73 - Handling Regulatory Feedback & Resubmissions (S5E13)

All right, so today we're gonna dive into something
that I think a lot of people in drug development
kind of get anxious about. And it's this whole
world of dealing with the FDA's feedback. You
know you go through all this work to develop
this drug and then you submit everything and
then you get this like Huge response back and
you got to figure out like okay. How do we deal
with this? How do we respond? It's like this
big puzzle almost yeah You've you've poured so
much into this and it can feel like a real setback
totally when you first get that feedback, but
it's it's such an important piece of this whole
process yeah, and you know, at the end of the
day, you want safe and effective drugs out there.
So we got to go through these hoops. Exactly.
It's for a good reason. Yeah. And it's not just
about like the FDA telling you what to do. Right.
It's a back and forth. It's a dialogue. It's
an ongoing conversation. So today, what we want
to do is really unpack. how to have that conversation
effectively with the FDA. What are the different
ways they communicate with you? And then how
do you use all that feedback to actually make
your application stronger and get that drug approved?
Absolutely. So we'll be looking at things like
strategies for tackling that feedback. What does
that resubmission process look like? And how
do you think strategically about the different
types of meetings that you can have with the
FDA? Exactly. And one thing I really want to
emphasize is that, you know, Getting feedback
doesn't mean that you failed It's actually a
good sign that they're looking at it. Yeah, they're
giving you feedback. They're engaged They're
engaged exactly and and so, you know think of
it as this iterative process It goes back and
forth and the whole point is to refine that dossier
and make it the best it can be Okay, so you get
this feedback and it could be you know, just
a few pages or it could be a whole novel, right?
Where do you even start? What's the first step
when you're tackling? regulatory feedback. Well,
I think the first thing is to really be organized
and meticulous. Don't just skim it. You really
need to read through every single comment, every
question, every concern they raise. You know,
it's like being a detective. You have to understand
why they're asking what they're asking. Sometimes
a comment might seem small, but it could point
to a bigger issue. So it's not just about like
answering the question on the surface. Exactly.
You got to kind of figure out the why behind
the question. Exactly. Why are they asking this?
What's the rationale behind it? OK, so once you
understand that why, what's the best way to actually
structure your response? So the most important
things are clarity and conciseness. Your response
to each point needs to be direct and clear. You
want to avoid jargon as much as possible. And
if you have to use technical terms, make sure
you define them really clearly. You want the
reviewers to understand what you're saying. Think
of it like a scientific publication. Gotcha.
So just like in a paper, you're presenting your
findings in a really clear and logical way. And
I imagine it's not enough to just state your
answer. Right. You kind of got to show your work,
too. You do. Every response needs to be supported
by data. OK. Or a really strong scientific rationale.
So for example, if they're asking for more data
on a particular side effect, you need to explain
why you made the choices you made. You need to
provide evidence from the literature or maybe
from your own data to support your approach.
Same thing if they have questions about manufacturing.
You've got to give them details about your controls,
testing procedures, and how you ensure quality.
And you know what I'm thinking is like, in any
kind of process like this where it's complicated
and there are a lot of moving parts, There are
bound to be times where you don't agree with
the feedback or where something seems contradictory.
Maybe the feedback contradicts something else
in the regulations. Right. Or even like different
parts of the FDA might seem to be saying different
things. How do you handle those situations? Yeah,
that's a great point. And it does happen. So
when you encounter a situation where you disagree
with the feedback or you see a conflict, the
key is to be respectful and professional. You
need to clearly explain your perspective, provide
the data and the reasoning that support your
position, and you might even reference specific
parts of the regulations that you think are relevant.
So it's like you're laying out your argument.
Exactly. It's like a scientific debate. You present
your evidence, you make your case, and you keep
in mind that the goal is patient safety and effective
treatment. You're both working towards the same
goal, ultimately. Exactly. You mentioned earlier
these different types of meetings that you can
have with the FDA. Right. It seems like that's
a way to kind of get ahead of things and maybe
address potential issues before you even get
that formal feedback. Exactly. Can you walk us
through the different types of meetings? Yeah.
The FDA has this tiered system of meetings, type
A, type B, and type C, and they're designed to
help you communicate with them throughout the
entire process of drug development, and each
type has a specific purpose. Okay, let's start
with type A meetings. When would you typically
request one of those? So type A meetings are
for the really critical issues, things that could
seriously impact your whole development program.
You know, like if the FDA puts a clinical hold
on your trial because of safety concerns, or
if there's a big disagreement about the design
of a study, these are situations where you need
to talk to the FDA right away. Like an emergency
almost. Exactly. It's your emergency hotline
to the FDA. OK, so that's type A for emergencies.
Yeah. What about type B meetings? So type B meetings
happen at key milestones in your drug development.
Things like the pre -IND meeting, before you
even start clinical trials. So you can talk about
your overall plan. Then there's the end of phase
one meeting, where you look at the initial safety
data, the pharmacokinetic data. And then there's
the really important end of phase two, pre -phase
three meeting. And that's where you talk about
the design of your pivotal phase three trial.
The ones that are going to support your eventual
approval. Exactly. So the goal here is to get
the of DA's input and make sure everyone's on
the same page. It's like getting expert advice
at these really crucial points in your development.
Exactly. OK, so we've got type A for emergencies,
type B for these key milestones. What about type
C meetings? What are those for? Type C meetings
are kind of like the catch -all category for
questions or issues that don't fit into type
A or type B. Gotcha. So maybe you need to clarify
a specific regulation or you want guidance on
some aspect of your pre -clinical or clinical
program that's not tied to a specific milestone.
OK. Or maybe you're using a new analytical method
and you just want to get their take on it. So
it's like office hours with the FDA. Exactly.
You just go in and ask them questions about specific
things. Yeah. valuable because it can prevent
problems down the road. So being proactive and
using these meetings strategically can really
help make the whole process smoother. Absolutely.
You get a better understanding of what the FDA
expects. You can address concerns early on and
you might avoid delays or surprises later. So
let's say you've had your meetings, you've gotten
feedback on your application. And now you need
to make changes and maybe resubmit. Right. How
does addressing that feedback actually make your
dossier stronger and more likely to be approved?
So by directly addressing the feedback, you're
basically building a more complete and convincing
argument for your drug's safety and efficacy.
OK. You're filling in the gaps, addressing their
concerns, and making the whole package stronger.
So it's like you're putting together a puzzle.
Exactly. And the FDA is pointing out where there
are missing pieces or where things don't quite
fit. Yep. And when you make those revisions,
whether it's getting more data, clarifying information,
or even changing your protocols, you're showing
that you're taking their input seriously and
that you're committed to meeting their standards.
And this back and forth, this whole process of
getting feedback, making changes, and maybe re
-submitting, that's normal, right? It's very
normal. It's not a sign that you've done something
wrong. Not at all. It's just part of the process.
Most drug applications go through multiple rounds
of review. OK. So it's really a refinement process.
Each round makes the application better. Exactly.
Now something that we talked about before was
the importance of avoiding redundancy when you're
putting together your resubmission. Right. I
can imagine the reviewers don't want to read
the same thing over and over again. They don't.
How do you be concise and really highlight the
changes you've made? Yeah. So when you resubmit,
you need to clearly show what you've changed
based on the feedback. OK. Don't just copy and
paste huge sections from your original submission.
Right. A good practice is to create a separate
document that links each piece of feedback to
the specific place in your updated dossier where
it's been addressed. OK, so it's like a roadmap
for the reviewers. Exactly. They can see exactly
how you've responded to each point. That makes
a lot of sense. It makes the review process much
more efficient. And it shows that you're paying
attention to detail. So I think this has been
really helpful. We've covered a lot of ground
today. We have. And I think the main takeaway
is that Regulatory feedback, it's not something
to be scared of. It's an opportunity to improve
your application. Resubmission is a normal part
of the process. And using those different types
of FDA meetings strategically can really help
you navigate the whole process more effectively.
Absolutely. And I think it's important to remember
that you and the FDA are working towards the
same goal, which is getting safe and effective
medicines to patients. And that's a goal we can
all get behind. Definitely. So on that note,
I want to leave you with something to think about.
We've talked a lot about seeking and incorporating
feedback, communicating effectively with stakeholders,
and using different channels for that communication.
But what about applying these principles outside
of drug development? Oh, that's interesting.
Think about your own field, your own projects.
Could adopting a similar mindset lead to better
outcomes, even if you're not developing a new
drug? That's a really good question. So something
to ponder as you go about your day. I like it.
Thanks for joining us for this deep dive. Thanks
for having me. And we'll see you next time.