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510k Project Management-An Inside Look at Our Process

“510k Project Management-An Inside Look at Our Process” explains how the 510k Table of Contents is used for client submissions. A free download is provided. 

Table of Contents Screen Capture 510k Project Management An Inside Look at Our Process

Despite all the perceived changes to the FDAs pre-market notification process (i.e., 510k process), the format and content requirements have not changed much. The most significant change to the 510k process was the introduction of the Refusal to Accept Policy (http://bit.ly/FDA-RTA-Policy) in 2012. The RTA process did not, however, change requirements for format and content. The RTA process simply provides a checklist for reviewers to screen submissions to ensure the submission is complete and follows the required format. Actual content requirements are found in a 2005 guidance document titled, “Guidance for Industry and FDA Staff: Format for Traditional and Abbreviated 510(k)s” (http://bit.ly/510k-Content). To ensure that you don’t deviate from this required format, use a standardized template for the Table of Contents.

Overview

There are 20 sections to a 510k submission. For each section, Medical Device Academy’s consulting team created a template for the documents to be included in that section. Each section is assigned a volume number (i.e., 1-20), and typically there is an overview document for the section that is identified by Vol x Doc 1. We also use a consistent header and footer for every document to clearly identify the subject device of the submission, name of the section and the volume/document numbers. In addition to the templates our consulting team created, there are several FDA forms that must be used for specific sections. These forms are a mixture of MS Word® documents and PDF documents that must be edited in Adobe Acrobat®.

Table of Contents Used as a Project Management Tool

When one of our consultants is starting a new 510k project, we use a spreadsheet version of the Table of Contents. This allows us to perform a gap analysis of the existing documentation available from the client. If the client owns the 510k for the predicate device, then the client may only need to update documents to reflect changes. If the client has a Technical File, then most of the information is available, but the consultant must revise the format and organization of the content to fit our 510k document templates. In one of the columns of the spreadsheet, the consultant performing the gap analysis makes comments about what is available and what needs to be done to complete the 510k submission.

Status of Documents

In order to communicate the status of documents in the gap analysis, and throughout the 510k project, the consultant will color code the sections of the table of contents:

  • green = ready for submission
  • blue = ready for the client’s review and approval
  • yellow = document requires revision and/or reformatting of content
  • red = the information does not appear to be available

Our consulting team also uses this same color coding approach when we create a Technical File or a Design Dossier for CE Marking. We will include cross-references to document and report numbers if controlled documents are available. We also add two columns to track our estimated and actual consulting time for the project. Estimated hours required to complete each section are provided, and then as the project progresses, we update the spreadsheet to include the actual time spent on each section.

Using Dropbox

We share the planning spreadsheet and the documents created for each section of the 510k submission with our clients using https://www.dropbox.com/. In each client’s Dropbox folder, we have sub-folders for the 20 sections of the 510k Table of Contents. As we finalize each document, the documents are reviewed and approved by the client. After final approval of the documents, each document is saved as a PDF–as required for eCopy submissions (http://bit.ly/FDA-eCopy). Periodic updates are provided to the client via conference calls, but the client can view progress on the overall 510k submission project almost real-time by reviewing the 510k Table of Contents in spreadsheet form.

Coordinating Our Team

We also use our 510k Table of Contents to help identify who is responsible for each section of a 510k submission. Not every consultant is an expert in electrical safety (section 17), biocompatiblity (section 15) and pre-clinical animal studies (section 19). In fact, most of Medical Device Academy’s consultants are specialists in a narrow discipline. Therefore, it is common for us to assign different sections to different consultants. By using the same templates and process for each submission, a team can work efficiently from 3 or 4 countries simultaneously on the same 510k submission.

Prioritizing Section Completion

Each section of the 510k submission must be completed, but order of completing the sections is important. For example, we find that the first section to complete is in section 4–the Indications for Use. This section is important, because the Indications for Use should match the predicate device we are claiming substantial equivalence to in section 12.

Another section we like to work on very early in the project is section 13 for Proposed Labeling. The labeling includes the Instructions for Use (IFU), and the IFU must include a statement of the Indications for Use. The sections we prioritize last are the sections that summarize verification and validation testing that has been done. These sections are done last, because we find we are almost always waiting for a test report at the end of the project. We also find that testing sometimes need to be repeated.

Please fill in the form at the bottom of this page if you would like to receive Medical Device Academy’s template for the 510k Table of Contents. We will also update our Table of Contents and send it to you if there are changes to the 510k requirements after the FDA has completed its retrospective review of the 2005 guidance document later this year (http://bit.ly/FY2015-Proposed-FDA-guidance).

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

 

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Why Design Controls Are Important to 510k Submissions

why design 510k Why Design Controls Are Important to 510k Submissions

This blog explains how many sections of a 510k submission have a direct correlation to Design Controls.

If you are developing a medical device for the U.S. market, there is a decent chance you will need to prepare a 510(k) submission. Of course, there are some devices that do not require a submission, and also those that require a more involved PMA. But, if your medical device falls into the FDA Class II category, a 510(k) submission is required for market clearance.

Regardless of the device classification, Design Controls are a critical component to medical device product development. Design Controls demonstrate you have designed and developed a medical device that meets user needs, is safe and effective.

The relationship between Design Controls and regulatory submissions is strong. Design Controls are needed to ensure that you have the data to support your submission to the FDA for pre-market notification. A traditional FDA 510(k) submission contains 20 sections, and many of those sections are linked directly to Design Controls.

Indications for Use

The indications for use statement in a 510k submission describes the clinical application of a medical device. Before starting a medical device product development project, there must be a clinical need defined. This clinical need evolves into indications for use and results in User Needs. User needs describe what the end-user (including patient) expect the medical device to do. User needs are the pre-cursor to a medical device’s Design Inputs.

Declarations of Conformity

A 510k submission includes making declarations of conformity to any industry standard used during medical device product development. Some common standards include ISO 10993 (for biocompatability) and IEC 60601 (for electrical safety). Your medical device may require that you demonstrate compliance to other industry standards.

Any standards you reference as part of your medical device project have a direct relationship to Design Controls. Specifically, standards often specify requirements, acceptance criteria, and test methods. The contents of each standard must be translated directly into Design Inputs for your medical device or you must provide a justification of why the specific clause is not applicable. Additionally, declaring conformity to a standard means you will need to prove you meet the criteria within the standard. This is done via Design Verification activities.

Substantial Equivalence

The entire premise of a 510k submission is to demonstrate that your medical device is substantially equivalent to another medical device which has received FDA 510k market clearance. Doing so often requires head to head testing and other activities to demonstrate your product is equivalent to a predicate device. Activities to support substantial equivalence are often captured as Design Verification activities.

Proposed Labeling

The proposed labeling is included with a 510k submission. Labeling includes the labels applied directly to the product and packaging, as well as instructions for use and user manuals. Labeling is part of the Design Outputs captured during product development. Labeling also tells the user about residual risks that design controls were not able to completely eliminate.

Sterilization & Shelf Life

If your medical device requires sterilization, you must provide details regarding sterilization methods and specifications with your 510k submission. Sterilization methods and specifications are Design Outputs. Expect to also provide a sterilization validation protocol, as well as results, with your 510k. These are Design Verification activities.

The same is true with shelf life activities. Shelf life definitions are defined as Design Outputs, usually via product labeling. These labeling claims of shelf life must subsequently be verified during design verification.

Biocompatibility

If your product has contact with a patient and/or end-user, you need to demonstrate biocompatibility within your 510(k) submission. Biocompatibility requirements must be defined as Design Inputs, and the Design Verification data must include evidence of meeting these requirements.

Software

If your medical device includes software, there is quite a bit of documentation you are expected to provide as part of a 510k submission. Things like Software Requirements Specifications (part of Design Inputs), Software Design Specifications (part of Design Outputs), and Software Verification Test Plan & Results (part of Design Verification). Depending upon the level of risk, risk management documentation may also be required for devices involving software.

Electromagnetic Compatibility

If your medical device includes electronics, you need to demonstrate electromagnetic compatibility and overall electrical safety within the 510k. This involves IEC 60601 and all the applicable parts of this standard to your product. Electrical requirements should be specified as Design Inputs. All the test results are Design Verification activities.

Performance Testing

All bench, animal, and clinical performance testing must be provided with your 510k submission. Required performance testing is specified for some device classifications with documented Special Controls Guidance Documents, while other device classifications require only that you provide performance testing demonstrating that the device in your submission is equivalent to the predicate device. This performance testing must be specified as verification and validation testing in your Design Plan.

 

jon d speer Why Design Controls Are Important to 510k SubmissionsJon Speer is a medical device veteran with more than 16 years experience. Jon specializes in helping medical device start-up companies with design project management. His experience with start-ups gave him the idea to develop a software solution to help companies document Design Controls. If you are interested in learning more about the software solution, greenlight.guru, you can find him on Google+, Twitter, and LinkedIn.

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The Three Biggest Changes in the Latest 510k Guidance

510k pmn The Three Biggest Changes in the Latest 510k GuidanceThis blog describes the three biggest 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 has been 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 been already 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 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 same intended use must be made against the labeling, not against what you state 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 technological 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.

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5 Common Gaps in 510k Documentation When Converting to a Technical File

MDA techinical file blog 5 Common Gaps in 510k Documentation When Converting to a Technical FileThis blog, 5 Common Gaps in 510k Documentation When Converting to a Technical File offers practical courses of action to consider related to this topic. Below are 5 parts of a Technical File (TF) you are likely to be missing in your 510k documents:

  1. The biggest one first. Clinical evidence – The FDA states clinical data is not needed for most devices cleared by the 510(k) process.” The MDD 93/42/EEC (annex X) and proposed MD Regulation (Annex II) require a clinical evaluation to be performed and the evaluation report to be part of the TF. Once formulated, the report becomes “clinical evidence” of the safety and performance of the medical device for demonstrating conformity with the relevant Essential Requirements (ER).

Here’s how to fill this gap using 5 steps offered by MEDDEV 2.7.1 Rev. 3:

  1. Identify the ERs 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 safety and performance of your device. Even some generally unusable studies may produce relevant data. It is important 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 Info systems. 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 the medical condition and device technology.

Now sum it up in a report.

  1. ER or General Safety and Performance Requirements Checklist – This central component of the TF is based on the Annex I of the three Medical Device Directives, or from the Proposed Regulation, 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.
  • Method used to demonstrate conformity –harmonized standard, Common Technical Specification (CTS), etc…?
  • Specific Standard or CTS applied
  • Evidence of conformity  
  • –  the controlled document/s demonstrating fulfillment of the ER.
  1. Post-Market Clinical Follow up (PMCF) Plan (and report) – The FDA requires PMS activities only once they have requested it from the manufacturer. A PMS plan then needs to be submitted. Manufacturers may not yet have formulated such a plan.

No worries. If you are performing 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 14971:2007 § 9 and TR 24971§ 4). Reference this in your TF. What about the PMCF report?  Well, if you’ve performed post-market surveillance, develop one. Otherwise, see the next item below.

  1. RM Report

While not required by the FDA in your 510k submission, you most likely have fulfilled this ISO 14971 requirement. Reference it in your TF. Ensure you also include in the report a confirmation that appropriate methods are in place to obtain production and post-production information. If detailed enough, you can reference the report as a PMCF report (http://bit.ly/PMCFStudies), as well.

  1. Risk class/applicable classification rule (based on Annex VII (proposed EU regulations) or Annex IX (MDD)) – FDA defines Classes I through III, which are obviously not parallel to Classes A-D in the proposed Regulation, nor the classes I, IIa, IIb or III of the current MDD.

Using either of the latter systems, identify the relevant rule and classify your device. Document in your TF.

Avraham Harris is a GMP, GCP and regulatory consultant, and can be contacted at HARC.regulatoryaffairs@gmail.com.

 

 

 

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

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

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

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

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

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

Electrosurgical Devices for General Surgery

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

Bipolar Electrosurgical Vessel Sealers

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

How to Document Compliance in Your 510(k) Submission

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

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

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

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

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Why the FDA 510k Process Needs to Change Now: A Proposed Solution

The author says three factors are accelerating the need for change to the current FDA 510k process, and offers a proposed solution.

%name Why the FDA 510k Process Needs to Change Now: A Proposed SolutionWhen a company’s marketing literature tells you how a new device is totally different from competitor products, and the 510k summary for the same new device states that it is “substantially equivalent,” you can understand why the FDA may not fully support the 510k process for innovative, medium-risk devices.

There are many things wrong with the FDA 510k process, but the concept of using a predicate device and demonstrating equivalence is inherently a wrong approach for innovative devices. A preliminary report about the 510k process was released in 2010 (http://bit.ly/510kreport). The report states, “While the concept of ‘substantial equivalence to a predicate’ is generally reasonable, CDRH’s application of this standard has, in certain cases, raised concerns.” Specifically, the use of predicate devices that were withdrawn from the market due to issues of safety or effectiveness, and the use of so-called “split predicates” may not ensure patient safety or device efficacy.

The FDA attempted to address issues identified in the report by issuing a draft guidance document for 510k submissions, but industry hated it. The FDA has also gradually requested more clinical study data to demonstrate that the new device is substantially equivalent to the predicate device. This practice results in unexpected delays and much higher costs of regulatory approval. The FDA’s published guidance for 510k content (http://bit.ly/510kContent) indicates that “Clinical data is not needed for most devices cleared by the 510(k) process.” However, more than 10% of 510k submissions now require clinical data because the 510k for predicate devices included clinical data in order to demonstrate safety and effectiveness.

More recently, the FDA issued a draft guidance document for the De Novo process (http://bit.ly/DeNovoGuidance). The De Novo process allows the FDA to reset the submission requirements for devices that are not substantially equivalent and specify new requirements. The process has been used most for new In Vitro Diagnostic (IVD) products, and it is quite similar to the concept of Common Technical Specifications (CTS) introduced for IVD products in Europe.

Why the FDA 510k Process Needs to Change Now

The simultaneous confluence of three factors is accelerating the need for change in the 510k process. First, the cost of healthcare is skyrocketing. Therefore, patients and healthcare providers are desperately searching for less expensive treatment solutions. Second, insurance providers are demanding clinical evidence that new products are more effective than existing products that cost less. Third, evidence-based medicine is becoming mainstream. Physicians are no longer accepting the word of salespeople and marketing literature. Instead, physicians demand clinical data demonstrating that products are safe and effective. Users also want detailed information regarding patient selection criteria.

The collision of these three factors has exponentially increased the value and importance of clinical data, but only 10%+ of the 510k cleared devices have clinical data at the time of product launch. Regulatory clearance to market a product is nearly useless if the product is not reimbursed, and users will not adopt its use. The modular Premarket Approval (PMA) process supports (http://bit.ly/PMAmethods) the need for preliminary safety data prior to clinical use, followed by a clinical study to demonstrate efficacy. However, 510k products are lower in risk and efficacy, and can often be demonstrated with simulated use, animal testing and cadavers.

As medical devices become more complex and innovative, bench-top testing and pre-clinical testing is not always adequate to demonstrate safety and efficacy for 510k products. Complex and innovative devices are extremely difficult to predict how the devices will interact with a broader population of users and patients, and it is difficult to predict the long-term effects of the devices—beyond the duration of a pre-market, clinical study.

The PMA process requires pre-market clinical data, but PMAs require exponentially greater amounts of data than a 510k submission, and the FDA requires supplemental approval of almost every minor change (e.g., – changing a component supplier, or changing a test method). If the PMA process is too burdensome for most devices, and the 510k process is not adequate, what is the right process for the next generation of devices?

The De Novo process offers one solution, but it is still a pre-market notification process. In order for the De Novo process to be effective for innovative devices, a Special Controls Guidance Document needs to include a requirement for both pre-market clinical studies and Post-Market Surveillance (PMS).

Pilot Parallel FDA-CMS Review Process

In 2011, the FDA initiated a pilot program to allow companies to have PMA and CMS (http://bit.ly/Medicare-Medicaid) review processes occur in parallel (http://bit.ly/ParallelReview). The concept behind this pilot program is that the same clinical data must be reviewed for PMA approval and CMS reimbursement. If the pilot program is effective, products will be approved and reimbursed at the same time. However, this pilot program is only applicable to PMA products at this time. This program could be expanded to 510k products, where clinical data is presented as part of the application, but most 510k products do not warrant a clinical study.

Another Solution

The best tool to measure the safety of a new device is a clinical study, but U.S. clinical studies focus on demonstrating efficacy. Therefore, the FDA should consider using smaller clinical studies, without comparisons to predicate devices, to demonstrate safety, rather than efficacy. This is the approach used by European Notified Bodies for medium and high-risk, innovative devices. This approach can also be integrated with a Special Controls Guidance Document for De Novo products.

For complex, innovative devices, the efficacy of the device is not reliably measured by clinical studies, because outcomes are highly dependent upon users. Pre-market clinical studies can only estimate efficacy due to the small number of users. The lack of accurate efficacy predictability is why the FDA requires PMS for many PMA products. The best tool to measure efficacy is Post-Market Clinical Follow-up (PMCF) studies—not the pre-market clinical studies the FDA uses to evaluate PMA applications. This is also the type of data that is required for CMS reimbursement and physician adoption.

Innovative devices are forcing regulations to evolve. The goal of regulators should be to produce a best-in-class method of evaluating which devices should be approved, reimbursed and adopted as the standard of care.

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Three Ways to Streamline the 510k Process

The author proposes three ways to streamline the 510k process through self surveys, scorecards and modular submissions.

Modular submissions are already used for PMA submissions. Self-surveys and scorecards are tools that most companies utilize to evaluate vendors. Why not implement these solutions to make 510k reviews more efficient?

A few weeks ago I posted a blog about the Triage pilot program at the FDA. I received some great comments by email and this blog discusses this subject more in-depth with some specific ideas for streamlining the 510k process. Here’s the argument for considering these three proven methods:

Self-Surveys

In my previous posting about the Triage pilot program, I suggested using the existing FDA traditional 510k screening checklist and converting this into a similar “SmartForm.” Another way to think of this concept is by comparing it with a “Self-Survey.” Self-surveys are sent by companies to suppliers in order to gather information about the supplier as justification for approving them; Elsmar Cove has some discussion threads specific to the supplier self-surveys if you are unfamiliar with this method of torture. The critical step in the design of surveys is to require the submitter to provide references to procedures and forms, or to explain why something is not applicable. This same strategy is used by BSI for their auditor combined checklists. Instead of checking “yes/no,” the auditor must reference a page in their audit notes where the objective evidence of conformity or nonconformity can be found. A submitter should fill in the checklist, rather than an FDA reviewer, because this forces the submitter to verify that everything required is included. Canada has a similar requirement called a “submission traceability table” for Medical Device License Applications (see Appendix A). Self-surveys also replace some of the tedious searching by a reviewer with cross-referencing work by the submitter. 

Scorecards

Another tool that supplier quality uses for supplier evaluations is the Scorecard: Elsmar Cove has a few discussion threads, including one with an example to download. For the purpose of the 510 process, I suggest developing scorecards for both the reviewer AND the submitter. The primary metrics for these scorecards would be on-time delivery and completeness of the submission for a submitter. “On-time delivery” requires advanced planning and communication of the submission with the FDA. This is important, so that the FDA has adequate time prior to submission to identify the best reviewer(s) for the submission. The completeness of the submission should be 100% of a self-survey, SmartForm or checklist used to prepare the submission. The primary metrics for the reviewer would be on-time completion and accuracy of the review.

The FDA already has target turn-around timescales for decisions (i.e., – 90 days), but there are different phases of review and multiple people the are involved in the reviews. Therefore, the measurement of reviewer time should be more granular. The accuracy of the reviewers should be validated by requiring all deficiencies to be re-evaluated by a peer or superior prior to involving the company. Submission sections without any findings should also be reviewed on a sampling basis as a double check. Over time, the FDA should be able to use these scorecards to match up a reviewer with a submitter. It is critical that at least one of the parties is experienced, so we don’ t have the “blind leading the blind” situation. For those that are offended by the concept of a required second reviewer–get over it. Radiologists are periodically graded with images that are “red herrings.”

Modular Submissions

My third suggestion is to consider adopting some of the Premarket Approval (PMA) processes for the 510k process. In particular, pre-IDE meetings and modular submissions seem to be logical process improvements. There is typically one component of the submission that is a little behind the rest, and can delay a submission. Under the current system, nothing is submitted or reviewed for a 510k, unless it is complete. However, it would enable companies to get new and improved products to market faster if submissions were modular. Validation. such as shelf-life and sterilization validation, is rarely the cause for an “Not Substantially Equivalent” (NSE) letter, but these tests are routinely the last few reports completed for a submission.

Adopting a modular submission process for 510k would allow companies to submit sections of the submission as they are completed. This modular approach would alleviate the time pressure on both sides, and this proposed change should result in earlier product launch dates for industry. The other component of this process is the pre-IDE Meeting. Prior to initiating a clinical study, companies will submit a plan for the study to the FDA. The intent is to obtain agreement on the validation testing that will be performed by the company–including the number of patients and the design of the clinical study. These meetings would also be valuable for 510k submissions where the company and the FDA need a forum to discuss what verification and validation testing will be required–especially for mixed-predicate devices and devices that are significantly different from a predicate device.

What do you think about these proposed changes to the 510k process?

Please share your own ideas for streaming the 510k process–including any comments regarding the FDA‘s plans for change.

Posted in: 510(k)

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

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 in order 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 certain 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 clear, 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 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 a 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 biggest shortfall of the Triage program is the target product types. IVD devices are quite different from other device types. Each IVD has unique chemistry, 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.

Posted in: 510(k)

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