Mixed Emotions About FDA

I’ve shared some recent trials and tribulations on current medical device product development projects and FDA submissions. The saga continues. Last week, I received a round of questions from FDA on a 510(k). Yes, we made it through the RTA phase and into the substantiative review. Some of the questions were familiar themes from this submission, having already fielded FDA questions on the same topics during RTA stage of review. As I read the questions, I was more than a little frustrated and agitated. I felt as though the evidence provided, teleconferences with FDA, and email correspondence suggested that what was provided would meet FDA expectations. I thought wrong. A couple of the topics seemed to be somewhat time consuming to address. Project timeline out the window!

And as I received the FDA questions, I was putting the finishing touches on a complimentary submission. A second submission that had direct ties and linkage to the content of the first. As I took a break from compiling the second submission to read 510(k) questions, I immediately put the breaks on. Based on FDA comments, there was no point in sending the second 510(k) until the questions were answered. Second project timeline be damned too!

Did I say frustrating?

But at the same time, as a potential consumer and recipient of medical device technologies, reading the level of depth and detail of the FDA 510(k) questions was also encouraging. The types of data and information expected is a little bit remarkable and definitely thorough. More thorough than just about any other 510(k) submission I’ve read or been a part of. As a consumer, I felt that FDA is doing the proper due diligence to ensure new devices introduced in the U.S. are as safe and effective as possible.

I immediately shared the list of questions with the medical device startup. It was a Friday, and not exactly the news any of us wanted going into a weekend. But as the startup CEO lamented, FDA establishes the rules for medical device companies. There is little we can do except to react and adjust. And that’s just what we are doing.

Delivering Bad News: 510(k) Submission Will Be Late

The past couple months have been a whirlwind, pushing to get a medical device product ready for a 510(k) submission by mid June. Yes, we have an aggressive timeline. And yes, just like any other product development project, we have had our share of unexpected issues. All in all, we were still moving toward mid June.

That is until last week. One of the critical components is a silicone molded part. We received first articles last week and all looks great. However, we only received a handful. And we need to do some destructive testing to support the FDA 510(k) submission. When I found out this news, the target submission date was about 3 weeks away. Learning this, though, will likely push our submission back about 2 – 3 weeks.

Sucks! I instantly started beating myself up a bit. How could this happen? Why wasn’t our 510(k) date clear to everyone? And then I accepted that this was clear and that the team knows our important milestone dates. I could continue to whine and moan, realizing doing so would not do any good. Time to regroup and adjust.

Also time to give the medical device startup a call to deliver the bad news. Boo! Delivering bad news is not ever the top of my list. This was no exception. I dialed the number, actually kind of hoping for voice mail this time. Not today. It had been a few days since my last phone call with the startup. I used the first few minutes as an opportunity to give some project updates. And then I just spilled my guts on the likely 510(k) delays.

We talked through pros, cons, risks, and alternatives. Yes, we could take a business risk and proceed with only testing a few samples. However, the startup agreed that the risk wasn’t worth it, especially since we are only talking about a couple weeks. Bad news delivered. Bad news received by startup.

Yes, delivering bad news always sucks. But hiding it and trying to correct it seldom works.

Medical Device Accelerator in Memphis, TN

The medical device industry has several geographic pockets. Memphis, TN is one of these, especially in orthopedics.

I recently read about this medical device accelerator located in Memphis called ZeroTo510. They seem to have all the key pieces for a medical device concept to get off the starting blocks. Part incubator, part educator, part investor, part mentor. The program is geared towards helping medical device inventors and entrepreneurs get to a FDA 510(k) submission, while providing guidance and direction along the way

While I have no idea how successful this program has been, the model is very intriguing. So much so that I wonder if something like this could be piloted in central Indiana.

Medical Device Product Development in 12 Months

Can it be done? I guess before you answer, it might be helpful for me to share a few more details.

  • Device is pretty clearly a class II with dozens of potential predicates.
  • This is essentially a “me too” product.
  • The project seems to be well-funded.
  • Product development has been outsourced to firms with expertise.

So do you think this medical device can be brought to market in 12 months time?

I believe so. Granted there isn’t much wiggle room in the schedule. And of course, there will be a FDA 510(k) submission involved. But getting this product ready for launch in a year seems feasible.

We had the project kickoff on November 26, 2012 and really got started the first part of December. So far, we have finished the planning phase, including definition of clear, objective design input requirements. The rest of the schedule is laid out. Yes, we all know that medical device product development is full of uncertainties and surprises.

I’ll keep you posted as to our progress along the way.


Medical Device Entrepreneurs Need to Start at the Beginning

But where is this? I guess because of the years of experience I have with medical device product development, I often times take the process too much for granted. This became a little evident to me the other day while talking with a medical device inventor / entrepreneur.

The inventor is an ER doctor who developed an idea for a novel solution to a problem he has had to treat a few times. I had the opportunity to hear the doctor speak at an event a couple weeks ago. He was very humble and apologized several times for being out of his element. But the doctor spoke very well, almost eloquently, about the issue. The audience was on the edge of their seats, listening intently. When it was time for Q&A, nearly half the audience threw their hand up to ask a question. I think the question and answer session lasted as long, maybe even longer than the presentation.

A few days afterward, I had a chance to connect with the inventor via email. He humbly admitted again that he was out of his element and wanted to know if I would be interested in talking to him. Of course. We had that first, semi in-depth conversation a couple days ago. I provided a high-level overview of medical device product development. And the doctor was very hungry for knowledge on this topic. He understood that we needed to start at the beginning and asked question after question to understand what this means and where the beginning actually begins.

It was actually very refreshing for me. Not always, but many times when working with inventors / entrepreneurs, they are more concerned about the end rather than starting at the beginning. Within the next couple weeks, I expect to have a face to face meeting with the doctor. He asked if we could use this time to review medical device product development process and discuss FDA Design Control regulations.

Pre-Market Notification Process for Medical Devices – A 510(k) Step by Step Example

Thanks again to Rob Packard for providing another guest post. Rob is a Regulatory Affairs and Quality Management System expert whose specialty is helping companies with regulatory submission of a Design Dossiers for CE Marking of high-risk Class III medical devices. You can read more of Rob’s work (and his colleagues) at Medical Device Academy blog

Thank you for reading my previous posting on Creo Quality, “CE Marking Process for Medical Devices – A Step by Step Example” from August 14th. This third posting in the series explains the process for obtaining US FDA Clearance for medium-risk Medical Devices.

For our example, we will be using the same hypothetical client for Jon to help.

Jon’s client called to say that they are now ready to tackle the US market. As with the Canadian and European markets, the US FDA considers cyanoacrylate a medical device when it is used as a topical adhesive. Jon’s first step is to determine the device classification. Jon’s client was considering asking the FDA to identify the classification of topical adhesives using the 513(g) submission process, but Jon had a free solution. Jon showed them my blog from September 11th (http://wp.me/p19REq-8E)—which conveniently used another topical adhesive as an example.

The information provided in my earlier blog identifies topical adhesives as a Class 2 device with the three-letter product code “MPN”. This product classification also gives Jon’s client additional options that are not available to all companies that are trying to achieve 510(k) clearance for the first time. Most new products can only achieve initial 510(k) clearance from the US FDA by submitting a “traditional” 510(k). This process is supposed to take 90 days—assuming there are no significant questions about the submission and there are no backlogs with the reviewer.

For some products, there are recognized consensus standards (i.e. – ISO Standards) that define the performance requirements for a medical device or a Special Controls document published by the FDA that identifies which performance Standards the FDA requires for a specific product classification. In the case of topical adhesives, the FDA has published a Special Controls document. When there is a Special Controls guidance document available, the company may submit an “Abbreviated 510(k)” instead of a Traditional 510(k). An Abbreviated 510(k) contains summaries of all the testing results required in the Special Controls document or in an ISO Standard recognized by the US FDA. Since all the required performance testing presented in an Abbreviated 510(k) is in accordance with a previously accepted standard, the FDA reviewer only has to verify that the performance testing identified in the Special Controls document or the ISO Standard has been completed and acceptance criteria have been met. Therefore, the reviewer needs less time and clearance can be achieved in 60 days—instead of 90 days.

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

As Jon reads through the Special Controls Guidance document, he realizes that a specific format for Abbreviated 510(k)’s is described for topical adhesives. Therefore, Jon modifies his normal template to match the FDA format for topical adhesive Abbreviated 510(k)’s. As Jon reads further, he realizes that there will be some additional testing required that his client may not have anticipated.

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


The risks of adverse tissue reaction, chemical burns, and infection have all been addressed by biocompatibility testing and sterility testing. Jon’s client also performed animal testing to identify any problems in a simulated use environment. However, the client did not perform any testing to specifically address unintentional bonding, wound dehiscence, applicator malfunction or delayed polymerization. Some of these questions were asked and answered during the CE Marking application process, but the client did not have formal protocols and test reports to address these risks.

Another difference between testing that Jon’s client performed in the past and the US FDA’s requirements for a 510(k) submission is the concept of a predicate device. Jon’s client needs to select a similar topical adhesive that received a 510(k). Ideally, a recent 510(k) should be selected because “old” technology may no longer be considered acceptable from a safety standpoint. In the case of topical adhesives, the applicator is one of the primary differences between legacy products and more recent 510(k) products. The most recent version of Surgiseal™ (see picture below) is an example of a new applicator for a monomeric, 2-octyl cyanoacrylate similar to the product Jon’s client is selling in Canada and Europe.

Jon’s client has a similar applicator design to the pictures above, and therefore Surgiseal is selected as the predicate device for this hypothetical 510(k) submission. For all the testing protocols that need to be created for this 510(k) submission, comparative testing is performed with a sample of Surgiseal and a sample of product made by Jon’s client. In each of these protocols, the acceptance criteria is performance “not worse than Surgiseal”.

In addition to completing the testing required for the 510(k) submission, Jon’s client also needs to add procedures to their Quality System to address unique US FDA requirements. Jon’s client already has a training procedure, but the data analysis procedure does not address the requirement for statistical techniques in 21 CFR 820.250. There are also requirements for maintaining a device master record (21 CFR 820.181), medical device reporting (21 CFR 803) and corrections/removals (21 CFR 806).

Jon’s client completed all of the required testing protocols comparing their new product with Surgiseal™ within 10 weeks. During this same period, Jon helped them to update their procedures to meet the FDA’s specific requirements that are not included in Canadian or European legislation or the ISO 13485 Standard. Finally, Jon’s client was ready to pay their fee for the 510(k) submission and submit the 510(k) for review. The FDA reviewer requested copies of a few of the reports that were summarized in the submission: biocompatibility testing reports, sterilization validation reports, and a usability report that was created to address human factors concerns related applicator malfunction and use errors. Each of these reports were provided by email within 24 hours of the request. The reviewer had no further questions, and the 510(k) clearance letter was issued within 55 days of initial receipt.

After receipt of the 510(k) clearance letter, Jon’s client registered with the FDA as a device manufacturer and specifications developer and began selling in the USA.

FDA 510(k) or CE Marking?

Today’s guest post comes from Rob Packard. Rob is a Regulatory Affairs and Quality Management System expert whose specialty is helping companies with regulatory submission of a Design Dossiers for CE Marking of high-risk Class III medical devices. You can read more of Rob’s work (and his colleagues) at Medical Device Academy blog

I’ve read a few business plans that propose to obtain a 510(k), CE Marking and a Canadian Medical Device License all in six months. My first impression is, “Lots of Luck!” Often I will ask how many people are working on this ambitious regulatory project. If the answer in “one”, they haven’t even got a clue. For a low-risk device this MIGHT be possible, but there are “If” qualifiers:

  1. If the device is a Class 2 device in the US requiring a 510(k), and the device is extremely similar to the predicate device, the 510(k) might get approved within 90-120 days.
  2. If the device is a Class IIa device in Europe, an expedited review ($$$) can be as short as 90 days.
  3. If the device is a Class 2 device in Canada, a Medical Device License can be approved in less than 60 days.
  4. If the company has already completed all the verification and validation testing, including any electrical safety and shelf-life testing, a regulatory expert can assemble a submission for all three markets in less than 60 days—assuming the design team has already written most of the documentation.
  5. If the regulatory expert has successfully submitted multiple applications to each of these markets previously, they will have templates to work from and know exactly what each country wants—including formatting.
  6. If the company already has a registered Quality Management System (i.e. – ISO 13485:2003 with CMDCAS), then they won’t need to have a Phase 1 audit, open a bunch of CAPAs, have a Phase 2 audit, and open some more CAPAs.

On rare occasions a motivated team can accomplish the impossible. For example, I started helping a team last year around August 1st. The team was half-way done with their Technical File for CE Marking, already had a 510(k), and they had just finished a pre-assessment audit for ISO 13485. After an obscene amount of work, we achieved CE Marking of their Class IIa device by mid-November (~100 days). CMDCAS and a Canadian Medical Device License application would have killed us, so we postponed that goal for this year.

Why would you want to commit your team to such a ridiculous goal of 3 regulatory approvals in a 6-month period?

The answer is that most companies have the common sense not to. Instead, most companies pick one market and focus on that. Most US-based companies pick the US market and submit a 510(k) first. Why?!

The 510(k) process is harder than CE Marking, new technology takes three years longer on average to get approved in the US than Europe, and the rules change faster than the US FDA publishes guidance documents to explain what they are doing.

Canada is the least rigorous of the three markets I mentioned (If you really want easy, New Zealand only requires registration—there is no “approval” at all for that market.). The Canadian market is 10% of the US Market size, and New Zealand is…well not worth comparing. Europe, however, is a big market.

Most small and mid-sized medical device companies rely upon distributors to sell their devices rather than developing their own direct sales force. What difference does it make if you are selling to a distributor in Austin, TX or Galway, IRE? If your company is going to use distributors, pick the easier regulatory hurdle first and work your way up the ladder of difficultly while your distributors bring in some cash.

Success in any business is about sales, sales and sales.

Before you even start designing a medical device, you should be talking to potential distributors. Distributors and sales people are one of the best sources of product ideas. If you are a CEO/founder hopeful, you are more likely to succeed if your background is sales and marketing. Engineers can invent 100’s of medical devices and mousetraps (MD&M), but it is rare to find an inventor that can sell—let alone explain the difference between the strategic marketing plan and the advertising plan.

My advice is to start with the strategic marketing plan for Canada and then one or two countries in Europe. If you have trouble identifying distributors for your type of device in these markets, then you are not competent as a sales and marketing person. You need to get help!

If you don’t know where to look for help, you might ask your regulatory expert. Regulatory experts have to research the competitor products in order to identify known risks and typical adverse events. Regulatory experts also need to identify the competing products before they can be certain of a regulatory pathway. Authorized representatives are sometimes quite helpful in identifying distributors too.

My final advice is to save the US Market for last!

What Are Your Thoughts About the Current FDA 510(k) Process?

I recently posted this question on the Medical Devices Group on LinkedIn. The article “FDA Rule Clears Medical Devices Without Human Testing” got me thinking about this topic. I posed a few additional comments about this topic in the discussion on LinkedIn:

  • Do you think human clinical trials should be required for line extensions and product modifications that require 510(k) submission? Why or why not?
  • Do you think conducting human clinicals would really reduce product issues in the field?
  • If FDA were to require human clinicals for all 510(k)s, do you think there would be a reduction in new medical products introduced into the U.S. market?

The few comments posted were insightful, suggesting that U.S. medical device companies are likely to introduce new products and technologies overseas first.

I’ll admit, I was hoping for more dialog and comments on this and decided to post this on the CQ blog. Please chime in.

April 26, 2012 – Analysis of Recent FDA Guidance Documents (part 2)



Please join the Indiana Medical Device Manufacturers Council (IMDMC) for our

Part 2 – Analysis of Recent FDA Guidance Documents Workshop
RESCHEDULED for April 26, 2012
 CLE Credits Have Been Requested




9:55 am EST Welcome



Section 522 Post Market Surveillance Guidance document

(FINAL issued in July 2010)

Natalie S. Heck, MS, RAC, Zimmer Inc.



Risk Based Clinical Trials Monitoring (DRAFT issued in August 2011)

Kara Mezger, Zimmer Inc.



Use of Exculpatory Language and Informed Consent Guidance

Leah Kendall, Epstein Becker & Green

12:15 Lunch provided


Proposed Changes to the Common Rule

Indiana University Representative TBA (invited)



Draft Guidance on Unsolicited Requests for Off-Label Use

David Chadwick, Cook Medical



Moderated Q&A Panel

Ralph Hall, Faegre Baker Daniels

3:00 Adjourn




Registration Fees:  $125 IMDMC Member / $175 Non-Member
Discounts available for members registering more than 5 registrants on the same form.

Location: Montage, 8580 Allison Pointe Blvd, Indianapolis, IN 46250


Please register to attend the event now!




February 22, 2012 – IMDMC 510(k) Submission Guidance Workshop



Please join the Indiana Medical Device Manufacturers Council (IMDMC) for our

Analysis of Recent 510(k) Submission Guidances Workshop
on February 22, 2012


9:30-10:30 EST Welcome / New 510(k) paradigm Ralph Hall, Faegre Baker Daniels
10:30-11:00 Use of Experts Daniel J. Dillon, MS, RAC (US)
MED Institute
11:00-11:15 Break
11:15-12:15 5 Hot Topics!
Center Science Council
Chemical action/definitions
de novo
Ralph Hall, Faegre Baker Daniels
Gretchen Bowker, Pearl IRB
Scott Thiel, The Anson Group
Brandon Hipsher, DePuy Orthopaedics
Daniel J. Dillon, MED Institute
12:15-1:00 Lunch provided
1:00-2:15 Modifications Scott Thiel, The Anson Group
2:15-2:45 New HDE Guidance Jack Rogers, Beckman Coulter (invited)
2:45-3:15 Appeals Brandon Hipsher, DePuy Orthopaedics
3:15 pm Adjourn

Registration Fees: $125 IMDMC Member / $175 Non-Member

Location: Montage, 8580 Allison Pointe Blvd, Indianapolis, IN 46250

Please register to attend the event now!


What Comes First: Design Input Requirements or Prototype?

Okay, this is kind of a trick question. Actually, what should come first the the unmet clinical need. But once you’ve identified the unmet clinical need, what do you do next? Do you define the product’s design inputs? Or do you proceed to building some type of prototype?

I’ve taken both approaches. And I’ve often wondered which is best–which is correct.

I think I now know which approach makes the most sense. Build the prototype first.

Why? A prototype is so much better at communicating than words can ever be. Put a prototype in the hands of end-users, and they can tell you everything that is right about it. More importantly, they can tell you everything that is wrong too.

Capturing and documenting design input requirements becomes so much easier when end-users are able to conceptualize the product, especially if they can hold and manipulate it in their hands.

So go build the prototype. It doesn’t have to be perfect. It doesn’t have to be made using production materials or processes. It has to be good enough to communicate a solution to others.

Then take the information you learn with this prototype and document the design input requirements. And refine the prototype to learn more and more until you have the product design right.

It’s important, though, to not get too stuck in this cycle. It’s easy to do, especially for engineering types. Don’t try to make the perfect product with all the bells and whistles. Know when the product is good enough to address the unmet clinical needs and get it to the market as quickly as possible. Be sure you’ve proven its safety and efficacy, and of course be sure to document all of this along the way.

New FDA Draft Guidance: When to File 510(k)

We’re working with a medical device company now that has several products that received market clearance via 510(k). Many of these products have incurred changes since being launched. The company has done a good job of reviewing FDA 510(k) decision trees to determine whether another submission is required. However, sometimes product changes fall into a gray area where it’s not entirely clear whether a new 510(k) submission is required.

FDA recognizes that these decisions are not always black and white and has drafted a new guidance document for when to file a 510(k). Below are some links about this topic:

Reforming the 510(k) process: the FDA’s latest guidance

FDA Issues Draft Guidance, “510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device”

Do You Need New 510(k) Submission? – FDA Clarifies

FDA Provides Draft Guidance for 510(k) Premarket Submission

510(k) Review Times Increase Because of Poor Submissions

FDA recently released a report analyzing 510(k) review time. The analysis showed that review times have increased due to the poor quality of data and information provided as part of the 510(k) submission. FDA requests for additional information from submissions steadily increased from 38% in 2001 to 77% in 2010. Requests for additional information obviously increases review time.

CQ has been involved with quite a few 510(k)s during this period of time, ranging from large to early stage start-up medical device companies. Some of the companies we’ve worked with were submitting their very first 510(k), while others were “old pros”. Based on my experiences and anecdotes from my business partner, I definitely agree with the conclusions of this analysis. There were some 510(k)s that probably lacked key data and information. And we received requests for additional information from FDA. The submissions which were more thorough had quicker reviews. Yes, sometimes these also received requests for more information. However, these cases were usually handled via email correspondence and phone calls, all while not stopping the review time clock.

Start-ups seem especially anxious to submit a 510(k) to FDA, usually because this milestone is directly linked to a fund-raising event. I blogged about this some time ago. I think the more meaningful milestone is 510(k) clearance but understand somewhat why there is emphasis on the submission. Regardless, the FDA analysis indicates quality of submission has a direct correlation to review time. Start-ups (and others submitting 510(k)s) take note.

You can read a couple other posts on this topic by clicking the links below:

New FDA study: Insufficient 510(k) submissions causing bulk of 510(k) review delays

FDA 510(k) Reviews Result in More Questions Than Ever