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

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 99^th-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.

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

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How do you audit design controls using the process approach?

A new connection I made on LinkedIn joined the RA Review Group, and they suggested that anything related to the topic of Design and Development would be of interest for a blog topic. Therefore, I thought I would share a secret with everyone reading my blog…

This blog has been moved to the following location and the name has been changed: http://bit.ly/AuditDesign.

This blog website and the blogs within it are gradually being transferred over to my new website: http://www.MedicalDeviceAcademy.com. The titles may change, and there may be minor revisions to the content as the blogs are reviewed and edited. There will be a subscription list created for the new blog site. If you would like to be added to the list for the new blog site, please email me directly at: rob@13485cert.com.

I have left the links to the videos I love.

Entertainment for this week is Diana Krall‘s recording of Bésame Mucho. I have also included another recording by Andrea Bocelli with English and Spanish subtitles for anyone that wondered what the words meant. The song loses a little of it’s appeal in translation, but English is not one of the Romance Languages.

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

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 3^rd 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.

The Ultimate Design Control SOP

Disclaimer: There is no need to create the Ultimate Design Control SOP. We need medical devices that are safer and more effective.

If Adele is worthy of six Grammy Awards, she’s probably worthy of a blog link too. Rumor has it that this is my personal favorite from Adele.

In my previous blog posting, I indicated six things that medical device companies can do to improve design controls. While the last posting focused on better design team leaders (WANTED: Design Team Needs Über-Leader), this posting focuses on writing stronger procedures. I shared some of my thoughts on writing design control procedures just a few weeks ago, but my polls and LinkedIn Group discussions generated great feedback regarding design control procedures.

One of the people that responded to my poll commented that there was no option in the poll for “zero”. Design controls do not typically apply to contract manufacturers. These companies make what other companies design. Therefore, their Quality Manual will indicate that Clause 7.3 of the ISO 13485 Standard is excluded. If this describes your company, sit back and enjoy the music.

Another popular vote was “one”. If you only have one procedure for design controls, this meets the requirements. It might even be quite effective.

When I followed up to poll respondents asking how many pages their procedures were, a few people suggested “one page”. These people are subscribing to the concept of using flow charts instead of text to define the design control process. In fact, I use the following diagram to describe the design process all the time: The Waterfall Diagram!

From the US FDA Website.

I first saw this in the first AAMI course I took on Design Controls. This is on the FDA website somewhere too. To make this diagram effective as a procedure, we might need to include some references, such as: work instructions, forms, the US FDA guidance document for Design Controls, and Clause 7.3 of the ISO Standard.

The bulk of the remaining respondents indicated that their company has eight or more procedures related to design controls. If each of these procedures is short and specific to a single step in the Waterfall Diagram, this type of documentation structure works well. Unfortunately, many of these procedures are a bit longer.

If your company designs software, active implantable devices, or a variety of device types—it may be necessary to have more than one procedure just to address these more complex design challenges. If your company has eight lengthy procedures to design Class 1 devices that are all in the same device family, then the design process could lose some fat.

In a perfect world everyone on the design team would be well-trained and experienced. Unfortunately, we all have to learn somehow. Therefore, to improve the effectiveness of the team we create design procedures for the team to follow. As an auditor and consultant I have reviewed 100+ design control processes. One observation is that longer procedures are not followed consistently. Therefore, keep it short. Another observed I have made is that well-design forms help teams with compliance.

Therefore, if you want to rewrite your design control SOP try the following steps:

1. Use a flow chart or diagram to illustrate the overall process
2. Keep work instructions and procedures short
3. Spend more time revising and updating forms instead of procedures
4. Train the entire team on design controls and risk management
5. Monitor and measure team effectiveness and implement correct actions when needed

The following is a link to the guidance document on design controls from the US FDA website.

Refer to my LinkedIn polls and discussions for more ideas about design control procedures:

1. Medical Devices Group
2. Elsmar Cove Quality Forum Members Group

In addition to the comments I made in this blog, please refer back to my earlier blog on how to write a procedure.

What is the Design Input?

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.