is primary predicate

– Thermometer is secondary predicate added as a convenience

– Two predicates fall under different classifications

– The additional feature cannot alter the risk profile of the urinary catheter



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Equivalence Data

• Intended Use

• Technological Characteristics – Materials, Design, Energy Source, Other Features

• Performance Data – Biocompatibility

– Electrical Safety & Electromagnetic compatibility (EMC)

– Software verification and validation

– Mechanical and acoustic testing

– Animal Study

– Clinical Study



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Section 2 - Table of Contents

• 20 Sections

• Create a Template (http://bit.ly/510k-ToC)

• eCopy Guidance (http://bit.ly/FDA-eCopy)

• RTA Checklist (http://bit.ly/Acceptance-Checklist)

http://bit.ly/510k-Format



http://bit.ly/510k-ToC




http://bit.ly/FDA-eCopy





http://bit.ly/Acceptance-Checklist









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Use ToC as Planning Tool

• red = the information does not appear to be available

• yellow = document requires revision and/or reformatting of content

• blue = ready for the client’s review and approval

• green = ready for submission

• Add a column to assign team responsibilities

• Prioritize task completion



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Example of ToC Tool

Section # Description of 510(k) Section Comments Assigned To Target Completion Date

1 Medical Device User Fee Cover Sheet (Form FDA 3601) Missing Client

2 Table of Contents Missing Rob Packard

3

510(k) Cover Letter & CDRH Premarket Review

Submission Cover Sheet

May want to add a confidentiality statement and

need to include coverletter Client

4 Indications for Use Statement

Does not match the predicate - is this more

narrow or just different Rob Packard

5 510(k) Summary or 510(k) Statement

You have both and only need one; there is a new

guidance for 510k summary Client

6 Truthful and Accuracy Statement ok - must be signed Client

7 Class III Summary and Certification need to explain why it's not applicable Rob Packard

8 Financial Certification or Disclosure Statement need to explain why it's not applicable Rob Packard

9 Declarations of Conformity and Summary Reports

Need all the form 3654s completed for each

applicable standard and a summary document--

ideally in tabular format Rob Packard

10 Executive Summary Need to review in detail, but looks good Client

11 Device Description

You might want these to be documents

referenced rather than embedded figures TBD

12 Substantial Equivalence Discussion

Needs lots of work to comply with current

guidance - July 24, 2014 Rob Packard

13 Proposed Labeling

Needs to include PDF of labels and IFU; IFU

needs to include indications for use and it must

match Section 4 exactly Client

14 Sterilization and Shelf Life Missing TBD

15 Biocompatibility Missing TBD

16 Software need to explain why it's not applicable Rob Packard

17 Electromagnetic Compatibility and Electrical Safety need to explain why it's not applicable Rob Packard

18 Performance Testing – Bench

Missing - should include simulated use--maybe

with an anotomical "dummy" TBD

19 Performance Testing – Animal need to explain why it's not applicable Rob Packard

20 Performance Testing – Clinical need to explain why it's not applicable Rob Packard

21 Other N/A N/A














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Team Member Selection

• Boilerplate – 1, 3, 6 & non-applicable

• 9 - Declarations of Conformity (FDA Form 3654)

• Biocompatibility & Sterility – 14 & 15

• Software & EMC – 16 & 17

• Labeling - 13

• Performance Testing

– Bench Testing - 18

– Animal Testing - 19

– Clinical Studies – 20 + Sections 7 & 8



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Planning Performance Testing

• Look for a special controls guidance document 1st.

• Look for any device-specific standards (e.g., ASTM F483)

• Review each of the possible 510(k) Summaries carefully

• Order 510(k) submissions through FOI



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Bench Testing

• ASTM testing methods

• Simulated use experiments

• Validation tools (known input data for software/hardware devices)

• Finite Element Analysis (FEA)

• Cadaveric studies



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Animal Studies

• The agency allows rationales for reduction of sample number in order to spare the lives of animals.

• Try to find another submission or 510(k) summary that specifies the number of animals

• Test more than once per animal or your device and the predicate in each animal (i.e., animal is it’s own control)

• Small animal vs. large animal and duration…



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Human Studies • 10-15% of 510(k) submissions require clinical study

data • Steps:

– Study Synopsis – Investigator Package – Protocol Approval – Conduct Study – Summary Report

• Non-significant risk studies do not require IDE • IRB approval is always required • Paper data collection vs. electronic data collection



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FDA Pre-Sub Meetings

• Guidance released February 18, 2014

• Consultants and RA Experts have used these for years, but weren’t called “pre-sub” meetings

• Do your homework 1st

• In-person vs. Tcon

• Timing = Prior to Performance Testing

• Identify Proposed Predicate Device(s)

http://bit.ly/FDA-Pre-Sub









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Additional Resources • 17 Blogs about 510(k) Submissions

– http://medicaldeviceacademy.com/category/510k/

• 5 On-Demand Webinars – http://medicaldeviceacademy.com/510k-submission-

predicate-device/ – http://medicaldeviceacademy.com/live-webinar-on-510k-

submissions-fda-pre-sub-meetings/ – http://medicaldeviceacademy.com/live-webinar-on-510k-

submissions-substantial-equivalence/ – http://medicaldeviceacademy.com/510k-submission-section-

4-indications-for-use-webinar/ – http://medicaldeviceacademy.com/510k-project-

management-webinar/



http://medicaldeviceacademy.com/category/510k/

http://medicaldeviceacademy.com/category/510k/

http://medicaldeviceacademy.com/510k-submission-predicate-device/








http://medicaldeviceacademy.com/live-webinar-on-510k-submissions-substantial-equivalence/

































http://medicaldeviceacademy.com/510k-submission-section-4-indications-for-use-webinar/

















http://medicaldeviceacademy.com/510k-project-management-webinar/









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Q&A

Rob Packard

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+1.802.281.4381

rob13485

