510(k)

FDA pre-market notification submission for medical devices.

Best human factors questions?

Best human factors questions to ask the FDA during a pre-submission meeting, and what information content do you need in a 510k?

Human factors questions to ask the FDA?

The FDA did not start enforcing the requirement to apply human factors and usability engineering to medical device design until 2017 because the final version of the human factors guidance document was not released until February 3, 2016. Approximately ninety percent of the human factors testing reports submitted to the FDA in 510k pre-market submissions are deficient because the 510k submission content only includes the final summative testing report. The FDA needs a complete usability engineering file, and the human factors information needs to comply with FDA guidelines for the format and content of a 510k pre-market submission–not just IEC 62366-1:2015.

Follow the FDA guidance 1024x180 Best human factors questions?

What human factors information does the FDA want?

For several years, FDA submission deficiency letters indicated that you should not include the frequency of occurrence in your estimation of use-related risks. Still, the FDA never provided this information in a guidance document. On December 9, 2022, the FDA finally released a draft human factors guidance regarding the format and content of a 510k pre-market submission. The new draft guidance includes a use-related risk analysis (URRA) requirement in table 2 (copied below).

Table 2 example of tabular format for the URRA 1024x354 Best human factors questions?

In this new draft FDA guidance, the FDA identifies three different human factors submission categories. For the first category, only a conclusion and high-level summary are needed. For the second category, a user specification is also needed. For the third category, you need a comprehensive human factors engineering report with the following elements described in Section IV of the draft FDA guidance:

Submission Category 1, 2, and 3

  • Conclusion and high-level summary

Submission Category 2 and 3

  • Descriptions of intended device users, uses, use environments and training
  • Description of the device-user interface
  • Summary of known use problems

Submission Category 3 only

  • Summary of preliminary analyses and evaluations
  • Use-related risk analysis to analyze hazards and risks associated with the use of the device
  • Identification and description of critical tasks
  • Details of validation testing of the final design

Before spending tens of thousands or hundreds of thousands of dollars on human factors testing, you want to ensure the FDA agrees with your human factors testing plan. Otherwise, you will pay for the testing twice: once for your initial submission and a second time in your response to the FDA request for additional information to address deficiencies. Testing can cost more than your electrical safety testing. The facility needs the right equipment and space for the testing; you need support personnel to set up the equipment; you need to recruit participants; you need to compensate participants; and you need device samples.

When can you ask the FDA human factors questions?

The FDA cannot provide consulting advice on a submission, and the agency will not review data during pre-submission meetings. The FDA can provide feedback on protocols, specifications, and scientific justifications. Therefore, you should submit questions to the FDA in a pre-submission when you have a draft protocol, a draft specification, or a draft justification for why a task is not critical. Pre-submissions are “non-binding.” You can change your design and approach to human factors. Therefore, don’t wait until your information is 100% finalized. Share your documentation at the draft stage during the development phase and before your design freeze. You need these answers when you are planning a study and obtaining quotes. 

What are the best human factors questions to ask in a pre-sub?

In the FDA guidance for pre-submission meetings, the FDA provides suggested questions to ask:

  • Does the Agency have comments on our proposed human factors engineering process?
  • Is the attached use-related risk analysis plan adequate? Does the Agency agree that we have identified all the critical tasks?
  • Does the Agency agree with our proposed test participant recruitment plan for the human factors validation testing?

The above examples are only suggestions, but the best approach is to provide a brief example of what the human factors information will look like and ask the FDA to comment on the examples. The FDA does not have time to review data during a pre-sub meeting, but the FDA can review a few rows extracted from your URRA and comment on your proposed approach to the human factors process.

Human factors questions that are not appropriate

The FDA pre-submission guidance cautions you only to ask 3-4 questions for each meeting request because the FDA has difficulty answering more questions in a 60-minute teleconference. Therefore, you should not ask questions already answered in the FDA guidance. The new draft guidance includes examples of when a device modification can leverage existing human factors information and when new information is needed to support a premarket submission. Instead of asking a question specific to leveraging existing human factors information, provide your rationale for leveraging existing data and ask if the FDA has any concerns with your overall approach to human factors.

Recommended human factors action items

Create a procedure for your human factors process that includes detailed instructions for creating the information required in a usability engineering report and templates for each document.

Best human factors questions? Read More »

Software validation documentation for a medical device

Learn why you need to start with software validation documentation before you jump into software development.

When do you create software validation documentation for a medical device or IVD?

At least once a week, I speak with the founder of a new MedTech company that developed a new software application as a medical device (SaMD). The founder will ask me to explain the process for obtaining a 510(k), and they want help with software validation documentation. Many people I speak with have never even heard of IEC 62304.

Even though they already have a working application, usually, validation documentation has not even been started. Although you can create all of your software validation documentation after you create a working application, certain tasks are important to perform before you develop software code. Jumping into software development without the foundational documentation will not get your device to market faster. Instead, you will struggle to create documentation retroactively, and the process will be slower. In the end, the result will be a frustrating delay in the launch of your device.

What are the 11 software validation documents required by the FDA?

In 2005 the FDA released a guidance document outlining software validation documentation content required for a premarket submission. There were 11 documents identified in that guidance:

software validation documentation 1024x385 Software validation documentation for a medical device

What the FDA guidance fails to explain is that some of these documents need to be created before software development begins, or your software validation documentation will be missing critical design elements. Therefore, it is important to create a software development plan that schedules activities that result in those documents at the right time. In contrast, four of the eleven documents can wait until your software development is complete.

Which of the software validation documents can wait until the end?

The level of concern only determines what documents the FDA wants to review in a submission rather than what documents are needed for a design history file. In fact, the level of concern (LOC) document is no longer required as a separate document in premarket submissions using the FDA eSTAR template because the template already incorporates the questions that document your LOC. The revision level history document is simply a summary of revisions made to the software during the development process, and that document can be created manually or automatically at the end of the process, or the revision level history can be a living document that is created as changes are made. The traceability matrix can also be a living document created as changes are made, but its only purpose is to act as a tool to provide traceability from hazards to software requirements, to design specifications, and finally to verification and validation reports. Other software tools, such as Application Lifecycle Management (ALM) Software, are designed to ensure the traceability of every hazard and requirement throughout the entire development process. Finally, unresolved anomalies should only be documented at the time of submission. The list may be incomplete until all verification and validation testing is completed, and the list should be the shortest at the time of submission.

What documentation will be created near the end of development?

The software design specification (SDS) is typically a living document until your development process is completed, and you may need to update the SDS after the initial software release to add new features, maintain interoperability with software accessories, or change security controls. The SDS can not begin, however, until you have software requirements and the basic architecture defined. The verification and validation activities are discrete documents created after each revision of the SDS and must therefore be one of the last documents created–especially when provided to the FDA as a summary of the verification and validation efforts.

Which validation documents do you need first?

At the beginning of software development, you need a procedure(s) that defines your software development process. That procedure should have a section that explains the software development environment–including how patches and upgrades will be controlled and released. If you don’t have a quality system procedure that defines your development process, then each developer may document their coding and validation activities differently. That does not mean that you can’t improve or change the procedure once development has begun, but we recommend limiting the implementation of a revised procedure when making major software changes and discussing how revisions will be implemented for any work that remains in progress or has already been completed.

When do the remaining software validation documents get created?

The remaining four software validation documents required for a premarket submission to the FDA are:

  1. Software description
  2. Software hazard analysis
  3. Software requirements specification (SRS)
  4. Architecture design chart

Your development process will be iterative, and therefore, you should be building and refining these four documents iteratively in parallel with your software code. At the beginning of your project, your design plan will need a brief software description. Your initial software description needs to include the indications for use, a list of the software’s functional elements, and the elements of your user specification (i.e., intended patient population, intended users, and user interface). If you are using lean startup methodology, the first version of your device description will be limited to a minimal viable product (MVP). The target performance of the MVP should be documented as an initial software requirements specification (SRS). This initial SRS might only consist of one requirement, but the SRS will expand quickly. Next, you need to perform an initial software hazard analysis to identify the possible hazards. It is important to remember that software hazards are typically hazardous situations and are not limited to direct physical harm. For each potential hazard you identify in your hazard analysis, you will need a software requirement to address each hazard, and each requirement needs to be added to your SRS. As your software becomes more complex by adding software features, your device description needs to be updated. As you add functions and requirements to your software application, your SRS will need updates too. Finally, your development team will need a tool to track data flow and calculations from one software function to the next. That tool is your architecture design chart, and you will want to organize your SRS to match the various software modules identified in your architecture diagram. This phase is iterative and non-linear, you will always have failures, and typically a team of developers will collaborate virtually. Maintaining a current version of the four software documents is critical to keeping your development team on track.

How do you perform a software hazard analysis?

One of the most important pre-requisite tasks for software developers is conducting a hazard analysis. You can develop an algorithm before you write any code, but if you start developing your application to execute an algorithm before you perform a software hazard analysis, you will be missing critical software requirements. Software hazard analysis is different from traditional device hazard analysis because software hazards are unique to software. A traditional device hazard analysis consists of three steps: 1) answering the 37 questions in Annex A of ISO/TR 24971:2020, 2) systematically identifying hazards by using Table C1 in Annex C of ISO 14971:2019, and 3) reviewing the risks associated with previous versions of the device and similar competitor devices. A software hazard analysis will have very few hazards identified from steps 1 and 2 above. Instead, the best resource for software hazard analysis is IEC/TR 80002-1:2009. You should still use the other two standards, especially if you are developing software in a medical device (SiMD) or firmware, but IEC/TR 80002-1 has a wealth of tables that can be used to populate your initial hazards analysis and to update your hazard analysis when you add new features.

How do you document your hazard analysis?

Another key difference between a traditional hazard analysis and a software hazard analysis is how you document the hazards. Most devices use a design FMEA (dFMEA) to document hazards. The dFMEA is a bottom-up method for documenting your risk analysis by starting with device failure modes. Another tool for documenting hazards is a fault tree diagram.

Fault Tree Example from AAMI TIR 80002 1 2009 300x239 Software validation documentation for a medical device
Copied from Section 6.2.1.5 from AAMI / IEC TIR 80002-1:2009

A fault tree is a top-down method for documenting your risk analysis, where you identify all of the potential causes that contribute to a specific failure mode. Fault tree diagrams lend themselves to complaint investigations because complaint investigations begin with the identification of the failure (i.e., complaint) at the top of the diagram. For software, the FDA will not allow you to use the probability of occurrence to estimate risks. Instead, software risk estimation should be limited to the severity of the potential harm. Therefore, a fault tree diagram is generally a better tool for documenting software risk analysis and organizing your list of hazards. You might even consider creating a separate fault tree diagram for each module of your software identified in the architecture diagram. This approach will also help you identify the potential impact of any software hazard by looking at the failure at the top of the fault tree. The higher the potential severity of the software failure, the more resources the software team needs to apply to developing software risk controls and verifying risk control effectiveness for the associated fault tree.

Software validation documentation for a medical device Read More »

FDA CCP now accepts FDA eSTAR & eCopy

Finally, we can use the new FDA CCP to eliminate FedEx shipments, and 100% of your submissions will be electronic through the portal.

July 2022 Update for the FDA eCopy process

The FDA created a Customer Collaboration Portal (CCP) for medical device manufacturers. Initially, the portal’s purpose was to provide a place where submitters could track the status of their submissions and verify the deadlines for each stage of the submission review process. Last week, on July 19, the FDA emailed all active FDA CCP account holders that they can upload both FDA eCopy and FDA eSTAR files to the portal 100% electronically. The FDA released an eSTAR draft guidance as well. Since our consulting team sends out submissions daily, everyone on the team was able to test the new process. If you have a CCP account, you no longer need to ship submissions via FedEx to the Document Control Center (DCC).

FDA CCP step-by-step uploading process

When you are uploading an FDA eCopy for medical device submission to the Document Control Center (DCC), using the new FDA CCP, the following steps are involved:

  1. Confirm your eCopy complies with FDA’s eCopy guidance.
  2. Compress your eCopy into a “.zip” file.
  3. Sign in to the portal on the login page
  4. Click on the “+” symbol on the left panel of the webpage (if you hover over the “+” symbol, you will see “Send a submission”)
  5. Select your desired upload format (pre-submissions, meeting minutes, breakthrough device designations, and withdrawal letters must be submitted as an eCopy)Format Selection 1024x515 FDA CCP now accepts FDA eSTAR & eCopy
  6. Click on the “Next” button that appears below the selection formats once a format is selected
  7. Drag & drop your single “.zip” file here, or browse for it.
  8. Click on “Send” button to complete the uploading process.Send Step 1024x528 FDA CCP now accepts FDA eSTAR & eCopy
  9. Verify that the FDA CCP site gives you a confirmation for the successful uploading of your submission.Confirmation that eCopy was sent 1024x556 FDA CCP now accepts FDA eSTAR & eCopy

FDA Q&A about the new FDA CCP Submission Uploading Process

  1. Medical Device Academy Question: Who will be permitted to use the FDA CCP to upload submissions for the DCC? FDA Response: We will first offer this feature in batches to people like you who already use CCP so we can study its performance. We will then refine it and make it available to all premarket submitters.
  2. Medical Device Academy Question: What do you need to use the FDA CCP? FDA Response: You don’t need to do anything to participate since you already use CCP. We will email you again when you can start sending your next submissions online.
  3. Medical Device Academy Question: Suppose another consultant asks me to submit an eSTAR or eCopy for them, or I do this for a member of my consulting team. Is there any reason I cannot upload the submission using my account even though the other person is the official submission correspondent and their name is listed on the cover letter? FDA Response: The applicant and correspondent information of the submission is still used when logging the submission in. The submitter (i.e., the person uploading the submission) is not used in any part of the log-in process. The submission portal is essentially replacing snail mail only; once the DCC loads the submission, whether it be from a CD or an online source, the subsequent process is identical to what it used to be, for now.
  4. Medical Device Academy Question: Is there any type of eCopy that would not be appropriate for this electronic submission process (e.g., withdrawal letters, MAF, or breakthrough device designations)? FDA Response: You can use the eCopy option to submit anything that goes to the DCC, so all your examples are fair game, though interactive review responses would still be emailed to the reviewer.
  5. Medical Device Academy Question: How can I get help from the FDA? FDA Response: If you have questions, contact us at CCP@fda.hhs.gov.

FDA CCP now accepts FDA eSTAR & eCopy Read More »

What’s new in the 2022 draft cybersecurity guidance?

On April 8, 2022, the FDA released a new draft cybersecurity guidance document to replace the 2018 draft that the industry does not support.

Why was the draft cybersecurity guidance created?

Due to the ubiquitous nature of software and networked devices in the medical industry, the impact of cybersecurity attacks is becoming more frequent and more severe. The WannaCry Ransomeware Attack is just one example of this global cybersecurity issue. The FDA is responding to the need for stronger cybersecurity controls by issuing a new draft cybersecurity guidance for 2022.

The first four paragraphs of the introduction explain why we need this, and WannaCry is mentioned in the second paragraph of the background section. This new guidance is only a draft, but this is the FDA’s third attempt at regulating the cybersecurity of medical devices. The first guidance was finalized in 2014. That’s the 9-page guidance we currently have in effect. The guidance mentions risk 11 times and there is no mention of testing requirements or a bill of materials (BOM). The 2018 draft guidance (24-pages) met with resistance from the industry for a lot of reasons. One of the reasons mentioned by Suzanne Schwartz in an interview is the inclusion of a cybersecurity bill of materials (CBOM). The industry felt it would be too burdensome to disclose all of the hardware elements that are related to cybersecurity. Therefore, the FDA rewrote the 2018 draft and released a new draft on April 8, 2022 (49-pages).

Untitled presentation e1650071404761 What’s new in the 2022 draft cybersecurity guidance?

You might have expected the FDA to soften its requirements in the face of resistance from industry, but the new draft does not appear to be less robust. It is true that the CBOM was replaced by a software bill of materials (SBOM). However, the SBOM must be electronically readable and it must include:

  • the asset(s) where the software resides;
  • the software component name;
  • the software component version;
  • the software component manufacturer;
  • the software level of support provided through monitoring and maintenance from the software component manufacturer;
  • the software component’s end-of-support date; and
  • any known vulnerabilities.

You can be sure that the medical device industry will view providing an SBOM as a hefty burden. After all, a machine-readable SBOM is more complex than UDI labeling requirements. An SBOM will not fit on the “Splash Screen” for anyone’s software application. Companies may provide documentation through the company website with a link in their software to that information. The format of the information could be in the “Manufacturer Disclosure Statement for Medical Device Security (MDS2).” However, MDS2 is a 349-line item Excel spreadsheet to be used as a checklist (i.e. quite a bit longer than the GUDID data elements spreadsheet), and it took the FDA eight years to complete the transition for the UDI Final Rule (i.e. 2013 – 2021).

The 2018 draft cybersecurity guidance document from the FDA required a cybersecurity bill of materials (CBOM). CBOM was defined as “a list that includes but is not limited to commercial, open source, and off-the-shelf software and hardware components that are or could become susceptible to vulnerabilities.” Therefore, the FDA’s change from a CBOM to an SBOM eliminated the requirement to disclose the hardware components. Despite the change in disclosure requirements, manufacturers will still be expected to monitor potential hardware vulnerabilities to cybersecurity attacks. It should also be noted that the language in the PATCH Act (a new bill submitted to the House of Representatives and to the Senate for ensuring the cybersecurity of medical devices) specifically requires manufacturers “to furnish a software bill of materials as required under section 524B (relating to ensuring the cybersecurity).”

 Structure of the draft cybersecurity guidance

The 2022 draft cybersecurity guidance organizes the requirements into four major principles:

  1. cybersecurity as part of device safety and the quality system regulations
  2. designing for security
  3. transparency
  4. submission documentation

The draft cybersecurity guidance recommends the implementation of a Secure Product Development Framework (SPDF). However, there is not much detail provided in the guidance for a SPDF. In the past, the term for this type of process was referred to as a Secure Software Development Lifecycle (i.e. Secure SDLC). However, in February 2022, the NIST Computer Security Resource Center (CSRC) released version 1.1 of the Secure SDLC guidance which is now titled “Secure Software Development Framework (SSDF) Version 1.1: Recommendations for Mitigating the Risk of Software Vulnerabilities.” This guidance provides guidance on the implementation of best practices for reducing the risk of software vulnerabilities because existing standards for managing the software development lifecycle do not explicitly address software security (e.g. IEC 62304-1:2015). The SSDF recommends implementing a core set of high-level secure software development practices that can be integrated into your SDLC process. Your software development team will also require cybersecurity training.

Design for security is the second principle of the draft cybersecurity guidance

Under this new draft cybersecurity guidance, the FDA will be evaluating the cybersecurity of devices based on the ability of the device to provide and implement the following security objectives:

  • Authenticity, which includes integrity;
  • Authorization;
  • Availability;
  • Confidentiality; and
  • Secure and timely updatability and patchability.

Transparency of cybersecurity information is for users

The draft cybersecurity guidance seeks to give device users more information pertaining to the device’s cybersecurity controls, potential risks, and other relevant information. This information will be in the form of an SBOM that is electronically readable. This information shall include disclosure of 1) known vulnerabilities or risks, 2) information to securely configure and update devices, and 3) communication interfaces and third-party software.

In addition to providing an SBOM, the FDA draft cybersecurity guidance includes requirements for cybersecurity labeling in section VI(A). There are 15 specific labeling requirements identified by the FDA for sharing with device users to improve the transparency of cybersecurity information. The first of these requirements is recommendations from the manufacturer for cybersecurity controls appropriate for the intended use environment (e.g., antimalware software, use of a firewall, password requirements). This first labeling requirement is identical to the 2018 draft guidance. Several of the other requirements are copied from the 2018 draft guidance, but others are new and/or reworded cybersecurity labeling requirements.

FDA Submission Documentation Requirements

The 2022 FDA draft cybersecurity guidance includes requirements for FDA submission documentation. Submission documentation must include a security risk management plan and report. The draft cybersecurity guidance explains on page 13 (numbered 9) that “performing security risk management is a distinct process from performing safety risk management as described in ISO 14971:2019.” Therefore, instead of using your safety risk management process, your software development team will need to have a different risk management process for software security. Details on the content for security risk management plans and reports can be found in AAMI TIR57:2016 – Principles for medical device security—Risk management. Appendix 2 also provides guidance for the inclusion of a) call flow diagrams, and b) information details for an architecture view.

Cybersecurity testing requirements for your FDA submission

The biggest impact of this new draft guidance may be the requirement for testing. The 2014 guidance has no testing requirement, the 2018 draft guidance mentioned testing 5 times in a few bullet points, but this new draft guidance mentions testing 43 times. The testing requirements for cybersecurity risk management verification include:

  1. Security requirements
  2. Threat mitigation
  3. Vulnerability testing
  4. Penetration testing

This guidance also includes a paragraph with multiple bullets of requirements for each of the four types of testing. This would essentially double the size and scope of the current software section for a 510k submission, and manufacturers will need to create new procedures and templates for their cybersecurity risk management process. For example, penetration testing requirements include the following elements:

  • Independence and technical expertise of testers,
  • Scope of testing,
  • Duration of testing,
  • Testing methods employed, and
  • Test results, findings, and observations.

Differences between the cybersecurity guidance documents

The following table provides a high-level overview comparing the four cybersecurity guidance documents released by the FDA, including the 2016 guidance on post-market management of cybersecurity:

Screenshot 2022 04 16 12.48.51 AM 1024x291 What’s new in the 2022 draft cybersecurity guidance?

Vulnerability management plans

The FDA draft cybersecurity guidance document also has a requirement for manufacturers to develop a plan for identifying and communicating vulnerabilities to device users after the release of the device. The FDA requires this plan to be included in your device submission. The vulnerability management plan should include the following information (in addition to the requirements of the 2016 guidance for postmarket cybersecurity management):

  • Personnel responsible;
  • Sources, methods, and frequency for monitoring for and identifying vulnerabilities (e.g. researchers, NIST NVD, third-party software manufacturers, etc.);
  • Periodic security testing to test identified vulnerability impact;
  • Timeline to develop and release patches;
  • Update processes;
  • Patching capability (i.e. rate at which update can be delivered to devices);
  • Description of their coordinated vulnerability disclosure process; and
  • Description of how manufacturer intends to communicate forthcoming remediations, patches, and updates to customers.

What’s the next step for the draft cybersecurity guidance?

In March the “Protecting and Transforming Cyber Health Care Act of 2022 (PATCH Act)” was introduced to the House of Representatives and the Senate. The goal of the PATCH Act is to enhance medical device security by requiring manufacturers to create a cybersecurity risk management plan for monitoring and addressing potential postmarket cybersecurity vulnerabilities. The FDA seeks comments on the draft cybersecurity guidance through July 7, 2022. Given the support of the new bill in the House of Representatives and Congress, it is likely that the FDA will get the support it needs for this new guidance. 

What’s new in the 2022 draft cybersecurity guidance? Read More »

Feedback options for your pre-sub meeting request

This article analyzes feedback options offered for a pre-submission meeting request and gives you insight into which option is best for you.

Pre submission meeting request feedback options Feedback options for your pre sub meeting request

In 2021 the FDA published an updated guidance document about pre-submission meeting requests (i.e., pre-sub meetings). The purpose of a pre-submission meeting is to ask and obtain answers to your questions directly from the FDA. The guidance document has great advice on what to ask the FDA and what you should not ask. The best time to be asking the FDA questions is before you begin your verification and validation testing. The FDA can give you valuable feedback on your testing plan to demonstrate safety and efficacy, but if you already started your testing it’s too late. Unfortunately, the guidance document has no advice on which method of feedback to select or why.

What is the last section of your pre-sub?

The last section of your pre-submission meeting request should indicate what method of feedback you prefer and what your preferred dates are for a potential meeting with the FDA. There are three options offered for methods of feedback:

  1. a face-to-face meeting
  2. a conference call
  3. an email response

Feedback option 1 – A Face-to-Face Meeting

Some executives believe that face-to-face meetings are critical in establishing relationships with people. However, you need to understand the culture of the people your are trying to build a relationship with. The FDA is an overworked bureaucracy, and government agencies have security concerns. When the FDA meets with visitors they must go to a different building and arrange for their guests to pass through security. This is more work and takes more time. To justify the extra work and time, you need a compelling reason why a face-to-face meeting with the FDA is necessary.

Traveling to the FDA will cost your team money and time that conference calls and emails will not. More importantly, you are limited to one hour for a pre-submission meeting. One hour is barely enough time to ask questions and listen to the answers. You only have minutes to introduce your company, your team and the describe the product. There is no time for relationship building. The best way to impress the FDA is to: 1) prepare thoroughly, 2) conduct an efficient meeting, and 3) ask smart questions.

There is one time when you should visit the FDA face-to-face–if you have a powerful demonstration and video just isn’t good enough.

Feedback option 2 – Conference Call

Conference calls save you time and money, but conference calls also save the FDA time and effort. You won’t personally meet people from the agency, but you can communicate information prior to the meeting and you can provide videos of simulated use for your device. Conference calls do have the advantage of allowing you to mute the call for a moment and make a comment among your team members without the agency listening as well. Whenever you are discussing a performance testing plan or a clinical study protocol with the FDA, you will probably want a conference call to enable clarification questions.

Feedback option 3 – Email

Email responses from the FDA are highly underrated in value. When you specify an email response, you generally receive a response to your questions sooner. You also should receive more information, because each person from the agency is able to provide an hour of their time to write detailed feedback. In a conference call, you are speaking for part of the hour and only one person from the FDA can speak at a time. Therefore, you almost always have less feedback during conference calls and face-to-face meetings. The primary downside to email as a feedback method is that it is not interactive.

Update Related to Covid-19 Pandemic

The FDA is not allowing face-to-face meetings during the Covid-19 pandemic. Three of the pre-subs Medical Device Academy submitted during the pandemic were rejected by the FDA due to insufficient FDA resources. We are also noticing increased delays in the pre-sub timeline. Two pre-subs had a 5-month scheduling lead-time instead of 60-75 days. Due to these delays, we have advised many clients to skip the presub if testing requirements are well defined in guidance documents and predicate 510k summaries. Althought the email option should theoretically result in a faster response from the FDA, during the pandemic we have actually seen that the teleconference options has been faster. My theory is that the teleconferences are require coordinating the schedules of multiple people, and therefore there is more focus by lead reviewers in making sure the feedback is provided in time for the scheduled teleconference. 

Which feedback option will you pick?

Regardless of which feedback method you choose, you can always follow-up with supplemental questions and obtain additional feedback from the FDA after you receive the initial response to your pre-submission meeting request. If you are planning a clinical study, you might seek interactive feedback in a conference call during the pre-submission meeting. Then you can follow-up with a clinical study protocol as a supplement to obtain additional feedback from the FDA.

Additional Resources

If you are interested in learning more about a pre-submission meeting request to the FDA, consider watching and listening to a webinar on the topic.

Feedback options for your pre-sub meeting request Read More »

How to find updated FDA forms for a 510k

Before you complete FDA forms for your 510k submission, you need to made sure you have the most updated FDA forms.

How do you know if the FDA form you are using is current?

The FDA assigns numbers to each FDA form and the document control number is found in the bottom left footer of the document. In addition, the top right-hand header of the document will have an expiration date for the form (see the picture below). Often the changes to FDA forms are minor, but you should only submit the current version of the FDA form which has not expired.

FDA Form 3881 screen capture How to find updated FDA forms for a 510k

What happens if you are using an expired FDA form?

In the past, if you included an obsolete document in your submission the FDA would often ignore this an proceed with the review of your submission anyway. Now FDA reviewers will identify the obsolete form and require you to resubmit the document on the current version of the form. If the reviewer is conducting an initial Refusal to Accept (RTA) screening, and one of the required items in the RTA screening are identified, then you will receive an RTA Hold letter and the RTA checklist will include a comment that you have used an obsolete version of an FDA Form.

If there are no deficiencies identified in the RTA checklist, the reviewer may still send you an email asking you to submit the document on the correct form. This could be a formal amendment (e.g. K123456/A001) or it could be as an informal email of the corrected document. This type of request could also be identified after the substantive review is complete in the form of a comment in an Additional Information (AI) Request or as part of an Interactive Review Request. An AI Request must be responded to with a formal supplement submitted to the Document Control Center (DCC) as a supplement to the original submission (e.g. K123456/S001) or as an informal ammendment submitted by email.

Examples of updated FDA forms for your 510k submission

Expired forms are frequently submitted to the FDA because submitters are using templates that have not been properly maintained or the submitter modified a form that was submitted in a previous 510k submission. The most common examples include: FDA Form 3514 (i.e. Submission Coversheet), FDA Form 3881 (i.e. Indications for Use), and the RTA Checklist.

Where can you find updated FDA forms?

Recently one of our clients noticed that the 510k template folder we share with people that have purchased our 510k course included obsolete templates for Financial Disclosure. There are three financial disclosure forms that can be used for a 510k submission or De Novo Classification Request:

  1. FDA Form 3454, Certification: Financial Interest and Arrangements of Clinical Investigator (PDF)
  2. FDA Form 3455, Disclosure: Financial Interest and Arrangements of Clinical Investigators (PDF)
  3. FDA Form 3674, Certification of Compliance, under 42 U.S.C. , 282(j)(5)(B), with Requirements of ClinicalTrials.gov (PDF)

We normally update these FDA forms as soon as the new form is released, but this financial disclosure forms are only used in about 10-15% of 510k submissions.

The current version of most FDA forms can usually be found by simply conducting an internet search for the form using your favorite browser. However, sometimes you may find a copy of the document that was editted by a consultant to facilitate completion of the document as an unsecured PDF or Word document. Although this is convenient, you should not use these “bastardized” forms. You should use the original secured form provided by the FDA. These native forms require Adobe Acrobat to complete the form and save the content. The most current version of the FDA form can be found using the FDA’s Form search tool.

Editing and Signing FDA Forms

Most of the FDA forms are secured and you can only enter information in specific locations. If there is a location for a signature, usually the signature cannot be added in Adobe to the secured form. In these situations, our team will save the document as a “Microsoft Print PDF” format. Once the document has been saved in this “non-native” format, you can manipulate almost anything in the document. Then we will add signatures using the “Fill and Sign” tool in Adobe Acrobat or we will use the “Edit” tool. Editing also gives us ability to make corrections when the document has incorrect information filled in the form somewhere.

Another option for adding dates and signatures is for you to save the document as a non-secure PDF. Then using an electronic signature software tool like Docusign, you can request that another person add their electronic signature or you can add your own electronic signature. Some companies prefer to do this to ensure the electronic signature meets 21 CFR Part 11 requirements, but the FDA accepts scanned images of a signature that was added to the document without certification in a 510k submission. This is even true for the Truthful and Accuracy Statement for a 510k. That document can be attached as a PDF in an FDA eSTAR template or you can electronically sign the eSTAR template if the person preparing the eSTAR is also the person signing the Truthful and Accuracy Statement.

Tips and Tricks for maintaining templates

Our company is a consulting firm, and we do not have a formal document control process that would be typical of our clients. However, we do have a shared Dropbox folder where we maintain the most current version of 510k templates. Any obsolete versions we move to an archive folder. However, there are ways to improve this informal system. You can include a date of the document in the file name. For example, “Vol 4 001_Indications for Use (FDA Form 3881) rvp 2-7-2022.” This indicates that this file is the FDA Form 3881 which is the indications for use form used in Volume 4 of the 510k submission. The document is the first document in that volume. The date the form was revised and saved is February 7, 2022 and the author’s initials are “rvp.”

If you are saving 510k templates you might consider adding an expiration date to the file name. For example, “Vol 4 001_Indications for Use (FDA Form 3881) exp 06-30-2023.” This file name indicates that the form’s expiration date is June 30, 2023. The inclusion of an expiration date in the file name is a visual reminder of when you will need to search for an updated FDA form.

A third way to manage your FDA Forms is to include them in your documents of external origin. ISO 13485:2016, Clause 4.2.4, requires that you maintain control of documents of external origin. Therefore, if your company has a formal quality system, a list or log of documents of external origin is the best way to manage FDA forms. Your log should indicate the date the updated FDA form was created, any parent guidance documents should be cross-referenced, and the expiration date of the FDA form should be identified. By using a log of this type, you can sort the list by expiration date or by the date of creation if there is no expiration date identified. Sorting the list will help your team prioritize which documents need to be reviewed next for new and revised versions.

Additional 510k submission resources

The FDA will be updating the 510k guidance for the new FDA eSTAR template by September 2022. Medical Device Academy will be systematically updating all of our templates and training webinars related to preparation of 510k submissions. We will also be preparing for the transition from FDA eCopy submissions to electronic submissions via a Webtrader Account.

You can keep up-to-date on template revisions in one of two ways:

  1. Purchase our 510k course, and you will receive access to the updated templates as they are created. We will send email notifications each time a template is updated.
  2. Register for our New Blog email subscription for automated email notifications of when a new blog is released about updated FDA forms, templates, and webinars.
  3. Register for our New Webinar email subscription for automated email notifications of when a new or revised webinar is scheduled and for email notification of our newest live streaming YouTube videos.

How to find updated FDA forms for a 510k Read More »

eSTAR draft guidance is here, and wicked eSubmitter is dead.

I hated the the FDA eSubmitter template which was discontinued May 30, 2021. Finally we have eSTAR draft guidance for the new eSTAR template.

eSTAR draft guidance button eSTAR draft guidance is here, and wicked eSubmitter is dead.

History of 510k electronic submissions

The FDA has experimented with a multitude of pilot 510k submission programs over the years to streamline and improve the 510k submission content, formatting, and to facilitate a faster review process. The Turbo 510k program was one of the first successful pilot programs. In 2012 I wrote one of my first blogs about how to improve the 510k process. In September 2018, the FDA launched the “Quality in 510k Review Program Pilot” for certain devices using the eSubmitter electronic submission template. The goal of the this pilot program was to enable electronic submissions instead of requiring manufacturers to deliver USB flash drives to the FDA Document Control Center (DCC). I hated the eSubmitter template, and the FDA finally discontinued availability of the eSubmitter template on May 30, 2021. During the past 15 years, the FDA gradually streamlined the eCopy process too. Originally we had to submit one complete hardcopy, averaging 1,200 pages per submission, and one CD containing an electronic “eCopy.” Today, the current process involves a single USB flash drive and a 2-page printed cover letter, but today’s eCopy must still be shipped by mail or courier to the DCC.

eSTAR Pilot Program is Launched

During the 15-year evolution of the FDA eCopy, CDRH was trying to develop a reliable process for electronic submissions of a 510k. CBER, the biologics division of the FDA, has already eliminated the submission of eCopy submissions and now 100% of biologics submissions must be submitted through an electronic submissions gateway (ESG). In February 2020, CDRH launched a new and improved 510k template through the electronic Submission Template And Resource (eSTAR) Pilot Program. The eSTAR templates include benefits of the deceased eSubmitter template, but CDRH has incorporated additional benefits:

  • the templates use Adobe Acrobat Pro instead of a proprietary application requiring training;
  • support for images and messages with hyperlinks;
  • support for creation of Supplements and Amendments;
  • availability for use on mobile devices as a dynamic PDF;
  • ability to add comments to the PDF; and
  • the content and logic mirrors checklists used by CDRH reviewers.

Medical Device Academy’s experience with the eSTAR Templates

Every time the FDA has released a new template for electronic submissions we have obtained a copy and tried populating the template with content from one of our 510k submissions. Unfortunately, all of the templates have been slower to populate that the Word document templates that our company uses every day. On May 16 we conducted an internal training for our team on the eSTAR submission templates, and we published that training as a YouTube Video (see embedded video below). Then nine days later the FDA released updates to the eSTAR templates (version 0.7). The new eSTAR templates are available for non-IVD and IVD products (ver 0.7 updated May 27, 2021).

Sharon Morrow submitted our first eSTAR template to the FDA in August and we experienced no delays with the 510k submission during the initial uploading to the CDHR database, there was no RTA screening process, and CDRH did not identify any issues during their technical screening process. Shoron’s first eSTAR submission is now in interactive review, which is a better outcome than 95%+ of our 510k submissions. I have several other eSTAR submissions that are almost ready to submit as well. The other 510k consultants on our team are also working on their first eSTAR submissions.

Finally the CDRH releases an FDA eSTAR draft guidance

On September 29, 2021 the FDA released the new eSTAR draft Guidance for 510k submissions. This is a huge milestone because there have not been any draft guidance documents created for pilot programs. The draft indicates that the comment period will last 60 days (i.e. until November 28, 2021). However, the draft also states that the guidance will not be finalized until a date for requiring electronic submissions (i.e. submission via an ESG) is identified. The draft indicates that this will be no later than September 30, 2022. Once the guidance is finalized, there will be a transition period of at least one year where companies may submit via an ESG or by physical delivery to the FDA DCC.

Are there any new format or content requirements in the FDA eSTAR draft guidance?

There are no new format or content requirements in the eSTAR draft guidance, but the eSTAR template itself has several text boxes that must be filled in with summary information that is not specified in the guidance for format and content of a 510k. The information requested for the text boxes is a brief summary of non-confidential information contained in the attachments of the submission. Therefore, these boxes can information that would normally be in the overview summary documentst that are typically included at the beginning of each section of a 510k. If your overview documents do not already have this information, then you may have some additional work to do in order to complete the eSTAR templates. An example of one of these text boxes is provided below:

Summary of electrical mechanical and thermal testing eSTAR draft guidance is here, and wicked eSubmitter is dead.

Another example of additional content required by the eSTAR templates is references to page numbers. Normally the FDA reviewer has to search the submission for information that is required in their regulatory review checklist. In the new templates the submitter is now asked to enter the page numbers of each attachment where specific information can be found. The following is an example of this type of request for a symbols glossary:

Reference to symbols glossary in labeling eSTAR draft guidance is here, and wicked eSubmitter is dead.

Are there any changes to the review timelines for a 510k in the eSTAR draft guidance?

The eSTAR draft guidance indicates that a technical screening will be completed in 15 calendar days instead of conducting a RTA screening. I believe that the technical screening is less challenging than the RTA screening, but the FDA has not released a draft of the technical screening criteria or a draft checklist. I would imagine that the intent was to streamline the process and reduce the workload of reviewers performing a technical screening, but we only have guesses regarding the substance of the technical review and so far our performance is 100% passing (i.e. 1 of 1). The next step in the 510k review process is a substantive review. Timelines for the substantive review are not even mentioned in the new draft guidance, but the FDA usually has the review clock details in Table 1 (MDUFA III performance goals) and Table 2 (MDUFA IV performance goals) of the FDA guidance specific to “Effect on FDA Review Clock and Goals.” In both tables, the goal is 60 calendar days, and our first eSTAR submission completed the substantive review in 60 days successfully. The 180-day deadline for responding to an additional information (AI) request has not changed in the eSTAR draft guidance, but our first submission is now interactive review. I believe this suggests that companies may have a higher likelihood of having an interactive review with their CDRH lead reviewer instead of being placed upon AI Hold, but we won’t have enough submissions reviewed by the FDA to be sure until the end of Q1 2022.

Register for our new webinar on the FDA eSTAR draft guidance

We hosted a live webinar on Thursday, October 21, 2021 @ Noon EDT. The webinar was approximatley 37 minutes in duration. In this webinar we shared the lessons learned from our initial work with the eSTAR template. Anyone that registers for our webinar will also receive a copy of our table of contents template that we updated for use with the eSTAR templates. Unlike a 510k eCopy, an eSTAR template does not require a table of contents but we still use a table of contents to communicate the status of the 510(k) project with our clients. Finally, we reviewed the eSTAR draft guidance in detail. If you would like to receive our new eSTAR table of content template and an invitation to our live webinar, please complete the registration form below.

About the Author

Rob Packard 150x150 eSTAR draft guidance is here, and wicked eSubmitter is dead.
Robert Packard is a regulatory consultant with 25+ years of experience in the medical device, pharmaceutical, and biotechnology industries. He is a graduate of UConn in Chemical Engineering. Robert was a senior manager at several medical device companies—including the President/CEO of a laparoscopic imaging company. His Quality Management System expertise covers all aspects of developing, training, implementing, and maintaining ISO 13485 and ISO 14971 certification. From 2009-2012, he was a lead auditor and instructor for one of the largest Notified Bodies. Robert’s specialty is regulatory submissions for high-risk medical devices, such as implants and drug/device combination products for CE marking applications, Canadian medical device applications, and 510(k) submissions. The most favorite part of his job is training others. He can be reached via phone 802.258.1881 or email. You can also follow him on Google+LinkedIn or Twitter.

eSTAR draft guidance is here, and wicked eSubmitter is dead. Read More »

How much does a 510k cost?

How much a 510k costs is the most common question I receive from customers, and there are three parts to the cost of a 510k.

There are three parts to the 510k cost of submission:

  1. Testing
  2. Submission Preparation
  3. FDA User Fees

The highest cost is testing

The testing cost is the most significant cost, but I think the average is around $100K for our clients. For devices that only consist of a software (i.e., software as a medical device or SaMD), the testing costs are less, but the cost of documenting your software validation and cybersecurity will be more extensive than the cost of preparing your 510k and the FDA user fee. The more you can do in-house, the lower the testing costs will be. Biocompatibility testing for a non-invasive device might be only $13,000, but a long-term implant can cost as much as $100,000 for implantation studies. Sterilization validation testing depends upon the method of sterilization and whether you are doing a single-lot method or a full validation. Typical costs for EO sterilization validation are around $15,000, and then you should add several thousand more for the shelf-life testing.

For devices that are powered and/or have software, you will need to perform software validation in accordance with IEC 62304 ed 1.1 (2015). There are also five FDA guidance documents that apply:

  1. General Principles of Software Validation; Final Guidance for Industry and FDA Staff (January 2002)
  2. Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices (May 2005)
  3. Guidance for Industry, FDA Reviewers and Compliance on Off-The-Shelf Software Use in Medical Devices (September 2019)
  4. Guidance for Industry and Food and Drug Administration Staff Content of Premarket Submissions for Management of Cybersecurity in Medical Devices (October 2014)
  5. Guidance for Industry, FDA Reviewers and Compliance on Postmarket Management of Cybersecurity in Medical Devices (December 2016)

You can do all of the software validation in-house, but some firms outsource the software validation. In the long term, you need to learn this, and it pays to hire an expert in IEC 62304 to help your team learn how to document software validation if you have not done this before. Typically, software validation documentation will be between 300 and 1,000 pages long.

Electrical safety and EMC testing are often the most expensive part of the testing process for our customers. EMC testing should always be done first to ensure you can pass the immunity and emissions testing. If you must modify the device to pass the EMC testing, you must repeat any electrical safety testing. The total cost of this testing is typically $50-60K.

Performance testing is the last part of the testing process. Performance testing should be performed on sterile and aged products if your product requires sterility and claims a shelf-life. Most of the testing is benchtop testing only to demonstrate performance. This includes simulated use testing (e.g., summative usability testing), cadaver testing, and computer modeling. Benchtop performance testing typically takes tens of thousands of dollars to complete, but you might be able to do the testing in-house. If animal testing is required, this typically costs around $100K. Finally, if a human clinical study is required (i.e., ~10% of 510k submissions), you should expect to spend between $250K and $2.5 million. Some simple clinical studies (e.g., IR thermometers) cost less than $100K, but these resemble benchtop performance testing in many ways.

The second highest cost is the cost of submission preparation

Medical Device Academy has two different options for preparation consulting fees. Your first option is hourly consulting fees. The second option is a flat fee. As of July 2023, we are charging $3,500 for pre-submission preparation and $17,500 for 510k submission preparation.

510k cost #3 is the cost of the FDA user fee

You have three options for your FDA user fees:

  1. Third-party review
  2. FDA review (standard user fee)
  3. FDA review (small business user fee)

The first option is to avoid the FDA altogether and submit to a third-party reviewer. We only recommend one third-party reviewer (i.e., Regulatory Technology Services), because the other companies do not have sufficient experience to have predictable review times and positive outcomes. The typical RTS third-party review cost is 6% more than the FDA Standard fee.

The second option is to submit directly to the FDA. The standard user fee for FDA review of a 510k is $21,760 for FY 2024.

The third option is to apply for small business status. For companies that have annual revenues of less than $100 million USD, the FDA will grant you small business status. For companies with small business qualifications, the FDA user fee is reduced to $5,440.

FY 2024 User Fees 1024x568 How much does a 510k cost?

Reduce 510k cost by applying for small business status

Any medical device company with revenues of less than $100 million annually can apply, but you must apply each year. There is no application fee, but you must complete FDA Form 3602 if you are a US firm. The form must be completed for each subsidiary too. FDA Form 3602A must be completed for foreign firms, and the national tax authority must verify the accuracy of your income statement on the form to submit it to the FDA. If your national tax authority refuses to sign the form, you can justify it, but I don’t know anyone who has done this yet. The qualification review by the FDA requires 60 days. Therefore, you should apply every year in August for the next fiscal year (October 1, 2023 – September 30, 2024, is FY 2024). The form will request that you include your Organization ID #. A Dun & Bradstreet Number (DUNS #) is also required if your firm is located outside the USA. Finally, you need to attach a copy of your tax return. Therefore, you must file your tax return–even if your firm had a loss or had no revenues. You can also use R&D tax credits in the USA or Canada if you are a start-up device company developing a new device.

About the Author

Rob Packard 150x150 How much does a 510k cost?

Rob Packard is a regulatory consultant with 25+ years of experience in the medical device, pharmaceutical, and biotechnology industries. He is a graduate of UConn in Chemical Engineering. Robert was a senior manager at several medical device companies—including the President/CEO of a laparoscopic imaging company. His Quality Management System expertise covers all aspects of developing, training, implementing, and maintaining ISO 13485 and ISO 14971 certifications. From 2009 to 2012, he was a lead auditor and instructor for one of the largest Notified Bodies. Robert’s specialty is regulatory submissions for high-risk medical devices, such as implants and drug/device combination products for CE marking applications, Canadian medical device applications, and 510(k) submissions. The most favorite part of his job is training others. He can be reached via phone at 802.258.1881 or by email. You can also follow him on Google+LinkedIn, YouTube, or Twitter.

How much does a 510k cost? Read More »

How to pass the FDA Refusal to Accept (RTA) Screening Process

This article helps you understand how to pass the FDA Refusal to Accept (RTA) screening process 510k submissions – updated April 2022.

Refusal to Accept How to pass the FDA Refusal to Accept (RTA) Screening Process

What is an RTA Checklist?

The “RTA” in RTA Checklist stands for Refuse to Accept. The FDA uses this tool to determine if your 510(k) submissions will be accepted or not for a substantive review. Accepted, not approved because this is simply a verification that the required information is included in your submission. As stated in the 2022 FDA guidance document for the FDA’s Refuse to Accept Policy for 510(k)s “a minimum threshold of acceptability and should be accepted for substantive review.”(Ref.1). That does a nice job summarizing the RTA checklist. It is a tool used to help assess whether or not your submission contains the required information to continue with a more thorough review of the contents of the submission itself. 

What does the Refusal to Accept (RTA) policy apply to?

The Refusal to Accept (RTA) policy applies to all 510k submissions. The RTA checklist or more checklists apply specifically to each 510(k) submission type:

  • Traditional 510k
  • Abbreviated 510k
  • Special 510k

There is a different RTA checklist for each submission type. The checklists are in the Refuse to Accept Policy for 510(k)s guidance document. Specifically, in the PDF document that the FDA reissued in April 2022, the checklists can be found in the following areas:

  • Traditional 510k – Appendix A.
  • Abbreviated 510k – Appendix B.
  • Special 510k – Appendix C.

Note that the title of the checklist refers to an ‘acceptance checklist.’ It is not called the RTA checklist until you get to the footer of the page. It is also listed as an acceptance checklist on the FDA website. The best way to think of the process is as preliminary screening by the FDA. 

What does the FDA look at during the Refusal to Accept (RTA) screening process?

During the screening process, the assigned RTA screener will review the 510k submission and try to identify all of the requirements listed in the applicable RTA checklist. The person screening your submission is required to answer “yes,” “no,” or “n/a” to the questions in the checklist. This person must also enter the document and the page where the information can be found in the submission. Finally, if an element required by the refusal to accept (RTA) checklist cannot be found, then the screener adds a comment at the end of that section in the checklist. The comment will state what your deficiency is and it may even identify a guidance document that can help you address the issue. If you are missing requirements, you will receive an email from the RTA screener with the completed RTA checklist attached. We call this an “RTA Hold” letter. If your submission is not rejected, then your 510k is administratively complete, and you will receive an automated email indicating that your submission was accepted and the substantive review will begin.

Refusal to Accept (RTA) Time Frame

As stated in the guidance document, the Refusal to Accept policy includes “an early review against specific acceptance criteria and to inform the submitter within the first 15 calendar days after receipt of the submission if the submission is administratively complete, or if not, to identify the missing element(s).” (Ref. 1). If the assigned screening person is unable to complete the process within 15 calendar days, then you will receive an automated email stating that they were unable to complete the RTA checklist within 15 calendar days, and your submission is automatically moved to the substantive review stage of the 510k review process.

Taking the time to perform your gap analysis before submitting could avoid a simple error. For example, if you forget to include the signed Truthful and Accuracy Statement in your submission, it could take 15 days to be notified of that missing element. The person screening your submission could email you to provide this missing element in an interactive review to avoid placing your submission on hold. Still, they are not required to give you a chance to provide this interactively by email. If you do receive an RTA Hold letter, you might be able to correct missing elements on the same day, but the 510k review clock is automatically reset when your 510k is placed on RTA Hold. When you respond to an RTA Hold letter, there will be another 15-day refusal to accept (RTA) screening of your submission.

What do you do with the information in the comments of the RTA checklist?

The RTA checklist is the criteria that your submission is being evaluated against. Suppose your submission has deficiencies during the initial review against the RTA Checklist. In that case, the FDA will refuse to accept it, and the substantive review will not begin until those deficiencies have been corrected. Since the FDA does not hide what they are looking for or how they will evaluate your submission, use that to your advantage. Assuming that you have correctly determined the type of 510k submission you have, perform a gap analysis of your submission against the RTA checklist. Either perform these actions in-house or hire an outside consultant to do them for you, but make sure you don’t try to check your own work because you will miss something. 

Scope of the FDA Refusal to Accept Guidance Document

The scope of the FDA guidance document is provided for the benefit of the FDA personnel reviewing your submission and not specifically for the 510k submitter. It also provides a loose framework for systematically and consistently reviewing submissions. This ensures all submissions receive equal, nonbiased treatment. There are some things that this guidance document does not address or alter by its own admission. One is the “substantial equivalence decision-making process once the submission has been accepted for review.” Refusing to accept (RTA) guidance also does not address FDA user fees. Other guidance documents address those issues.

What are the most common reasons for FDA refusal of your 510k submission?

Although there are dozens of reasons (43 to be exact) why the FDA could reject your submission in the 35-page RTA checklist, most of the refusals (~80%) result from a small percentage (~20%) of reasons. The most common is that your submission is poorly organized. Either you did not provide a table of contents, your submission is not organized in accordance with the sections outlined in the guidance, or the pages of your submission are not properly numbered. When trying to review a 1,200-page submission, poor organization is extremely irritating and wastes the reviewer’s time. If it were my decision, I would refuse to complete the entire checklist until you gave me a properly organized submission.

The second most common reason for refusal is submitting a device description that is inadequate. The FDA needs more detail than most companies provide for the device description because they need to understand the differences between your device and the predicate device. This includes much more than just the indications for use. Who are the intended patients and users? What is the intended environment of use? What are the materials for patient-contacting components? What is the source of power for your device? Which design features does your device include when compared to the predicate? What is the user interface for your device? Which accessory devices are needed with your device? You can even make the mistake of being inconsistent in your submission by not repeating the content in the device description in other sections of the 510k submission. It is important to duplicate certain content verbatim in other documents, such as the 510k summary, the executive summary, the substantial equivalence comparison, and the instructions for use. Paraphrasing and summarizing certain information will not work.

The third most common reason for refusal of your submission is likely related to software validation documentation. In addition to complying with the recognized IEC 62304 standard, you must also comply with the five software guidance documents published by the FDA. The FDA and 3rd-party reviewers use an 11-item checklist based on the 2005 FDA guidance document on software validation documentation. In addition, if your device has any of the following five elements, your submission must also comply with the two FDA guidance documents on cybersecurity:

  1. Cloud communication
  2. Network connection (active or not)
  3. Wireless communication in any form
  4. USB/serial ports/removable media
  5. Software upgrades (this includes patches)

Finally, biocompatibility is the one testing section of your 510k submission that is most likely to result in refusal to accept by the FDA out of the seven sections requiring testing reports. There are several reasons why biocompatibility results in more refusals than the other six testing sections. First, the FDA requirements go above and beyond the ISO 10993-1 standard requirements. Second, the FDA requires that you submit full testing reports for biocompatibility, while you can submit summaries for other sections (e.g., sterilization validation). Third, many submitters try to provide a rationale for why testing is not required for their device. Still, the FDA has very stringent requirements for the use of a biological risk assessment or a biocompatibility certification statement in lieu of testing.

Do you have to follow the RTA checklist exactly?

You can, but you are also not bound by it. Like all guidance documents, they “contain nonbinding recommendations”. The checklist is released as part of a guidance document, so it is a guidance and not a regulatory requirement. That being said, if your submission is missing an element in the checklist, your 510k submission will be considered administratively incomplete unless you provide a clear explanation as to why the checklist element does not apply to your submission or you explain how you meet the 510k submission requirement in another way.

Medical devices vary wildly, and there is no one size fits all approach. The FDA recognizes that and includes some wiggle room that gives them some discretion in reviewing submissions. However, 100% of the 3,500+ submissions received each year are screened using the refusal to accept (RTA) checklist, and the screening person’s job is to verify that your submission meets the criteria. As it says in the guidance document:  

“The purpose of the 510(k) acceptance review is to assess whether a submission is administratively complete, in that it includes all of the information necessary for FDA to conduct a substantive review. Therefore, the submission should not be accepted and should receive an RTA designation if one or more of the items noted as RTA items in the checklist are not present and no explanation is provided for the omission(s). However, during the RTA review, FDA staff has the discretion to determine whether missing checklist items are needed to ensure that the submission is administratively complete to allow the submission to be accepted. FDA staff also has the discretion to request missing checklist items interactively from submitters during the RTA review. Interaction during the RTA review is dependent on the FDA staff’s determination that outstanding issues are appropriate for interactive review and that adequate time is available for the submitter to provide supporting information and for FDA staff to assess responses. If one or more items noted as RTA items on the Acceptance Checklist are not present, FDA staff conducting the acceptance review should obtain management concurrence and notify the designated 510(k), contact person, electronically that the submission has not been accepted. “ (Ref. 1).

The portion above notes that explanations may be provided for omitted portions of the submission. So, the answer to the question is that no, you do not have to follow the RTA checklist exactly. However, if you should purposefully omit a section you should provide an explanation and your rationale justifying why the omission is appropriate for your individual device and 510(k) submission. Again, just because you have included an alternative approach or justification does not automatically mean it will be accepted. The FDA personnel who are conducting the acceptance review will judge whether or not your deviation is acceptable.

What if your 510k submission is refused?

If your submission is refused, you will be provided with a copy of the completed RTA checklist, and each of the deficiencies you must address will be highlighted. Sometimes, there will be an attachment to the checklist that has additional issues that are not in the RTA checklist, but the reviewer thinks you may need to address them later. You might also see comments that are not highlighted. These are suggestions from the reviewer that you may or may not choose to address.

There is a 180-day timeline for response to an RTA Hold letter. The response must be submitted to the CDRH Document Control Center (DCC) as an eCopy, and the response must be received within 180 days. If the response is not received within 180 days, your submission will be automatically withdrawn on the 181st day. Your response may not be piecemeal. You must address all of the issues in the RTA checklist or your submission will be placed on RTA Hold again (i.e., RTA2). If you are not sure how to organize your response, a previous blog posting and YouTube video address this topic directly.

About the Author

20190531 005146 150x150 How to pass the FDA Refusal to Accept (RTA) Screening ProcessMatthew Walker – QMS, Risk Management, Usability Testing, Cybersecurity

Matthew came to us with a regulatory background focused on OSHA and NFPA regulations when he was a Firefighter/EMT. Since we kidnapped him from his other career, he has worked in medical device quality systems and technical/medical writing and is a Lead Auditor. Matthew has updated all of our procedures and is currently a student in Champlain College’s Cybersecurity and Digital Forensics program. We are proud to say he is also a Golden Keys and Phi Theta Kappa Honor Society member! Matthew participates in our audit team and is passionate about risk management and human factors engineering. Always the mad scientist, Matthew pairs his professional life in regulatory affairs with hobbies in the culinary arts, as he also holds a Butchers/Meat Cutters certificate from Vermont Technical College.

Email: Matthew@FDAeCopy.com

Connect on Linkedin: http://www.linkedin.com/in/matthew-walker-214718101/

How to pass the FDA Refusal to Accept (RTA) Screening Process Read More »

Additional Information Request

How is your response to an Additional Information Request different from an RTA response?

A poor RTA response will cause a two-week delay, but an additional information request only gets one chance to avoid the dreaded NSE letter.

An Additional Information Request (i.e. AI Request) is typically received just before the 60th day in a 90-day 510k review, while a Refusal to Accept (RTA) Hold is typically received on the 15th day. If your response to your first RTA Hold (i.e. RTA1) is inadequate, the reviewer will issue another RTA Hold letter (i.e. RTA2) and your 510(k) review clock will be reset to 0 days. You will have another 180-days to respond to RTA2, and issues identified in an RTA Hold are usually easy to address. Most RTA Hold issues also have one or more guidance documents that are available to help you to obtain an RTA Accept letter. You can always request a submission-in-review (SIR) meeting to clarify what information the reviewer needs to address the RTA deficiencies too. If you want to learn more about responding to an RTA Hold, please read last week’s blog. The rest of this article is specific to responding to requests for additional information.

What happens after 60 days during a 510k review?

On the 60th day of the 510k review clock, or a few days prior to the 60th day, the lead reviewer must determine if they need to issue an Additional Information (AI) Request. The alternative to an AI Request is for the lead reviewer to issue a letter indicating that you have entered the Interactive Review Phase. This only happens if the reviewer believes they can make a decision regarding substantial equivalence in the next 30 days. If the decision is to issue an Interactive Review Letter, then the lead reviewer believes that only minor issues remain and there is only the need for interactive email responses between the lead reviewer and the submitter. An interactive review is the ideal outcome of the substantive review process but it rarely happens.

If you receive an Additional Information Request, what are your options?

The AI letter will indicate that you have 10 days to request a clarification meeting with the reviewer. The wording of this section of the AI letter is provided below:

“FDA is offering a teleconference within 10 calendar days from the date on this letter to address any clarification questions you may have to pertain to the deficiencies. If you are interested in a teleconference, please provide (1) proposed dates and (2) a list of your clarification questions via email at least 48 hours before the teleconference to the lead reviewer assigned to your submission. We would like to emphasize that the purpose of the meeting is to address specific clarification questions. The teleconference is not intended for the review of new information, test methods, or data; these types of questions could be better addressed via a Submission Issue Q-Submission (Q-Sub). For additional information regarding Q-Subs, please refer to the Guidance for Industry and FDA Staff on Medical Devices: Requests for Feedback and Meetings for Medical Device Submissions at https://www.fda.gov/media/114034/download.”

If you wait too long to request the teleconference, then FDA will require you to submit a formal pre-sub meeting request or “Submission in Review” (SIR) meeting request. If you request a SIR meeting within 60 days of receiving an AI Request, the FDA will schedule a SIR meeting with you within three weeks of receiving the request–assuming resources are available. If you wait longer than 60 days to request the SIR meeting, then the FDA will default to their normal target of 60-75 days for scheduling a pre-sub meeting. For example, if you submit your SIR meeting request on day 75, and the FDA takes 75 days to schedule the meeting, you will be granted your SIR meeting at 150 days and you will only have 30 days remaining to respond to the AI Request before your submission is automatically withdrawn.

Therefore, it is important to request a clarification meeting immediately after you receive the AI Request. While you are waiting for your clarification meeting, you should immediately begin preparing any draft testing protocols that you want the FDA to provide feedback on during a SIR meeting. Then after you have the clarification meeting, you should submit your SIR meeting request and include any draft testing protocols you have prepared. This may include a statistical sampling rationale, a proposed statistical analysis method, a summative usability testing protocol, or a draft protocol for some additional benchtop performance testing. The FDA can review examples of preliminary data, a protocol, or a proposed method of analysis. The FDA cannot, however, provide a determination of substantial equivalence.

The Most Common Mistakes in Responding to an Additional Information Request

Most companies make the mistake of asking the lead review if they provide specific additional information, “Will this be sufficient to obtain 510(k) clearance?” Unfortunately, the FDA is not able to provide that answer until the company has submitted the additional information and the FDA review team has had time to review it thoroughly. This is done only when the submitter delivers an FDA eCopy to the Document Control Center at CDRH, and the review team is able to review the information. This new information is assigned a supplement number (e.g. S001), and it will typically require three weeks to review the information. Then the lead reviewer may request minor modifications to the labeling, instructions for use, or the 510k summary. This request is an interactive request, and the submitter must respond within a very short period (e.g. 48 hours), and the wording of the request may be “Please provide the above information by no later than COB tomorrow.”

FYI: “COB” means “close of business.” Wow. The FDA loves acronyms.

Best Practices in Responding to an Additional Information Request

If you receive an AI request on a Friday afternoon, 58 days after your initial submission, you should immediately request a clarification teleconference with the FDA reviewer for the following week. The only exception is if you only have minor deficiencies that you feel are completely understood. During the days leading up to the clarification teleconference, your team should send a list of clarification questions to the lead reviewer and begin drafting a response memo with a planned response to each deficiency. After the clarification meeting, you will have approximately 6-7 weeks to submit a SIR meeting request. However, you should not wait that long. Your team should make every effort to submit your SIR meeting request within 2-3 weeks. If the FDA takes 3 weeks to schedule your meeting, then you will have used approximately 6 weeks of your 26 weeks to respond to the AI Request.

In your SIR meeting request, you should always try to provide examples or sample calculations to make sure the FDA review team understands what you are proposing to submit in your supplement. For example, the FDA reviewers do not have enough time to review your entire use-related risk analysis (URRA) in a SIR meeting request. However, you can provide an example of how you plan to document a couple of use-related risks. Then you can show how these risks would translate into critical tasks. Finally, you could provide a draft summative usability testing protocol for FDA feedback. The FDA review team doesn’t have enough time available to review much more. You will only have one hour for your SIR meeting.

How to Prepare Your Response

In section “V” of the FDA guidance on deficiency responses, the FDA recommends that you restate the issue identified by the reviewer in your response. Next, your response should include one of the following:

  1. the information or data requested, or
  2. an explanation of why the issue is not relevant, or
  3. alternate information with an explanation of why the information you are providing addresses the issue.

Before you respond to an AI Request, you should look up any FDA guidance documents referenced in the AI Hold letter to make sure that you address each requirement in the applicable FDA guidance document(s).

The most important technique to learn when you are responding to regulators is to organize your response in a tabular format that is numbered in exactly the same order that the request was made. Typically there will also be sub-parts to certain issues. In that case, you should duplicate the numbers and/or letters of each sub-part and segregate each sub-part in a different row of the table. Personally, I like to alternate the color of the font I use in the table to make it even more obvious which information is a restatement of the reviewer’s comment and which information is the company’s response to the AI Request.

Why you don’t get a second chance to respond to an AI Request

Once you respond to an AI Request, and the DCC receives your FDA eCopy, the FDA review clock will then resume the countdown to 90 days. In our example above, you received the AIR Request on the 58th day. The FDA must review everything you submitted and make a final substantial equivalence decision before the 83rd day because they still need to submit their recommendations to senior management in their branch. If any changes to the labeling, instructions for use, or the 510k are required, you should receive those requests several days before (i.e. 76-83 days). You can respond to interactive requests via email, and then the final SE decision will be made. If you do not respond to all of the deficiencies in the AI Request, the FDA reviewer will not have enough time to request that you address the remaining gaps and finish their review. Therefore, an incomplete AI Response will certainly result in a non-substantial equivalence (NSE) letter.

If you need to respond to an additional information request from the FDA reviewer, we can review your planned response to identify potential gaps. If you need help please use our calendly app to schedule a call with a member of our team.

About the Author

Rob Packard 150x150 How is your response to an Additional Information Request different from an RTA response?

Robert Packard is a regulatory consultant with 25+ years of experience in the medical device, pharmaceutical, and biotechnology industries. He is a graduate of UConn in Chemical Engineering. Robert was a senior manager at several medical device companies—including the President/CEO of a laparoscopic imaging company. His Quality Management System expertise covers all aspects of developing, training, implementing, and maintaining ISO 13485 and ISO 14971 certification. From 2009-2012, he was a lead auditor and instructor for one of the largest Notified Bodies. Robert’s specialty is regulatory submissions for high-risk medical devices, such as implants and drug/device combination products for CE marking applications, Canadian medical device applications, and 510(k) submissions. The most favorite part of his job is training others. He can be reached via phone 802.258.1881 or email. You can also follow him on Google+LinkedIn or Twitter.

How is your response to an Additional Information Request different from an RTA response? Read More »

Scroll to Top