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.
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
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 subcontractors – The 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!
Amend section 505(k)(3)(C) of the FDC Act to expand the post-market risk identification and analysis system and apply the section to medical devices, and
To encourage the FDA to finally issue the final form of the UDI rule.
Global cooperation has always been the dream of the idealists.
The final form of the UDI rule has been issued, but what is the future of post-market risk identification and analysis?
Most healthcare companies are either drug companies or device companies—not both. The US has developed a system for approval of combination products, but Europe and the US have separate systems for addressing post-market data collection for drugs and devices. Why not use the same system for both? The frequency of reporting is usually risk-based. Why couldn’t the depth of post-market data be risk-based as well? For drug we can continue to have the full reporting requirements, but for devices the depth of reporting could be classification dependent or product code dependent.
Another measure included in the European plan is to improve the functioning of the vigilance system for medical devices. This would include, facilitating and actively encouraging patients, healthcare professionals and other groups to report all adverse events. The US is implementing electronic medical records throughout the healthcare system. This provides a vehicle for facilitating this type of systematic reporting.
Europe continues to struggle to establish a single European database for medical devices, but what about establishing a global medical device database?
Other measures in the European plan call for the introduction of an implant passport specifying the unique product code of the implant. With the introduction of the UDI rule, all US products will eventually have a unique product code—not just implants. Wouldn’t it make sense to incorporate this bar coding system into the implant passport for Europe? This could also be integrated with the implant registry card requirements for Canada. The GHTF presented draft guidance for a medical device UDI system on November 4, 2010.
The idea behind the GHTF was to harmonize the similar initiatives around the globe. Instead, GHTF is disbanded and legislators are developing parallel requirements that have the same purpose. This doubles or triples the regulatory burden for companies, and the opportunity to identify adverse event trends globally is diminished. Regulators from the “Big 5”, the GHTF’s founding members, elected to dissolve the GHTF in order to form a new entity consisting solely of regulators. Until this group is established and effective, some ad hoc working groups are needed to fill the gap.
A globally harmonized vigilance reporting system for drugs and devices seems to be the biggest opportunity to gain from cooperation. Please share your own ideas and comments here or on LinkedIn.
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.
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?
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.
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.
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.”
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.
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.
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!
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:
Use a flow chart or diagram to illustrate the overall process
Keep work instructions and procedures short
Spend more time revising and updating forms instead of procedures
Train the entire team on design controls and risk management
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:
I just wanted to thank everyone for reading my blog. It's hard to make the dry and boring worth reading about. I have also created a formal Thank You page on my personal website: http://13485cert.com/qc-is-dead/.
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Best Practices in Audit Program ManagementMarch 9, 2013
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