Michelle: I’m working on two different projects for a different kind of ultrasound equipment. And the FDA, back in early 2018, published a draft guidance document for 510(k) submissions and ultrasounds.

Joe: Okay.

Michelle: Also in late 2018, one of my clients had a pre-submission with the FDA, where the FDA was very particular about, not the draft, but the older final guidance document. They didn’t even mention [the draft] to my client.

Mind you, I wasn’t part of this pre-submission. So they didn’t even mention to my client. Oh, by the way, there’s a draft out there, you may want to just be aware of, they said, “No, you know, here’s the final guidance document.”

It was the older one, they said, and then then they went on to give them very specific advice out of that guidance document about their Indications For Use statement.

So what they wrote in their pre-sub, the FDA gave them very specific feedback, it didn’t have this type of information or that type of information, the FDA really wanted to see it. And per the guidance document for ultrasounds, it should contain all of these things.

So, I was looking up something different in the guidance document. I was trying to Google a particular form or table it referenced, and get a little clarification on on how to best use it. And I noticed, that day(!), the previous draft guidance document went final.

Now, all that very specific feedback that FDA had given on the Indications For Use statement that they wanted to see, all this other detail had been removed. And they specifically said they no longer needed that detail in the final guidance document.

Joe: Okay.

Michelle: So the Indications For Use statement, which we had just finalized, and we’re about to populate in the 510(k), do you have any idea how many times the Indications For Use statement shows up in a 510(k)?

Joe: From the way you asked the question, I’ll assume very many.

Michelle: Yes. It’s probably at least a half dozen. Okay, at least.

How had we pushed that Indications For Use statement into all 510(k) places, we might have had to rework it all to meet the new final guidance document, even though the final guidance document is opposite of the specific feedback the FDA told them in the pre-submission in September.

Joe: Okay, so now what?

Michelle: So now, we emailed the FDA who’s on holiday, by the way. And so now we’re waiting and we email them that said, “Okay, we got this specific feedback to you from you, we are executing it to the letter based on the now-obsolete guidance document, we are a month away from our submission. What do you want? Is it okay for us to continue working underneath this specific feedback you gave us in September? Or do we have to change horses midstream now, and go with this new final guidance document?”

This is a direct impact to all those guidance documents. You know, every year for the past two years, you and I have done a post about how many FDA guidance documents are coming out and how they impact industry. This is a very specific example of a draft guidance document impacting a project that’s in midstream.

Joe: I hear you. What, as a reader, would I do with this information, besides, “Be aware of a new guidance document, and that it changed materially from…”

Oh, pardon me. What you just got is not guidance. It is what do you call it when it’s, like, the law? Regulation?

Michelle: It’s still a guidance document. But it was recommended by the FDA in a pre-submission. FDA told the company specifically not only follow this guidance, but for your Indications For Use statement, make it look like this, per the guidance document.

Joe: Okay, so design your IFU to look like this piece of paper, and they just said, “You know what, we want a different piece of paper now.”

We want it to say different things.

I would suspect FDA would say, “Sorry, yeah, we changed our mind. Please do it the new way.”

Michelle: They could.

That’s the temperamental nature of submissions and guidance documents and whatnot. And typically, I knew the draft was out there — typically, had the company not done a pre-submission….

I work towards draft guidance documents, even though they’re not final because they reflect the FDA’s current thinking. But because this client met with FDA without me, they did not know that the FDA’s recommendations in their pre-sub was opposite of this draft guidance thing.

Joe: Maybe I missing the point I thought you had a pre-submission. In the pre-submission, you got an answer from FDA. They sent you ‘Guidance Document A.’

Great.

We had a pre-submission, which is what we should do. We got guidance from FDA.

We’re working hand-in-hand with FDA, that’s best practice.

I’m ready to go back to FDA now to submit for real. And they say, “Yeah, so we changed the guidance to ‘Guidance B.’

This is not the first time this has happened in the life of the industry. What is the implication for me because if the if the thing is, just be aware, the earth can move beneath your feet?

Sorry, then you haven’t really taught me anything that I can use?

Michelle: Well, the point is that you have — this conversation is a little frustrating.

I have put this content out three or four times a year every year, and I feel like you and I keep getting stuck in this conversation about ‘What are guidance documents and draft guidance documents, and how does it even impact everything’ even mean!

I’ve also had customers tell me, “Michelle, those are just draft guidance documents. They’re not legally binding.

You tell the FDA that they’re just drafts.”

And I’m, like, “You’ve got to have a plan. I mean, this is what they’re thinking.

You have to have a plan to educate them on their thinking if you don’t agree with it.

You can’t just turn a submission in, whether it’s legally binding or not, and not have a plan to at least address it, even if you don’t do what’s in it.”

So you can’t just go to the FDA and say, “Nuh-uh.”

I had somebody do that and their submissions stayed stuck at the FDA for ten months until they finally got out of that childish kind of back-and-forth and just did what the FDA was asking in the guidance documents originally.

Michelle: And so this is the second time in my career this has happened. The first time was a supposed draft guidance document the FDA said that it’s draft, but effective immediately, we expect every submission going in to have the testing and labeling and risk mitigations that are specified in this guidance document.

We were halfway through the development project for a major medical device company that had their own team of regulatory people. And their whole team came back, regulatory, engineering, and everything and said, Michelle, you just tell the FDA that that’s a draft guidance document, and we don’t intend to follow it. And here’s why.

Joe: You made me smile. “Go back to the FDA and just say, ‘Nuh-uh.'”

Michelle: So there has to be a whole strategy that you have when there are draft guidance documents.

Joe: So the point you’re making in simple ‘Joe talk,’ “You have the privilege of pushing back and saying that’s not fair, or that doesn’t make sense?”

Michelle: So in the case, where the client just said, “Nuh-uh, we’re not gonna do that. You tell FDA, it’s a draft guidance.”

Joe: Yeah, that’s silly. It just sounds like, “Okay, good luck with that strategy.”

Michelle: It put their submission on hold, and it took them 10 months…

Joe: Yeah, I just watched the thing…

Michelle: … that the FDA would accept.

Joe: At the risk of frustrating you further, I’m still at an impasse.

This is the information that I have:

1. FDA drafts something.
2. In this case, not only did FDA draft something, but you sat with them.
3. And they said, this is the specific draft, I’d like you to consider.

Michelle: No, they did not mention the draft at all.

They only mentioned the dated final guidance document, which is all they can really require you to do is the final guidance, the draft was out there.

And they didn’t even make the company aware that we have a draft guidance document.

Joe: Let me stop you. The final guidance was called “Joe’s Store,” but they had a draft for “Joe’s Stores.”

They said, “Joe’s Store is out there. Go and use Joe’s Store.”

We go ahead and did Joe’s Store.

They or we or you or some part of the story, were unaware that Joe’s Stores was being drafted so that when Joe’s Stores was final, they moved the goalposts from Store to Stores.

And it would have been nice if I knew they were thinking about Stores.

Is that what you just said?

Michelle: Yes, to a to a point, because I knew they were thinking about Stores, but the client did not. And I was not involved in the pre-submission meeting with the FDA.

Joe: I see.

Michelle: And because the FDA was very specific about using Store, singular. Not only did they not mention that Stores was out there, their guidance to the company was very specific of the content that was in Store for a particular line item of things that FDA was concerned about.

Joe: You told me you were not involved in the pre-submission. So I’m going to assume that this company hired you after they had a pre-submission.

Michelle: Correct.

Joe: Okay. And when they hired you, after the pre-submission, you said, “Well, tell me about the pre-submission”. And they told you all about Store.

Michelle: They gave me the FDA response. So the FDA gave them a three-page written response…

Joe: … that said, “Go use Store.”

Michelle: Yes. And not only go use Store, but I want your Indications for Use statement to look exactly like Store.

Joe: Right. Now, was it — in the most delicate way I can challenge — was it a missed opportunity on Michelle’s part, when you got that, that you said, “They’re talking about Store? Did they talk to you about Stores at all? Should we ask them about Stores?”

Did you do that?

Michelle: I did not do that because this project is on a very expedited timeline. And the FDA was very, very specific. And that guidance document had already been in draft for a year. And it’s not uncommon for the guidance documents to be in draft for years.

So I had no reason to expect, especially with very specific feedback from the FDA — because Stores was out there. FDA knew Stores was out there.

They knew Stores contained the opposite advice they gave the client in the pre-submission.

So if the FDA knows that Stores is out there, and it contains different recommendations than what they tell my client, in the interest of time, I go word-for-word by what the FDA told them to do.

Because one thing you have to do in a submission is if you have had prior conversations with the FDA, you have to include them.

And you have to include a discussion or a reference to where you incorporated those recommendations — or where you chose not to, and why.

Joe: I’m wondering if the lesson learned is frustrating but — no matter what, when your regulatory team, whether outsourced or internal, is working with FDA final, double check there’s not a draft out there somewhere.

Michelle: No, I knew there was a draft out there. It’s like you need to take the extra time — even if you don’t think you have time because you’ve committed stuff to investors — to go back to the FDA and say, “You knew Stores was out there when you gave this recommendation.

Did you really mean Store or Stores?

But the FDA is never going to tell you, “There’s a draft out there” because they can’t require you to follow a draft unless they said this was effective immediately.

Joe: I’m hoping there is a black-and-white here. Can we declare that? You know, Michelle Rule #1 is always, always, always ask FDA if there is a draft?

Michelle: No. You don’t have to ask. Drafts are in the guidance document database.

Joe: So, always, always, always check if there’s a draft.

Michelle: Yes, always check if there’s a draft.

And then — despite getting very specific feedback from the FDA about following the final — push them on their thinking about the draft, and how it’s going to impact and change the very specific feedback that they get you to do, should make the draft a new final.

That’s the other thing, not all drafts end up making it to a final.

And not all drafts end up making it to a final in the content that was published in the draft because the public comment period can change. The FDA can change the content of the draft based on the public comments.

Joe: I’m wondering if in this case, if we keep with the Store / Stores analogy, you were working on Store when Stores draft became stores final. And that’s a problem now that Stores final is final.

Right? Are we only concerned here…

Michelle: Had it not gone final…

Joe: Then we could have gone with Store.

Michelle: … there would be nothing the FDA could say about why did you follow Store versus Stores.

Joe: Right. And you told me that the window of how long is the draft-to-final period could be days to years and decades.

Michelle: Yeah.

Joe: So what can I, given these very disparate things…

Look, one day it was Store, then it became Stores.

And I have no idea how long this timeline is? I know you told me do Store. I knew there was something out here. I’m going to do Store because that’s what you told me. Now you’ve changed the rules.

So I think the best I can divine from this conflict is, at the time they told us Store, say, “Hey, we’re aware of Stores. If I do Store, and you switch to Stores, are you going to be okay with me doing Store or do you want me to do “Store asterisk,” which has some Stores elements to it.

Right? If they had done that, you would have avoided this problem.

Michelle: Exactly.

Joe: Ta-Da!

Michelle: And this is why you also need to get a professional involved with all your conversations with the FDA, because they speak a different language.

It sounds like English.

Joe: Just as I’m talking Store versus Stores.

So is it really like, if you don’t know the nuances here, you’re going to be as simple as Joe Hage saying Store versus Stores.

Is that what you’re talking about?

Because the subtleties in the difference between the final and the draft, which are potentially hundreds of pages long, are so precise that you could easily miss this?

Michelle: Yes.

You will have no idea what the impact is. Why would you challenge them on…?

Joe: Right. Yeah.

Michelle: How would you even know the impact of what they said versus what they told you they were thinking were that radically different?

Joe: I’m with you completely. I want to shift now to my risk profile.

How risk averse or risk seeking am I?

You’ve now helped me understand there’s a potential issue when you attempt to do this without someone who knows this stuff backwards and forwards.

There’s an economic value there.

I wouldn’t be willing to pay a million dollars for someone who knows this stuff backwards and forwards. But I’d certainly pay $1.

What is the point at which I say, “You know what, I know this could change but hell, I’m not going to certainly pay a million dollars for this help. You know, 10,000 is reasonable. 20 will save me you know, six months of time.

What is the market equilibrium for the incremental value I get by hiring someone as professional as you?

Now, I’m not asking you for your rate. And I know this situation depends on is that a huge launch? Or is it a small thing?

If I were to oversimplify this, how could I explain the value?

Michelle: Had we been the ones to prepare the pre-submission. to prepare the questions to FDA, be in the meetings and follow ups with FDA, you’re looking at 10 to 20 hours…,

Joe: …which is not that much of an expense.

Michelle: Or and even if you had done your own pre-submission and all you did was get me in the room to read the FDA response, then ask them questions, or just even interpret it for you right afterwards, then you just that you just pay by the hour for that, then that’s just a couple of hours. And I’ll give you a whole list of questions that, “Oh, wow, you might not realize the implications of this.”

Joe: Is the client in question pre-revenue? And how many employees do they have?

Michelle: They signed a contract with me over a year ago.

Joe: When was the pre-submission?

Michelle: September of 2018. And they signed a contract in August.

And they wouldn’t even invest a couple of hours here or there until they got a grant.

Joe: So this this sounds to me, similar to my experience at an advertising agency, short-lived for this very reason: “Yeah, you you have me available, but I’m billable hours and if I can get by this without involving the agency, let me save some money.”

This is not a place to save some money.

Michelle: Exactly. And now she’s committed to investors she’s going to have commercialized product by the end of the year. And she didn’t follow anything the FDA said because she didn’t know what it meant.

Joe: Okay. I know understand very clearly. Thank you for investing the time.