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Archive for the ‘pre-IDE’ Category

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.

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.

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