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FDA User Fee Increase for FY 2018 – Strategic Implications

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

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

You didn’t know the FDA user fee increased?

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

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

Implications of the De Novo FDA user fee increase

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

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

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

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

Implications of the 510k FDA user fee increase

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

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

Implications of establishment registration FDA user fee increase

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

What you can do about the FDA user fee increase now

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

Learning how to submit a small business qualification form

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

Posted in: 510(k), FDA

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FDA QSIT Inspection of Design Validation: Part 2-Software

qsit FDA QSIT Inspection of Design Validation: Part 2 SoftwareThis article reviews FDA QSIT inspection requirements of design validation, and is specific to devices containing software.

If the product selected has software, then the investigator is instructed by the FDA QSIT Inspection Manual (http://bit.ly/QSITManual) to consider reviewing software validation. Since inadequate software validation causes many quality problems with devices, you should be shocked if an investigator doesn’t review software validation of a device containing software. Software-containing devices are also the only devices that manufacturers are required to submit a risk analysis for when submitting premarket notifications (i.e., 510k submissions).

Software Validation

Validation confirms that a device meets the user needs. Software validation is no different. In the case of software validation, the “device” is the final complete software program in the operating environment in which it is intended to be used (i.e., operating system and hardware), and the “” is the “software design requirements” document.

In order to facilitate the validation of software, a traceability matrix is typically used to facilitate construction of validation protocols. The traceability matrix will identify each requirement in the left-hand column of the matrix. The columns to the right of the requirements should include the following:

  1. hazard identification
  2. potential severity of harm
  3. P1 – probability of occurrence
  4. P2 – probability of occurrence resulting in harm
  5. risk controls
  6. design outputs or references to the code modules that are responsible for each requirement
  7. references to verification and validation testing for each risk control
  8. estimation of residual risks
  9. risk/benefit analysis of each risk and overall risk
  10. traceability to information disclosed to users and patients or residual risks

Since failure of each module can easily result in multiple failure modes, the above approach to documenting design requirements and risk analysis is generally more effective than using an FMEA. This approach also has the benefit of lending itself to assessing risk each time new complaints, service reports and other post-market surveillance information is gathered.

The use of a traceability matrix also lends itself to the early stages of debugging software modules and unit validation. Each software design requirement will typically have a section of code (i.e., software module) that is associated with it. That module will be validated initially as a standalone unit operation to verify that it performs the intended function. In addition to verifying correct function, the software validation protocol should also verify that incorrect inputs to the module are caught by the embedded risk controls for that module. The correct error code should be generated and applicable alarms should be triggered.

Finally, after each individual requirement has been verified, the entire software program must be validated as well. When changes are made, the module and the entire program must be re-validated. Inspectors and auditors will specifically review changes made in recent versions to verify that revalidation of the entire program was performed–not just unit testing. You must also comply with IEC 62304, medical device software – software lifecycle processes. This is required for CE Marking as a harmonized standard, and recognized by the US FDA (http://bit.ly/Recognized-Consensus-Standards). One of the implications of applying IEC 62304 is that you must consider the risk of using software of unknown pedigree or provenance (SOUP).

Software Risk Analysis

Each requirement of the software design requirements document will typically have a risk associated with it if the software fails to perform that requirement. These risks are quantified with respect to severity of harm and probability of occurrence of harm. Probability of occurrence of harm has two factors: P1 and P2 as defined in Annex E of ISO 14971:2007 (http://bit.ly/14971-Webinar).

P1 is the probability of occurrence, and for software, we have two factors. First, the situation must occur that will trigger a failure of the software. Second, does the software have a design risk control that prevents harm or provides a warning of the potential for harm? P2 is the probability that occurrence will result in harm; P2 has one factor. P2 is determined by evaluating the likelihood that failure will result in harm if the risk control is not 100% effective.

An investigator reviewing the risk assessment should verify that risk has been estimated for each software design requirement. There should be a harm identified for each software design requirement, or the traceability matrix should indicate that no harm can result from failure to meet the software design requirement. Next, the risk assessment should indicate what the risk controls are for each requirement identified with a potential for harm. In accordance with ISO 14971, design risk controls should be implemented first in order to eliminate the possibility of harm. Wherever it is impossible to eliminate the possibility of harm, a protective measure (i.e., alarm) should be used.

Each risk control must be verified for effectiveness as part of the software validation. In addition, the residual risk for each potential harm is subject to a risk/benefit analysis in accordance with EN ISO 14971:2012, Annex ZA Deviation #4 (http://bit.ly/14971dev4). The international version, ISO 14971:2007 (which is recognized by the US FDA and Health Canada), allows companies to limit a risk/benefit analysis to only risks that are unacceptable. Therefore, the European requirement (i.e., EN ISO 14971:2012) is more stringent. Companies that intend to CE Mark medical devices should comply with the the EN version of the risk management standard instead of the international version for risk management.

Posted in: FDA

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7 Steps to Respond to an FDA 483 Inspection Observation

7 steps fda 483 blog 7 Steps to Respond to an FDA 483 Inspection ObservationResponding in 15 days is one of 7 steps on how to respond to an FDA 483 inspection observation. Blog also includes advice from a former FDA investigator. 

When an FDA investigator has an inspection observation, the investigator issues an FDA 483. This is the FDA’s form number. If your company receives an FDA 483, how you respond to the FDA 483 is crucial to avoiding a Warning Letter. In the words of a former FDA investigator, “Many, many times I have seen an [Official Action Indicated (OAI)] classified inspection that had been recommended for a Warning Letter by the compliance branch be set aside based upon the response of the firm.”

The best way for your company to respond to an FDA 483 is by writing a cover letter, and then every observation needs to be addressed in the response as a separate CAPA–unless the root cause is identical for two observations. Make sure that your response includes the following seven steps below:

  1. respond within 15 business days (earlier is better)
  2. use your CAPA form and a cover letter–instead of a memo
  3. document the investigation that was conducted with a concisely stated root cause
  4. identify containment measures and corrections to address each specific observation by the FDA inspector
  5. identify corrective actions planned and the date(s) you expect to complete implementation
  6. Include documentation of containment, corrections and corrective actions that are completed at the time you submit the response
  7. follow-up with a memo confirming that all the corrective actions are complete and include all related documentation–including training for any new procedures or any new corrective actions that warranted training

Respond to the FDA 483 violation(s) in less than 15 business days

The FDA has always involuntarily required a medical device firm, or any firm under FDA jurisdiction that received an FDA 483, to respond in writing to the FDA 483 to the District Office within 15 business days. As of two years ago, (http://www.gpo.gov/fdsys/pkg/FR-2009-08-11/pdf/E9-19107.pdf) it became mandatory that a response from any FDA 483 must be received by the Agency within 15 business days, or an automatic Warning Letter is issued. You need to respond aggressively to FDA 483s with corrective actions, and submit your response early.

Use your CAPA forms instead of a memo

I have asked several former FDA investigators whether they would prefer to see firms submit responses in memo format, or by using their CAPA forms and a cover letter. Some told me that they prefer to see firms use their CAPA forms, while others don’t seem to have a preference. Nobody from the FDA has ever indicated a preference for a memo. I see no point in doubling your work and risking transcription errors. If you have an electronic system that does not have an output format that is easy-to-follow, go ahead and copy-and-paste the information from your electronic database to your memo. If the CAPA system output is easy to follow, just use a cover letter and copies of the forms.

Document the investigation and root cause

This is definitely my pet-peeve, but a one-sentence “root cause” is not enough for an FDA 483 response. Regardless of whether I am doing a mock-FDA inspection, an internal audit or a supplier audit–I expect you to document how you determined the root cause (http://robertpackard.wpengine.com/five-tools-for-conducting-root-cause-analysis/). If it’s trivial and obvious, then it must have been something important, or I would not have written a nonconformity. Therefore, you should be looking beyond the immediate scope of the FDA 483 to ensure that a similar problem cannot occur elsewhere. In the language of the FDA, this is a preventive action, because you are preventing occurrence with another process or product. Most ISO certification auditors are purists and they won’t accept this as a preventive action. You will have to show the purists something special–maybe from your data analysis.

Don’t forget containment and correction

For every 483 observation, including the subparts, you need to identify if immediate containment is necessary and how you can correct the problem. Whenever possible, you should attempt to implement the containment and corrections during your FDA inspection. In fact, it would be fantastic to give the FDA inspector a copy of the new CAPA you initiated during the audit. The new CAPA would identify containment and corrections that have been, or will be implemented–including any nonconformity(s) you initiated to quarantine product. You may still get an FDA 483 inspection observation, but you are likely to convert a possible Official Action Indicated (OAI) into a Voluntary Action Indicated (VAI). You can also modify the CAPA wording later to include a cross-reference to the FDA 483 and quote the exact wording the inspector uses.

Explain the corrective action plans and timelines

Clarity, brevity and realistic plans are critical in this section of your response. I prefer a table that looks like the example shown below.

7 steps 483 chart 7 Steps to Respond to an FDA 483 Inspection Observation

Show the FDA you have already taken action

Whenever possible, you want to show the FDA that you are taking action without delay. If you revised the SOP for MDRs and scheduled a group training for July 15, then you should provide the FDA a copy of the revised procedure and a copy of the agenda for your planned training session. The only caution is to only commit to actions you are certain you will implement. You can always do more, but it will be much harder to explain why you did not implement an action you submitted in your FDA 483 response.

Follow-up before the FDA does

The FDA’s compliance office will be looking for a response when an FDA 483 is issued, and they will review your response. The investigator will get a copy of the FDA 483 response and the investigator will comment on the response. The compliance office and the investigator enter their comments into a CDRH database, but the comments are only general, as to whether the response is adequate or inadequate and will require additional review.

If you do not hear back from the FDA, do not assume that the compliance office or the investigator were satisfied. You should also follow-up several months later (earlier if possible) with a letter that includes evidence of the completed corrective actions, and your verification of effectiveness. If the verification is compelling and received in less than six months of the inspection, you may convince the compliance office to hold off a planned Warning Letter.

If you are interested in root cause analysis and improving your CAPA process, please click on this link for another webinar recording: http://robertpackard.wpengine.com/5-ways-improve-capa-process/. A webinar recording titled “7 Steps to Respond to an FDA 483” is now available at the following link: http://robertpackard.wpengine.com/7-steps-respond-fda-483-inspection-observation-webinar/.

Posted in: FDA

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The FDA Inspection: 8 Action Items For the First 30 Minutes

fda30min 300x156 The FDA Inspection: 8 Action Items For the First 30 Minutes   The author presents an 8 item action plan and discussion for getting your FDA inspection off to a good start, beginning when FDA enters your facility. When an FDA inspector arrives at the reception desk of your facility, the last thing that you want is a Keystone Kops scenario with people running around in a panic and keeping the inspector waiting. This is your first opportunity to make a professional impression, and you never want to give an inspector the impression that you have something to hide. What happens during the first 30 minutes of arrival is critical. While medical device inspections are often announced several days in advance, there is no obligation for the Agency to do so. Therefore, your team needs training and a plan. This training should involve more than just reading the Quality System Inspection Technique (QSIT) manual (http://bit.ly/QSITManual), and conducting a mock FDA inspection. Last year, Rob Packard wrote a blog about “10 FDA Inspection Strategies that Don’t Work” (http://bit.ly/QSITmistakes), but the following activities need to be executed in the first 30 minutes to ensure your next inspection starts smoothly.

The FDA Inspection: 8 Immediate Actions to Take
1. Receptionist-Personnel Contacts  (Time Zero)

I once witnessed a receptionist sarcastically comment to an inspector that people must be thrilled when they walk in the door. That was not a great start to the inspection. Ensure that your receptionist and additional personnel who may sit at the desk are trained, understand what to do and know how to behave when an FDA inspector(s) arrives. This exercise should not cause panic. You need a simple work instruction located at the reception desk and a list of key staff members to contact immediately. The head of the Quality department, or Management Representative, is usually the first call.

2. Have Chain of Command in Place (Time = 1 minute)

DO NOT keep the inspector waiting in the lobby. Have a communication chain in place to ensure that other appropriate personnel are available in the event that the first point of contact cannot be reached. It is reasonable to ask the inspector to return at a later date ONLY if all individuals with the technical expertise to participate in the inspection are not on site, or are out of the country. The agent will make the decision whether to honor this request, but the expectation is that there is always someone with whom they can work with. Never make this request to put off the inevitable.

3. Ask To See Inspector Credentials (Time = 2 minutes)

Ask to see the inspector’s credentials, and ensure that you give them more than a cursory glance. This is important to avoid allowing an imposter posing as an Agency employee from gaining access to your business. While a rare occurrence, it has been known to happen. Some investigators are officers of the Public Health Service and may be in uniform. However, even these officers are not required to wear a uniform to all visits. Note:  Section 5.1.1.2 of the FDA Investigations Operations Manual (http://bit.ly/FDAIOM) instructs inspectors to provide their credential to top management, but copying of official credentials is not allowed.

4. Escort Inspector to Inspection Room (Time = 5 minutes)

Make sure that you can have the inspector escorted to a suitable room with the respective hosts within five minutes of arrival. This will involve ensuring that it is clearly understood by all administrative staff and key management that any other meeting may need to be curtailed, or moved immediately to another location in order to provide an appropriate space for the inspection. Providing substandard accommodations, such as a very cold or warm room is not a good strategy for shortening the inspection time, and is a ploy easily recognized by the Agency, though not appreciated. Note:  Rob Packard taught an audio seminar earlier this year where the use of inspection war rooms was covered in more detail—including a diagram with a proposed layout for the room (http://bit.ly/FDAInspectionSeminar).

5. Ready the FDA Inspection War Room (Time = 10 minutes)

Immediately after your inspection room is identified, you need to prepare your back room or “war room.” This room should be located near the inspection room, and set up at a moment’s notice with staff who can expertly execute their respective roles. You will need a mode of communication between the inspection and war rooms, runners to retrieve documents and records in the shortest time possible, as well as a technical individual to review these documents to ensure that they are appropriate and accurate before being provided to the inspector. This room should be ready within ten minutes of arrival.

6. Ensure You Have Emergency Supplies & Copies (Time = 15 minutes)

Your war room will need supplies. You should have a mobile cart equipped with inspection supplies ready and waiting at all times. Suggestions for the contents of your war room cart include: laptop, projector, staplers, staples, pens, blank folders, a label maker,and a stamp for “uncontrolled copies.” Your supplies need to make it to the war room within 15 minutes of arrival.

7. Ready the Frequently Requested Documents (Time = 25 minutes)

Don’t wait for the inspector to tell you which documents are invariably requested at the outset of any inspection. This includes, but is not limited to, the organizational chart, an index of all procedures, CAPA log, and your nonconformance logs for medical devices—all dating back to the last inspection. This doesn’t mean that you should offer these documents to the inspector. You want to prepare these before they are requested, so that they can be provided quickly, but you should keep the copies in the war room until the inspector requests each document and record. Copies of these records and documents should be stamped and ready within 25 minutes of arrival.

8. Relax (Time = 30 minutes)

It sounds as though this process is a race against time. It is not. No one engaging with the inspector should be running in and out of the room gasping for breath, or perspiring profusely from the effort. Keeping the inspector waiting can be perceived as a stall tactic, perhaps arousing suspicion that you are creating records “on the fly” in the war room (definitely not a strategy that I recommend), or that you are having difficulty locating the requested documents, and are not in control of your Quality Management System (QMS). The most important aspect is to manage your QMS, so that you are always ready for an inspection at a moment’s notice. If you prepare in advance, you shouldn’t need to do anything more than ask if the inspector would like coffee before the inspection begins.  

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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.

Posted in: 510(k)

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Section 513(g)-How to Request FDA Device Classification Information

This blog provides a five step process in how to request FDA device classification information. A screen shot of the FDA website of each step is included.

If your company is currently registering with the US FDA, you are probably reviewing the guidance document this month for the FY2013 user fees. On page six and seven, there is a table of these fees, but you might have overlooked 513(g). Section 513(g) is a provision in the law that allows for companies to request device classification information from the FDA.

For example, if your company was developing a new product, and you were having difficulty identifying the regulatory pathway, 513(g) is your friend. In my opinion, these fees are modest: $3,348 = Standard Fee, and $1,674 = Small Business Fee. Most consultants will charge at least ten hours of consulting to identify the regulatory pathway for a company. I would charge quite a bit less, because it takes me a lot less than ten hours. I still think the FDA’s pricing is a good deal, because getting information directly from the source is always more valuable than an “expert.”

The US FDA has published a guidance document explaining the process for 513(g) requests. This guidance document was released on April 6, 2012. The guidance explains what information companies need to provide in order to submit a 513(g) request. The guidance also has a fantastic list of FDA resources on page five. These are the very same resources that the “experts” use—including yours truly.

Just as any good lawyer tries to avoid asking questions that they don’t already know the answer to, I recommend that you first try using these resources yourself. Once you think you know the answer, your request for classification information will be easier to organize.

Here’s how I would proceed to request FDA device classification information: 

Step 1

Identify another device similar to yours. If you can’t do this, you need serious help. You need a similar device that is already sold on the market to use as a predicate device. If you cannot identify a predicate, then you can’t use the 510(k) process—or you don’t know your competition. Either way, there are challenges to overcome. For example, if you are trying to launch a new topical adhesive made from cyanoacrylate—“Dermabond” might be the first predicate device that comes to mind.

registration and listing Section 513(g) How to Request FDA Device Classification Information

Step 2

Use the registration and listing database on the FDA website to find the company that manufacturers the device. The link for this is #4 on my helpful links page. This link also will provide you with connections to the classification database—which you can use to find the classification for any device. However, the registration and listing database is less likely to lead you astray. When I type “Dermabond” into the field for the proprietary device name, I get a list of five different product listings.

5 listings for dermabond Section 513(g) How to Request FDA Device Classification Information

Step 3

Clicking on any one of these five will take you to a listing page for the corresponding company. On that page, you will find the three-letter product code that identifies the device classification and the applicable regulations for that device.

device listing for dermabond1 Section 513(g) How to Request FDA Device Classification Information

Step 4

Clicking on the three-letter product code (i.e., – “MPN” in our Dermabond example), takes you to the Product Classification page. This is where you will find that Dermabond, and other tissue adhesives, are Class II devices that require a 510(k) submission. In addition, the Product Classification page identifies an applicable guidance document to follow for design verification and validation testing. This is also called the “Special Controls Document.”

mpn product classification Section 513(g) How to Request FDA Device Classification Information

Step 5

Click on the “TPLC Product Code Report” link. This link will provide you with a report of all the 510(k)’s recently granted to your competitors, problems customers have experienced with their products, and recalls for the past five years. This is extremely valuable information as a design input—as well as competitive information for your marketing team.

tplc total product life cycle report for mpn Section 513(g) How to Request FDA Device Classification Information

TPLC Report for Product Code “MPN” – Topical Adhesive

Posted in: FDA

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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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