FDA 510(k) Submission Tips & Best Practices
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This document provides an overview of the FDA 510(k) submission process for medical devices. It begins with background on FDA authority over medical devices and device classification. It then covers key aspects of preparing a 510(k) submission, including what a 510(k) is, where and when to start the process, how FDA reviews submissions, and tips for formatting a 510(k). The document reviews the typical 510(k) review cycle and outcomes, including potential requests for additional information and decisions of substantial equivalence or non-equivalence. It aims to help medical device companies navigate the 510(k) process and timelines.
![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to be withdrawn, and we will delete it from our review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.”](https://image.slidesharecdn.com/fda-510k-submission-process-webinar-160823192418/85/FDA-510-k-Submission-Tips-Best-Practices-33-320.jpg)
![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](https://image.slidesharecdn.com/fda-510k-submission-process-webinar-160823192418/85/FDA-510-k-Submission-Tips-Best-Practices-34-320.jpg)
![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.](https://image.slidesharecdn.com/fda-510k-submission-process-webinar-160823192418/85/FDA-510-k-Submission-Tips-Best-Practices-35-320.jpg)
![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.](https://image.slidesharecdn.com/fda-510k-submission-process-webinar-160823192418/85/FDA-510-k-Submission-Tips-Best-Practices-36-320.jpg)
FDA 510(k) Submission Tips & Best Practices
- 1. FDA 510(k) Submission Insider Tips, Tricks & Timelines Allison C. Komiyama, PhD, RAC akomiyama@acknowledge-rs.com AcKnowledge-RS.com
- 2. u Quality Management Software Exclusively for Medical Device Companies u Single Source of Truth u Manage design controls, risk and quality in a single, easy to use solution u Customers & Partners All Over the Globe u www.greenlight.guru Sara Naab, Co-founder & Quality Director “The proof is in the pudding. We passed our audit with flying colors. She was in and out in 2 hours and sent us our certificate in the mail, no questions asked.”
- 4. Today’s goals u 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 4
- 5. Today’s goals u 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 5
- 6. 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/
- 7. 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
- 8. What is FDA’s Authority? Federal Food Drug and Cosmetic Act (FD&C Act) u Medical Device Amendments u May 28, 1976 u Regulations implementing the FD&C Act u Title 21 Code of Federal Regulations (21 CFR) Parts 800-1299 http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/
- 9. FDA Classification – Risk Based Categories Classification 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
- 10. Today’s goals u 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 10
- 11. Preparing a 510(k): What is a 510(k)? 21 U.S.C. United States Code, 2010 Edition Title 21 - FOOD AND DRUGS CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT SUBCHAPTER V - DRUGS AND DEVICES Part A - Drugs and Devices Sec. 510 - §360 Registrationof producers of drugs or devices (k) Report preceding introductionof devices into interstate commerce Each person who is required to register under this sectionand who proposes to begin the introductionor delivery for introduction into interstatecommerce for commercial distributionof a device intended for human useshall, at least ninety days before making such introduction or delivery, report to the Secretary or personwho is accreditedunder section 360m(a)of this title (in such form and manner as the Secretaryshall 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.”
- 12. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/default.htm Preparing a 510(k): Where do I start?
- 13. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ContactUs--DivisionofIndustryandConsumerEducation/ucm20041265.htm Preparing a 510(k): Who can I call?
- 14. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080235.htm Preparing a 510(k): When should I submit?
- 16. http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm284443.pdf Preparing a 510(k): How does FDA decide?
- 18. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm084365.htm Preparing a 510(k): How do I format a 510(k)?
- 19. 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
- 20. Today’s goals u 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 20
- 21. 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
- 22. 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
- 23. 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
- 24. 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 checklist u You will learn who your reviewer is u You have 180 days to respond u Reviewer might ask for pre-submission u By Day 15 L Refuse to Accept J Accepted
- 26. 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
- 27. 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) ALLOWED u Reviewer might ask for Q-‐sub u If necessary, communicate with reviewer before starting or submitting response u FDA clock resumes when response is received J Interactive review u FDA clock still running u Allowed even if deficiencies are more significant than “minor,” if they can be addressed in a timely manner
- 28. 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
- 29. 510(k) Decision– Communication with Reviewer u By day 90 you can expect a decision L Not substantially equivalent u You cannot market your device u Typically due to lack of predicate, not adequate information to demonstrate equivalence, issues with safety/efficacy J Substantially equivalent u You can now market your device! (Don’t forget general controls!)
- 30. 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 30 105 110 110 112 99 110 112 133 138 160 170 164 160 123 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
- 31. 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?
- 32. Today’s goals u 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 32
- 33. 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.”
- 34. 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
- 35. 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.
- 36. 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.
- 37. Today’s goals u 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 37
- 38. 510(k) Tips é 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 submission é 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 time é Choose your predicates wisely é Be nice to the reviewers u If possible, send device to the reviewer after it is accepted (can be a tested device that has been returned) 38
- 41. FDA Databases http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm
- 42. Questions? Allison C. Komiyama, PhD, RAC akomiyama@acknowledge-rs.com AcKnowledge-RS.com