January 28, 2025 • 20 mins
Welcome back for another deep dive! Today, we’re diving into something that’s at the heart of getting life-changing medications into the hands of patients: the Common Technical Document, or CTD. While it might sound like a dry topic, it’s actually one of the most important tools in the global drug approval process—a true game-changer for both science and public health.
Imagine this: you’ve developed a groundbreaking new drug that could change lives. Before it can reach the market, it has to navigate a maze of regulations worldwide. That’s where the CTD steps in—a universal format that streamlines this journey, acting like a passport for your drug as it crosses regulatory borders.
We’re breaking it all down in this episode, from the CTD’s modular structure—five sections that tell the complete story of a drug—to how it has evolved into its digital counterpart, the eCTD. You’ll discover how this living, breathing document not only facilitates approval but also ensures medications are safe, high-quality, and produced responsibly.
Along the way, we’ll connect the dots between the CTD and other critical filings, like the Drug Master File (DMF), investigational new drug applications (INDs), and the ultimate goal for any new treatment—the New Drug Application (NDA). We’ll even venture into biologics and see how the CTD supports cutting-edge innovations like gene therapies and monoclonal antibodies.
But it doesn’t stop there. The CTD is not just a tool for approval; it’s a cornerstone of ongoing patient safety. Through post-marketing surveillance, it continues to evolve, incorporating real-world data to ensure that medications perform safely and effectively long after they hit the shelves.
So, join us as we unpack the fascinating world of the CTD—a seemingly technical system with a profoundly human impact. It’s a story about innovation, global collaboration, and an unwavering commitment to patient health. Let’s dive in and explore the backbone of modern medicine together!
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
Welcome back for another deep dive.
(00:02):
Today we're gonna tackle a topic
I know you've been wanting to learn more about.
The Common Technical Document.
Ah, the CTD.
Yeah, or CTD for short.
It's this really important piece of the puzzle
when it comes to bringing new drugs to market
all over the world.
It really is.
And we've got a whole bunch of like regulatory documents
and guidelines and research papers
(00:24):
kind of piled up in front of us here.
So let's dive right in and see if we can like
pull out the key stuff.
Yeah, I think bringing medications to market
is such a great phrase because that's really at the heart
of what the CTD is designed to do.
It's to like streamline that whole process.
So imagine you've developed like a groundbreaking new drug,
you know, something that's gonna change things for patients.
(00:46):
But before you can share that with the world,
there's this whole obstacle course of regulations
and that's where the CTD comes in.
So it's kind of like a passport for new drugs.
Like it helps them travel across
all the different regulatory borders.
Exactly.
It's the standardized format that drug companies use
when they're applying to get new drugs
or treatments approved, like two agencies all over the world.
(01:08):
And before we had the CTD, it was kind of like
trying to put together a puzzle,
but all the pieces were from different sets.
Oh yeah.
Every country had its own format and its own requirements.
And it made things so time consuming
and resource intensive for developers.
It sounds like a logistical nightmare.
It was.
I can only imagine the delays that caused
(01:29):
in getting treatments to patients.
Oh, for sure.
Yeah.
Without a unified system, it created a ton of redundancy,
you know, doing the same thing over and over in inefficiency.
So the CTD really changed the game
because it gave everyone involved
in the drug approval process, the researchers,
the manufacturers, the regulators, a common language.
Okay.
So the CTD establishes a universal format,
(01:50):
but how does it actually work?
I've heard it set up in modules.
Can you unpack that a bit?
Definitely.
Think of the CTD as a really organized filing cabinet.
Okay, yeah.
With like five main drawers or modules.
And each module serves a specific purpose
and presents the information in a consistent way.
Okay, so I'm picturing these five drawers.
Yes.
What goes in each one?
(02:11):
Well, let's start with module one.
That's where you find all the administrative stuff,
the prescribing information.
Okay.
Like the cover letter and table of contents
for the drug application.
It's got things like the drug's name, its proposed name,
how it's given and what it's intended to be used for.
So it's like introducing the drug to the regulators.
Yeah.
Giving them the basic facts and figures.
(02:31):
Yeah, exactly.
What about module two?
Module two is that high level view of the whole submission,
you know, like the executive summary.
It summarizes all the key findings from the other modules
so the reviewers can quickly grasp
the essential info about the drug.
So it's like giving the regulators a roadmap
to navigate the whole document.
Exactly.
And then there's module three,
(02:52):
and this is where it gets really interesting,
especially with your interest in all those regulations.
This section really digs into the quality of the drug.
Okay, so is this where all those CFR documents
come into play?
Yes.
The ones that detail all the manufacturing
and quality control standards?
Exactly.
Module three is all about making sure
the regulators are confident the drug is made
(03:12):
to the highest standards, that it's safe, effective,
and that it's produced consistently every time.
So you'll find details about the manufacturing process,
quality control measures, and all the stability testing.
So showing that the drug is made carefully, precisely,
and it follows all those CFR guidelines.
Yep.
Then we move on to module four,
(03:33):
and this is where we enter the non-clinical world.
All the pre-clinical data goes here,
you know, animal studies, lab results.
Basically any research that happened
before the drug is tested in humans.
So it's like building the case for why the drug
is a good candidate for human trials.
It's showing the potential of the drug.
Exactly, and showing that, you know,
it's not gonna cause harm.
And then finally we get to module five,
(03:54):
and this is all about the human data.
So this is where we see the clinical trials.
Yes.
The results of the drug in actual people.
Absolutely.
Module five is like the heart of the CTD.
It's where the data from the human clinical trials lives.
Okay.
You know, showing if the drug is effective,
if it's safe for people.
You'll find all the study details,
(04:16):
demographics, efficacy results,
any adverse effects that pop up during the trials.
So I've got the intro in module one.
Yes.
The executive summary in module two.
Yeah.
Manufacturing details in module three,
the pre-clinical research in four.
And finally the human data in five.
It's like the whole story of the drug.
Yeah, it is.
From lab to clinic.
(04:36):
But what about in the digital age?
Right.
I mean, we can't be shipping pallets of paper
all over the globe, can we?
Yeah, you raise a great point.
The CTD has evolved, of course,
to keep up with technology.
Of course.
So now we have what's called the electronic
common technical document.
Catchy.
Or ECTD.
ECTD.
So no more paper cuts for all those reviewers.
Not quite, but it's definitely a step in the right direction.
(04:57):
The ECTD is essentially the digital version
of that paper CTD.
Yeah.
And it has so many benefits.
Like what?
Faster submissions, I bet.
Absolutely.
Submissions happen electronically.
So much faster.
But it's not just speed.
Right.
It's efficiency.
It's clarity.
The agencies can easily search, navigate,
and annotate electronic documents.
(05:18):
So the whole review process is streamlined.
And I bet it saves a few trees too, right?
Yeah.
Cutting down on all that paper.
Definitely.
The ECTD is much more sustainable,
which is a major plus.
So the ECTD is faster, more efficient,
and better for the planet.
A win-win-win.
But is this CTD format just for brand new drugs?
Are there other scenarios where it comes up?
(05:40):
You're thinking outside the box.
I like it.
The CTD format is really versatile.
It's used for lots of different filings beyond those new drug
applications.
OK, so give me some examples.
What else is it used for?
Well, there's the drug master file.
We call it the DMF.
And this is a document all about one specific drug substance.
A manufacturer might submit this to support a drug application
(06:01):
without having to reveal all their trade secrets.
So they can say, hey, we've got this awesome ingredient that
works great, but we're not telling you
exactly how we make it.
Exactly.
It's a way to protect intellectual property.
But they're still providing the info needed
to show the safety and quality of the product.
Clever.
What else?
Well, then we have the BDMF, the Biologic Drug Master File.
(06:21):
And that's the same idea, but for biological products,
like vaccines, gene therapies, monoconal antibodies.
These are big, complex molecules, usually
made using living organisms.
So the whole process is really complicated.
Yes, the BDMF, highlighting the whole field of biologics,
which is growing so rapidly.
(06:41):
Yes, exactly.
And then we can't forget the IND, the Investigational New
Drug Application.
This is what you need to get the go ahead to even start
human clinical trials.
Oh, right.
The IND.
And we were talking about clinical trials
before with module 5 of the CTD.
It's all connected.
Exactly.
It all ties together.
So the IND is what gets you into the human testing arena.
You give the FDA all the info they
(07:03):
need to assess if the trials are safe and ethical.
Precisely.
Now get ready for the big ones, the NDA and the ANDA.
The NDA, the New Drug Application,
is the ultimate goal.
This is what you submit when you're looking for approval
to market a new drug.
So years of research all come down to this massive document.
Yes.
No pressure.
Right.
And then there's the ANDA, the Abbreviated New Drug
(07:25):
Application.
This is the pathway for generic drugs.
OK, I see.
And it's abbreviated because they
don't have to do all the original clinical trials.
They just have to prove their generic is
the same as the brand name drug that's already approved.
So it's like the express lane for drug approvals,
which makes sense because generics
are so important for making treatments
affordable and accessible.
(07:45):
Absolutely.
The ANDA is essential for patient access.
So the CTD format is used for new drugs, biologics,
investigational drugs, and generics.
It's really amazing how this one format has revolutionized
the whole industry.
It really has.
And it might seem bureaucratic, but it
serves such a crucial purpose, ensuring patient safety
and helping develop new treatments.
(08:07):
It's really interesting how something like a document
can have such a huge impact on global health.
We've covered a lot of ground in this first part
of our deep dive, exploring the structure of the CTD,
how we got to the ECTD, and all the different types of filings
that fall under the CTD umbrella.
But let's keep going.
I'm really interested in digging a little deeper
(08:27):
into some of these topics, especially
the connection between the CTD and all those CFR
documents we touched on.
That's where things get really interesting
from a regulatory perspective.
Definitely.
It's important to understand how these regulations play out
in the real world.
That's how we ensure the quality and safety of the medications
that people rely on.
Absolutely.
(08:47):
So let's jump right back in and see what else we can learn.
Sounds good.
You're so right.
Those CFR documents are where it all
happens in terms of making sure drugs are safe and high quality.
And module three of the CTD is where all that comes together.
It's like the bridge between the CFR's requirements
and all those nitty gritty details of how a drug is made.
OK, so let's walk across that bridge.
(09:08):
I mentioned my interest in the CFR.
And I'm particularly interested in Title 21, which I know
covers food and drugs.
So how does the CTD, specifically module three,
demonstrate compliance with all those regulations?
Think of Title 21 as the rule book
for making pharmaceuticals.
And module three is like the company's playbook showing
how they follow all those rules.
(09:28):
OK, so I see it.
The CFR sets the standards.
And then module three is where the companies
show they're meeting them.
Exactly.
Like CFR 21 part 211 that lays out
super specific regulations for everything,
from what qualifications personnel need,
to how equipment has to be maintained.
Remember those hand washing and lab coat things we talked about?
(09:49):
Yeah, all those details that seem small but actually
make a huge difference for preventing contamination
and making sure the drug is high quality.
Right.
All those details are laid out in the CFR.
And in module three, companies would give their standard
operating procedures for things like personnel hygiene,
equipment cleaning, and how they monitor the environment.
All that proves that they're sticking to the CFR.
(10:11):
So it's like a checklist.
The CFR says do this and that.
And module three is where the company is like, look, we did it.
Here's the proof.
Exactly.
And it's more than just checking boxes.
The CFR, especially part 211, really stresses
good manufacturing practices.
GMP, I've heard that a lot.
What does that actually mean in practice?
(10:31):
How does that translate into what
happens on the factory floor?
Think of GMP as like the driving force behind every single step
of making a drug.
It's about building quality into every stage,
from where they get the raw materials
to how the final product is packaged.
So it's not just about testing the final product
but making sure quality is baked in from the very beginning.
Exactly.
(10:53):
GMP means manufacturers have to have strong systems in place
for everything, training employees,
making sure equipment works right,
dealing with issues that pop up, and complaints.
There's a holistic approach to making sure everything's
consistent and reliable.
And how does module three connect to that?
Module three is where the company shows
their commitment to GMP.
They include tons of documentation
(11:13):
on their process, the quality control, and any validation
studies they've done.
And it's all got to be aligned with GMP and the CFR guidelines.
So it's like giving the regulators a backstage pass
to the whole manufacturing operation,
showing them exactly how they're maintaining those standards.
Exactly.
Module three is all about being transparent and accountable.
(11:33):
They give the regulators all the information
they need to judge if the manufacturing process is
high quality and reliable.
It's really cool how these kind of boring regulatory documents
actually boil down to something so important,
keeping patients safe.
It's good to know all these systems are in place
to make sure the medications we all need are made the right way.
(11:54):
It's all about public health, and that's
what the CFR and module three do.
OK, so we've dug into the CFR and module three.
And we've seen how they work together
to keep drug quality high.
But let's go back to those other CTD filings
we talked about earlier.
You mentioned the drug master file, the DMF.
Can you give an example of when a company might
(12:16):
use one of those, like a real world example?
Sure.
Let's say there's this company that developed
this amazing new excipient, that inactive ingredient.
The things that help the drug dissolve or be absorbed better.
OK, so not the actual drug, but something
that helps it work better.
Yeah.
So they may not want to share their secret formula
with every other company who wants to use it.
(12:38):
So they would put together a DMF that
gives all the information about the excipient's safety,
how it's made, and its quality, but without giving away
the exact recipe.
So they're sharing the recipe, but not telling you
what the secret ingredient is.
Yeah, I like that.
Clever.
So when another company wants to use that excipient
in their drug, they can just reference that DMF
in their application, and they don't have to generate all
(12:58):
that data themselves.
That saves so much time and effort and resources.
Exactly.
It really speeds things up for everybody.
Yeah, and it encourages innovation.
Companies can specialize in their own thing,
and they don't have to start from scratch every time.
Now, what about the BDMF, the Biologic Drug Master File?
Yeah.
What's different about that one, since biologics are so unique?
It serves a similar purpose, but it's
(13:20):
made specifically for biological products, which
tend to be more complicated than those small molecule drugs.
Right.
Biologics come from living things.
Right.
So the whole manufacturing process is way more complex.
Absolutely.
A BDMF would have details about the cell lines used,
the conditions they're grown in, how they're purified,
(13:40):
and the quality control tests.
So it's like this really detailed blueprint
for making these really complex drugs,
making sure everything is consistent and high quality.
Exactly.
It assures the regulators that the biologics
are being made to the same standards
as traditional pharmaceuticals.
The CTD really is like this versatile toolkit
(14:01):
with different tools for different jobs.
Companies can pick the right tool
based on the type of product they're making
and the regulatory pass they're on.
I like that.
Yeah, it's a flexible system that
works for so many drug products and situations.
OK, let's talk about those really big applications,
the INDE and the NDA.
Right.
Those are the ones that make or break a drug.
(14:21):
You could say that.
The INDE, the Investigational New Drug Application,
is like the first big hurdle.
It's what you send to the FDA before you can even
start testing in humans.
So you're asking for permission to start human trials.
Right.
And what makes the INDE so important?
What's in it?
What does the FDA need to see?
The INDE is basically everything you
(14:42):
need to lay the foundation for clinical trials in people.
It's all the preclinical data, animal studies, toxicology,
manufacturing info, all of it.
Everything that supports moving to human testing safely.
So it's like you're saying to the FDA,
here's all the evidence we have that this drug is promising
and we don't think it will be too risky for people.
Yeah.
And it also outlines the plan for the trial,
(15:05):
how it will be designed, how many people will be in it,
the dosage, all that.
The FDA needs to know everything to make sure
the trial is safe and ethical.
They look at the science, who's doing the research, everything.
That's a really thorough review.
They're the gatekeepers, protecting people
and making sure the research is good science and it's ethical.
Yeah.
And what happens if they say yes?
(15:27):
Then the fun begins.
Right.
Then the company can move forward with the human trials.
Yeah.
And those trials can take years.
Years.
With thousands of people.
But if everything looks good, the drug works, it's safe,
then they can go for the next big milestone, the NDA.
The NDA, the new drug application, the ultimate goal.
This is the one that can really change people's lives.
(15:49):
It's the culmination of all that work.
It is.
What makes the NDA so important and what all is in it?
The NDA is everything.
It's all the data collected over years and years of work.
Preclinical studies, all the clinical trial results,
manufacturing details, everything.
It's like the encyclopedia of that drug.
Yeah.
It's the whole story, from an idea in the lab
(16:10):
to potentially a lifesaving treatment.
Exactly.
And the FDA goes over it with a fine-tooth comb.
I bet.
Every single piece of data to decide if it meets the standards
for safety, efficacy, and quality manufacturing.
That review is a big deal.
It can really make a difference for patients
who are waiting for new treatments.
It really can.
And if the FDA approves that NDA,
(16:32):
then that drug can finally be made available to patients.
That's a huge win for the company.
Yeah.
And most importantly, for the patients who will benefit.
It's pretty amazing to think about that journey
that a drug goes on.
It is.
From the very first discovery to when a patient finally
gets it.
And the CTD is there for all of it.
It's a guide, a record keeper, and ultimately, it
(16:52):
protects patients.
That's a great way to put it.
The CTD might seem like just a technical thing,
but it's a foundation for the whole industry.
It makes sure new drugs are made responsibly and with care.
So we've talked about the NDA, that exciting moment
when a drug is finally approved and it can be sold.
But the story doesn't end there, does it?
No, not at all.
(17:12):
That's where post-marketing surveillance comes in.
It's a really important part of drug development
that often gets overlooked.
OK.
Even after a drug has been through those rigorous trials
and it's gotten the FDA's approval,
there's still a lot to learn about it,
how it works long term and how it affects different people
in the real world.
So it's kind of like releasing a new species into an ecosystem.
(17:35):
You studied it in a controlled environment,
but now you have to see how it adapts out in the real world.
I like that analogy.
That's exactly what post-marketing surveillance
is all about, gathering real world data,
seeing if there are any unexpected side effects
or risks and even benefits that didn't show up in the trials.
That makes sense.
Clinical trials are important, of course,
but they can only tell you so much.
(17:57):
Right.
They happen in a controlled setting and for a limited time.
The real world is way more complicated.
Exactly.
Post-marketing surveillance helps
us get a much bigger picture of the drug
and we can spot any potential problems
that we didn't see before.
And how do you do that surveillance?
Are we talking about tracking every single patient who
takes the drug?
Not quite that detailed.
(18:18):
There are different ways to collect data.
A common one is spontaneous reporting.
Health care providers and patients
can report anything unusual to the FDA.
So it's a team effort.
Everyone in health care is working together.
Yeah.
And there are also some more proactive methods,
like doing observational studies or looking
at big health care databases to see any patterns or trends
(18:40):
in how the drug is being used.
What happens if they find something
concerning, like a safety issue?
Does that mean the drug is pulled off the market?
Not always.
It really depends on what the concern is
and how serious it is.
Sometimes they might just update the label
with a new warning or some precautions.
If it's more serious, they might investigate further.
Or in rare cases, if the risks outweigh the benefits,
(19:01):
they could pull it.
So it's always evolving.
You're always learning more and adjusting as you go
to make sure patients are safe.
Absolutely.
And the CTD actually plays a big role in that.
Really?
Yeah.
Remember all those modules we talked about?
Yeah.
They're still important after the drug is approved.
OK.
Help me understand how that works.
How does the CCD connect to all this post-marketing stuff?
Well, as new information comes up, the CTD gets updated too.
(19:24):
Like module 5, that's where the clinical trial data is.
They can add information from post-marketing studies
or any new research.
So it's not a one and done kind of thing.
It's a living document that changes as we
learn more about the drug.
Exactly.
That's one of the best things about the CTD.
It's this organized system for keeping
track of all the information about a drug
(19:45):
from the very beginning all the way through to when
it's being used in clinics.
So it's not just about getting a drug approved.
It's about making sure it's used the right way
and that it's safe for patients.
You got it.
The CTD might seem like this boring hurdle,
but it's really a powerful tool for protecting public health.
Well said.
I think we've done it.
(20:06):
We've explored the complex world of the common technical
document.
We looked at the structure, how it connects to the CFR,
and all the different filings that are part of it.
We even talked about how it's involved throughout the entire
life of the drug.
Yeah, from the very first research all the way
to post-marketing surveillance.
That's amazing.
It is.
This has been a really enlightening deep dive.
(20:26):
Thanks for joining us as we explore
the ins and outs of the CTD.
We hope you learned something new
and that you can appreciate how complex and how important it
is.
It might seem like a boring bureaucratic thing,
but it's really all about making sure
that the medications we all rely on
are developed safely and responsibly.
Very well said.
And that's a wrap on our deep dive
(20:47):
into the common technical document.
Until next time.
Welcome back for another deep dive.
(00:02):
Today we're gonna tackle a topic
I know you've been wanting to learn more about.
The Common Technical Document.
Ah, the CTD.
Yeah, or CTD for short.
It's this really important piece of the puzzle
when it comes to bringing new drugs to market
all over the world.
It really is.
And we've got a whole bunch of like regulatory documents
and guidelines and research papers
(00:24):
kind of piled up in front of us here.
So let's dive right in and see if we can like
pull out the key stuff.
Yeah, I think bringing medications to market
is such a great phrase because that's really at the heart
of what the CTD is designed to do.
It's to like streamline that whole process.
So imagine you've developed like a groundbreaking new drug,
you know, something that's gonna change things for patients.
(00:46):
But before you can share that with the world,
there's this whole obstacle course of regulations
and that's where the CTD comes in.
So it's kind of like a passport for new drugs.
Like it helps them travel across
all the different regulatory borders.
Exactly.
It's the standardized format that drug companies use
when they're applying to get new drugs
or treatments approved, like two agencies all over the world.
(01:08):
And before we had the CTD, it was kind of like
trying to put together a puzzle,
but all the pieces were from different sets.
Oh yeah.
Every country had its own format and its own requirements.
And it made things so time consuming
and resource intensive for developers.
It sounds like a logistical nightmare.
It was.
I can only imagine the delays that caused
(01:29):
in getting treatments to patients.
Oh, for sure.
Yeah.
Without a unified system, it created a ton of redundancy,
you know, doing the same thing over and over in inefficiency.
So the CTD really changed the game
because it gave everyone involved
in the drug approval process, the researchers,
the manufacturers, the regulators, a common language.
Okay.
So the CTD establishes a universal format,
(01:50):
but how does it actually work?
I've heard it set up in modules.
Can you unpack that a bit?
Definitely.
Think of the CTD as a really organized filing cabinet.
Okay, yeah.
With like five main drawers or modules.
And each module serves a specific purpose
and presents the information in a consistent way.
Okay, so I'm picturing these five drawers.
Yes.
What goes in each one?
(02:11):
Well, let's start with module one.
That's where you find all the administrative stuff,
the prescribing information.
Okay.
Like the cover letter and table of contents
for the drug application.
It's got things like the drug's name, its proposed name,
how it's given and what it's intended to be used for.
So it's like introducing the drug to the regulators.
Yeah.
Giving them the basic facts and figures.
(02:31):
Yeah, exactly.
What about module two?
Module two is that high level view of the whole submission,
you know, like the executive summary.
It summarizes all the key findings from the other modules
so the reviewers can quickly grasp
the essential info about the drug.
So it's like giving the regulators a roadmap
to navigate the whole document.
Exactly.
And then there's module three,
(02:52):
and this is where it gets really interesting,
especially with your interest in all those regulations.
This section really digs into the quality of the drug.
Okay, so is this where all those CFR documents
come into play?
Yes.
The ones that detail all the manufacturing
and quality control standards?
Exactly.
Module three is all about making sure
the regulators are confident the drug is made
(03:12):
to the highest standards, that it's safe, effective,
and that it's produced consistently every time.
So you'll find details about the manufacturing process,
quality control measures, and all the stability testing.
So showing that the drug is made carefully, precisely,
and it follows all those CFR guidelines.
Yep.
Then we move on to module four,
(03:33):
and this is where we enter the non-clinical world.
All the pre-clinical data goes here,
you know, animal studies, lab results.
Basically any research that happened
before the drug is tested in humans.
So it's like building the case for why the drug
is a good candidate for human trials.
It's showing the potential of the drug.
Exactly, and showing that, you know,
it's not gonna cause harm.
And then finally we get to module five,
(03:54):
and this is all about the human data.
So this is where we see the clinical trials.
Yes.
The results of the drug in actual people.
Absolutely.
Module five is like the heart of the CTD.
It's where the data from the human clinical trials lives.
Okay.
You know, showing if the drug is effective,
if it's safe for people.
You'll find all the study details,
(04:16):
demographics, efficacy results,
any adverse effects that pop up during the trials.
So I've got the intro in module one.
Yes.
The executive summary in module two.
Yeah.
Manufacturing details in module three,
the pre-clinical research in four.
And finally the human data in five.
It's like the whole story of the drug.
Yeah, it is.
From lab to clinic.
(04:36):
But what about in the digital age?
Right.
I mean, we can't be shipping pallets of paper
all over the globe, can we?
Yeah, you raise a great point.
The CTD has evolved, of course,
to keep up with technology.
Of course.
So now we have what's called the electronic
common technical document.
Catchy.
Or ECTD.
ECTD.
So no more paper cuts for all those reviewers.
Not quite, but it's definitely a step in the right direction.
(04:57):
The ECTD is essentially the digital version
of that paper CTD.
Yeah.
And it has so many benefits.
Like what?
Faster submissions, I bet.
Absolutely.
Submissions happen electronically.
So much faster.
But it's not just speed.
Right.
It's efficiency.
It's clarity.
The agencies can easily search, navigate,
and annotate electronic documents.
(05:18):
So the whole review process is streamlined.
And I bet it saves a few trees too, right?
Yeah.
Cutting down on all that paper.
Definitely.
The ECTD is much more sustainable,
which is a major plus.
So the ECTD is faster, more efficient,
and better for the planet.
A win-win-win.
But is this CTD format just for brand new drugs?
Are there other scenarios where it comes up?
(05:40):
You're thinking outside the box.
I like it.
The CTD format is really versatile.
It's used for lots of different filings beyond those new drug
applications.
OK, so give me some examples.
What else is it used for?
Well, there's the drug master file.
We call it the DMF.
And this is a document all about one specific drug substance.
A manufacturer might submit this to support a drug application
(06:01):
without having to reveal all their trade secrets.
So they can say, hey, we've got this awesome ingredient that
works great, but we're not telling you
exactly how we make it.
Exactly.
It's a way to protect intellectual property.
But they're still providing the info needed
to show the safety and quality of the product.
Clever.
What else?
Well, then we have the BDMF, the Biologic Drug Master File.
(06:21):
And that's the same idea, but for biological products,
like vaccines, gene therapies, monoconal antibodies.
These are big, complex molecules, usually
made using living organisms.
So the whole process is really complicated.
Yes, the BDMF, highlighting the whole field of biologics,
which is growing so rapidly.
(06:41):
Yes, exactly.
And then we can't forget the IND, the Investigational New
Drug Application.
This is what you need to get the go ahead to even start
human clinical trials.
Oh, right.
The IND.
And we were talking about clinical trials
before with module 5 of the CTD.
It's all connected.
Exactly.
It all ties together.
So the IND is what gets you into the human testing arena.
You give the FDA all the info they
(07:03):
need to assess if the trials are safe and ethical.
Precisely.
Now get ready for the big ones, the NDA and the ANDA.
The NDA, the New Drug Application,
is the ultimate goal.
This is what you submit when you're looking for approval
to market a new drug.
So years of research all come down to this massive document.
Yes.
No pressure.
Right.
And then there's the ANDA, the Abbreviated New Drug
(07:25):
Application.
This is the pathway for generic drugs.
OK, I see.
And it's abbreviated because they
don't have to do all the original clinical trials.
They just have to prove their generic is
the same as the brand name drug that's already approved.
So it's like the express lane for drug approvals,
which makes sense because generics
are so important for making treatments
affordable and accessible.
(07:45):
Absolutely.
The ANDA is essential for patient access.
So the CTD format is used for new drugs, biologics,
investigational drugs, and generics.
It's really amazing how this one format has revolutionized
the whole industry.
It really has.
And it might seem bureaucratic, but it
serves such a crucial purpose, ensuring patient safety
and helping develop new treatments.
(08:07):
It's really interesting how something like a document
can have such a huge impact on global health.
We've covered a lot of ground in this first part
of our deep dive, exploring the structure of the CTD,
how we got to the ECTD, and all the different types of filings
that fall under the CTD umbrella.
But let's keep going.
I'm really interested in digging a little deeper
(08:27):
into some of these topics, especially
the connection between the CTD and all those CFR
documents we touched on.
That's where things get really interesting
from a regulatory perspective.
Definitely.
It's important to understand how these regulations play out
in the real world.
That's how we ensure the quality and safety of the medications
that people rely on.
Absolutely.
(08:47):
So let's jump right back in and see what else we can learn.
Sounds good.
You're so right.
Those CFR documents are where it all
happens in terms of making sure drugs are safe and high quality.
And module three of the CTD is where all that comes together.
It's like the bridge between the CFR's requirements
and all those nitty gritty details of how a drug is made.
OK, so let's walk across that bridge.
(09:08):
I mentioned my interest in the CFR.
And I'm particularly interested in Title 21, which I know
covers food and drugs.
So how does the CTD, specifically module three,
demonstrate compliance with all those regulations?
Think of Title 21 as the rule book
for making pharmaceuticals.
And module three is like the company's playbook showing
how they follow all those rules.
(09:28):
OK, so I see it.
The CFR sets the standards.
And then module three is where the companies
show they're meeting them.
Exactly.
Like CFR 21 part 211 that lays out
super specific regulations for everything,
from what qualifications personnel need,
to how equipment has to be maintained.
Remember those hand washing and lab coat things we talked about?
(09:49):
Yeah, all those details that seem small but actually
make a huge difference for preventing contamination
and making sure the drug is high quality.
Right.
All those details are laid out in the CFR.
And in module three, companies would give their standard
operating procedures for things like personnel hygiene,
equipment cleaning, and how they monitor the environment.
All that proves that they're sticking to the CFR.
(10:11):
So it's like a checklist.
The CFR says do this and that.
And module three is where the company is like, look, we did it.
Here's the proof.
Exactly.
And it's more than just checking boxes.
The CFR, especially part 211, really stresses
good manufacturing practices.
GMP, I've heard that a lot.
What does that actually mean in practice?
(10:31):
How does that translate into what
happens on the factory floor?
Think of GMP as like the driving force behind every single step
of making a drug.
It's about building quality into every stage,
from where they get the raw materials
to how the final product is packaged.
So it's not just about testing the final product
but making sure quality is baked in from the very beginning.
Exactly.
(10:53):
GMP means manufacturers have to have strong systems in place
for everything, training employees,
making sure equipment works right,
dealing with issues that pop up, and complaints.
There's a holistic approach to making sure everything's
consistent and reliable.
And how does module three connect to that?
Module three is where the company shows
their commitment to GMP.
They include tons of documentation
(11:13):
on their process, the quality control, and any validation
studies they've done.
And it's all got to be aligned with GMP and the CFR guidelines.
So it's like giving the regulators a backstage pass
to the whole manufacturing operation,
showing them exactly how they're maintaining those standards.
Exactly.
Module three is all about being transparent and accountable.
(11:33):
They give the regulators all the information
they need to judge if the manufacturing process is
high quality and reliable.
It's really cool how these kind of boring regulatory documents
actually boil down to something so important,
keeping patients safe.
It's good to know all these systems are in place
to make sure the medications we all need are made the right way.
(11:54):
It's all about public health, and that's
what the CFR and module three do.
OK, so we've dug into the CFR and module three.
And we've seen how they work together
to keep drug quality high.
But let's go back to those other CTD filings
we talked about earlier.
You mentioned the drug master file, the DMF.
Can you give an example of when a company might
(12:16):
use one of those, like a real world example?
Sure.
Let's say there's this company that developed
this amazing new excipient, that inactive ingredient.
The things that help the drug dissolve or be absorbed better.
OK, so not the actual drug, but something
that helps it work better.
Yeah.
So they may not want to share their secret formula
with every other company who wants to use it.
(12:38):
So they would put together a DMF that
gives all the information about the excipient's safety,
how it's made, and its quality, but without giving away
the exact recipe.
So they're sharing the recipe, but not telling you
what the secret ingredient is.
Yeah, I like that.
Clever.
So when another company wants to use that excipient
in their drug, they can just reference that DMF
in their application, and they don't have to generate all
(12:58):
that data themselves.
That saves so much time and effort and resources.
Exactly.
It really speeds things up for everybody.
Yeah, and it encourages innovation.
Companies can specialize in their own thing,
and they don't have to start from scratch every time.
Now, what about the BDMF, the Biologic Drug Master File?
Yeah.
What's different about that one, since biologics are so unique?
It serves a similar purpose, but it's
(13:20):
made specifically for biological products, which
tend to be more complicated than those small molecule drugs.
Right.
Biologics come from living things.
Right.
So the whole manufacturing process is way more complex.
Absolutely.
A BDMF would have details about the cell lines used,
the conditions they're grown in, how they're purified,
(13:40):
and the quality control tests.
So it's like this really detailed blueprint
for making these really complex drugs,
making sure everything is consistent and high quality.
Exactly.
It assures the regulators that the biologics
are being made to the same standards
as traditional pharmaceuticals.
The CTD really is like this versatile toolkit
(14:01):
with different tools for different jobs.
Companies can pick the right tool
based on the type of product they're making
and the regulatory pass they're on.
I like that.
Yeah, it's a flexible system that
works for so many drug products and situations.
OK, let's talk about those really big applications,
the INDE and the NDA.
Right.
Those are the ones that make or break a drug.
(14:21):
You could say that.
The INDE, the Investigational New Drug Application,
is like the first big hurdle.
It's what you send to the FDA before you can even
start testing in humans.
So you're asking for permission to start human trials.
Right.
And what makes the INDE so important?
What's in it?
What does the FDA need to see?
The INDE is basically everything you
(14:42):
need to lay the foundation for clinical trials in people.
It's all the preclinical data, animal studies, toxicology,
manufacturing info, all of it.
Everything that supports moving to human testing safely.
So it's like you're saying to the FDA,
here's all the evidence we have that this drug is promising
and we don't think it will be too risky for people.
Yeah.
And it also outlines the plan for the trial,
(15:05):
how it will be designed, how many people will be in it,
the dosage, all that.
The FDA needs to know everything to make sure
the trial is safe and ethical.
They look at the science, who's doing the research, everything.
That's a really thorough review.
They're the gatekeepers, protecting people
and making sure the research is good science and it's ethical.
Yeah.
And what happens if they say yes?
(15:27):
Then the fun begins.
Right.
Then the company can move forward with the human trials.
Yeah.
And those trials can take years.
Years.
With thousands of people.
But if everything looks good, the drug works, it's safe,
then they can go for the next big milestone, the NDA.
The NDA, the new drug application, the ultimate goal.
This is the one that can really change people's lives.
(15:49):
It's the culmination of all that work.
It is.
What makes the NDA so important and what all is in it?
The NDA is everything.
It's all the data collected over years and years of work.
Preclinical studies, all the clinical trial results,
manufacturing details, everything.
It's like the encyclopedia of that drug.
Yeah.
It's the whole story, from an idea in the lab
(16:10):
to potentially a lifesaving treatment.
Exactly.
And the FDA goes over it with a fine-tooth comb.
I bet.
Every single piece of data to decide if it meets the standards
for safety, efficacy, and quality manufacturing.
That review is a big deal.
It can really make a difference for patients
who are waiting for new treatments.
It really can.
And if the FDA approves that NDA,
(16:32):
then that drug can finally be made available to patients.
That's a huge win for the company.
Yeah.
And most importantly, for the patients who will benefit.
It's pretty amazing to think about that journey
that a drug goes on.
It is.
From the very first discovery to when a patient finally
gets it.
And the CTD is there for all of it.
It's a guide, a record keeper, and ultimately, it
(16:52):
protects patients.
That's a great way to put it.
The CTD might seem like just a technical thing,
but it's a foundation for the whole industry.
It makes sure new drugs are made responsibly and with care.
So we've talked about the NDA, that exciting moment
when a drug is finally approved and it can be sold.
But the story doesn't end there, does it?
No, not at all.
(17:12):
That's where post-marketing surveillance comes in.
It's a really important part of drug development
that often gets overlooked.
OK.
Even after a drug has been through those rigorous trials
and it's gotten the FDA's approval,
there's still a lot to learn about it,
how it works long term and how it affects different people
in the real world.
So it's kind of like releasing a new species into an ecosystem.
(17:35):
You studied it in a controlled environment,
but now you have to see how it adapts out in the real world.
I like that analogy.
That's exactly what post-marketing surveillance
is all about, gathering real world data,
seeing if there are any unexpected side effects
or risks and even benefits that didn't show up in the trials.
That makes sense.
Clinical trials are important, of course,
but they can only tell you so much.
(17:57):
Right.
They happen in a controlled setting and for a limited time.
The real world is way more complicated.
Exactly.
Post-marketing surveillance helps
us get a much bigger picture of the drug
and we can spot any potential problems
that we didn't see before.
And how do you do that surveillance?
Are we talking about tracking every single patient who
takes the drug?
Not quite that detailed.
(18:18):
There are different ways to collect data.
A common one is spontaneous reporting.
Health care providers and patients
can report anything unusual to the FDA.
So it's a team effort.
Everyone in health care is working together.
Yeah.
And there are also some more proactive methods,
like doing observational studies or looking
at big health care databases to see any patterns or trends
(18:40):
in how the drug is being used.
What happens if they find something
concerning, like a safety issue?
Does that mean the drug is pulled off the market?
Not always.
It really depends on what the concern is
and how serious it is.
Sometimes they might just update the label
with a new warning or some precautions.
If it's more serious, they might investigate further.
Or in rare cases, if the risks outweigh the benefits,
(19:01):
they could pull it.
So it's always evolving.
You're always learning more and adjusting as you go
to make sure patients are safe.
Absolutely.
And the CTD actually plays a big role in that.
Really?
Yeah.
Remember all those modules we talked about?
Yeah.
They're still important after the drug is approved.
OK.
Help me understand how that works.
How does the CCD connect to all this post-marketing stuff?
Well, as new information comes up, the CTD gets updated too.
(19:24):
Like module 5, that's where the clinical trial data is.
They can add information from post-marketing studies
or any new research.
So it's not a one and done kind of thing.
It's a living document that changes as we
learn more about the drug.
Exactly.
That's one of the best things about the CTD.
It's this organized system for keeping
track of all the information about a drug
(19:45):
from the very beginning all the way through to when
it's being used in clinics.
So it's not just about getting a drug approved.
It's about making sure it's used the right way
and that it's safe for patients.
You got it.
The CTD might seem like this boring hurdle,
but it's really a powerful tool for protecting public health.
Well said.
I think we've done it.
(20:06):
We've explored the complex world of the common technical
document.
We looked at the structure, how it connects to the CFR,
and all the different filings that are part of it.
We even talked about how it's involved throughout the entire
life of the drug.
Yeah, from the very first research all the way
to post-marketing surveillance.
That's amazing.
It is.
This has been a really enlightening deep dive.
(20:26):
Thanks for joining us as we explore
the ins and outs of the CTD.
We hope you learned something new
and that you can appreciate how complex and how important it
is.
It might seem like a boring bureaucratic thing,
but it's really all about making sure
that the medications we all rely on
are developed safely and responsibly.
Very well said.
And that's a wrap on our deep dive
(20:47):
into the common technical document.
Until next time.
Popular Podcasts
Crime Junkie
Does hearing about a true crime case always leave you scouring the internet for the truth behind the story? Dive into your next mystery with Crime Junkie. Every Monday, join your host Ashley Flowers as she unravels all the details of infamous and underreported true crime cases with her best friend Brit Prawat. From cold cases to missing persons and heroes in our community who seek justice, Crime Junkie is your destination for theories and stories you won’t hear anywhere else. Whether you're a seasoned true crime enthusiast or new to the genre, you'll find yourself on the edge of your seat awaiting a new episode every Monday. If you can never get enough true crime... Congratulations, you’ve found your people. Follow to join a community of Crime Junkies! Crime Junkie is presented by audiochuck Media Company.
24/7 News: The Latest
The latest news in 4 minutes updated every hour, every day.
Stuff You Should Know
If you've ever wanted to know about champagne, satanism, the Stonewall Uprising, chaos theory, LSD, El Nino, true crime and Rosa Parks, then look no further. Josh and Chuck have you covered.