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Posts Tagged ‘FDA’

What is the future of reprocessed, single-use devices?

In Unique Device Identifier, Vigilance Reporting on November 5, 2012 at 2:39 pm

In 1999 the FDA conducted a meeting to discuss reprocessing of single-use devices (SUDs). In August 2000, a guidance document was published to communicate the FDA’s enforcement policy for 3rd parties and hospitals that reprocess SUDs. Many reports have been published on this topic in the USA, Europe and Canada since that time.

I couldn’t think of an ideal song title to match up with reprocessing, but I was listening to my Amy Winehouse station on Pandora at 2am…it just seemed to fit.

In an article published earlier this year, Daniel J. Vukelich, Esq. (President of the Association of Medical Device Reprocessors), explained that 95% of the reprocessing is performed in the USA, and “AMDR is confident that reprocessed SUDs will continue to play an increasingly important role in our healthcare system”.

OEMs are deeply concerned about reprocessing of SUDs—and it’s not just about the money. Jon Speer recently wrote a blog that voiced some of the industry’s concerns. Specifically, the post addressed the issue of complaint investigation.

The FDA published a guidance document that outlines the process for adverse event reporting of reprocessed SUDs .

The problem is that even with electronic medical records, not all the necessary information regarding traceability is included in those records. This situation is about to change dramatically in the next few years as new global regulatory requirements force companies to implement Unique Device Identification (UDI) and as Europe implements the proposed regulations (Article 15).

How do you anticipate these changes will impact the prevalence of reprocessed SUDs globally?

Will these changes result in changes to your company’s product labeling of risks associated with re-use of SUDs?

If you would like to see the comments others have, please join the following LinkedIn Group: Medical Device: QA/RA. If you are not already a member of the parent group (Medical Device Group), you should join.

Advice from the FDA – Come early, be loud and stay late

In IDE, IND, NDA, PMA, pre-IDE, pre-IND, US FDA on September 21, 2012 at 6:20 am

For the past two days, I was fortunate enough to attend a training seminar hosted by the FDA in Washington, DC. This was a “free” seminar (i.e. – travel expenses only). The session was split into two rooms. One room focused on the drug-side regulations and the other side focused on the device-side regulations. My strength is device-side. Therefore, I spent most of my time listening to the speakers on the drug-side. Throughout the training there was one common theme that was repeated by the speakers: Come Early, Be Loud, and Stay Late.

It’s much too late for me to still be awake, but I’m still recovering from motion sickness on my train ride back from DC. I feel compelled to write a blog posting, but I just don’t have the motivation for something technical tonight. Therefore, I beg you to forgive my attempt to impart philosophy rather than knowledge. Hopefully, you will find it useful. If not, at least you can enjoy the beautiful singing of Madeleine Peyroux.

“Come Early”

The speakers recommend that companies plan their submissions well in advance and talk to the appropriate FDA project manager about their plans before they start clinical studies.

“Be Loud”

The speakers recommend that companies communicate with as many people as they can at the FDA to make sure they have identified all the critical issues to address in the study design.

“Stay Late”

The speakers recommend that companies think ahead so that if (or when) things don’t go as planned, the clinical study results can be salvaged.

In simple, and more practical terms, every speaker emphasized the importance and value of consulting with the FDA instead of guessing what type of data will be needed for a submission. One of the other participants brought this up at lunch on the first day. He mentioned an example where the FDA agreed with a company on specific data that would be required for acceptance of an NDA. Then, the company did exactly what the FDA said and the FDA required more data. He then described another case where the FDA specified data and the company refused to comply—but the FDA granted approval.

This other participant and I both agreed that most companies are afraid to ask the FDA for agreement on what data is required, because the company may not like the FDA’s answer. My personal belief is that the FDA is better at identifying what data will be required than most companies, because the FDA has a broader perspective than companies do. There will always be exceptions, but my recommendation is to ask the FDA’s opinion whenever you have a question—just make sure you do your homework before you ask an inane question that is already in their guidance documents.

I believe this advice also applies to every regulatory agency in the world.

Section 513(g) – How to request classification information from the FDA

In 510(k), Device Classification, MDUFMA, Medical Device, Section 513(g), US FDA on September 11, 2012 at 11:28 am

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 6 and 7 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.

During Labor Day Weekend, my family went to the Southern Vermont Garlic Festival in Bennington, VT. We were fortunate enough to hear Molly Durnin play songs from her new album on acoustic guitar. We loved it and bought the CD—which is also available on iTunes. Here’s my favorite track from the new album.

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 5. 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:

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, you’re all buggered up. 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 Database Entry Form

Step 2

Use the registration and listing database on the FDA website to find the company that makes 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.

Listings for “Dermabond”

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.

One of the 5 Dermabond Listings

Step 4

Clicking on the three-letter product code (i.e. – “MPN” in our Dermabond example), this takes you to the Product Classification page. This is where you will find that Dermabond, and other tissue adhesives, are Class 2 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

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, the problems customers have experienced with their products, and the 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 Report for Product Code “MPN” – Topical Adhesive

The New EU Regulations – 21 Days and Counting!

In CE Mark, Medical Device Report (MDR), Uncategorized, Vigilance Reporting on September 5, 2012 at 6:28 am

The EU Directive will become Regulations…but when? September 26 the proposed regulations are scheduled to be released in draft form. Plans for implementation of the Interim Measures have already begun, but the regulations will not be finalized for 18-24 months while the politics takes over. My magic 8-ball tells me that there is a precedent on this side of the pond that can help us predict the future.

A few weeks ago I published a posting with a cheeky Brit–Lily Allen. Here’s one of Lily’s own favorites by a another talented British singer, song writer named Kate Nash.

Throughout the history of healthcare regulations worldwide there have been three rules that are never broken:

  1. Regulations always get tougher.
  2. Regulations are only partially effective.
  3. Regulations cost everyone more money.

The PIP scandal lit a fire under the European Parliament, the Council and Notified Bodies. Now all three stakeholders are fighting to show the public that they are doing everything they can to ensure safety. Unfortunately, no matter what changes are made it is extremely difficult to prevent unethical behaviors.

Before I make predictions, we all need to remember that there is a larger news story–the European Economy.

The status of the European Economy will have the greatest impact on new regulations. My best evidence is the US FDA.

The FDA has been trying to improve the turnaround on submission reviews for my entire career. For a period of about 8 years, matching closely with the Presidential terms of George W. Bush, it seemed to get easier to get products through the FDA logjam. Then the global economy tanked and political winds changed in 2009.

Over the past three years, Republican’s have gained power and Congress is now pushing the FDA to actually improve the metrics for product approval. The FDA will now have 200 additional reviewers, and every plan for improving turnaround that has been tried is back on the table.  The FDA was given the funds to grow its army of inspectors first, and now the FDA is granted additional funds to hire additional reviewers and train them.

The European Union includes countries that are struggling to provide basic services, while other countries don’t want to bail their European neighbors out of debt. How is the European Parliament and the Council going to increase regulation of medical devices when everyone knows that regulations will cost more money?

The short answer is…they can’t.

One of two things must happen before true change can occur:

  1. another healthcare scandal could trigger this change, or
  2. the economy could improve.

Based upon the sluggish recovery of the US economy, I don’t see how #2 will happen in Europe during the next 18-24 months. I can’t predict #1, but historically scandals are years apart.

MAGIC 8-BALL TIME

I predict that the draft regulations will get watered down during the co-decision period. The most popular legislative tool is the “transition period”. For example, UDI legislation was passed in 2007 in the US but the proposed rule was not published by the FDA until 2012. The proposed rule includes a 7-year transition period for implementation of the new rule.

If the new EU regulation is finalized in 18-24 months, we can expect a long transition period during which various pieces of the regulations will be implemented. This transition period is essential for Notified Bodies to gradually increase their staff and for training new auditors. This will also give companies several years to organize their own plans for addressing the new regulations.

The one change I predict to happen quickly is consolidation. 60+ Notified Bodies are more expensive for the EU to support than a few large Notified Bodies. The FDA is a single, centralized regulatory body. The EU will not achieve the same degree of centralization, but I predict “a great consolidation”.

My final prediction is related to the vigilance process. In the US the MDR process has become highly automated and electronic submissions with a public database are the norm. This has allowed the FDA to rely on data analysis to identify problems and redirected the burden of data entry from the FDA to industry. We can expect Europe to follow this trend, by centralizing all vigilance reporting. The only remaining question about vigilance is how long will the transition period need to be for revision 8 (of MEDDEV 2.12/1).

FDA Inspection Strategies that DON’T Work

In 510(k), US FDA on August 30, 2012 at 3:53 am

If you were just notified of an FDA inspection and you don’t think you are ready, using tricks to hide your problems is a huge mistake. I have heard a few recommendations over the years for “secrets” to hide those problems. In this post, I share my favorite “secrets”–and why they DON’T work.

Here are my top 10 ways to make an FDA inspection worse:

10. Stalling when the inspector makes a request – This just irritates inspectors. At best the inspector will use the waiting time to identify additional documents to sample or to review the information you have provided more closely. At worst the inspector will accuse the company of not cooperating with the inspection and the inspector may return the following week with several more team members to help them. Whenever this occurred during a 3rd party audit that I conducted, I would move on to another area and interview someone. However, before I left the person that was slow to respond, I provided the person with a list of documents and records that I expected to be waiting for me upon my return. In extreme cases, I had to bluntly tell the management representative that I needed documentation more quickly. As an instructor, I teach auditors techniques for coping with this tactic.

9. Suggesting records for the inspector to sample – This is specifically forbidden in the case of 3rd party inspections and audits. The FDA has work instructions for identifying sample sizes and samples are supposed be selected randomly. In reality, samples are rarely random and usually the inspector is following a trail for a specific lot, part number, etc. When clients offered me samples, I tried to be polite and review the record they provided. However, I also would request several other records–or follow a trail as I have indicated above. Another approach I often use is to focus on high-risk items (i.e. – a risk-based approach to sampling). In general, you can expect the FDA inspectors to sample more items than a registrar–and sample sizes are often statistically derived if the number of records is sufficiently large. When sample sizes are quite small, I recommend sampling 100% of the records since the previous inspection/audit. This is not always possible for 3rd party auditors, but internal auditors often can achieve this.

8. Outsourcing processes to subcontractorsThe FDA recently re-instated the requirement for contract manufacturers and contract sterilizers to be registered with the FDA by October 1, 2012. Therefore, hiding manufacturing problems from the FDA by outsourcing manufacturing is increasingly more difficult to do. In addition, the FDA focuses heavily on supplier controls and validation of outsourced processes. Therefore, an inspector will identify high-risk processes performed by subcontractors and request documentation of process validation by that supplier. If the company does not have the validation reports–this could quickly escalate to a 483–and possibly a visit to the subcontractor.

7. Trying to correct problems during the inspection – This is what I like to call the document creation department. At one company I worked for, we noticed a mistake across several of the procedures and made a change overnight between the 1st and 2nd day of the audit. When the auditor asked for the procedures in the morning, he asked “Is the ink dry yet?” The auditor then proceeded to request records that demonstrated compliance with the newly minted procedures. As you might have guessed, this resulted in several nonconformities. When clients attempt to correct problems found by an inspector, the inspector typically will respond with the following statement, “I applaud you for taking immediate action to contain and correct the problem. However, you still need to perform an investigation of root cause and develop a corrective action plan to prevent recurrence. To do this investigation properly may take several days.” I also teach auditors to memorize this phrase.

6. Writing a letter to file – When companies make minor design changes, one of the most common approaches is to “write a letter to file.” This phrase indicates that the design team is adding a memo to the Design History File (DHF) that justifies why design validation is not required or why regulatory notification/approval is not required. The FDA used to publish a decision tree to help companies make these decisions. In fact, such a decision tree is still part of the Canadian significant change document. The FDA recently withdrew a draft document that eliminated many perceived opportunities to utilize the “letter to file” approach. However, the FDA will still issue a 483 to a company if the inspector can identify a change that required validation that was not done or a 510(k) that was not submitted for a design change. In fact, the FDA specifically looks for these types of issues when an inspector is doing a “for cause” inspection after a recall or patient death.

5. Shut it down – Not running a production line that has problems is a favorite strategy for hiding problems. However, the FDA and auditors will simply be forced to spend more time sampling and reviewing records of the problematic production line. If you need to shut a line down, make sure everything is identified as nonconforming and segregate rejected product from good product carefully. You should also use these problem lines as an opportunity to show off your investigation skills and your ability to initiate CAPAs. If you simply forgot to validate some equipment or do some maintenance, take your lumps and keep production running. If you are a contract manufacturer, never shut it down without notifying the customer. If you do not tell your customer, you will get a complaint related to on-time delivery and a 483.

4. Storing all records off-site – I first heard about this tactic during an auditor course I was co-teaching. During the course we had many reasons why the company should be able to provide the records in a timely manner. However, I have experienced this first-hand as a 3rd party auditor. When this happens, I do three things: 1) I increase my sampling of records that are available, 2) I carefully review the supplier controls and supplier evaluation of the storage facility (assuming it is outsourced), and 3) I verify that the company has a systematic means for tracking the location (i.e. – pallet and box) for every record sent to storage. FDA inspectors will simply move along to another record and follow-up on their earlier request with a second visit or a request to send a copy of the document to them after the inspection.

3. Identifying information as confidential – A company can claim information is confidential and may not be shared with the public, but very little information is “Confidential” with regard to the FDA or Notified Bodies. Therefore, this strategy almost never works. In fact, this will enrage most FDA inspectors. In training courses, I train auditors to ask the auditee to redact confidential information. For example, a CAPA log may have confidential information in the descriptions but the trend data on opening and closing dates is never confidential.

2. The FDA is not allowed to look at those records – Although this statement is technically true for internal audit reports and management reviews, the FDA always says that they can get at this information through the CAPA system. What the FDA means is that there should always be evidence of CAPAs from internal audits and management reviews. If there is not, then this will quickly become a 483. Another person I met tells the story that when they agreed to share the management review records with the inspector, the inspector rarely issued a 483. When they refused to share the management review with the FDA, the inspection went quite badly from that point forth. I don’t agree with being vindictive, but it happens.

1. Show me where that is required – This is just silly. Inspectors and auditors are trained on the regulations, while you are trained on your procedures. Spend your time and effort figuring out how your procedures meet the regulations in some way. Challenging the inspector excites the inspector. We all like a challenge–and we rarely lose. One auditee tried this approach with me in front of their CEO. This experience gave me the opportunity to show off that I had memorized the clause in question–and the corresponding guidance document sections. I think the CEO realized quickly that the Management Representative was not terribly qualified.

My final advice is to do your best to help the inspector do their job, and treat every 483 as “just an opportunity to improve.” Just make sure you submit a response in 14 days or you will receive a warning letter too!

UDIs Required by the FDA (Draft for 120-day Review) – It’s about time!

In Medical Device, Medical Device Report (MDR), recall, Unique Device Identifier, US FDA on July 5, 2012 at 4:50 am

Unique Device Identifiers (UDIs) are nothing new. MASH tents in the military use 2-D bar coding to track the use of instruments in mobile operating rooms in the field. Just image how hard it is to count forceps and vascular clamps during a wave of shelling from a nearby front. That’s just one way UDI’s can be used to benefit patients and healthcare providers. Click here for the proposed rule.

For this week’s entertainment, I picked something a little different.

I am positive that some companies, and their lobbyists, will fight the latest regulations from the FDA regarding labeling requirements. However, this makes even more sense than electronic medical records. UDIs will enable faster and more accurate product recalls and MDRs. Click here for more information (I have copied the example provided by the FDA).

Unique Device Identifier

This is the unique device identifier example provided by the US FDA.

If you are trying to recall product, the last thing you want is to continue to send out letters three and four times to facilities that have no idea when or if your product was used. The medical facilities want to close out these requests for information quickly too. UDIs present a solution for assuring correct and complete responses by hospitals the first time.

How UDI Helps with Recalls

  • Locating devices in inventory
  • Locating product in distribution centers
  • Identifying product after it is removed from the outer box
  • Tracking product to each individual patient

How UDI Helps with MDRs

If you’ve been in the business long enough, you have seen more than one complaint about a product that you don’t even make. When this happens the company is obligated to open an investigation to make sure and the complaint gets recorded in the complaint files. The proposed rule includes identification of the manufacturer. Therefore, 100% of complaints should go to the correct company. Also, the company should always receive a lot number—something that almost never occurs.

What do you think about UDIs?

Has your company already taken steps to implement UDIs?

US FDA Launches a Pilot Program for Modular 510(k) Submissions

In 510(k), Design Verification, Medical Device, Novelblogg, US FDA on June 28, 2012 at 8:22 am

Sorry if you feel mislead, but this is a regulatory fantasy. I thought I would experiment with something different to celebrate 5,000 views! I call it a novelblogg. I should probably trademark the term but that’s just nonsensetalk. I hope you enjoy the music video selection this week, because listening to The Smiths never goes out.

April 2013

Jim, the Director of Engineering at The Cat’s Meow (TCM), bumps into Caroline in the hallway as they both rush to the board room for a surprise meeting with the CEO. Caroline is the Director of QA/RA, and Steve is the CEO.

“Caroline, do you know what the meeting is about?”

“No, but I’m sure it must be related to AAOS. Steve has been pissed ever since he got back from the show.”

Steve enters the conference room with a stack of handouts which he hands to Caroline and asks her to pass the stack around to the rest of the group.

“Thank you for being on-time everyone. I have important news related to The Bees Knees [TBK], and I want everyone to take this information back to their individual teams after this meeting. TBK had a small group of orthopedic surgeons in one of the private meeting rooms at the show. One of these surgeons is friendly to TCM, and they were kind enough to give us the inside track. [pause] TBK is developing a new metal-on-ceramic total knee system, and they plan to launch it at AAOS next year.”

Jim made a low whistle, and Caroline said, “None of the ceramic materials cleared by the FDA could withstand impact from a metal femoral implant. Is it a new material?”

“Great question Caroline. I have been researching that question ever since I got back from AAOS and I finally discovered which material they are using. The femoral component is titanium with a nitride coating, and the tibial component is a single piece of ceramic with a nano-coating. The combination was invented by a start-up company developing a new ceramic wheel bearing, but the company went out of business. They never followed-up their provision patent with a patent application. Now the material has no patent protection and TBK has already started their verification testing.”

“Who’s selling the ceramic?”

“I can’t be 100% certain, but I think the original company supplied TBK with prototype samples for durability testing. Now they are developing an in-house casting process. The chemist I spoke with believes that the nano-coating is a special mold release agent that becomes fused with the ceramic when they sinter the parts in a vacuum furnace.”

“So what’s our counter attack?”

“That’s why you are all here. I was hoping the team might have some ideas for a new product we can launch by next year’s AAOS meeting. In order to launch by AAOS, we need to submit the 510(k) by when Caroline?”

“Well…actually the FDA just announced a pilot program for 510(k) submissions using a new software system. They promise it will dramatically reduce review timescales, but I don’t have any details yet. I already took the on-line training webinar, and I received a password to the beta version of the software. Pilot programs are risky, but this might be the only way we could catch TBK.”

“Jim, what would we need to change about the Orion Knee in order to adapt it for use with a ceramic tibia?”

May 2013

Caroline and Jim have a pre-submission conference call with an FDA reviewer involved in the pilot program.

“Jim and I were reading through the guidance documents you sent to us, and we were hoping you could explain the optional modular submission pathway to us.”

“Sure Caroline. The FDA’s PMA process has a modular submission pathway as well. This was the basis for the modular 510(k) pilot process. The intent was to allow companies to define the content of the submission up-front and allow the company to submit modules as they are completed instead of waiting until all testing is completed.”

“The durability testing of our ceramic tibial component is expected to be the last verification testing protocol that we complete. Can we submit this as a separate module?”

“Exactly. Shelf-life and durability testing is typically the last testing completed prior to submission. Since these tests have well-defined ASTM test methods, I can assign a reviewer independent from the other modules. You mentioned that this ceramic component will be cast and then sintered in a vacuum furnace to create the nano-coating?”

“Yes, that’s our plan.”

“Make sure you use production material rather than production equivalents for the durability testing. The FDA cannot accept verification data for ceramics based upon prototype material. This has resulted in recalls and adverse events for other ceramic implants.”

“That could be a problem. Jim tells me that we will have twenty different size castings, and the process validation won’t be completed on all the sizes prior to the start of our durability testing.”

“Have you identified which size casting represents the worst-case device?”

“Yes. The smallest size is the thinnest and will therefore be the most susceptible to damage. Therefore, we plan to use this for our verification testing.”

“That’s good, but you will also need to demonstrate that the samples used were made under conditions that are validated to produce the weakest implant such as the extreme high or low temperature in your process range.”

“We have determined that the sintering process is the most critical factor in producing a strong implant. At lower temperatures the sintering is not sufficient to produce a dense implant and the implants are sometimes brittle. At higher temperatures, the sintered implant is nearly indestructible.”

“You will need to provide some preliminary data to this affect before I can agree to using implants sintered at the lower temperature limit, but this seems like an appropriate solution.”

“Can we submit the verification protocol along with the preliminary data in order to get the FDA’s acceptance of the durability testing protocol?”

“Yes, you should submit the protocol and the preliminary data prior to submission of that module. I will assign a reviewer with expertise in ceramics to ensure that the protocol and data are reviewed thoroughly.”

June 2013

Caroline and Jim submit the protocol and preliminary data to the reviewer. The reviewer identifies a problem with the protocol. The force chosen for cyclic testing simulates the average theoretical weight of a person walking down a flight of stairs. However, the reviewer indicates that adverse event trends for ceramic implants indicate that most of the device failures occur with heavier patients walking down stairs. Therefore, the reviewer indicates that the force should simulate the 99th-percentile of weight for an adult male walking down stairs. Jim decides to repeat finite element analysis (FEA) with the higher force requirement. The FEA report indicates that implants sintered at the lower temperature may not be thick enough for this force. Therefore, Jim has to modify the casting mold for the four thinnest implant molds. The smallest was sent back to the manufacturer to be modified first and the testing protocol was updated.

July 2013

The revised casting for the smallest implant was received and implants were sintered at the lower limit of the temperature range for sintering. The protocol was executed in early August and the duration is 104 days. Therefore, the final report and module should be completed just before Thanksgiving 2013.

In parallel with TCM’s durability testing, TBK is conducting its own durability testing on prototype material, because the process validation of the new casting is not completed. Their regulatory director has drafted a rationale for use of production equivalents, but there has been no discussion with the FDA regarding TBK’s traditional 510(k) submission. Therefore, no reviewer is identified and no sections of the submission will be reviewed until all testing is completed in October.

September 2013

TCM receives confirmation that all submitted modules have been cleared by the FDA—including labeling and other marketing materials. The initial marketing content included a claim that the new metal-ceramic material “lasts longer than conventional UHMW polyethylene implants.” The FDA reviewer, however, would not allow comparison statements in the marketing literature because the 510(k) process only allows for substantial equivalence. Caroline and the Director of Marketing spoke with the reviewer directly the Tuesday after Labor Day. The Director of Marketing asked if it would be acceptable to share side-by-side video of the durability testing that is in progress with a caption that states “TCM’s new metal-ceramic materials are ‘not inferior’ to TCM’s current UHMW polyethylene implants.” At the time of the question, the metal-ceramic materials were showing almost no signs of wear, while the UHMW polyethylene implants were showing signs of creep and pitting on the polished surface. By the end of the verification testing, everyone expected catastrophic failure of the UHMW polyethylene implants. “Not Inferior” would be a gross understatement, but an accelerated video demonstration of the 104-day study would be more powerful than words or pictures.

TBK has all of the sections of their 510(k) submission ready—with the exception of the durability testing.

October 2013

TCM is waiting to complete the durability testing. TBK hires a courier to deliver the 510(k) submission on October 22, 2013.

November 2013

TCM has delays in compiling the final durability report, and the submission of the final module is not until Tuesday, December 2, 2013.

TBK has not received any questions regarding the submission yet.

December 2013

TCM receives a 510(k) clearance letter on Friday, December 19—only 17 days after submission of the final module.

TBK’s Director of Regulatory Affairs receives a request for data demonstrating that the prototype ceramic material used for durability testing represents worst-case for durability testing.

January 2014

TCM’s 510(k) letter is posted on the FDA website the first week of January. TBK’s regulatory director is fired the second week of January.

March 2014

AAOS is a huge success for TCM. TBK does not exhibit at AAOS in 2014.

Q2 2014

TCM sets an all-time quarterly sales record. Caroline and Jim get big bonuses. TBK receives a 510(k) letter on June 23, 2014—244 days after submission. The new Director of RA starts work on at TBK on the same day. The person is already trained on the new modular 510(k) submission process and received their first 510(k) letter using the pilot process in January.

The Smiths Collage

You can find the original at: http://www.layoutsparks.com/pictures/smiths-0. Thank you for sharing.

3 Ways to Fix the 510(k) Process: Self-Surveys, Scorecards and Modular Submissions

In 510(k), Elsmar Cove, eSubmitter, Medical Device, PMA, pre-IDE, SmartForm, Turbo 510(k), US FDA on June 26, 2012 at 5:47 am

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 510(k) reviews more efficient?

For entertainment we have Pomplamoose’s cover of “Single Ladies”. My wife Lisa is a big fan of Pomplamoose, and this song is one of my favorites.

A few weeks ago a posted a blog about the Triage pilot program at the FDA. I received some great comments by email and I thought I would go a little more in depth with some specific ideas for improvement of the 510(k) 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 510(k) 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 the supplier; 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(k) 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. The “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 is used to prepare the submission. The primary metrics for the reviewer would be on-time completion of the review 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.” 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 3rd suggestion is to consider adopting some of the pre-market approval (PMA) processes for the 510(k) process. In particular pre-IDE meetings and modular submissions seam to be logical process improvements. There is typically one component of the submission that is a little behind the rest and holding up a submission. Under the current system, nothing is submitted or reviewed for a 510(k) 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 510(k) 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. These meetings would also be valuable for 510(k) 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 510(k) process?

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

“Triage” for 510(k) – I’m underwhelmed

In 510(k), Design Inputs, Design Verification, eSubmitter, ISO, IVD, Medical Device, pre-IDE, SmartForm, Turbo 510(k), US FDA on June 2, 2012 at 1:47 pm

This week I pulled another song from the movie August Rush.

Thursday, Congress voted 96 to 1 for 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; and

3)      those for whom immediate care might make a positive difference in 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; and

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 the 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 the #2 than it spends on the #1 category of submissions. The FDA should also get involved in group #3 submissions much earlier.

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 get some feedback from the FDA the company is 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 something new 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 3rd 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.

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 3rd 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.

What is the Design Input?

In 510(k), CE Mark, CE Medical, Class IIb, Class III, Design & Development, Design Inputs, Design Outputs, Design Validation, Design Verification, ISO 13485, Medical CE, Medical Device, Risk Management on May 12, 2012 at 7:09 pm

Micky, this is for you.

I have been directly involved in dozens of design projects throughout my career, and during the past three years I have audited 50+ Design Dossiers for CE Marking of Medical Devices. Throughout most of these design projects, I have noticed one common thread—a misunderstanding of design inputs.

ISO 13485 identifies the requirements for Design Inputs. These requirements are:

  1. Functional (7.3.2a)
  2. Performance (7.3.2a)
  3. Safety (7.3.2a)
  4. Statutory / Regulatory (7.3.2b)
  5. Previous and Similar Designs (7.3.2c)
  6. Essential Requirements (7.3.2d)
  7. Outputs of Risk Management (7.3.2e)
  8. Customer Requirements (7.2.1)
  9. Organizational Requirements (7.2.1)

The most common error seems to be the failure to include the outputs of risk management. For those of you that have used design FMEA’s—that’s what the right-hand columns are for. When you identify suggested actions to mitigate risks with the current design, these actions should be translated into inputs for the “new and improved” model.

The second most common error seems to be failure to consider regulatory requirements. There are actually two ways this mistake is frequently made: 1) Canadian MDR’s were not considered as design inputs for a device intended for Canadian medical device licensing, and 2) an applicable ISO Standard was not considered (i.e. – “State of the Art” is Essential Requirement 2 of the Medical Device Directive or MDD).

The third most common error, and the one that drives me crazy, is confusion of design outputs and design inputs. For example: an outer diameter of 2.3 +/- 0.05 mm is not a design input for a 7 French arterial catheter. This is a design output. The user need might be that the catheter must be small enough to fit inside the femoral artery and allow interventional radiologists to navigate to a specific location to administer therapy. Validation that the new design can do this is relatively straight forward to evaluate in a pre-clinical animal model or a clinical study. The question is, “What is the design input?”
Design inputs are supposed to be objective criteria for verification that the design outputs are adequate. One example of a design input is that the catheter outer diameter must be no larger than a previous design that is an 8 French catheter. Another possible design input is that the catheter outer diameter must be less than a competitor product. In both examples, a simple measurement of the OD is all that is required to complete the verification. This also gives a design team much more freedom to develop novel products than a narrow specification of 23 +/- 0.05 mm allows for.

If you are developing a Class II medical device for a 510(k) submission to the FDA, special controls guidance documents will include design inputs. If you are developing a Class IIa, Class IIb or Class III medical device for CE marking, there is probably an ISO Standard that lists functional, performance and safety requirements for the device. Regulatory guidance documents and ISO Standards usually reference test methods and indicate acceptance criteria. When you have a test method and acceptance criteria defined, it is easier to write a verification protocol. Therefore, design teams should always strive to document design inputs that reference a test method and acceptance criteria. If this is not done, verification protocols are much more difficult to write.

In my earlier example, the outer diameter of 2.3 +/- 0.05 mm is a specification. Unfortunately, many companies would document this as an input and use the final drawing as the output. By making this mistake, “verification” is simply to measure the outer diameter to verify that it matches the drawing. This adds no value and if the specifications are incorrect the design team will not know about it.

A true verification would include a protocol that identifies the “worst-case scenario” and verifies that this still meets the design input requirements. Therefore, if the drawing indicates a dimensional tolerance of 2.3 +/- 0.05, “worst-case” is 2.35 mm. The verification process is to measure either a previous version of the product or a competitor’s catheter. The smallest previous version or competitor catheter tested must be larger than the upper limit of the design output for outer diameter of the new catheter.

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