Regulatory Open Forum

The way I see this is from an FDA standpoint.  If I have a question and I am looking for an answer, how do I find it.  For a lengthy deficiency list, most likely FDA have this categorized.  Key is organization of the format so they can easily find what they are looking for.  Remember there are multiple reviewers and those care about their particular question they submitted.  Therefore helping them find it helps the review go faster.

The cover letter should explain the format you are using.  For example: EXACT copy of the question per the letter with Question # as assigned by FDA and page of the FDA letter where you can find that question; then answer is right below or reference to an attachment which answers the question. 

Next, create a table of contents arranged according to their categories and question # they assigned to it as found in their letter. 

Then, follow the format you said you're going to use.  Use italics or bold font, etc. to differentiate their questions from your answer within the body of your response.  For example: 

Question#11 (FDA letter page 7).  FDA exact question copied here.

Company Answer here.  See 009_Attachment 11-2.

Of course, I am not including all the other requirements for submissions in here, just the formatting for the response section. I've never had FDA get confused where the answer is to their question when I did it this way.  There are of course other ways out there too. Good luck, hope that helps.

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Clarisa Tate
Medical Device, RA & QA
Bay Area, CA
USA
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Hi Mark,

FDA doesn't spell out their preferred response format and I agree with the previous responses.  Some things that might help you with your response:

- Reviewers will often (not always) list the deficiencies in the order of how critical your response will be at them determining substantial equivalence.  The big ticket deficiencies are usually the first ones listed and those are the ones I would focus on in your discussion with FDA. 

- Reviewers are trained to write their deficiencies in four-part harmony.  Their deficiency should include a statement of what you provided in your 510(k), why that information is not sufficient, what additional info is needed, and why this requested additional info is necessary to answer a regulatory or scientific question.  Understanding what it is they think you left out, and why they need that information can be very valuable when drafting your response.  Also, did the reviewer give you an "alternatively" statement in any of their requests?  This can be telling of what they actually want you to do based on the two options they've given you. 

You asked about the meeting you'll have with FDA and it really depends on the nature of the meeting.  If you've submitted a pre-sub during the hold, you can ask a lot more about whether FDA agrees with your proposed pathway (e.g. test plan, justifications, etc.)  If it's more of a 'clarification call' to discuss the deficiencies, I've had mixed success getting regulatory guidance from the reviewer.  Sometimes they will say "yes, that answer should be sufficient" or "why don't you just do the one test and we'll be good."  It can be good to get it straight from their mouth about what they actually want from you if it's not clear in the deficiency.  On the other hand, if you try to ask too many questions about your proposed pathway (and they agreed to call because they thought you had minor questions about what they meant in their deficiency), you might get some push back.  At this point they could ask you to submit a pre-sub to ask your questions and get their feedback (side-note: it's not a typical 75-90 day pre-sub, they're actually supposed to respond to you within 21 days for a submission-related pre-sub).

If you want some strategy help, please feel free to email or call me.  I'd be happy to chat with you.

Best regards,

Allison

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Allison Komiyama PHD, RAC
Principal
Acknowledge Regulatory Strategies
San Diego CA
United States
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It sounds from the fact that they are requesting several pieces of additional information that the changes or additions to your submission are significant.  It is always a good idea to resend a revised version of your original submission with all the changes incorporated and highlighted in yellow.  This way you both will have a completed copy of the full submission the FDA accepted, assuming that accept your responses without additional requests.

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John Minier RAC
Sr. Manager, Regulatory Affairs
Integra Lifesciences
Plainsboro NJ
United States
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To concur with others here, there is no "preferred" format, but the format the reviewers are familiar with is the one in the deficiency list.  I would follow its order and use its language.  I typically bold, italicize, or otherwise highlight each deficiency in order and then insert my response below.  I allow for the possibility that the person reviewing my response had nothing to do with the original deficiency, so I try to include all the information needed to understand my response, without requiring the reviewer to dig back through the original 510(k).

Submissions Issues - I agree with David's general reaction.  From there, my take is that, if they got a lengthy deficiency list, they should think twice about trying to close the barn door at this point.  I personally would avoid trying to "justify" anything unless very large sums of money would be required to correct a deficiency as stated, or unless I thought addressing the deficiency as stated might actually jeopardize product safety or performance.  I would acknowledge the deficiency, address it (often beyond what I would have done if I'd gotten it right in the original submission) rather than try to justify it, and hope that I have not dug myself a hole I will not be able to crawl out of.  I would use the word "regret" a lot, as in "Company X regrets having omitted..."

One caveat.  Sometimes the original submission was so bad that the deficiencies simply cannot be addressed as written, because the reviewer could not understand the submission, and therefore the deficiencies are too far off target to be able to be addressed.  In that case, I would "regret" the confusion caused by the submission, carefully explain the actual situation, and then wait for FDA to come back with yet another deficiency list that is more on target.  Yes, you could go for a meeting to discuss them, but it will probably take longer to get the meeting and then respond to the deficiencies post-meeting, than to simply respond promptly and wait for the next letter.  Then, if things are still a mess, that is when I might consider requesting a meeting.

Unlike David, I will not kindly offer to make harsh comments about the submission. My harsh comments are directed at companies that suck up FDA resources with bad submissions because they refuse to seek adequate professional assistance up front, and then continue in that mode, even after they get a "rather lengthy deficiency list."  In this case, my harsh comment is that I don't do salvage operations, and my best suggestion would be to meekly withdraw the original application and find someone who can do it right the second time, since clearly they have lost the opportunity to do it right the first time.  They may well get clearance faster this way than continuing down the tortured path they have chosen for themselves.

Grumph.

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Julie Omohundro RAC
Durham NC
United States
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