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Third party review of 510(k) submissions – When it makes sense and which third party to choose?

third party review Third party review of 510(k) submissions – When it makes sense and which third party to choose?

What is a Third Party Review?

A third party review is the review of a 510(k) that has been submitted directly to a third party rather than the FDA themselves. Back in 1997 as part of the FDA Modernization Act  or FDAMA the ‘Accredited Persons Program’ was created. This allowed the FDA to accredit persons, or ‘third parties’ to conduct the primary review of certain 510(k) submissions. One of the goals of this program was to be able to make the submission and review process faster and more efficient.

The third party review is not a full alternative to submitting a 510(k) to the FDA. Third parties are authorized by the FDA to conduct the primary review of specific types of devices only. Only certain devices are eligible for third party review. The FDA keeps a database of those devices here in one of their medical devices databases (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfThirdParty/current.cfm).

The use of a third party review also does not bypass the FDA. The third party is only conducting the primary review of the 510(k) and then forwarding the submission, the review of the submission and the post review recomendation to the FDA. The FDA then has a 30 day timeline to issue a final determination of the submission.

How many 510(k) submissions use a third party review?

In 2016, I did an analysis of 510(k) submissions reviewed by the general and plastic surgery panel. I reviewed submissions that received clearance between January 1, 2015 and August 10, 2016. Of the 690 510(k) clearances that were issued by the panel, only nine (9) were submitted for third party review. Although third party reviewers were responsible for only 1.3% of the submissions I reviewed, there are other device classifications with higher percentages of reviews being conducted by third party reviewers. In fact, there were a total of 114 submissions that were issued 510(k) clearance through a third party review process during that period.

For this article, I reviewed the 3,023 510(k) clearances that were issued in the past 12 months (i.e., May 23, 2016 through May 23, 2017). Only 75 of the 510(k) submissions issued (2.5%) were submitted for third party review. Of these 75 submissions, the average review time by the FDA (after the third party review is completed) was 46 days. Since the average review time for the FDA of a traditional 510(k) is 183 days (based upon my data analysis from 2016), third party review can potentially reduce your 510(k) clearance timeline by months.

Why do only 2.5% of 510(k) submitters utilize a third party review?

Originally, my theory was that only a limited number product classification codes are eligible for third party review. The FDA is trying to expand the third party review program, but 44% of third party reviews are for the radiology panel. Another 13% were for the general hospital panel, and 13% more of the reviews were for the cardiovascular panel. Finally, less than 7% were reviewed for the dental panel. The remaining 17 submissions were reviewed for other panels. A closer look at the product classification codes shows that there are only a few product codes within these panels that are being reviewed by third parties.

I also had a second theory for why so few submitters are using third parties. As I reviewed the actual 510(k) summaries for these 75 submissions, I noticed there were only four (4) companies listed as third party reviewers in the last 12 months:

  1. Regulatory Technology Services, LLC (http://www.markjob.com/) = 56 submissions
  2. Third Party Review Group, LLC (http://www.fdathirdpartyreview.com/) = 15 submissions
  3. TUV SUD America, Inc. (http://www.tuv-sud-america.com) = 3 submissions
  4. Center for Measurement Standards of Industrial in Taiwan = 1 submission

2018 Updated- FDA’s reporting of the first three quarters of 2018

Compared with the above information the first three quarter reportings for 2018 list a total of more third party reviewers. Currently in the quarterly reports from the FDA there are the following 3rd party reviewers:

  1. AABB = 5 or less
  2. Center for Measurement Standards of Industrial (CMSI) = 5 or less
  3. New York State Department of Health (NYSDOH) = 5 or less
  4. Nordic Institute of Dental Materials (NIOM) = 5 or less
  5. Regulatory Technology Services, LLC. (RTS) = 36
  6. Third Party Review Group, LLC. (TPRG) = 13
  7. TUV SUD America, INC. (TUV) = 5 or less

The FDA keeps an up to list of approved third party reviewers under the Medical Devices Databases. Titled Current List of Accredited Persons for 510(k) Review under the FDA Modernization Act of 1997- (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfthirdparty/Accredit.CFM?party_key=8).

As of Quarter Three there have been a total of 53  Third Party 510(k) Submissions Accepted. A majority of these completed by Regulatory Technology Services, LLC, and Third Party Review Group, LLC (TPRG). 36, and 13 respectively. All of the others have 5 or less but these numbers may increase once the fourth quarter report is released.

When should you chose a third party review instead of submitting directly to the FDA?

Always check the 510(k) database to see if third party reviewers were used for your product’s classification code. Ideally, a third party reviewer has been involved in a device that is in the same product classification and possibly that device would be a suitable predicate for you to select for your 510(k) submission. If your search yields no results, your device may not be eligible for a third party review. However, you can always contact one of the four third party reviewers listed above.

In general, the third party review process is an excellent way to shorten your 510(k) clearance timeline by months. The cost is significantly more than the FDA user fee. However, faster time to market is almost always worth the increased fee. Therefore, if a third party review is available I recommend taking advantage of this option.

Do you need help?

Medical Device Academy offers a regulatory pathway analysis service for $1,500. For those of you that are only interested in the US market, rather than including the EU and Canada, the cost for this service is only $750. Do you need help identifying the product classification for your device, determining the required performance testing and selecting a predicate device? We can do this for you in one week or less. Do you need an expedited review? We can also determine if your product is eligible for third party review and obtain a quote for you.

Posted in: 510(k)

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FDA User Fee Increase for FY 2018 – Strategic Implications

This article identifies strategic implications of the FDA user fee increase for FY 2018 that was published by the FDA last week.

FY 2018 MDUFA Fees FDA User Fee Increase for FY 2018   Strategic Implications

You didn’t know the FDA user fee increased?

In August, the FDA publishes the new FDA user fee schedule for the next fiscal year, which begins on October 1. Last year the FDA published an updated small business guidance document in early August that included the fee schedule. This year, the release of the FY 2018 FDA user fee schedule was delayed until the end of August, because the re-authorization of user fees was not approved until August 18, 2017.

The MDUFA IV user fee schedule was negotiated in October of 2016, and the new user fee schedule proposed to increase the user fees to $999.5 million. That negotiated plan called for an increase in standard fees for 510k submissions while keeping small business fees lower. The final enacted MDUFA IV user fees follows this plan. There is a significant difference between PMA fees and 510k fees in the new fee schedule. There was a 33% increase for all PMA-related standard and small business fees. However, standard 510k fees increased by 125%, while small business fees for a 510k increased by 13%. The establishment registration fees increased by 37%, and there is still no discounted registration fee for small businesses. Finally, the biggest change is there will now be a fee for De Novo applications.

Implications of the De Novo FDA user fee increase

Congress authorized the MDUFA III fees in 2012 for five years, and there were no fees associated with De Novo applications. In 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) also streamlined the De Novo application process. The purpose of having no fees, and for streamlining the process, was to encourage medical device innovation. However, only 40% of De Novo application reviews were completed within 150 days during 2015 and 2016. The balance of the applications required 200 to 600+ days to complete. Negotiations between the FDA and industry in 2016 resulted in an agreement to trade an increase in FDA user fees for a decrease in the review time required for 510k clearance. However, the FDA also committed to decreasing the De Novo application review time to less than 150 days as follows:

De Novo application decision goals for MDUFA IV 1024x118 FDA User Fee Increase for FY 2018   Strategic Implications
Unfortunately, the agreed FDA user fee for De Novo applications in MDUFA IV for FY 2018 are $93,229 as a standard fee and $23,307 for small businesses. During the past 5 years, during MDUFA III, companies that felt they had a potential De Novo application would try to persuade the FDA that a borderline 510k submission should be a De Novo application instead. However, under MDUFA IV you will be more likely to persuade the FDA that a borderline classification should be considered for a 510k submission instead of a De Novo application.

In addition, you should plan your De Novo application more carefully than you might have for a free application. Pre-submission meeting requests should always be submitted during the development process, and these pre-sub requests should be submitted at least 90 days prior to your design freeze. Special consideration should also be devoted to risk analysis and gathering preliminary data to demonstrate the effectiveness of the risk controls you select to ensure that the clinical benefits of your device outweigh the residual risks of the device after implementing risk controls. Ideally, you will gather enough evidence to create a draft special controls guidance document to submit to the FDA as a supplement to your pre-submission meeting.

If you are planning a De Novo application for FY 2018, you should expect your FDA reviewer to pay special attention to ensuring that there are no unnecessary delays in the review process. You should also monitor the FDA recent final guidance webpage for release of a final guidance document for De Novo applications. The draft guidance was released on August 14, 2014. Creating a final guidance will probably be priority for FY 2018.

Implications of the 510k FDA user fee increase

The standard FDA user fee for a 510k increased 125% from $4,690 to $10,566. However, the absolute dollar amount of a 510k submission is still less than cost of biocompatibility testing or sterilization validation. Therefore, the increase should not significantly decrease the number of submissions. However, the small business fee has only been increased by 13%. Therefore, if you are a small business (i.e., income < $100 million), you should complete an application for small business qualification as soon as you can (i.e., October 1, 2017) to make sure that you are eligible for the discounted fee when you submit your next 510k submission. If you need help preparing your small business qualification form, there will be a webinar on this topic Friday, September 8, 2017.

When you are planning a 510k submission, you should also determine if your device product classification is eligible for third party review. In the past, the increased cost of the third party review made submission of a 510k to a third party reviewer unattractive. However, the fees for third party reviews range from $9,000 to $12,000 typically. Therefore, its possible that there may be no difference in the fee for a third party review unless your company is a qualified small business.

Implications of establishment registration FDA user fee increase

The increase in the annual establishment registration fee is 37% for medical device firms to $4,624. If you are already registered as a medical device firm, you should increase your annual budget for the establishment registration fee accordingly. If you are about to launch a new product, remember that you are required to register and list your product within 30 days of distribution of your product. Therefore, if shipments are going to begin in September, you don’t need to register until October (i.e., after the start of the new fiscal year). Therefore, you may be able to avoid paying the FY 2017 establishment registration and only pay the FY 2018 establishment registration. This would not be the case for foreign firms that need to import the product prior to distribution.

What you can do about the FDA user fee increase now

You may not be able to change the user fee schedule for FY 2018, but there are three things you can do now to improve your situation. First, if you are a small business, you can speak to your accounting department and get them to provide a copy of the FY 2016 tax return so that you can complete the small business qualification form on October 1. Second, you should contact Regulatory Technology Services and the Third Party Review Group to obtain a quote for a third party review of your 510k submission instead of submitting directly to the FDA. Third, you should add a reminder to your calendar for August 1, 2018 to start reviewing the FDA website and other sources for a FY 2019 FDA user fee schedule.

Learning how to submit a small business qualification form

If you have not completed a small business qualification form before, you can learn how to prepare your application for small business qualification by registering for my webinar on Friday, September 8, 2017.

Posted in: 510(k), FDA

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510k Submission, Section 14-Sterilization Validation and Shelf-life

This article explains the process for preparing the sterilization validation and shelf-life section of a 510k submission.

sterilization validation 510k Submission, Section 14 Sterilization Validation and Shelf lifeSterilization validation and shelf-life, Section 14, is typically one of the last sections of a 510k submission to be completed. However, most of the work in preparing this section of your 510k submission should be completed more than a month prior to actually completing the associated testing. The reason why you can write this section, prior to receiving the results, is that your results are 99% predictable. If you are unlucky enough to be part of the 1% that have surprising results during sterilization validation, then you will need to make changes and repeat your testing.

Design Planning Aspects Related to Sterilization Validation

During your design and development process, sterilization validation testing is part of design verification testing—not design validation. This testing is verification, rather than validation, because you are testing in accordance with recognized standards (i.e., design inputs) to ensure that the sterilization process parameters are adequate to consistently meet the sterility specification (i.e., design output). In your design plan, it is critical to understand which of the following three categories your sterilization process falls under:

  1. Traditional Sterilization (e.g., ethylene oxide)
  2. Non-traditional Sterilization (e.g., Hydrogen Peroxide)
  3. Novel, Non-traditional Sterilization (e.g., Chlorine Dioxide)

It is critical that you identify which category your sterilization process falls into, because the review process used by the FDA for each category of sterilization process is different. Traditional sterilization processes have recognized standards that a reviewer can easily compare your validation methods with.

Non-traditional sterilization methods are becoming more popular for products that are sensitive to degradation caused by high temperature, or exposure to radiation or ethylene oxide. However, the FDA has identified non-traditional sterilization processes as being a priority for inspection. Therefore, after your product receives 510k clearance, you can expect an FDA inspection sooner than products that use traditional sterilization methods (i.e., 6-12 months instead of 12-24 months). 

Novel, Non-Traditional Sterilization

The novel, non-traditional sterilization methods require a different 510k clearance process, because the FDA requires an internal consultation from the Infection Control Devices Branch (INCB) prior to issuing 510k clearance. A consultation is needed for evaluation of the sterilization process, because reviewers lack sufficient expertise in the field of microbiology and sterilization to evaluate novel sterilization processes. The INCB can also provide a consult for non-traditional sterilization processes, but this is not typically needed if the process is following established ISO Standards for sterilization validation. 

For novel, non-traditional sterilization processes, an INCB consult is required, and it is recommended to consult with the FDA early regarding the use of this type of sterilization process. Part of the reason for this early consultation is that a pre-clearance priority inspection is required prior to issuing the 510k. The FDA published a draft guidance on this topic in 2008 that can be found at the following webpage – Click Here

The image below shows where the INCB is located within the hierarchy of the FDA’s organization.

incb 510k Submission, Section 14 Sterilization Validation and Shelf life

Creating Summary Technical Documentation (STED)

The sterilization validation and shelf-life section of a 510k submission may be copied from the summary technical documentation (STED) that you prepare for CE Marking applications or a Canadian Medical Device License Application. Instead of including all of the protocols and testing reports from your validations, the regulators only require a summary of the validation activities and results. If the STED is thorough and well-organized, the reviewer should not request validation reports. However, if the STED is incomplete, then the reviewer is likely to request a copy of the validation reports.

Any STED should include the following elements:

  1. Identification of the validation dates
  2. Identification of the organization(s) that performed the validation
  3. Reference to the ISO standard or other recognized standard that was used
  4. Identification of any deviations from the referenced standard
  5. Number of lots and samples per lot tested
  6. Description of the testing performed—including testing parameters
  7. Identification of the document control numbers and revisions for protocols and reports
  8. Acceptance criteria for the validation
  9. Summary of the results

For your STED specific to sterilization validation and shelf-life, you will also need to ensure you include a description of the packaging used to maintain the device’s sterility (primary packaging) and a description of the packaging used to protect the primary packaging (i.e., secondary packaging).

For a 510k submission, you will only need to make a few modifications to the STED that you use for European CE Marking and Canadian licensing. First, you need to ensure you are referencing standards recognized by the FDA, and if you followed a different method, the differences need to be documented in Section 9 of your submission on FDA Form 3654 for each Standard.

Second, you will need to include a reference to Ethylene Oxide (EO) residual testing summarized in Section 15 for biocompatibility (not applicable to non-EO methods of sterilization). EO residual testing must be performed in accordance with ISO 10993-7. You should also include an outline of the validation methods that were used in your comparison of substantial equivalence in Section 12 of your submission. Finally, you should reference the methods used briefly in your executive summary (i.e., Section 10) and the 510k summary (i.e., Section 5)—assuming that you did not use a 510k statement.

If you are writing your first STED for sterilization validation and shelf-life, I recommend reviewing the RTA checklist in advance.

You may want to organize your STED with headlines that address each of the questions outlined in the RTA checklist.

You should also be aware that although the FDA references the 2002 guidance document K90-1 for the format and content of the sterilization validation section, there is a 2008 draft guidance the represents the FDA’s current thinking on the topic of sterilization validation. That draft guidance document is also identified as a priority for the FDA to release as a final guidance in FY 2015 (i.e., prior to October 1, 2015).

Additional 510k Training

The new 510k book, “How to Prepare Your 510k in 100 Days,” ships on Monday, February 6th 2017. There is also an on-line 510k course series consisting of 24 webinars. Please visit my webinar page to purchase individual webinars. We also have live 510k workshops

Posted in: 510(k)

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510k Submissions for Electrosurgical Devices-FDA’s 2 New Guidance Docs

imgres 2 510k Submissions for Electrosurgical Devices FDAs 2 New Guidance Docs

For 510k submissions for electrosurgical devices, the author provides insight into FDA’s two new guidance documents, including how to document compliance.

A colleague asked me if I had noticed any changes to the FDA webpage summarizing the content requirements for a 510(k) submission (http://bit.ly/510k-Content). The page was last updated on March 18, 2014. However, when I compared the current page with a version I had saved in August 2013, I was able to confirm that there were no changes to the page, except for hyperlinks to content referenced on the page. Six new guidance documents were released by FDA in March, but two of these were specific to electrosurgical devices:

  1. Premarket Notification [510(k)] Submissions for Electrosurgical Devices for General Surgery (http://bit.ly/Electrosurgical-510k)
  2. Premarket Notification [510(k)] Submissions for Bipolar Electrosurgical Vessel Sealers for General Surgery (http://bit.ly/Bipolar-510k)

For those of you that are preparing 510(k) submissions, you may find the draft guidance documents for electrosurgical devices and bipolar electrosurgical vessel sealers to be quite helpful–even if you are are not submitting a 510(k) for these types of devices. These two draft guidance documents include specific recommendations for the content and format of the substantial equivalence table and performance data presented. In addition, labeling requirements for the device include a long list of warnings that should be included in the IFU for this type of device.

Electrosurgical Devices for General Surgery

This guidance was released on March 24, 2014 and provides an update to the 510(k) submission requirements for electrosurgical devices in general. If you are preparing a 510(k) submission for this type of device, you should systematically verify and document how your submission complies with this guidance. Compliance with this guidance is not instead of, but in addition to FDA guidance on the format and content of a 510(k) submission. Specifically, you should incorporate a table into one of the sections of the submission that lists each of the recommendations of the product-specific guidance document.

Bipolar Electrosurgical Vessel Sealers

This guidance was also released on March 24, 2014 and provides an update to the 510(k) submission requirements of bipolar electrosurgical vessel sealers for general surgery. This guidance includes all the same requirements as the guidance for Electrosurgical Devices, but the bipolar vessel sealing draft guidance also has one additional requirement. The draft guidance provides a prescriptive outline for a preclinical chronic animal study, including the minimum number of animals and number of weeks post-procedure that the animals should be studied. In the past, the FDA has requested clinical studies in humans to demonstrate the long-term safety of the sealed vessels, but this draft guidance specifically states that human clinical studies are not required unless the device being submitted uses different “device technology and/or mechanism of action is significantly different when compared to the predicate.”

How to Document Compliance in Your 510(k) Submission

Medical Device Academy’s consulting team created a template for Section 9 of a traditional 510(k) submission that includes an overview document with the following sub-sections:

  1. FDA Special Controls
  2. FDA Device-Specific Guidance
  3. Voluntary Product Safety Standards
  4. FDA Recognized Standards

Sub-Section 1 of Medical Device Academy’s template for Section 9 of a traditional 510(k) submission includes a brief statement that there are no Special Controls guidance document for the product being submitted. For sub-section 2 we use a table identifying where each of the requirements of product-specific guidance documents can be located. If one of these two draft electrosurgical guidance documents is applicable to your device, we recommend including a table in Section 9 of your submission. For sub-sections 3 and 4, FDA requires that manufacturers complete a Standards Data Report for 510(k)s (FDA Form 3654, http://bit.ly/Form-FDA-3654) for each of the applicable test standards FDA recognizes. Failure to complete Form 3654 for 100% of the applicable standards FDA recognizes results in an immediate Refusal to Accept (RTA, http://bit.ly/FDA-RTA-Policy) letter.

58% of 510(k) submissions were rejected in 2013 during the initial 15-day administrative review. If you received already “Refusal to Accept” (RTA) letter, or you need help preparing your submission, please contact Glenn Melvin, Director of Business Development; by phone at (561) 308-3093 or by email at glenn@robertpackard.wpengine.com; to learn more about our consulting services, to schedule a call or to request a proposal.

Posted in: 510(k)

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