fda 510(k) submission tips & best practices

FDA 510(k) SubmissionInsider Tips, Tricks & Timelines

Allison C. Komiyama, PhD, [email protected]

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Today’s goalsu FDA’s authority & device classification

u Preparing a 510(k)u What is a 510(k)?

u Where do I start? Who do I call?

u When should I submit?

u How does FDA decide?

u How do I format a 510(k)?

u Understanding the 510(k) review cycle

u Unpacking the FDA hold letter

u Additional tips & useful FDA databases

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FDA: “What We do”FDA is responsible for protecting the public health by assuring the safety, efficacy and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation.

FDA is also responsible for advancing the public health by helping to speed innovations that make medicines more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medicines and foods to maintain and improve their health.

http://www.fda.gov/AboutFDA/WhatWeDo/

What is a Medical Device?A device is:

u "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:

u recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,

u intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or

u intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes."

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/ucm051512.htm

What is FDA’s Authority?

Federal Food Drug and Cosmetic Act (FD&C Act)

uMedical Device AmendmentsuMay 28, 1976

uRegulations implementing the FD&C ActuTitle 21 Code of Federal Regulations (21 CFR)

Parts 800-1299

http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/

FDA Classification – Risk Based CategoriesClassification Risk Level Description Device Examples

I Low

~45% of devices

Not life supporting or sustaining

Many are 510(k) exempt

Tongue depressors, stethoscopes,

dental floss, elastic bandages, examination gloves, nonprescription

sunglasses

II Medium

~50% of devices

Generally require a 510(k)

Some are 510(k) exempt and some require PMA

Electrocardiographs, dental cement, gas analyzers, x-ray systems, powered

wheel chairs, fetal cardiac monitors

III High

Technologically innovative

Life-supporting or life-sustaining

Require a PMA

Implantable pacemakers, replacement heart valves,

automated external defibrillators, heart pumps










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Preparing a 510(k): What is a 510(k)?21 U.S.C. United States Code, 2010 EditionTitle 21 - FOOD AND DRUGSCHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACTSUBCHAPTER V - DRUGS AND DEVICESPart A - Drugs and DevicesSec. 510 - §360 Registration of producers of drugs or devices

(k) Report preceding introduction of devices into interstate commerceEach 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 360m(a) of this title (in such form and manner as the Secretary shall by regulation prescribe)…

“We will notify you when the processing of your 510(k) has been completed or if any additional information is required. YOU MAY NOT PLACE THIS DEVICE INTO COMMERCIAL DISTRIBUTION UNTIL YOU RECEIVE A LETTER FROM FDA ALLOWING YOU TO DO SO.”

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/default.htm

Preparing a 510(k): Where do I start?

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ContactUs--DivisionofIndustryandConsumerEducation/ucm20041265.htm

Preparing a 510(k): Who can I call?

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080235.htm

Preparing a 510(k): When should I submit?

http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm284443.pdf

Preparing a 510(k): How does FDA decide?

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm084365.htm

Preparing a 510(k): How do I format a 510(k)?

Preparing a 510(k): How do I format a 510(k)?u 1. Medical Device User Fee Cover Sheet

u 2. CDRH Premarket Review Submission Cover Sheet

u 3. 510(k) Cover Letter

u 4. Indications for Use Statement

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

u 6. Truthful and Accuracy Statement

u 7. Class III Summary and Certification

u 8. Financial Certification or Disclosure Statement

u 9. Declarations of Conformity and Summary Reports

u 10. Executive Summary

u 11. Device Description

u 12. Substantial Equivalence Discussion

u 13. Proposed Labeling

u 14. Sterilization and Shelf Life

u 15. Biocompatibility

u 16. Software

u 17. Electromagnetic Compatibility and Electrical Safety

u 18. Performance Testing – Bench

u 19. Performance Testing – Animal

u 20. Performance Testing – Clinical

u 21. Other










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Submit 510(k)

FDA Receipt of 510(k)

510(k) Accepted

Interactive Review

SE /Clearance

510(k)Refused

Hold /AI Letter

NSE

DAY 1

DAY 15DAY 60

DAY 90

New Device

510(k) Review Process

Submit your New Device to FDA

u Review FDA guidance documents

u Format for traditional and abbreviated 510(k)s; Aug 12, 2005

u The 510(k) program: Evaluating substantial equivalence in premarket notifications; Jul 28, 2014

u Refuse to accept policy for 510(k)s; Aug 4, 2015

u Pay User Fee (FY 16)

u Standard: $5,288

u Small business fee: $2,614

FDA Receives Your 510(k)

u Document Control Center receives your submission

u Review eCopy

u Review user fee

u Send receipt to sponsor with unique K#

u 510(k) electronically goes “upstairs” and is assigned to a lead reviewer

Acceptance Review

u Does your 510(k) fulfill the Refuse to Accept checklist?u Preliminary questions

u Organizational Elements

u Elements of a Complete Submission

u Lead reviewer will send email stating the outcome of the checklistu You will learn who your reviewer is

u You have 180 days to respond

u Reviewer might ask for pre-submission

u By Day 15L Refuse to AcceptJ Accepted

Acceptance Checklist

Substantive Review

u Lead reviewer sends out consults

u Medical/Clinical = Medical Doctor

u Bench Testing/ER Comp. = Biomedical/Mechanical Engineer

u Biocompatibility/Wear = Biologist, Toxicologist

u Sterilization/Shelf Life = Biologist

u Statistical Analyses = Biostatistician

u Animal Studies = Veterinarian

u Reviewer will send email including deficiency list once it is compiled

Substantive Review –Communication with Reviewer

u By day 60 you can expect a “Substantive interaction”L Request for Additional Information /

Telephone Hold u ONLY ONE HOLD (180 days) ALLOWEDu Reviewer might ask for Q-‐subu If necessary, communicate with reviewer

before starting or submitting responseu FDA clock resumes when response is

receivedJ Interactive review

u FDA clock still runningu Allowed even if deficiencies are more

significant than “minor,” if they can be addressed in a timely manner

510(k) Decision

u Response to deficiencies is reviewed

u Additional information may be requested (interactively)

u FDA targets for average TOTAL time to decision:

u 2013 = 135 days

u 2017 = 124 days

510(k) Decision–Communication with Reviewer

u By day 90 you can expect a decisionL Not substantially equivalent

u You cannot market your deviceu Typically due to lack of predicate, not adequate information to demonstrate equivalence, issues with safety/efficacy

J Substantially equivalentu You can now market your device! (Don’t forget general controls!)

How long will this take?u FDA clears >3,000 510(k) submissions/year

u In 2013, average time to clearance was ~123 days (depends on reviewing branch)

u 3/4 are Traditional 510(k)s

u 1/4 are Special or Abbreviated 510(k)s

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105 110 110 11299

110 112

133 138

160170 164 160

123

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Average Calendar Days for Traditional 510(k) to Clear

Pre-‐MDUFA MDUFA I MDUFA II MDUFA III

Change to an Existing Device

u Some changes to existing devices do not require a new 510(k)

u Review FDA guidance document:Deciding when to submit a 510(k) for a change to an existing device; Jan 10, 1997

u Labeling change?

u Technology or performance change?

u Materials change?










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FDA hold Letter

K###### is on Hold Pending Your Response

u “We have reviewed your submission K###### and have determined that additional information is required. Your file is being placed on hold pending a complete response to the attached deficiencies.

u Your response is due within 180 days from the date of this request, which is [Month DD, 20##]. If a complete response is not received in CDRH's Document Control Center within 180 days, we will consider this submission to be withdrawn, and we will delete it from our review system.”

Four-Part Harmony

u “[Reviewers] are trained to write deficiencies in “four part harmony,” which includes a statement of what was provided, why the information provided is not sufficient, what additional information is needed, and why the requested additional information is needed to answer a regulatory or scientific question.”

u “In such cases where the sponsor does not understand the basis for the request, FDA suggested that they contact the reviewer or branch chief to discuss it.”

-MDUFA III Reauthorization Minutes

Deficiency Example

u FDA Deficiency

In Section [#] of your original submission you indicated [Material A] is commonly used in medical devices; however you have not identified a predicate that uses the identical material. Therefore, the information provided is insufficient to determine substantial equivalence. In order to demonstrate adequate biocompatibility of the instruments manufactured from [Material A], please identify a predicate (with corresponding 510(k) number) that is manufactured from the identical material and has a similar contact profile (i.e. limited duration contact with a breached or compromised surface). Alternatively, please provide data from biocompatibility evaluation tests, per ISO 10993-1 for the [Material A] material. Testing should be completed on final, production quality devices, or an adequate rationale for why test samples are appropriate should be provided.

Deficiency Example

u FDA Deficiency

In Section [#] of your original submission you indicated [Material A] is commonly used in medical devices; however you have not identified a predicate that uses the identical material. Therefore, the information provided is insufficient to determine substantial equivalence. In order to demonstrate biocompatibility of the instruments manufactured from [Material A], please identify a predicate (with corresponding 510(k) number) that is manufactured from the identical material and has a similar contact profile (i.e. limited duration contact with a breached or compromised surface). Alternatively, please provide data from biocompatibility evaluation tests, per ISO 10993-1 for the [Material A] material. Testing should be completed on final, production quality devices, or an adequate rationale for why test samples are appropriate should be provided.










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510(k) Tipsé Do the right testing (do you need to submit a pre-‐submission?)

u Performance, biocompatibility, animal studies, sterilization validation, cleaning validation, etc.

é Request the reviewer you want (doesn’t always work)

é Bookmark the PDF version of the submissioné Write a clear device description

u Use pictures (also useful in test reports)

u Explain rationale behind design features

é Make sure the IFU statement matches throughout the document

é Fill out/include the appropriate forms:u e.g. FDA 3601, 3514, 3654, 3674

é Pay the User Fee ahead of timeé Choose your predicates wisely

é Be nice to the reviewersu If possible, send device to the reviewer after it is accepted (can be a tested device that has been returned)

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FDA Guidance Documents

http://www.fda.gov/RegulatoryInformation/Guidances/default.htm

FDA Forms

http://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/MedicalDeviceForms/default.htm

FDA Databases

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm

Questions?

Allison C. Komiyama, PhD, [email protected]

AcKnowledge-RS.com

fda 510(k) submission tips & best practices

Health & Medicine