510(k)

FDA pre-market notification submission for medical devices.

Combining a 510k Submission with CE Marking: 9 Sections that are Duplicated

3 Comments / 510(k) / By

This article explains how to reduce your workload by at least 35% if you integrate your two project plans for a 510k submission and CE Marking into one comprehensive regulatory plan.

510k submission and CE Marking Combining a 510k Submission with CE Marking: 9 Sections that are Duplicated

My first medical device regulatory submission was for CE Marking, while my second regulatory submission was for a 510k submission of the same product. This is a very common path for medical device regulatory submissions, but it is also an inefficient path. If you know that you will be submitting both types of documents, then you should plan for this from the start and reduce your workload by at least 35%.

The reason why you can quickly reduce your workload is that there are nine key sections in both submissions that are very similar. Therefore, you can write the content for those nine sections in such a way that the material can be used for your 510k submission and CE Marking.

9 Sections are Duplicates

Here are the nine key sections that the two types of regulatory submissions have in common:

  1. Device Description
  2. Labeling
  3. Sterilization & Shelf-Life
  4. Biocompatibility
  5. Software
  6. EMC/Electrical Safety
  7. Bench Testing
  8. Animal Testing
  9. Clinical Testing

There are 20 sections required by the FDA for a Traditional 510k submission, but often some of the sections are boiler plating, and other sections do not apply to the device being submitted. A few sections are unique to a 510k submission, such as:

  • Substantial Equivalence
  • 510(k) Summary
  • User Fee Cover Sheet Form 3601 & Submission Cover Sheet Form 3514
  • Declarations of Conformity on Form 3654
  • Table of Contents

Technical Files for CE Marking also have a few unique sections, such as:

  • Essential Requirements Checklist
  • Classification Rationale
  • CE Marking Application to Notified Body
  • Declaration of Conformity
  • Table of Contents

How to Construct Your Plan

In one of my previous blogs, I explained how I use the 510k Table of Contents as a project management tool for a 510k submission. You can do the same when you are constructing a combined plan for a 510k submission and CE Marking. The first step is to create the same kind of project management tool I use for a 510k submission (i.e., a Table of Contents) to manage your CE Marking Technical File. I recommend preparing your Technical File in accordance with the GHTF guidance document released by study group 1: N011:2008. This guidance mirrors the format that will be required in Annex III of the new European Medical Device Regulations that should be released next spring. I do not recommend using the NB-MED 2.5.1/rec 5 guidance document. Even though the content is similar to the GHTF guidance, the format is quite different. After I have two separate project plans organized in accordance with the Table of Contents, then I merge the two plans on a spreadsheet and consolidate the duplicate sections.

Scheduling Tasks & Project Management

If you are going to outsource sections of either submission, these nine sections should be written and reviewed by someone familiar with both types of submissions. The headers and footers will be unique to the type of submission, but I write the text in Google Docs without formating for ease of sharing and so I can use my Chromebook.

If you have an in-house team that prepares your 510k submissions and Technical Files, you might consider training the people responsible for each section on the requirements for each type of submission. This eliminates rewriting and reformatting later. I like to assign who is writing each section in a separate column of my Table of Contents planning tool. Then I will sort the sections by the expected date of completion. All the safety and performance testing, and any sections requiring validation, will typically be finished at the end of the project. Therefore, it is important to dedicate unique resources to those sections rather than asking one person to write several of those sections. You also will want to make sure any supporting documentation they need is completed early so that the project’s critical path doesn’t change. I typically use a Chromebook spreadsheet for all of this, because 20+ sections are just too few tasks to warrant the use of Microsoft Project or some other Gantt Chart planning tool. If you keep it simple, more of your team will read it and update it frequently.

RA Consulting Tip

I have several PCs (laptops and desktops of various vintages), but nothing is faster for writing plain text than a Chromebook. Then I export documents to Word format and work on tables and formatting of the information as needed. I can also jump on any computer with an internet connection and work on my documents. This enables me to travel very light when I need to. If you are a tablet user, there are some other solutions I prefer–such as Evernote.

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.

Combining a 510k Submission with CE Marking: 9 Sections that are Duplicated Read More »

HDE Application and 510k Submissions

1 Comment / 510(k) / By

This explains the differences between the regulatory pathways for a Humanitarian Use Device (HUD) or HDE and 510k submissions.

HUD Designation 300x229 HDE Application and 510k Submissions

HDE Application

In September 2019, the FDA released a final guidance document explaining the regulatory process for a Humanitarian Device Exemption (HDE) Application. HUD designation is for a product that affects less than 8,000 patients per year in the United States. The limitation of 8,000 There are three steps required before a HUD may be used at a user facility:

  1. HUD Designation Request to Office of Orphan Products Development (OOPD)
  2. HDE Application to Center for Devices and Radiological Health (CDRH)
  3. Investigational Review Board (IRB) approval of using the HUD

Note: The above regulatory pathway may not apply to combination products. In the case of combination products, you should contact the Office of Combination Products (OCP).

Major Differences between the HDE Application and a 510k submission

  • Unlike the 510k process, HDE approval is device approval rather than “clearance” for marketing and distribution.
  • If another equivalent (an actual term used is “comparable”) device is already being legally marketed, then the FDA may not approve an HDE application. In contrast, the first requirement for the determination of substantial equivalence of a subject device for a 510k submission is that the predicate device must be a legally marketed device that is equivalent.
  • There are no user fees, while 510k submissions generally are subject to FDA user fees; pediatric-only products are an exception to the requirement for 510k user fees.
  • There is no requirement to demonstrate the effectiveness of devices in an HDE application. Instead, devices approved for HDE must provide an acceptable benefit/risk analysis.
  • HDE-approved devices are not generally eligible to make a profit. Any device that a manufacturer intends to sell for more than $250 requires a report issued by an independent public accountant.
  • IRB approval for the use of HUD-approved marketing is required, but IRB approval is not for a clinical study, and IRB approval is not required in the case of an emergency.

The FDA guidance document also explains how HDE approval is different from pre-market approval (PMA).

HDE Application and 510k Submissions Read More »

Indications for Use Case Study

Leave a Comment / 510(k) / By / ,

This indications for use case study illustrates 510k requirements using the example of a spinal pedicle screw.

PASS LP Spinal System Indications for Use Case Study

Indications for Use Case Study

A hypothetical new client asked me if I could help them with a 510k submission for a new pedicle screw design. The company’s device utilizes a lower-profile version of a traditional pedicle screw that is pre-packaged with rods, hooks, clamps, and nuts. The pre-packaged system is gamma-irradiated, and the product is specially designed for pediatric patients. Unfortunately, the company was only able to find similar designs of pedicle screws that were for adult patients.

Identifying the FDA Regulation – Indications for Use Case Study

The applicable FDA regulation for a pedicle screw product is 21 CFR 888.3070 – pedicle screw spinal system. However, the only indication stated in this regulation is specific to “skeletally mature patients.” Therefore, the indications portion of the regulation does not apply to the subject device for my hypothetical client.

Case Study Product Classification

If you type in “pediatric” as a keyword into the product classification database, 12 different product classification codes result from that search. The applicable product classification code for this product is “OSH”—“Pedicle Screw Spinal System, Adolescent Idiopathic Scoliosis.” The definition for this product classification is: “Intended to stabilize the thoracolumbar spine as an adjunct to fusion using allograft and/or autograft to treat adolescent idiopathic scoliosis.” This is the desired indication because it is specific to pediatric patients. This product classification code also references “pedicle screw spinal system” as the regulation description, and there is a link provided for the 888.3070 regulation number.

Identifying a Predicate Device

97 establishment registration and listing entries are under the “OSH” product classification code. Medicrea Technologies, located in France, submitted one of the most recent 510k submissions (K150049) referencing this product code. Many other possible predicate devices could be used for this 510k submission. However, a recent 510k submission with the same indications for use is usually a good choice. The description of the potential predicate device in the 510k Summary indicates that the predicate is also pre-sterilized. Still, the predicate device description does not specify that it is a low-profile version. Additional research on the company’s website revealed that the PASS LP Spinal System is a low-profile polyaxial spine system. For a 510k submission, it is more important to select a predicate with the same indications rather than a predicate with all the same technological characteristics. However, This particular predicate device appears to have most of the same technological characteristics. The minor differences between the “Pass LP Spinal System” and the subject device are insignificant, and the K150049 was selected as a predicate device submission.

FDA Form 3881

The form has four sections to complete:

  1. The 510k number is assigned by the FDA to each premarket notification submission (usually not assigned yet).
  2. The device name is the subject of your 510k submission.
  3. The indications for use should match the indications for the use of the predicate device, and it should be similar to the indications for use as written in the regulations for the product classification.
  4. The type of device—prescription-only and/or over-the-counter use.

The form is completed using Adobe Acrobat Pro. The Form used to be a stand-alone document that would be included in Section 4 of the FDA eCopy, but now FDA Form 3881 is incorporated into the FDA eSTAR and PreSTAR templates. The FDA includes this page as part of the 510k Summary published on the FDA website for all 510k-cleared devices. For this case study, the 510k number is unknown. The name of the subject device is the “Miniflex Pedicle Screw Spinal System.” The indications for use are: “The Miniflex Pedicle Screw Spinal System is used for posterior non-cervical pedicle screw fixation in pediatric patients. The spinal implants are indicated as an adjunct to fusion to treat adolescent idiopathic scoliosis. The spinal implants are intended to be used with allograft and/or autograft. Pediatric pedicle screw fixation is limited to a posterior approach.” The device type is for “Prescription Use” only.

Writing Your Indications for Use

When writing an Indications for Use statement, the most straightforward approach is substituting your subject device’s name for the predicate device’s name. Ideally, you have chosen a predicate device that matches your subject device for the indications for use and the technical characteristics. However, it is possible to have a subject device with a narrower indication. For example, the predicate device may be indicated for both adult and pediatric patients, while your subject device may be specifically designed to fit pediatric patients better. For our case study, only the last paragraph of the predicate’s IFU applied to the subject device because the device was limited to pediatric use. Therefore, the last paragraph was copied, and the subject device name was substituted for the predicate device name.

Indications for Use Case Study – Broader Indications

The first step of the 510k review process is verification that the subject device has the same indications for use as the primary predicate device. Therefore, if broader indications for use are claimed for the subject device, then the 510k submission will likely be rejected as not substantially equivalent (NSE). In this case, you have a few options. One alternative for submissions that require a broader indication for use is to perform a clinical study to provide safety and efficacy for the broader indication. A second alternative is to submit a De Novo application.

You should request a pre-submission meeting with the FDA before pursuing either option. In the case of a clinical study, you should plan to provide the FDA with a clinical study synopsis that includes a benefit/risk analysis. The clinical study synopsis should also include a rationale for why the broader indication for use presents a non-significant risk if you plan to conduct the clinical study under good clinical practices (GCPs) instead of applying for an investigational device exemption (IDE). Suppose you plan to submit a De Novo application. In that case, it is recommended that you prepare a special controls guidance document before the pre-submission meeting to obtain feedback from the FDA. For novel devices of medium risk, your company may need to conduct a clinical study and submit a De Novo application.

Your Next 510k Submission

Most companies have plans for subsequent submissions to expand the functionality of the subject device. In this case, often, the subject device is the best choice of a predicate device for subsequent 510k submissions. In this case, you should attempt to make the initial application as broad as possible concerning indications for use. This will enable you to narrow the indications for use in future submissions without the device being NSE to your predicate device.

If you are interested in watching a webinar on the topic of indications for use, please visit the webinar page.

Additional 510k Training

The 510k book, “How to Prepare Your 510k in 100 Days,” is available as an eBook only with the purchase of our on-line 510k course series. Please visit the webinar page to purchase individual webinars.

Indications for Use Case Study Read More »

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

Leave a Comment / 510(k) / By / , , , ,

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 before actually completing the associated testing. The reason why you can write this section, before 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)

You must identify which category your sterilization process falls into because the review process used by the FDA for each category of the 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). 

The 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) before 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 the novel, non-traditional sterilization processes, and 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 before issuing the 510k. The FDA published draft guidance on this topic in 2008 that can be found on 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. 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., before 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

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

Performance Testing for a 510k Submission-Case Study-Part 2

Leave a Comment / 510(k) / By / , , ,

Performance Testing for a 510k Submission-Case Study-Part 2 explains the performance testing for a 510k submission to obtain clearance from the US FDA for marketing a new medical device. Performance testing is an essential part of new product development and is usually the last section that you can complete before your submission.  510k part 2 Performance Testing for a 510k Submission Case Study Part 2 In my previous 510(k) case study article (http://www.MedicalDeviceAcademy.com/510k-submission-fda-case-study), I showed you how to research the FDA classification database to determine if there is a special controls guidance document to follow in the preparation of your 510k submission. The example I used was for topical adhesives (i.e., MPN). Topical adhesives do not have any Recognized Consensus Standards listed. Instead, all the performance testing requirements are specified in the special controls guidance document.

In this case study article, I selected a different product code that has Recognized Consensus Standards, but it does not have a special controls guidance document. After identifying the device classification and product code, if there is no Special Controls Guidance, you need to plan your performance testing based upon other sources of information. If there is no Special Controls Guidance document, I use three methods for determining what performance testing is needed:

  1. Look for any device-specific standards
  2. Review other 510k summaries
  3. Order previous 510k submissions via FOIA requests

For this case study, the product code selected was a bone fixation screw (i.e., HWC). The number of predicate 510k submissions to choose from for this product code is extensive. There are 29 from Arthrex alone. Some of these 510k submissions include a 510k statement, while others include a 510k summary. A statement is not directly helpful in identifying any of the performance testing that was used for the clearance of the potential predicate device. However, 21 CFR 807.93 requires that the company that submitted the 510k shall provide a redacted copy of the 510k submission within 30 days of the request. If this is requested early in your 510k project, you should have a copy of the submission in time to plan your performance testing for verification and validation of the subject device. You can also order predicate 510k submissions through the Freedom of Information Act (FOIA) request process:

(http://www.fda.gov/regulatoryinformation/foi/howtomakeafoiarequest/default.htm).

In the case of a 510k summary, the summary indicates what performance testing was performed to demonstrate substantial equivalence. In the case of K103705, the section titled “Substantial Equivalence Summary” states that mechanical testing data for torque and pull-out testing was submitted for the subject device and the predicate device. Other 510k summaries may provide additional data or a more descriptive list of testing that was performed. In the case of this 510k example, there is a second product code listed: HRS, bone fixation plate. The HWC bone fixation screw product code indicates that there are 5 Recognized Consensus Standards:

Only three of the above standards are included in the list of eight Recognized Consensus Standards related to the HWS product code. One of those eight standards should probably be covered under the HWC product code, as well:

Now you have a total of six different device-specific standards that can be used for planning the performance testing of your bone screw. This is significantly more helpful than a 510k summary that says torque and pull-out testing was performed. After you have ordered and reviewed each of the standards, you then create a list of performance tests that apply to your screw and create an overall verification and validation plan.

It is essential to perform this review each time, because there may be new or revised testing methods established as the Recognized Consensus Standards are updated. If you outsource testing, then you will need to obtain a quotation from a testing lab for each of the applicable tests.

Once you have created a comprehensive testing list, and you have quotations for all the testing required, you need to schedule the testing and ship samples to the testing lab. Once testing has begun, this is the best time to start the preparation of your 510k submission. Performance testing often takes several months to complete. If you start preparing the 510k before you have ordered the testing, then you are starting too early, and you may have to change your performance testing summary multiple times.

If you start your 510k preparation after you order your testing, then you can create the entire performance testing summary. The only information that you will be missing is the final report number for each test being performed. For the most part, you do not need the specific results of the testing, because the tests are designed to show that the subject device is “equivalent” or “not worse” in performance. Quantitative comparisons between your subject device and the predicate device are not allowed by the FDA for a 510k submission. Your subject device must be “equivalent” or “not worse than” the predicate device concerning safety and efficacy.

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

Performance Testing for a 510k Submission-Case Study-Part 2 Read More »

510k Submission to the FDA (Case Study – Part 1)

6 Comments / 510(k) / By / , , ,

This article is the first part of a two-part case study providing an overview of the premarket notification process (i.e., 510k submission) to obtain clearance from the US FDA for marketing a new medical device. This first part of the series focuses on the initial steps of a 510k submission project: 1) identifying product classification, 2) identifying any applicable international standards and special controls guidance documents, and 3) selecting a primary predicate device.

case study 510K 510k Submission to the FDA (Case Study Part 1)

For this case study, I chose the maker of Krazy Glue® as a hypothetical new client. The company wants to start selling cyanoacrylate as a topical adhesive in the U.S. market. As with the Canadian and European markets, the US FDA considers cyanoacrylate a medical device when it is used as a topical adhesive. The first step toward obtaining FDA clearance for marketing the new product is to determine the device’s classification.

Device Classification

My client was considering asking the FDA to identify the classification of topical adhesives using the 513(g) submission process. Still, I provided the following reasons why the client should not use the 513(g) process:

  1. the 513(g) process takes 60 days to get a response from the FDA, while a qualified consultant can make the same determination in less than a day
  2. hiring a consultant typically costs less than the 513(g) fee (i.e., $3,387 for large companies and $1,694 for small businesses)
  3. the FDA’s classification determination is non-binding, and the accuracy of the FDA’s response is highly dependent upon the quality of the information provided by the company

In this case, I was able to answer the client’s question about device classification over the phone without any charge. The client indicated that they wanted to launch a product similar to Surgiseal. I was able to use the US FDA Registration and Listing Database to identify the product classification by merely typing “Surgiseal” in the field for “Proprietary Name.” Adhezion Biomedical LLC is registered as the manufacturer of Surgiseal. The three-letter product code “MPN,” and the device is a Class II device requiring premarket notification via a 510k submission.

This product classification also gives my client additional options that are not available to all companies that are trying to achieve 510(k) clearance for the first time. Most new products can only achieve initial 510(k) clearance from the US FDA by submitting a “traditional” 510(k). This process is supposed to take 90 days—assuming there are no significant questions about the submission, and the reviewer has a manageable workload to review. The average time for determination of 510k clearance is currently between 120 and 180 calendar days.

Applicable International Standards & Special Controls Guidance

For some products, there are recognized consensus standards (i.e., ISO Standards) that define the performance requirements for a medical device or a Special Controls document published by the FDA that identifies which performance Standards the FDA requires for specific product classification. In the case of topical adhesives, the FDA has issued a Special Controls document. When there is a Special Controls guidance document available (http://bit.ly/FDA-topical-adhesive), the company may submit an Abbreviated 510k instead of a Traditional 510k submission.

An Abbreviated 510k submission contains summaries of all the testing results required in the Special Controls document or an ISO Standard recognized by the US FDA. Since all the testing of performance needed to be presented in an Abbreviated 510k submission is in accordance with a previously accepted standard, the FDA reviewer only has to verify that the performance testing identified in the Special Controls document or the ISO Standard has been completed and acceptance criteria have been met. Therefore, the reviewer needs less time, and the FDA’s performance target for making a clearance decision is 60 days—instead of 90 days.

In addition to Special Controls documents, the FDA also has guidance documents related to 510k submissions, such as: “Format for Traditional and Abbreviated 510(k)s.” By following this document verbatim, my client can avoid a lot of time-consuming questions from a reviewer that is having trouble finding the information they are looking for. If a section of the suggested format is not applicable, I still include this section. However, I indicate the reason why this section is not applicable in a brief paragraph (i.e., a one-page section).

As I read through the Special Controls Guidance document, I realized that a specific format for an Abbreviated 510k is described for topical adhesives. Therefore, I need to modify my normal template to match the FDA format for a topical adhesive Abbreviated 510k submission. As I read further, I realized that there would be some additional testing required that my client may not have anticipated.

In the Special Controls document, there are several risks and recommended mitigation measures identified:

fig.1 510k 510k Submission to the FDA (Case Study Part 1)

The risks of adverse tissue reaction, chemical burns, and infection have all been addressed by biocompatibility testing and sterility testing. My client also performed animal testing to identify any problems in a simulated use environment. However, the client did not perform any testing to address unintentional bonding specifically, wound dehiscence, applicator malfunction or delayed polymerization. The client needs verification protocols and test reports to address these specific risks.

Selection of a Primary Predicate

Another unique requirement from the US FDA for a 510k submission is the concept of a predicate device. A predicate device is a similar product that currently has a valid 510k. In July 2014, the US FDA released a guidance document that clarifies that companies submitting a 510k should identify only one primary predicate–rather than identifying multiple predicates. Ideally, a recent 510k submission should be selected because “old” technology may no longer be considered acceptable from a safety standpoint. In the case of topical adhesives, the applicator is one of the primary differences between legacy products and more recent 510k submissions. The most recent version of Surgiseal™ is an example of a new applicator for a monomeric, 2-octyl cyanoacrylate.

My client has a similar applicator design, and therefore Surgiseal™ is selected as the primary predicate device for this 510k submission. For all the testing protocols that need to be created for this 510k submission, comparative testing is performed with a sample of Surgiseal™ and a sample of products made by my client. In each of these protocols, the acceptance criteria are performance “not worse than Surgiseal™.” 

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.

510k Submission to the FDA (Case Study – Part 1) Read More »

The Three Biggest Changes in the Latest 510k Guidance

Leave a Comment / 510(k) / By
510k pmn The Three Biggest Changes in the Latest 510k GuidanceThis blog describes the three most prominent changes in the latest 510k guidance document released on July 28, 2014.

This recently issued guidance (http://bit.ly/Substantial-Equiv-Guidance) for evaluating Substantial Equivalence (SE) is well written and informative, with well-chosen and written examples. For newbies to 510ks, this is the place to start. The guidance includes background information about the 510k process and links to other documents. If you are an experienced professional, this is a must-read insight into the FDA’s current approach. Use it to guide your strategy for your next submission, and make it as easy as possible for the reviewer to reach a decision of SE for your device.


Change #1: 510k Flowchart

The 1986 flowchart guiding the decision of SE was updated and re-formatted to improve clarity. A substantial part of the guidance explains the thinking process that guides a reviewer at each decision step. If you are in the middle of preparing a submission, as I am, then the guidance provides an opportunity to review your work against current FDA thinking and training and adjust your submission to align with the FDA.


Change #2: Predicate Selection

Much has already been written about how this document may alter your selection of a predicate device. The FDA clarifies that split predicates (one for intended use equivalence, another for technological equivalence) have been ruled out. The FDA also recently released another guidance document to assist with performing a benefit/risk analysis (http://bit.ly/SE-Benefit-RIsk) when you are developing a device with a different technology than the predicate. The checklist below is intended to help you review your submission when you have already chosen an appropriate predicate.

  1. If you are using multiple predicates, have you stated which one is your primary predicate, the one that is most similar to your device? The FDA must find your device substantially equivalent to one other device.
  2. Are you using secondary predicates only when you are combining features, have more than one intended use, or have additional indications for use?
  3. Is the intended use the same as that for the predicates? Carefully compare your Intended use and the Indications for use with those of the predicates. If they are worded differently, have you explained how they are nevertheless the same?
  4. Have you provided a rationale for your choice of predicates in a way that aligns with the guidance?
  5. Is your SE table organized such that the secondary predicates only support the additional indications for use?
  6. Has your predicate been involved in a design-related recall?
  7. Double-check the Indications for Use statement in your labeling. Regulations state that the determination of the same intended use must be made against the labeling, not against what you say in the submission. Of course, what is in the submission should match the labeling.
  8. Have you included a copy of the labeling for the predicate device, e.g., the user manual?
  9. Does your Description section have sufficient information about the technical characteristics? The FDA is quite specific about what they want to see. Check your Description against the lists on page 19, and at (http://bit.ly/510k-Content) and in any device-specific guidance.
  10. Does your SE table identify similarities and differences in technological characteristics in a structured way?
  11. Do you make it clear why each of the differences does not pose a significant safety or effectiveness concern?
  12. Clinical performance data. Do the examples in the guidance suggest that you might need clinical evidence after all?
  13. If you are using an animal study, does it comply with applicable parts of GLP regulation (http://bit.ly/21-CFR-58)? This was already flagged in the RTA checklist (http://bit.ly/FDA-RTA-Policy). If the RTA reviewer can’t tick those boxes for question 39, then your submission won’t make it through the review.

Change #3: 510k Summary Template

Eleven pages, a quarter of the guidance document, are devoted to the 510k Summary, which will be posted on the FDA website. The guidance states that “FDA intends to verify the accuracy and completeness of the information included in a 510(k) Summary.” Your reviewer will have been so instructed. There is no change to the regulatory requirements for the Summary, but anyone who has combed through these while searching for a predicate will know that many Statements are incomplete. 

The FDA states that their focus on the Summary is in the interests of transparency, and they are making their point quite clearly in this guidance. As well as explaining each requirement, an example is provided. Therefore, I will be using Appendix C as a template for my 510k Summary.

The Three Biggest Changes in the Latest 510k Guidance Read More »

Technical File Conversion – 5 gaps to avoid

1 Comment / 510(k) / By / , ,

Technical File conversion from a 510k submission is easy, but five elements are missing from a 510k that you will need to add.MDA techinical file blog Technical File Conversion 5 gaps to avoid

This blog, Technical File Conversion, offers practical courses of action to consider related to this topic. Below are five parts of a technical file you are likely to be missing in your 510k documents:

  1. Technical File Conversion Requires Clinical Evidence – The FDA states that clinical data is unnecessary for most devices cleared by the 510k process. The MD Regulation (Annex II) requires a clinical evaluation to be performed and the evaluation report to be part of the technical file. Once formulated, the report becomes “clinical evidence” of the safety and performance of the medical device for demonstrating conformity with the relevant General Safety and Performance Requirements (GSPRs).

Here’s how to fill this gap using five steps offered by MEDDEV 2.7.1 Rev. 3:

  1. Identify the GSPRs requiring clinical support. (e.g., the device “shall not compromise the clinical condition or the safety of patients, or the safety and health of users” and “any risks which may be associated with their use constitute acceptable risks when weighed against the benefits to the patient.”
  2. Identify and “data pool” existing clinical data relevant to the device and its intended use. This should include any available post-marketing data on the same or similar device. But it may also comprise data from clinical trials or clinical use of a previous generation or even a substantially similar device. Finally, if you are utilizing standard methodologies in your device, it may be possible to use data showing conformity to recognized standards.
  3. Evaluate the data to determine if it’s suitable for establishing the safety and performance of your device. Even some generally unusable studies may produce relevant data. It is vital to perform this evaluation systematically. You might draw a chart listing the relevant ERs on the left and indicate the data source supporting or contradicting it to the right. The evaluation must objectively consider both positive and negative data.
  4. Generate any clinical data still needed. Consider methods other than a clinical trial for generating this missing data, e.g., “Data Pull” existing field data of the same or similar devices that may not yet have been ‘pulled’ through your PMS/RM Post-Production Infosystems. If data is unavailable, you may have no choice in generating it through a small-scale clinical trial. If so, keep it small, focused on the questions at hand, and statistically significant.
  5. “Bring all the clinical data together” to reach conclusions about your device’s clinical safety and performance. Essentially, conduct a benefit-risk analysis. Involve qualified team members: e.g., experts in medical conditions and device technology.

Now sum it up in a report.

  1. General Safety and Performance Requirements Checklist – This central component of the technical file is based on Annex I of the MDR and IVD, respectively. There is no such review in a 510k.

Develop a checklist based on the principles in GHTF N68:2012 containing all of the following columns for each ER:

  • Applicable? – y/n; Is the requirement applicable? If not, why.
  • The method used to demonstrate conformity –harmonized standard, Common Specification (CS), etc…?
  • Specific Standards or CS applied.
  • Evidence of conformity  
  • The controlled document/s demonstrating fulfillment of the ER.
  1. Technical File Conversion Requirest Post-Market Surveillance– The FDA requires PMS activities only if it is mandated due to safety concerns and for Class III or devices with Humanitarian Device Exemptions (HDEs). A PMS plan must then be submitted. Manufacturers may not yet have formulated such a plan.

No worries. If you perform your RM activities in compliance with ISO 14971, you will have an RMP or separate system, including a plan for observations, assessment, and action (ISO 14971:2019 § ten). Reference this in your technical file. What about the PMCF report?  Well, if you’ve performed post-market surveillance, develop one. OTechnical File conversion from a 510k submission is easy, but five elements are missing from a 510k that you will need to add. Otherwise, see the next item below.

  1. Technical File Conversion includes a risk management report

While not required by the FDA in your 510k submission, you most likely have fulfilled this ISO 14971 requirement. Reference it in your technical file. Ensure you also confirm in the report that appropriate methods are in place to obtain production and post-production information. If detailed enough, you can also reference the report as a PMCF report.

  1. Risk class/applicable classification rule (based on Annex VII of the MDR) – FDA defines Classes I through III, which are not parallel to Classes 1, IIa, IIb, or III in the EU MDR.

Using either of the latter systems, identify the relevant rule, and classify your device—document in your technical file.

If you have finished your 510k technical file conversion, you might want to perform a technical file audit before submission to your notified body.

Technical File Conversion – 5 gaps to avoid Read More »

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

1 Comment / 510(k) / By / , , , ,

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 the content referenced on the page. FDA released six new guidance documents 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. Also, 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 the 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. Still, 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 is 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.

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

FDA Approval Process: “Triage” for 510(k)

1 Comment / 510(k) / By / , , ,

The Triage program for 510(k) submissions is reviewed. The goal of this FDA approval process program is to reduce review time from 90 to 30 days.

Thursday, Congress voted 96 to 1 for a bill to increase FDA user fees. The rationale is that the FDA needs more funding to be strong enough to properly regulate foods, drugs, and medical devices. One of the commitments linked with this new funding is to shorten the review of 510(k) submissions. To this end, OIVD has created a new program called “Triage.” The goal of this program is to accelerate the review of specific traditional 510(k) submissions to 30 days instead of 90 days.

In theory, this pilot program will help some companies get their 510(k) clearance letter faster, but simultaneously, the FDA will be able to concentrate resources on high-risk 510(k) submissions. This entire strategy seems to be the opposite of triage. Triage involves sorting sick patients into three categories:

1) Those who are likely to live, regardless of what care they receive

2) Those who are likely to die, regardless of what care they receive

3) Those for whom immediate care might make a positive difference in their outcome

If we apply the triage analogy to 510(k) submissions, we see three categories:

1)      510(k) submissions that are likely to be approved, regardless of how much time the FDA spends

2)      510(k) submissions that are likely to be rejected, regardless of how much time the FDA spends

3)      510(k) submissions whose approval or rejection is not apparent, but the FDA’s earlier involvement in the design and development process would substantially improve review time.

The FDA’s “triage” program is intended to demonstrate improvement in the time required to approve medical devices by sorting submissions into two groups: group #1 above and group # 2/3 from above. This will make the numbers look good, but the FDA should be spending even less time on #2 than it spends on the #1 category of submissions. The FDA should also get involved in group #3 submissions much earlier.

FDA Approval Process

The types of submissions that need more FDA reviewer time are devices that are higher in risk and where special controls guidance documents and or ISO Standards have not already been established for performance and safety testing criteria (i.e., – Category #3 above). In these cases, when a company tries to obtain some feedback from the FDA, they are asked to request a pre-IDE meeting. The company will not be necessarily performing a clinical trial, but this is the only vehicle the FDA has for justifying the time it spends providing feedback on proposed verification and validation testing plans. The FDA needs to develop a new model that is ideally suited for 510(k) products where guidance and Standards do not exist. This would also have the effect of reducing the number of “Not Substantially Equivalent” (NSE) letters the FDA issues.

If a company is developing a device that already has an applicable special controls document or ISO Standard, then the 510(k) pathway should be well-defined without the FDA’s help. Unfortunately, there is no easy mechanism for ensuring compliance with these external standards. This type of submission would benefit from software-controlled submissions and or pre-screening of submissions by third-party reviewers. The Turbo 510(k) software tool could lend itself to software-controlled submissions, but a proliferation of the Turbo 510(k) has been limited.

Submitting a 510(k)

If a company does not submit a 510(k) with all the required elements of a guidance document, the submission should not be processed. Implementation of validated software tools for each 3-letter product code would prevent incomplete submissions. At the very least, companies should be required to provide a rationale for any sections of submission that are not applicable.

One example of a possible software solution is currently used by third-party auditors at BSI. BSI uses a software tool that will not allow the auditor to generate a final report unless all the required elements have been completed. The FDA could use the existing screening checklist and convert this into a similar “SmartForm.” If the submission does not have all the required elements of the checklist, the submission form could not be generated from the software. This forces the task of pre-screening reviews back upon the submitter with the aid of a validated software tool.

The most significant shortfall of the Triage program is the target product types. IVD devices are quite different from other device types. Each IVD has unique chemistry, and there are a limited number of Guidance documents for IVDs, and IVD submissions represent only 10-20% of all submissions. Orthopedic, cardiovascular, general/plastic surgery and radiology devices each represent more than 10% of the submissions, and collectively they represent half of the submissions. These types of devices also have both special controls documents and ISO Standards defining the design inputs for design verification. Therefore, these four device types would be a better choice for a pilot program to expedite reviews.

FDA Approval Process: “Triage” for 510(k) Read More »

Scroll to Top