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Risk Management Requirements – 510k vs DHF

This article compares the risk management requirements for a 510k submission with the risk management requirements for your design history file (DHF).

Design Controls and Risk Management Risk Management Requirements   510k vs DHF

Risk Management Requirements and Design Control Requirements

Last week I presented a free webinar on how to combine risk management with design controls when planning to submit a 510k. Many questions were asking what the design control and risk management requirements are for a 510k.

What are the Design Control Requirements in a 510k?

There is no specific part of the regulations stating what the 510k design control requirements are. However, some aspects of the DHF are required as 510k design control documentation, but not necessarily in the exact form as maintained in the DHF. For example, Design Inputs and Design Outputs are presented as applicable recognized standards and design specifications, while others will remain precisely the same (i.e., verification and validation test reports).

What are the Risk Management Requirements in a 510k?

For 510k submissions, the only risk management requirements are the inclusion of risk documentation for devices containing software of at least moderate level risk. There are some exceptions to this as well, though, based on a few special control guidance documents—especially when the submission type is an abbreviated 510k. This is article identifies which of the DHF and RMF elements are 510k design control requirements and 510k risk management requirements.

510k Design Control Requirements

Design Controls are identified in 21 CFR 820.30. Every manufacturer of any class II or class III devices and certain Class I devices (class I devices with software, tracheobronchial suction catheters, surgeon gloves, protective restraints, radionuclide applicators, radionuclide teletherapy devices) need to control design per this regulation. The requirement for a Design History File is item j) and states:

“Each manufacturer shall establish and maintain a DHF for each type of device. The DHF shall contain or reference the records necessary to demonstrate that the design was developed following the approved design plan and the requirements of this part.”

The “requirements of this part” refer to the other bullets in 21 CFR 820.30 which can be summarized as:

a) Establish and maintain procedures to control the design of a device.

b) Design and Development Planning – Each manufacturer shall establish a plan that describes the design and development activities, and defines responsibilities for implementation.

c) Design Inputs – Manufacturers need to ensure design requirements relating to a device are appropriate and address the intended use of the device.

d) Design Outputs – Design outputs need to be documented in terms that allow an adequate evaluation of conformance to design input requirements. Design outputs that are essential for the proper functioning of the device should be identified.

e) Design Review – Formal documented reviews of design results should be planned and conducted at appropriate stages of device development.

f) Design Verification – Design verification confirms that the design output meets the design input requirements.

g) Design Validation – Design validation shall be performed under defined operating conditions on initial production units or their equivalents. It shall ensure that devices conform to defined user needs and meet the intended use of the device.

h) Design Transfer – Design transfer documentation shall ensure that the device design is correctly translated into production specifications.

i) Design Changes – changes should be identified, documented, validated/verified, reviewed, and approved before their implementation.

The Design History File is intended to be a repository of the records required to demonstrate compliance with your design plan and design control procedures. While companies are required to create and maintain this documentation according to the FDA regulation, not all of the documentation will be reviewed as part of the 510k. The following table compares the elements that comprise a DHF with the 510k design control requirements.

DHF Element 510k Design Control Requirements
Design Plan Not Required
User Needs Not Required
Design Inputs

Cover Sheet (Section 1) and

Declaration of Conformity (Section 9)

Some design inputs will appear in the form of standards in FDA Form 3514 (Cover Sheet) and the Declaration of Conformity FDA Form 3654 (Standards Data Report)

Design Outputs

Device Description (Section 11)

The Device Description lists the specifications of the device, and your Design Outputs document will help populate the Device Description. This can include drawings, pictures, or written specifications that describe your device.

Labeling

Proposed Labeling (Section 13)

The labeling is usually considered part of the Design Outputs within the DHF and is included specifically in the labeling section of the 510(k) submission. This includes both the Instructions for Use and any Package Labeling.

Verification and Validation Protocols

Not Required

You do not have to include the protocols, but the reviewer may ask to see them if they have any questions when reviewing the reports.

Verification and Validation Reports

Sterilization (Section 14)

Biocompatibility (Section 15)

Software (Section 16)

Electrical Safety and EMC (Section 17)

Bench Performance Testing (Section 18)

Animal Performance Testing (Section 19)

Clinical Performance Testing (Section 20)

Of course, not all of these sections will be applicable to every device. Still, you should include all relevant validation test reports within your submission in the appropriate part of the 510k. Typically, each of these sections will have a cover sheet that outlines the reports that are included within the section, and then you can just include the report from the DHF in its entirety behind the cover sheet in that section.

Process Validation Only required for sterilization validation typically, but there are exceptions for novel materials and coatings
Work Instructions Not Required for 510k
Design Review Meeting Minutes Not Required for 510k
Design Trace Matrix Only required for software
Risk Management File Sometimes – See Risk Management File Table Below
Post-Market Surveillance Plan Not Required, but a few exceptions for high-risk devices
Clinical Data Summary Required only if used to demonstrate safety and efficacy
Regulatory Approval It Will result from 510k Clearance, so nothing to be included in 510k submission.

510k Risk Management Requirements

Regarding the FDA regulations for risk management, there is a requirement under the Design Validation section of 21 CFR 820.30 that states:

“Design validation shall include software validation and risk analysis, where appropriate.”

For FDA compliance and CE Marking, both recognize ISO 14971 as the standard for risk management. FDA recognizes ISO 14971:2007 whereas EN ISO 14971:2012 is the European National version for CE Marking. Rob Packard wrote an article describing the contents of the risk management file as well as the specific differences in the requirements between the FDA and CE Marking with regard to ISO 14971.

For your 510k submission, the FDA only requires risk management documentation to be included if the product contains software, and the risk is at least a level of “moderate concern”. There are some other cases when risk management is required by special controls guidance documents, but even when it is required, you only have to submit your risk analysis. The table below describes the risk management requirements in greater detail.

RMF Element 510k Risk Management Requirement
Risk Management Plan Not Required
Hazard Identification

510ks with Software Only (Section 16)

Hazard Identification is only required for devices that have a software component. It is not required for most other devices.

Risk Assessment

510(k)s with Software (Section 16)

Certain Special Controls Guidance

The Risk Assessment is only required to be included in your device contains software, or if a special controls guidance document specifically requires a risk assessment. It is not required for other 510ks.

Risk Control Option Analysis Software and Certain Special Controls Guidance
Risk Control Verification and Validation

Sterilization (Section 14)

Biocompatibility (Section 15)

Software (Section 16)

Electrical Safety and EMC (Section 17)

Bench Performance Testing (Section 18)

Animal Performance Testing (Section 19)

Clinical Performance Testing (Section 20)

This will not be any additional or special documentation specific to Risk Management and was already included in the DHF breakdown above. Still, the verification and validation also relate to risk management in ensuring that the risks have been adequately mitigated.

Risk-Benefit Analysis

Not Required for 510(k)

Risk-Benefit analyses are only required for De Novo applications, Humanitarian Device Exemptions, and PMAs.

Informing Users and Patients of Risks

Labeling (Section 13)

Part of the risk management will appear in the Labeling section of the 510k as warnings, contraindications, and precautions within the Instructions for Use and Package Labeling.

Risk Management Report Not Required

Special Controls Guidance Documents with Risk Management Requirements

Your first step in preparing your 510k submission is to search the FDA Guidance Document Database to determine if there is an applicable guidance document for your device. You can read another blog we wrote to explain Special Controls Guidance documents, and how to determine if one applies to your device. The following list provides examples of Class II Special Controls Guidance documents that require risk analysis to be included within the 510k:

When there are 510k risk management requirements, the special controls guidance document will typically state, “We recommend that the summary report contain:

An identification of the Risk Analysis method(s) used to assess the risk profile in general as well as the specific device’s design and the results of this analysis. (Refer to Section 6 for the risks to health generally associated with the use of this device that FDA has identified.)

Discussion of the device characteristics that address the risks identified in this class II special controls guidance document, as well as any additional risks identified in your risk analysis.”

The special controls guidance will also identify risks to health that have been identified for products of that type, which you should be sure to include in your risk analysis as appropriate.

More Information on Design Control and Risk Management Requirements

Hopefully, you are now able to determine which elements of your DHF are 510k design control requirements and which elements of your RMF are 510k risk management requirements. If you would like more information about how to implement design controls and risk management within your product development process, please consider registering for one of our training webinars:

If you need any further information or specific assistance with your 510k submission, please feel free to send me an email at mary@fdaecopy.com or schedule a call with our principal consultant, Rob Packard. He can answer any of your medical device regulatory questions.


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Posted in: 510(k), Design Control, ISO 14971:2019 (Risk Management)

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Redacted 510k Database – Have you used the newest FDA tool?

This article describes the new database of redacted 510k submissions that was recently made available online for immediate download by the US FDA.

Number of Redacted 510k Available Since November 2000 Redacted 510k Database   Have you used the newest FDA tool?

Recently the FDA made redacted 510k submissions that were previously released through Freedom of Information Act (FOIA) requests available on-line for immediate download. There are 496 redacted 510k submissions available since November 2000–as indicated by the graph above. This is only a small fraction of the total number of 510k submissions, but the number that is available on-line will increase over time.

Types of redacted 510k Submissions

Of the 496 submissions, there is a mixture of submission types.

  • 382 are traditional 510k submissions
  • 97 are special 510k submissions
  • 17 are abbreviated 510k submissions
  • 14 were 3rd Party reviewed

What remains in a redacted 510k submission

The redacted versions do not include testing data, but you will find other goodies such as:

  • 3rd Party SE memorandums (where applicable)
  • Table of Contents
  • Pre-market Notification Cover Sheet (i.e., FDA Form 3514)
  • 510k Cover Letter
  • Indications for Use (i.e., FDA Form 3881)
  • 510(k) Summary
  • Truthful & Accuracy Statement
  • Device Description
  • Executive Summary
  • Substantial Equivalence Discussion (Partially Redacted)
  • Summary of Biocompatibility Testing (Partially Redacted)
  • Summary of Sterilization & Shelf-Life (Partially Redacted)
  • Proposed Labeling
  • Predicate Device Labeling
  • Declarations of Conformity (i.e., FDA Form 3654)
  • Deficiency Letter

This is valuable information that can be used to help select a potential predicate and to develop a verification and validation testing plan. If you are less experienced in the preparation of a 510k submission, it will help to see how other regulatory experts have organized their 510k submissions.

Learning more about redacted 510k submissions

To access this database, click on this link: Redacted FOIA 510k Database. To limit your search to only 510k submissions that are available as a redacted full 510k, just click on the box for “Redacted FOIA 510k.” If you are interested in learning more about how to make the most of this new resource, please sign up for my latest webinar on Monday, November 21 @ 9 am EST.

Posted in: 510(k)

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Abbreviated 510k or Traditional 510k?

The article briefly explains the three types of 510k submissions and identifies when you should be submitting an abbreviated 510k instead of a traditional 510k.

Abbreviated 510k Abbreviated 510k or Traditional 510k?Three types of 510k submissions

The FDA has three different target timelines for reviewing a 510k submission and issuing a decision regarding substantial equivalence (i.e., SE Letter):

  1. Special 510k
  2. Abbreviated 510k
  3. Traditional 510k

Special 510k submissions

The first type is a special 510k submission. The FDA target timeline for a special 510k is 30 days, but you can only submit a Special 510k for a modification of your device that already has a 510k issued. Also, a Special 510k is only possible if the device modification requires a single technical discipline to review the change. For example, changes to software and materials require a review of software validation and biocompatibility. Therefore, two reviewer specialists must coordinate their efforts, and the review cannot be completed in 30 days. In this case, an abbreviated or traditional 510k must be submitted instead.

Abbreviated 510k submissions

The second type of 510k submission is an abbreviated 510k. The FDA target timeline for review is 60 days. If there is a recognized standard specific to the type of device you are submitting, or the FDA has issued a guidance document addressing that device classification, then an abbreviated 510k submission is recommended. For example, a dental handpiece (i.e., product code is ) has a special controls guidance document that explicitly written for dental handpieces, and the guidance states that an abbreviated 510k submission is recommended. Besides, the FDA recognizes the latest standard for dental handpieces: ISO 14457:2012 (FDA Doc # 4-206).

Traditional 510k submissions

The third type of 510k submission is a traditional 510k submission. The FDA target timeline for review is 90 days. If you are submitting a 510k for a new device, or the device modifications require more than one functional area of expertise, then a special 510k is not an option. If there is no recognized standard for the device type and the FDA has not issued the guidance of a special control for your device classification, then an abbreviated submission is also not an option. A traditional 510k submission is your only option in this case.

How frequently is an abbreviated 510k submission type used?

In September 2016, there were 260 510k SE decisions issued by the FDA. Here’s the breakdown by type:

  • Special 510k – 47 submissions = 18%
  • Abbreviated 510k – 8 submissions = 3%
  • Traditional 510k – 205 submissions = 79%

In general, I think it requires a little more effort to write clear and concise summaries for the various sections of an abbreviated 510k than it does for a traditional 510k. But if you can get your product to market a month quicker then it’s worth it.

Posted in: 510(k)

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Product Launch Design Planning for a 510k Submission in 300 Days or Less

This article explains how to conduct design planning for a new medical device product launch that requires a 510k submission in 300 days or less.

Device Product Launch in 300 Days Product Launch Design Planning for a 510k Submission in 300 Days or Less

One of the most valuable pieces of information you can receive is a plan for your medical device product launch. Some companies contact me, asking for help in implementing their quality system. You should be implementing this step last if you are a start-up company. Some companies contact me asking for help preparing their 510k submission. But you need to seek help much earlier. The best time to contact an expert for help with your product launch is 300 days before you want to launch your product.

Three Major Milestones of a Product Launch

Three major milestones must be completed before a medical device product launch can proceed. First, you need to complete the design specifications for your device. Second, you need to complete the design verification and validation activities and summarize this testing in a 510k submission or another type of regulatory submission. Third, you need to implement a quality system that meets the requirements of 21 CFR 820 and/or ISO 13485:2016. Each of these three major tasks can be completed in less than six months, but with proper planning and motivation, all three can be completed sequentially in less than one year for many products. Completing all three milestones in 300 days is possible.

Break Your Product Launch into Phases

Whenever I plan a design project, I break the overall product development into chunks that are easily understood, with measurable milestones, and I establish a timeline that is aggressive but possible. The design process typically has six phases, but several of these phases are shorter than you want, and the overall process is too long for a single chunk. Therefore, I decided to break the six phases into three pieces: 1) product development, 2) verification and validation, and 3) regulatory clearance. The end of the first chunk is marked by a “design freeze” where your team will conduct a design review and approve the final design outputs before you begin verification and validation of your product design. The second chunk is marked by the submission of a 510k or some other regulatory submission. The third chunk is marked by the completion of your quality system and receipt of your 510k clearance letter from the FDA.

How Long Should Each Phase of the Product Launch Be?

In the past, I would choose a timeline of approximately 3-4 months for each major phase of product launch. However, I have been learning a lot about goal setting, and I now target 100 days for completion of most milestones. The reason is that 100 days is a time period over which most people can maintain their enthusiasm and motivation for completing a goal. If a goal takes longer than 100 days, then you should probably break down the goal into two or more smaller goals. If each of the three major phases of your product launch requires 100 days, then you can complete the overall product development and product launch within 300 days. One of the tools I recommend for planning and tracking your progress toward a 100-day goal is The Freedom Journal.

Product Launch Phase 1 – Your Design Plan

Your design plan should be the first thing you create. To create a design plan, you will need to identify the regulatory pathway–including all of the testing that is required for verification and validation of your new medical device. This design plan should identify all the design reviews, all the verification and validation testing that is required, and the regulatory approval process required before product launch.

Product Launch Phase 2 – Preparing Your 510k Submission

Once you have approved your design outputs during the “design freeze,” now you need to complete the verification and validation testing, during this phase you will need to make sure that you have identified all the testing, how many samples will be required for each test. You need to determine which steps of the testing process can be performed in parallel instead of performing tasks in series. For example, you will need to package and sterilize samples that are required for biocompatibility testing, but electrical safety testing samples can be non-sterile. Therefore, the packaging validation must be completed before biocompatibility testing, but the electrical safety and EMC testing can be performed in parallel with both activities. For most products, biocompatibility testing is one of the last tests that is typically completed, and the longest of these tests usually takes between 8-12 weeks. Therefore, 100 days is probably the fastest you can complete your verification and validation testing. During the entire verification and validation process, you should be preparing your 510k submission. This will ensure that the submission is ready when the last test report is received–instead of frantically rushing to complete the submission in just a few weeks at the end of the process.

Product Launch Phase 3 – Implementing Your Quality System

Many companies start their quality system at the beginning of the design process. However, you should only implement two procedures before completing your 510k submission: 1) design controls, and 2) risk management. These two procedures are needed to document your design history file (DHF) properly, and it is much harder to document your DHF after the design is completed. The balance of the procedures can be implemented in about 100 days, while your 510k submission should take between 90 and 180 days to receive clearance from the FDA. Therefore, you should be able to complete the quality system implementation before receipt of your 510k clearance letter.

“Rinse and Repeat” for Your Next Product Launch

Once you have completed your product launch, you should review the post-market surveillance from your customers during the first 90 days. I like to call this the 100-day review. One-hundred days after the first product launch is the perfect time to conduct your first management review meeting. You should have your first internal audit completed during the first 100 days, and you should have a lot of great feedback from customers during the first 90 days of product use. Therefore, top management can review the customer feedback, internal audit results, and progress toward other quality objectives to identify improvement action items needed. These improvements may be quality system improvements and/or product improvements. One of the outputs of your first management review meeting should also be an identification of your next product development.

Posted in: 510(k)

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eCopy Hidden System Files Created by Windows 10 Updates

This article explains how to debug problems created by Windows 10 updates, which automatically create eCopy hidden system files.

ecopy replacement for 510k submission 1024x422 eCopy Hidden System Files Created by Windows 10 Updates

If you are looking for a quick solution to remove a hidden system file from your eCopy flash drive, that you created using Windows 10, please follow the following steps:

  1. Enter the Command Prompt, a desktop app, by typing “CMD” into the Cortana search field.
  2. Then type the letter of the drive where your flash drive is located, followed by a colon (e.g., “D:”).
  3. Then type the following red text exactly (there is a single space before each forward slash): rmdir “system volume information”/s /q
  4. Then rerun the eCopy Validation Module to verify the system volume folder has been removed.
  5. Then eject the flash drive using the flash drive symbol in your taskbar to prevent any corruption of the flash drive.
  6. Now you can safely remove the flash drive and ship it to the FDA.
  7. Do NOT re-insert the flash drive into any computer before shipping–even at an office supply store.

We can also prepare your FDA eCopy for you and ship it to the FDA for a flat fee of $150. Details are found on our FDA eCopy webinar page.

The above picture is a USB flash drive with a replacement eCopy for a recent 510k submission I worked on. A couple of weeks ago, one of these little USB flash drives and the Microsoft Corporation conspired to create one of the most creative riddles I have ever solved in my entire life.

How do you delete a file you can see?

Not just any old hidden file, but a hidden system file called: “IndexerVolumeGuid.”

eCopy Hidden System Files

IndexerVolumeGuid is a special system file that was on my brand new USB flash drive in the System Volume Information Folder. This file keeps an index of the files in the System Volume Information Folder. Your computer can use that index to recover accidentally deleted information. Usually, this is a useful and desirable feature, but I purchased my brand new USB flash drive to send an eCopy 510k submission to the FDA Document Center. Unfortunately, the FDA Document Center cannot accept system files. The problem was that I couldn’t see the files, because they are hidden.

How can you delete a file you can’t see?

I had a software problem, and the process used to fix software problems is called debugging.

Debugging Windows Software Updates

There is a specific position that you should be in when you are trying to debug a software problem. First, you need to be sitting down and hunched over your computer. Second, you need to rest your forehead in your hand, sigh heavily and maybe even moan softly from time to time. I prefer to curse the genius programmers at Microsoft and repeat my mantra of “I can’t believe this. It’s ridiculous.” You know you are concentrating properly if the vein in your forehead is throbbing so much that other people can see it throbbing through your hand.

The most valuable tool for debugging software problems with Windows is Windows Help. It’s an online manual that has the answers to every conceivable question you can ask about Windows. The only time it’s failed to be helpful is when I’m trying to connect to the internet. The “online” nature of Windows Help limits its usefulness in solving problems with internet connections for some reason.

Finding eCopy Hidden System Files

I typed into Windows Help, “show hidden system files.” After 10 minutes of reading, I learned that the default setting for Windows Explorer is to hide system files, and bad things can happen if you unhide those files. I also learned that you could change the default setting by entering the Windows Control Panel, and then clicking on “Appearance and Personalization.” Finally, you click on “File Explorer Options,” click on “View” and then scroll through about 50 possible configuration options until you see the setting for “Hide Protected Operating System Files.” Then you deselect this option–despite the recommendation to keep these files hidden.

Finding the Control Panel

Next, I typed into Windows Help, “How to find Windows Control Panel.” Of course, there are about 20 different ways to reach the Windows Control Panel, but you only need one. Then I followed the instructions from Windows Help, and finally, I could see the hidden system folder, but I couldn’t delete it.

Next, I tried formatting the USB drive. That worked until I pulled the USB drive out and inserted it again. Windows has a cool new feature that automatically creates a hidden system folder on your USB drive–even if you don’t want one.

Disable Removable Drive Indexing

Windows Help again to the rescue. I learned that I needed to disable the removable drive indexing feature to do that I needed to use Group Policy Editor, which I didn’t have. Windows Help told me that I could use the Windows Registry Editor or “Regedit” program instead if I was unfortunate enough to be using something other than Windows XP. Next, Windows Help instructed me to open a folder called Windows Search. Windows Search was a folder found 7-levels deep in the registry of the computer, but it seemed to be missing from my computer. Again, Windows Help instructed me on how to create a Windows Search Folder and add a file called “DisableRemovableDriveIndexing.” Then I only needed to change the settings from a “0” to a “1” and reboot my computer.

Finally, 2 hours later, my USB drive no longer had eCopy hidden system files, and my computer would no longer create one automatically–until the next Windows update, which occurred a week later. Since I originally posted this article, there have been several Windows 10 updates, and each one has caused problems similar to the eCopy hidden system files. If you prepare your own FDA eCopy submission, please subscribe to my free FDA eCopy webinar updates to keep up with the latest Windows 10 “features” and how the changes will affect your eCopy preparations.

Other Resources

In August 2017, I recorded two relate webinars:

  1. 510k Lessons Learned
  2. FDA eCopy webinar

If you are interested in specific guidance related to eCopy hidden system files, or eCopy submission in general, you can also review the following FDA guidance documents:

  • eCopy Guidance – FDA Guidance document revised 12/3/2015; eCopy Program for Medical Device Submissions
  • eCopies Validation Module (a voluntary tool that verifies the format of an eCopy you have already developed on your local drive)

Posted in: 510(k)

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Special Controls Guidance Document – Content and Format

This article explains the content and format of a special controls guidance document issued for Class 2 medical devices regulated by the CDRH division of the US FDA.

Searching Guidance Documents Special Controls Guidance Document   Content and Format

There are many differences between Class 1 and Class 2 medical devices regulated by the FDA, but one of the primary differences is that many (not all) Class 2 medical devices have a special controls guidance document. Class 1 devices only have “general controls.” These “special” guidance documents can be found on the FDA website by searching the guidance document database. The title of each guidance document typically begins with “Class II Special Controls Guidance Document.” The middle of each title specifies the device type, and the end of the title states, “- Guidance for Industry and FDA Staff.” However, there are many exceptions.

Status of a Special Controls Guidance Document

A guidance document may be a final guidance or a draft guidance. Only the final guidance is considered official, however, draft guidance often indicate what the FDAs current thinking is on a topic. Draft guidance documents sometimes take years before they are approved as a final guidance. Sometimes the draft is so controversial that it will even be withdrawn. The FDA also publishes a list each year of planned guidance documents for the next fiscal year. Some of the final versions of special controls guidance documents were written in the 1990’s, but these documents remain the current final guidance until a new final guidance is approved. Often there is no urgent need to update a guidance document, because there are one or more active ISO Standards specific to the product classification and the standard(s) is recognized by the FDA.

Outline of a Recent Special Controls Guidance Document

Here is the general outline that is currently being used by the FDA for a special control guidance document for Class 2 devices:

  1. Introduction
  2. Topic – Background
  3. Pre-Market Notification – Background
  4. Scope
  5. Risks to Health
  6. Specific Device Description Requirements
  7. Performance Studies
  8. Device Specific Labeling
  9. References

Each product classification has the potential for slightly different requirements due to the differences in types of devices. For example, in vitro diagnostic products do not have animal studies and typically have human clinical study requirements for the performance section of the guidance document. However, an implant is more likely to have details about the materials of construction, biocompatibility and sterilization.

Searching the Guidance Database

There are 8 fields that are searchable for the guidance database.

  1. Product
  2. Date Issued
  3. FDA Organization
  4. Document Type
  5. Subject
  6. Draft or Final
  7. Open for Comment
  8. Comment Closing Date on Draft

For a De Novo application, I sometimes need to create a proposed draft special controls guidance. For this activity, I prefer to find a representative template. In order to do this, I will typically use four of these search fields. First, I narrow the product field to “medical devices” and the FDA organization to “CDRH.” Second, I select “guidance documents” for the document type. Finally, I select “premarket” for the subject and “final.” This narrows the list to 374 documents. Not all of the 374 documents are specific to a product classification, because some of these documents cover more general premarket issues such as risks of wireless telemetry.

You can further narrow your search by adding a word or words to the keyword search field. Therefore, if you are looking for a specific guidance you can find it very quickly.

Format of Special Controls Guidance Documents

If you submit a proposed draft guidance to the FDA (anyone can do this), there is no specific required format. However, I recommend copying the most recent format used by the FDA in order to minimize the amount of work required by the FDA for modifying the guidance prior to publishing your guidance as a draft. You also do not need to include all the sections of a guidance. Some of the guidance documents only update certain sections where technological characteristics have recently changed significantly. Most importantly, if you have a strong reason for deviating from what the FDA has always done–do it. The format of guidance documents has changed since the 90’s and will continue to do so.

Additional Resources

If you are preparing a premarket notification (i.e., 510k submission), you might have more questions than just guidance document availability. You might be interested in purchasing “How to Prepare Your 510k in 100 Days” or the on-line 510k Course or one of our Live 510k Workshops.

Posted in: 510(k)

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De Novo Application: The beginning of a new device product class

This article explains the FDA’s De Novo application process for regulatory clearance of medical devices that do not meet the requirements of a 510k submission.

De Novo Pathway 300x169 De Novo Application: The beginning of a new device product class

De Novo Application:
The beginning of a new device product class

The best regulatory experts plan regulatory submissions months before the performance testing is completed, and often the strategic regulatory pathway is determined before the design of the device even begins. If your design team is developing an innovative technology, you may have difficulty finding a predicate device that is substantially equivalent to your device. If you have not completed a De Novo application before, where do you start?

History of the De Novo Application

Historically, a De Novo application required that your device be submitted through the 510k process first. If the FDA determined that your device was not substantially equivalent to the predicate you chose, then you received a “Not Substantially Equivalent” (NSE) letter from the FDA. Once you receive an NSE letter, you have three options: 1) select a different predicate and re-submit, 2) re-submit the device through the Pre-Market Approval (PMA) process, or 3) submit the device through the De Novo application process. You were not allowed to submit a De Novo application until you received an NSE letter.

The De Novo application process was revised on July 9, 2012 to allow manufacturers to submit a De Novo application without a preceding 510k submission. This was done because there are many products that are technologically equivalent to a predicate device, but the indications for use are quite different. For example, many in vitro diagnostic (IVD) products are indicated for diagnosis of new viruses, but the device uses technology equivalent to another IVD product the manufacturer already makes. For this reason, most of the first 100+ De Novo application approvals were for IVD products.

De Novo Application Draft Guidance Document

The De Novo application process still (updated September 6, 2017) does not have an approved final guidance document. For now, there is only a draft guidance document. However, with the new fees being charged for De Novo applications as part of MDUFA IV for FY 2018 FDA user fees, you can expect that a final guidance document with an application checklist will be expedited.

Pre-Sub Meetings Prior to a De Novo Application

Pre-sub meetings are generally recommended by the FDA for manufacturers that intend to submit a De Novo application without a prior 510k submission and subsequent NSE letter. If the device is a Class II, a  pre-sub meeting allows the manufacturer to request input from the FDA,  regarding performance testing and special controls. The draft De Novo guidance document specifically recommends following the existing content guidelines for a pre-sub meeting request, but the guidance also recommends including the following elements in the pre-sub meeting request:

  1. Proposed product classification (i.e., Class I, Class II exempt, or Class II)
  2. Details of efforts previously taken in order to identify a predicate
  3. Risks and Risk/Benefit Analysis
  4. Proposed Performance Testing and/or Special Controls

Before you submit a pre-submission request for a potential De Novo application, you should consider the following questions. First, is your device suitable for a De Novo application (see point #2 above)? Second, when is the ideal time for you to submit your application? At least 90 days before your design freeze is needed if the meeting request is going to have any impact on the performance testing plans. Third, what questions do you want the FDA to answer regarding data requirements. Sometimes providing some preliminary data can help you persuade the FDA to accept less total data for approval of the final application. Finally, you may want to consider preparing a draft Special Controls Guidance for the FDA to review as a supplement to your pre-submission meeting. 

De Novo Applications for Class I and Class II Exempt Devices

Most manufacturers mistakenly assume that De Novo applications are only for devices that are Class II and will require a 510k submission for future product submissions in the same classification. However, the regulations require that the application cover letter include both a “Classification Summary” and a “Classification Recommendation.” The recommendation for a classification may be for Class I, Class II exempt or Class II non-exempt. If you recommend that the FDA classify the device as Class II exempt, then the recommendation must include a justification for why premarket notification is not required.

Regardless of which classification is recommended, the justification for classification needs to be based upon a risk/benefit analysis. Class I and Class II exempt classifications are likely to be recommended more in the future for many of the standalone software products that are being developed by manufacturers, because those software devices generally have a low risk. Existing product classifications may be used, but if the indications for use are not substantially equivalent to a predicate the manufacturers will submit a 510k and receive NSE letters. For the companies that are claiming substantial equivalence to products that already have a product classification that is exempt from premarket notification, manufacturers will continue to register and list products under existing classification codes until the FDA intervenes–even if the indications for use are not equivalent.

How to Modify Your 510k Templates

Twenty sections comprise a 510k submission, but regulatory experts typically use templates for each section in order to streamline the process of preparing a new device submission. For a De Novo application, a large percentage of the sections required for a 510k submission are the same. The draft guidance identifies one unique section to a De Novo application: the cover letter (i.e., Attachment II in the De Novo guidance). However, there are three sections of a 510k submission that also need to be eliminated for a De Novo application:

  1. Section 1: User Fee Cover Sheet, because De Novo applications do not require a user fee
  2. Section 5: 510k Summary or 510k Statement is not required, because this is not a 510k submission
  3. Section 12: Substantial Equivalence Comparison, because De Novo applications do not claim equivalence to a predicate

New De Novo Application Webinar

Companies developing devices with truly innovative technologies frequently have difficulty identifying suitable predicate devices. The best regulatory experts plan in advance for these regulatory submissions by honing their knowledge of the De Novo application process. On Thursday, January 28th we recorded a webinar sharing our tips and templates for De Novo applications. Click here to learn more about the webinar.

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Three (3) important technical file and 510k submission differences

This article summarizes the three (3) crucial technical files and 510k submission differences: 1) the risk management file, 2) the clinical evaluation report, and 3) the post-market clinical follow-up report.

3 different apples Three (3) important technical file and 510k submission differences

Three important technical file and 510k submission differences

ISO 14971 requires a risk management file, whether you are selling a medical device in the EU or the USA, but the US FDA doesn’t require that you submit a risk management file as part of the 510k submission. If you design and develop a medical device with software, you must submit a risk analysis if the software has a moderate level of concern or higher. However, risk analysis is only a small portion of a risk management file.

Only 10-15% of 510k submissions require clinical studies, but 100% of medical devices with CE Marking require a clinical evaluation report (CER) as an essential requirement in the technical file. The clinical evaluation report (CER) is an essential requirement (ER) 6a in Annex I of the Medical Device Directive (MDD). Even class 1 devices that are non-sterile and have no measuring function require a clinical evaluation report (CER). Yes, even adhesive tape with a CE Mark requires a clinical evaluation report in the technical file.

Annex X, 1.1c of the Medical Device Directive (MDD), requires that medical device manufacturers perform a post-market clinical follow-up (PMCF) study or provide a justification for not conducting a post-market clinical follow-up (PMCF) study. In the past, companies attempted to claim that their device is equivalent to other medical devices, and therefore a post-market clinical follow-up (PMCF) study is not required. However, in January 2012, a guidance document (MEDDEV 2.12/2) was published to provide guidance regarding when a PMCF study needs to be conducted. This guidance makes it clear that PMCF studies are required for many devices–regardless of equivalence to other devices already on the market.

Risk management file for technical file and 510k submission

The FDA only requires documentation of risk management in a 510k submission if the product contains software, and the risk is at least a “moderate concern.” Even though you are required to perform a risk analysis, a knee implant would not require submission of the risk analysis with the 510k. If a product is already 510k cleared, you may be surprised to receive audit nonconformities related to your risk management documentation for CE Marking. The most common deficiencies with a risk management file are:

  1. compliant with ISO 14971:2007 instead of EN ISO 14971:2012
  2. reduction of risks as low as reasonably practicable (ALARP) instead of reducing risks as far as possible (AFAP)
  3. reducing risks by notifying users and patients of residual risks in the IFU
  4. only addressing unacceptable risks with risk controls instead of all risks–including negligible risks

If you are looking for a risk management procedure, please click here. You might also be interested in my previous blog about preparing a risk management file.

Clinical evaluation report (CER) for technical file and 510k submission

The FDA does not require a clinical evaluation report (CER), and up until 2010, only some CE Marked products were required to provide a clinical evaluation report (CER). In 2010 the Medical Device Directive (MDD) was revised, and now a clinical evaluation report (CER) is a general requirement for all medical devices (i.e., Essential Requirement 6a). This requirement can be met by performing a clinical study or by performing a literature review. Since 510k devices only require a clinical study 10-15% of the time, it is unusual for European Class 1, Class IIa and Class IIb devices to have clinical studies. This also means that very few clinical studies are identified in literature reviews of these low and medium risk devices.

The most common problem with the clinical evaluation reports (CERs) is that the manufacturer did not use a pre-approved protocol for the literature search. Other common issues include an absence of documented qualifications for the person performing the clinical evaluation and failure to include a copy of the articles reviewed in the clinical evaluation report (CER). These requirements are outlined in MEDDEV 2.7/1, but the amount of work required to perform a clinical evaluation that meets these requirements can take 80 hours to complete.

If you are looking for a procedure and literature search protocol for preparing a clinical evaluation report (CER), please click here. You might also be interested in my previous blog about preparing a clinical evaluation report (CER).

Post-Market Surveillance (PMS) & Post-Market Clinical Follow-up (PMCF) Studies for technical file and 510k submission

Post-market clinical follow-up (PMCF) is only required for the highest risk devices by the FDA. For CE Marking, however, all product families are required to have evidence of post-market clinical follow-up (PMCF) studies or a justification for why post-market clinical follow-up (PMCF) is not required. The biggest mistake I see is that manufacturers refer to their post-market surveillance (PMS) procedure as the post-market surveillance (PMS) plan for their product family, and they say that they do not need to perform post-market clinical follow-up (PMCF) study because the device is substantially equivalent to several other devices on the market.

Manufacturers need to have post-market surveillance (PMS) plan that is specific to a product or family of products. The post-market surveillance (PMS) procedure needs to be updated to identify the frequency and product-specific nature of post-market surveillance (PMS) for each product family or a separate document that needs to be created for each product family. For devices that are high-risk, implantable, or devices that have innovative characteristics, the manufacturer will need to perform some post-market clinical follow-up (PMCF) studies. Even products with clinical studies might require post-market clinical follow-up (PMCF) because the clinical studies may not cover changes to the device, accessories, and range of sizes. MEDDEV 2.12/2 provides guidance on the requirements for post-market clinical follow-up (PMCF) studies. Still, most companies manufacturing moderate-risk devices do not have experience obtaining patient consent to access medical records to collect post-market clinical follow-up (PMCF) data–such as postoperative imaging.

Procedures & Webinars

If you are looking for a procedure for post-market surveillance (PMS), please click here. If you are interested in learning more about post-market surveillance and post-market clinical follow-up (PMCF) studies, we also have a webinar on this topic.

Posted in: 510(k), CE Marking

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How to create a template for 510k submission device description

This article explains how to create a template for a 510k submission device description (i.e., Section 11). The template addresses each of the requirements of a device description in the FDA refusal to accept (RTA) guidance document. The template also serves as a summary technical document (STED) for submission to a Notified Body for CE Marking.

Screenshot 2015 11 04 at 8.41.36 AM How to create a template for 510k submission device description

You would think that it’s tough to screw up the device description, but the FDA screening reviewer is completing a new refusal to accept (RTA) checklist (effective October 1, 2015). That checklist has specific requirements for a device description. If you copy the device description from your draft IFU, then you will probably receive an RTA letter on Day 15 of the RTA screening process. The review “clock” is reset to zero, and you have to revise your device description and re-submit.

There are four specific requirements (questions 9-12) in section “B” of the RTA checklist, which is titled “Device Description.” In addition to this, there are similar requirements for inclusion in a device description for technical file and design dossier submissions to Notified Bodies. Rather than creating two different device description documents, I prefer to create a template that addresses each of the regulatory requirements in a single controlled document. Therefore, I created a template for the 510k submission device description with the following headings for Section 11 of the 510k submission:

  1. Product or trade name
  2. General description—including the intended purpose. The general description must be consistent with the device description in the labeling, and this section of the document is intended to address section 10 of the refusal to accept (RTA) checklist.
  3. A list and description of each device for which a 510(k) clearance is requested in the submission. The list may refer to models, part numbers, various sizes, etc. This section of the document is intended to address section 11c of the refusal to accept (RTA) checklist. It may be helpful to combine this section with section 3 of the template, providing a table with a UDI device identifier for each product listed.
  4. UDI device identifier(s)—if available.
  5. Intended patient population, medical condition to be diagnosed and/or treated, and other considerations such as patient selection criteria.
  6. Principles of operation of the device. This section of the document is intended to address section 11a of the refusal to accept (RTA) checklist.
  7. A description of proposed conditions of use, such as a surgical technique for implants, anatomical location of use, user interface, how the device interacts with other devices, and/or how the device interacts with the patient. This section of the document is intended to address section 11b of the refusal to accept (RTA) checklist.
  8. Risk class and applicable classification rule, according to Annex VII (proposed EU regulations) or Annex IX (MDD). For this section, I will cross-reference to a controlled document that includes the complete classification rationale, while this section only includes the classification and the applicable rule(s).
  9. Explanation of novel features (be careful, this is a regulatory document and not a marketing document).
  10. Description of components, accessories, other medical devices, and other products that are not medical devices, which are intended to be used in combination with the device. The 510k number should identify each component/accessory that was part of a previous submission. Any component(s)/accessory(s) that have not received prior clearance should also be identified. Sometimes a side-by-side table for USA and EU markets is needed for accessories where different accessories are used in different markets. This section of the document is intended to address section 12a, b, and c of the refusal to accept (RTA) checklist.
  11. Description or a complete list of the various configurations/variants of the device that will be available
  12. General description of the key functional elements, formulation, composition, and functionality—including labeled pictorial representations (e.g., diagrams, photographs, and drawings)
  13. Raw materials incorporated into key functional elements and those making direct contact with the human body or indirect contact with the body
  14. Technical Specifications of the device and any variants and accessories that would typically appear in the product specification made available to the user, e.g., in brochures, catalogues and the like.
  15. Representative engineering drawing(s), schematics, illustrations, photos, and/or figures of the device. This section of the document is intended to address section 11d of the refusal to accept (RTA) checklist.
  16. Reference to similar and previous generations of the device. It is important to make sure these devices are included in the clinical evaluation report. If you are submitting a 510k submission, you want to make sure that any devices are registered and listed with the US FDA in the same product category. For a device with multiple predicates, it may be necessary to create a table that organizes the “similar” devices by intended use and technological characteristics.
  17. Requirements specific to the special controls guidance document. This section of the template is intended to address section 9 of the refusal to accept (RTA) checklist.

The last section of the device description STED is for any unique requirements specific to the special controls guidance document for the product classification I am working on. However, most of the requirements for a device description are met by the previous items in my outline. Therefore, I create a table that outlines each of the requirements of the special controls guidance document, and I provide a cross-reference to the section of the outline that includes this requirement. If there are requirements not covered elsewhere in the document, I address the requirement in the table itself. If there is no special controls guidance document, then I state that no special controls guidance document exists for the product.

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Biocompatibility for 510k Submissions vs CE Marking

asr 1 Biocompatibility for 510k Submissions vs CE Marking

Titanium is not biocompatible?!

This article compares the different documentation requirements of biocompatibility for 510k submissions with a technical file submission for CE Marking.

A couple of my clients recently received requests for additional information as part of their technical file submission for CE Marking. Both clients had titanium implants, and they submitted the same justification of biocompatibility for 510k submissions as they were now submitting for their technical file. They were providing a one-paragraph description of materials used and referencing the ASTM specification for implant-grade titanium. Both clients already had CE Marking for similar devices, and the wording of the justification for not conducting biocompatibility testing on the full device was identical to the previous submissions.

“Justifications are no longer permitted”

One of my clients questioned whether there was a new EN standard for implant-grade titanium that they might need to comply with. Their auditor told the other client that the Notified Body would no longer accept justifications for not conducting biocompatibility testing.

On behalf of my clients, I scheduled a meeting with their Notified Body to obtain clarification and to make sure that the policies for documentation of biocompatibility had not changed. The Notified Body had three important points to make:

  1. Justifications are PERMITTED as it states in EN ISO 10993-1:2009
  2. Competent Authorities noticed that some of the justifications accepted in the past were not sufficient
  3. What the FDA accepts for biocompatibility for 510k submissions is not sufficient for a technical file

FDA requirements of biocompatibility for 510k submissions

In 1995, the FDA published a biocompatibility guidance document. That guidance document includes a decision tree that asks a series of questions related to biocompatibility for 510k submissions that is intended to help manufacturers determine which biocompatiblity testing may be required for 510k submission of their new or modified device. The following questions are the critical items covered in that decision tree: 

  • Is the material the same as a marketed device?
  • Same manufacturing process?
  • Same chemical composition?
  • Same body contact?
  • Same sterilization method?
  • Is the material metal, metal alloy, or ceramic?
  • Does it contain any toxic substances (e.g., Pb, Ni, Cd, Zr)?
  • Does the master file have acceptable toxicology data?

In the past, I recommended that clients with titanium implants prepare section 15 of their 510k submissions by answering each of the questions above. 99% of the time, the predicate device is substantially equivalent to the 510k submission device with regard to the first five questions. Except in the case of coated implants, there was seldom a Device Master File to reference, and the metal was compliant with the ASTM standard for titanium implants–including the concentrations of heavy metals.

For other medical devices that were not made of just titanium or some other implant-grade metal, the manufacturer was forced into conducting biocompatiblity testing. In these cases, I directed the clients to follow the biocompatibility testing matrix published by the FDA.

New Draft Biocompatibility Guidance from the FDA

In 2013, the FDA published an FDA 2013 draft guidance document for biocompatibility with additional requirements for biocompatibility documentation and testing. The newer draft guidance appears to be the current expectation of the agency for 510k submissions, but the draft guidance has not been finalized yet.

The new 2013 draft guidance document from the FDA indicates that biocompatiblity testing reports must be provided with 510k submissions instead of merely summarizing the testing performed. The FDA clarifies in the draft that materials will not be evaluated alone, and the full device must be evaluated for biocompatibility instead. The FDA also specifies that the device evaluation must be for a sterilized device if the device is intended to be delivered in a sterile state to users/patients. This draft incorporates new ideas regarding toxic chemicals, such as colorants. The FDA also suggests that manufacturers discuss their testing plans with the FDA before starting the biocompatibility testing.

Despite the changes proposed in the 2013 draft guidance, there are no changes to the requirements of biocompatibility for 510k submissions if the device is a metallic implant that is substantially equivalent to a predicate device.

Technical File Differences for Biocompatibility

In theory, there should be very few differences between biocompatibility for 510k submissions and technical file requirements for CE Marking, because the FDA recognizes ISO 10993-1:2009, and the content of the standard is nearly identical to the European national version of the standard. For European CE Marking, the expectation is for the technical file to include documentation of conformity with the current state of the art for biocompatibility (i.e., EN ISO 10993-1:2009). Summary Technical Documentation (STED) is preferred by Notified Bodies to reduce the time and costs associated with the review of the technical documentation.

A STED that explains how your biocompatibility evaluation conforms to a harmonized European Standard is quite different from a justification based upon substantial equivalence. Notified Bodies expect you to review each of the elements of the harmonized standard and explain how you address it in the STED. In Clause 7 of EN ISO 10993-1:2009, there are seven elements recommended for a biological safety assessment:

  1. the strategy and program content for the biological evaluation of the medical device;
  2. the criteria for determining the acceptability of the material for the intended purpose, in line with the risk management plan;
  3. the adequacy of the material characterization;
  4. the rationale for selection and/or waiving of tests;
  5. the interpretation of existing data and results of testing;
  6. the need for any additional data to complete the biological evaluation; and
  7. overall biological safety conclusions for the medical device.

The fourth element of the biological safety assessment will undoubtedly include a reference to the implant-grade titanium that you are using. However, you also must address additional questions that are posed in Figure 1 of the standard. Issues that should be addressed in your biological safety assessment include:

  1. Are there any additives, contaminants, and residues remaining on the device?
  2. Are there any substances leachable from the device? 
  3. Are there any degradation components of the device?
  4. Are there other components, and how might they interact with the final product?
  5. What are the properties and characteristics of the final product?

 If you conducted a cleaning validation, you need to reference that process validation report. If you did the testing of EO residuals, you need to reference the ISO 10993-7 test report.

The message the Notified Bodies are sending you is that they agree that implant-grade titanium is biocompatible. Still, you need to systematically write a justification for not conducting the testing in accordance with the EN standard, and you have to cross-reference to your objective evidence throughout the STED. 

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