January 28, 2025 • 18 mins
This episode unpacks the fascinating world of Quality by Design (QbD) in drug development, guided by ICH Q8 and Q11 principles. We explore how QbD ensures quality is built into every stage of a drug's lifecycle, from identifying critical quality attributes (CQAs) to defining flexible design spaces for manufacturing.
Discover the shift from reactive to proactive approaches in pharmaceutical production, leveraging tools like risk assessment, process modeling, and statistical analysis to optimize quality and minimize variability. We also dive into how QbD benefits manufacturers by reducing waste and improving efficiency, while ultimately delivering safer and more effective medications to patients.
Join us as we break down the science, innovation, and real-world impact of QbD, showcasing how this approach is revolutionizing the pharmaceutical industry and driving continuous improvement.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
All right, everyone, get ready for a deep dive.
(00:02):
We're going deep into the world of quality by design.
QBD.
QBD.
That's right.
We've had tons of requests to explore this, especially
how it's laid out in that ICH Q8 guidance.
Absolutely.
Big focus on design space.
Oh, definitely.
And those critical quality attributes, those CQAs.
I just forget the CQAs.
And just to spice things up, we'll
(00:23):
throw in some ICH Q11 for good measure.
Sounds good to me.
We'll cover it all.
Even those all those acronyms.
Yeah, those acronyms like CQAs, CMAs, CPPs,
the whole alphabet soup.
We'll break it all down, make it clear and fun,
even if you're not a pharma whiz.
Right.
Now, you also wanted to know how QBD plays out
(00:44):
in the different phases of drug development, right?
Absolutely.
That's a key part.
Like, is it the same approach from start to finish?
Or does it kind of evolve over time?
Yeah, great question.
It definitely evolves.
It's not a one size fits all situation.
We'll look at how the details change
from those early preclinical studies
all the way to post approval.
Post approval.
That's a whole other world, right?
(01:06):
But before we get there, let's rewind.
Why did we even need QBD in the first place?
Was there like a big aha moment in the pharmaceutical world
that led to this?
Well, not a single aha moment, but there were definitely
some wake up calls.
The traditional way of developing drugs,
it had its limitations.
And sometimes those limitations, well,
(01:27):
they had some pretty serious consequences.
OK, now you've got me curious.
What kind of consequences are we talking about here?
Think back to the 1950s.
There was this drug, thalidomide,
marketed as a safe treatment for morning sickness.
But tragically, it caused severe birth defects
in thousands of babies.
Oh, wow.
(01:47):
That's heartbreaking.
It was a real tragedy.
What went wrong with thalidomide?
It wasn't so much a bad recipe, but a lack of understanding.
Back then, the focus was on making sure the drug was
chemically pure.
They weren't looking at the bigger picture,
like how does this drug interact with the body?
What are the potential side effects?
So it's kind of like you assume a cake is safe to eat just
because each ingredient on its own is safe.
(02:08):
Exactly.
But you haven't thought about how those ingredients might
react when you bake them together.
Perfect analogy.
Thalidomide was a turning point.
It forced the world to rethink how we develop and test drugs.
And that's where QBD comes in.
It's all about bringing science and risk assessment
to the forefront, making sure every step is well thought out
and quality is baked in from the very beginning.
(02:30):
OK, starting to see why QBD is such a game changer.
But how does ICHQ8 fit into all of this?
You mentioned it's like the heart of QBD.
Yeah, ICHQ8, it's the guiding document, the rulebook.
It lays out those key principles of QBD.
It really emphasizes understanding
the product and the process, the whole picture.
OK, so that's our foundation.
(02:51):
Now, let's talk about those critical quality attributes.
The CQAs.
Yes, CQAs.
That's what makes them so critical.
Well, think of CQAs as the non-negotiables.
These are the specific characteristics of the drug
that we absolutely have to control to ensure
that it works as intended and that it's safe.
OK, so give me an example.
I need a visual.
You know how I am?
Sure.
Let's say we're developing a new drug for high blood pressure.
(03:13):
OK.
One CQA could be the amount of the active ingredient
in each pill.
Makes sense.
If there's too much, it could cause dangerously low blood
pressure, too little, and it might not work at all.
So it's all about that balance.
Absolutely.
Finding that sweet spot.
Now, are CQAs the same for every single drug?
Nope.
That's what makes it interesting.
(03:33):
CQAs, they're unique to each drug,
and they depend on how the drug works in the body.
It's about identifying those specific characteristics
that we need to keep a close eye on to make sure the drug is
both safe and effective.
Got it.
So we've got our CQAs, the must haves for quality.
Where does the design space come into play?
OK, so the design space, think of it like a flexible blueprint.
(03:56):
It's a range of conditions, things like temperature,
pressure, ingredient concentrations,
where we know we can consistently meet those CQAs.
So it's like having a recipe, but with some wiggle room.
You can tweak certain ingredients
within a specific range, and you'll still
bake that perfect cake.
You got it.
It gives manufacturers some flexibility
without compromising on quality.
(04:16):
This is super important for large scale manufacturing,
because slight variations are bound to happen.
Right, it's not like baking one cake at home.
Exactly.
And the design space, it's proposed by the applicant,
but it needs to be approved by the regulatory authorities.
OK, so this is a collaborative effort.
Absolutely.
Now, what about ICHQ11?
We can't forget about that.
(04:37):
How does it fit into this whole QBD puzzle?
Right, think of ICHQ11 as the companion guide to ICHQ8.
It dives deeper into the development
of the drug substance, covering things
like selecting starting materials
and controlling those critical process parameters, or CPPs.
CPPs, more acronyms.
I'm telling you, it's a whole new language.
I know, right?
(04:58):
But CPPs, they're essentially the knobs and dials
we can adjust during manufacturing.
They're those variables that directly influence
those CQAs we talked about.
So like the oven temperature and baking time in our cake
analogy?
Exactly.
And controlling CPPs, it's all about staying
within our design space and making
sure each batch of the drug is consistently high quality.
OK, this is all fascinating.
(05:19):
This level of detail, I'm guessing
it's not needed in the very early phases of drug
development, right?
Good point.
QBD is about using the appropriate level of detail
at each stage.
In the early phases, like preclinical testing,
we're focused on understanding the drug's basic properties,
you know, how it behaves.
We're gathering information to build a foundation
(05:40):
for our QBD approach.
And looking for any potential safety concerns, of course.
So it's kind of like starting with a rough sketch
or moving on to the detailed blueprint.
Precisely.
Then as we progress into clinical trials,
you know, we learn more and we refine that QBD strategy.
It's an evolving process, always adapting to new information
and challenges.
I'm getting a much clearer picture now.
(06:02):
Now, how does validation fit into this process?
Validation is a crucial step.
It's like the final exam for our manufacturing process.
We need to prove that the process we've developed
consistently delivers a drug that
meets those quality standards.
All those standards we define so carefully.
So it's not just about saying, hey, trust us, this works.
It's about proving it.
(06:23):
Absolutely.
It involves rigorous testing and documenting everything
to demonstrate that it all works as intended.
And what about verification?
How is that different?
I always get those two mixed up.
Think of verification as those ongoing quality checks,
making sure everything is still running smoothly.
Like when you're driving, you're constantly
(06:44):
checking your mirrors, your blind spots.
You're making sure you're still on track.
So validation is like passing your driving test.
And verification is like proving you're still a good driver
every time you get behind the wheel.
Exactly.
Both are super important for making sure the drug is
safe and high quality.
OK, we've covered a lot here.
(07:04):
But I've got to ask, what happens
when you need to make changes to a drug
after it's already been approved?
I mean, that's got to happen sometimes, right?
It does happen, and that's where QBD really shines.
Because we have this deep understanding of the drug
and the process, we can assess the impact of any changes.
Will it affect those CQAs?
Will it push us outside of our design space?
(07:25):
It's like having that detailed map of the city again.
Right.
If you need to reroute traffic, you
can see how it will affect everything else.
Exactly.
QBD gives us that framework for making smart decisions
about post-approval changes.
We can move forward with confidence
knowing we're not messing with the quality or safety.
This is so insightful.
It sounds like QBD is really revolutionizing
(07:45):
the whole pharmaceutical industry.
It's not just about checking boxes.
It's about really understanding the science
and building quality into everything you do.
It really is a paradigm shift.
It's about putting quality and the patient
at the center of drug development.
Absolutely.
I'm eager to hear more about how QBD
works in those different phases of drug development.
We touched on it briefly, but can we go a little deeper?
(08:06):
For sure.
Let's explore how QBD changes and adapts
throughout the whole life cycle of a drug,
from the research lab to the pharmacy shelf.
Awesome.
This deep dive is already blowing my mind.
Can't wait to hear what else you've got for us.
So you're interested in how QBD looks
different at those various stages of drug development.
Yeah.
It's not like you just flip a switch
(08:26):
and suddenly everything's QBD, right?
I imagine there are different levels of, I don't know,
intensity depending on where you are in the process.
Are you doing full-on QBD when you're just
testing a new molecule in a Petri dish?
That's a great point.
In those early preclinical stages,
it's really about building that basic knowledge.
Like, what's this drug?
What's its chemical personality?
(08:47):
How does it behave in the body?
Are there any early signs of toxicity?
Things like that.
It was more exploratory at that point,
kind of like sketching out the rough draft of our quality
blueprint.
Exactly.
We're starting to identify those critical quality attributes,
those CQAs, those must-have features for safety
and efficacy.
(09:08):
And we start to get a feel for that potential design space.
But it's still early.
We're just getting started.
And then things get a lot more serious
when we move into clinical trials, right?
Absolutely.
Because now we're actually testing this drug in people.
Exactly.
And with each phase of clinical trials,
we gather more data about the drug's safety
and effectiveness in actual humans.
(09:31):
Real people, yeah.
This helps us refine our understanding of those CQAs.
What's truly essential for this drug to work well and be safe?
And we can start narrowing down that design space, that safe
zone for manufacturing.
So our blueprint gets more and more detailed as we go.
Exactly.
Adding in the electrical wiring, the plumbing,
making sure everything is up to code.
(09:51):
I love that analogy.
And it doesn't stop there.
Even after a drug is approved and it's out in the market,
QBD is still relevant.
Wait, really?
Yeah.
I thought getting approved was kind of like the finish line
for QBD.
That's a common misconception.
QBD isn't just about getting that stamp of approval.
It's about ensuring quality throughout the entire lifecycle
of the drug.
(10:12):
And that includes those post-approval changes
that might be necessary.
OK, yeah, let's talk about post-approval changes.
OK.
Because I can imagine there are all sorts of reasons why
you might need to tweak things once the drug's on the market.
Absolutely.
Maybe we need to scale up manufacturing
to meet a higher demand.
Or maybe we found a more efficient way
(10:32):
to produce the drug substance.
Makes sense.
Which could lower costs, make the drug more accessible.
Or what if some new safety concerns come up
after the drug's been used by more people?
That's a crucial point.
Monitoring the drug after it's approved
is a key part of that QBD mindset.
And sometimes new technologies come along,
(10:54):
or there are new scientific advancements that
allow us to improve the drug's formulation, or even
the manufacturing process.
So it's about continuous improvement, right?
Absolutely.
Always looking for ways to make a good drug even better.
But how does QBD actually make those post-approval changes
easier?
Isn't it just a ton of paperwork and regulatory hoops
to jump through?
(11:15):
This is where the real power of QBD comes in.
Because we've defined that design space.
And we have a deep understanding of those critical quality
attributes.
We can assess the impact of any proposed changes,
like will this tweak affect the drug's quality?
Will it affect its safety or effectiveness?
QBD gives us the framework to make those informed decisions.
(11:37):
Like that city map analogy again,
if you need to reroute traffic, you
can see how it will affect the entire system.
Precisely.
No surprises, no traffic jams.
And the FDA, they really like this.
They've been big supporters of QBD.
When a company can show they've embraced these principles,
it builds trust.
So they're more likely to be like, OK,
you've clearly done your homework.
(11:58):
You understand the science behind this.
You have our blessing.
Exactly.
It can really streamline the review process
and even lead to faster approvals, which ultimately
benefits everyone, especially the patients who
get access to those improved medications sooner.
You've convinced me on the why of QBD.
Now I'm curious about the how.
(12:19):
What are some of the tools and techniques
that are used in this process?
It all sounds pretty high tech.
One of the foundational tools is risk assessment.
It's about identifying potential sources of variability
in the manufacturing process and figuring out
how those variations might impact those CQAs.
It's all about prioritizing, focusing our efforts
(12:41):
on controlling those factors that are most critical.
So it's kind of like a triage system for a potential problem.
Exactly.
Figure out what could really go wrong
and focus on preventing that.
Another important tool is process modeling.
We can use mathematical models to simulate
the entire manufacturing process.
This allows us to see how different variables might
(13:03):
affect the final product.
So like a flight simulator, but for drug manufacturing.
Exactly.
You can test out different scenarios
and optimize the process before you even
start making the drug.
That's cool.
And then there's statistics, which plays a huge role.
Statistical analysis helps us understand variability
and set those boundaries for our design space.
And techniques like design of experiments or DOE
(13:25):
allow us to test different combinations of variables.
And find that sweet spot for the manufacturing process.
No.
So QBD brings together all of these scientific tools
and extra T's.
It really does.
It's a team effort with chemists, engineers,
statisticians.
Wow.
Even clinicians.
All working together.
To ensure the quality of that final drug product.
(13:45):
It's really impressive how thorough and scientific
this whole process is.
Right.
It's amazing how far we've come from those old trial and error
methods.
That's a really important point.
QBD represents a shift from a reactive approach
to a proactive approach.
We're not just trying to fix problems after they happen.
We're trying to prevent them in the first place.
So it's about building quality in from the beginning,
(14:07):
not just hoping for the best at the end.
Exactly.
That's the heart of QBD.
I'm really starting to appreciate
how much thought and science goes
into making sure these drugs are safe and effective.
It's a continuous process.
It is.
Of learning and improvement.
This deep dive has been so eye opening.
Yeah.
I feel like I've gained a whole new level of understanding
about drug development and the whole importance of quality.
(14:30):
That's great to hear.
But I'm also curious about the real world
impact of all this.
Can we talk about some tangible benefits?
What does QBD really mean for drug manufacturers
and for patients?
So we've talked a lot about the science and the why behind QBD.
But let's get practical here.
What are the actual benefits?
(14:51):
In the real world, is it all about keeping the FDA happy?
Not at all.
Or are there advantages for drug manufacturers?
Right.
And ultimately for patients?
That's the goal.
Yeah.
From a manufacturer standpoint, QBD can actually
lead to fewer batch failures.
OK.
Imagine you have to scrap a whole batch of medication
because it didn't meet the standards.
Yeah, that's a nightmare.
(15:12):
It's a huge waste of time, money, and resources.
Right.
Nobody wants that.
So QBD helps prevent those costly mishaps.
Gotcha.
So less waste.
Exactly.
And that's good for the bottom line.
Absolutely.
By really understanding those critical process parameters
and how they affect quality, manufacturers
can fine tune their processes, reduce variability,
(15:34):
and increase their chances of consistently producing
high quality medications.
Makes sense.
And less waste is also better for the environment, of course.
True, true.
OK, so there's a clear business case for QBD.
Definitely.
But what about the bigger picture?
Yeah.
How does this all benefit the patients who
rely on these medications?
Well, think about it.
(15:55):
When quality is built into every single step,
from the early research to manufacturing,
it ultimately leads to safer and more effective medications.
It just makes sense.
It does.
So it's not just about meeting those minimum requirements.
It's about exceeding them, aiming for that highest
possible level of quality.
I like that.
(16:15):
Striving for excellence.
Exactly.
And by encouraging innovation, as we talked about before,
QBD can lead to new and better treatments for diseases
that don't have good options right now.
So pushing the boundaries while keeping patients safe.
Absolutely.
This is really inspiring stuff.
It seems like QBD has the potential to really, truly
(16:36):
change the pharmaceutical industry for the better.
It does.
It really does.
And as more companies adopt these principles,
I think we're going to see even more benefits in the future.
It's an exciting time to be in this field, for sure.
I guess.
I feel like we've only scratched the surface of this topic.
This deep dive has been incredible.
It has.
I feel so much more knowledgeable
(16:57):
about drug development and just how important quality
is in that whole process.
I'm glad to hear that.
It's always great to see that spark of curiosity.
Absolutely.
Before we wrap up, any final thoughts for our listeners?
I would say keep learning.
Keep digging deeper.
Yeah.
Those ICH guidelines, Q8 and Q11,
they're publicly available.
(17:17):
You can read them for yourself.
Great point.
And there are so many resources online.
Tons of resources.
Through professional organizations
that can give you even more insights
into the world of QBD.
Awesome.
Well, a huge thank you to you, our listeners,
for joining us on this deep dive into the world of quality
by design.
Thanks for listening.
I hope you've come away with a new understanding
(17:38):
of the science and all the hard work that
goes into pronging safe and effective medications
to the people who need them.
It's been a pleasure.
And that's it for this deep dive.
Until next time, stay curious, stay informed,
and keep asking those great questions.
We'll see you next time.
And we'll be back to guide you through the amazing world
of science and tech, one deep dive at a time.
All right, everyone, get ready for a deep dive.
(00:02):
We're going deep into the world of quality by design.
QBD.
QBD.
That's right.
We've had tons of requests to explore this, especially
how it's laid out in that ICH Q8 guidance.
Absolutely.
Big focus on design space.
Oh, definitely.
And those critical quality attributes, those CQAs.
I just forget the CQAs.
And just to spice things up, we'll
(00:23):
throw in some ICH Q11 for good measure.
Sounds good to me.
We'll cover it all.
Even those all those acronyms.
Yeah, those acronyms like CQAs, CMAs, CPPs,
the whole alphabet soup.
We'll break it all down, make it clear and fun,
even if you're not a pharma whiz.
Right.
Now, you also wanted to know how QBD plays out
(00:44):
in the different phases of drug development, right?
Absolutely.
That's a key part.
Like, is it the same approach from start to finish?
Or does it kind of evolve over time?
Yeah, great question.
It definitely evolves.
It's not a one size fits all situation.
We'll look at how the details change
from those early preclinical studies
all the way to post approval.
Post approval.
That's a whole other world, right?
(01:06):
But before we get there, let's rewind.
Why did we even need QBD in the first place?
Was there like a big aha moment in the pharmaceutical world
that led to this?
Well, not a single aha moment, but there were definitely
some wake up calls.
The traditional way of developing drugs,
it had its limitations.
And sometimes those limitations, well,
(01:27):
they had some pretty serious consequences.
OK, now you've got me curious.
What kind of consequences are we talking about here?
Think back to the 1950s.
There was this drug, thalidomide,
marketed as a safe treatment for morning sickness.
But tragically, it caused severe birth defects
in thousands of babies.
Oh, wow.
(01:47):
That's heartbreaking.
It was a real tragedy.
What went wrong with thalidomide?
It wasn't so much a bad recipe, but a lack of understanding.
Back then, the focus was on making sure the drug was
chemically pure.
They weren't looking at the bigger picture,
like how does this drug interact with the body?
What are the potential side effects?
So it's kind of like you assume a cake is safe to eat just
because each ingredient on its own is safe.
(02:08):
Exactly.
But you haven't thought about how those ingredients might
react when you bake them together.
Perfect analogy.
Thalidomide was a turning point.
It forced the world to rethink how we develop and test drugs.
And that's where QBD comes in.
It's all about bringing science and risk assessment
to the forefront, making sure every step is well thought out
and quality is baked in from the very beginning.
(02:30):
OK, starting to see why QBD is such a game changer.
But how does ICHQ8 fit into all of this?
You mentioned it's like the heart of QBD.
Yeah, ICHQ8, it's the guiding document, the rulebook.
It lays out those key principles of QBD.
It really emphasizes understanding
the product and the process, the whole picture.
OK, so that's our foundation.
(02:51):
Now, let's talk about those critical quality attributes.
The CQAs.
Yes, CQAs.
That's what makes them so critical.
Well, think of CQAs as the non-negotiables.
These are the specific characteristics of the drug
that we absolutely have to control to ensure
that it works as intended and that it's safe.
OK, so give me an example.
I need a visual.
You know how I am?
Sure.
Let's say we're developing a new drug for high blood pressure.
(03:13):
OK.
One CQA could be the amount of the active ingredient
in each pill.
Makes sense.
If there's too much, it could cause dangerously low blood
pressure, too little, and it might not work at all.
So it's all about that balance.
Absolutely.
Finding that sweet spot.
Now, are CQAs the same for every single drug?
Nope.
That's what makes it interesting.
(03:33):
CQAs, they're unique to each drug,
and they depend on how the drug works in the body.
It's about identifying those specific characteristics
that we need to keep a close eye on to make sure the drug is
both safe and effective.
Got it.
So we've got our CQAs, the must haves for quality.
Where does the design space come into play?
OK, so the design space, think of it like a flexible blueprint.
(03:56):
It's a range of conditions, things like temperature,
pressure, ingredient concentrations,
where we know we can consistently meet those CQAs.
So it's like having a recipe, but with some wiggle room.
You can tweak certain ingredients
within a specific range, and you'll still
bake that perfect cake.
You got it.
It gives manufacturers some flexibility
without compromising on quality.
(04:16):
This is super important for large scale manufacturing,
because slight variations are bound to happen.
Right, it's not like baking one cake at home.
Exactly.
And the design space, it's proposed by the applicant,
but it needs to be approved by the regulatory authorities.
OK, so this is a collaborative effort.
Absolutely.
Now, what about ICHQ11?
We can't forget about that.
(04:37):
How does it fit into this whole QBD puzzle?
Right, think of ICHQ11 as the companion guide to ICHQ8.
It dives deeper into the development
of the drug substance, covering things
like selecting starting materials
and controlling those critical process parameters, or CPPs.
CPPs, more acronyms.
I'm telling you, it's a whole new language.
I know, right?
(04:58):
But CPPs, they're essentially the knobs and dials
we can adjust during manufacturing.
They're those variables that directly influence
those CQAs we talked about.
So like the oven temperature and baking time in our cake
analogy?
Exactly.
And controlling CPPs, it's all about staying
within our design space and making
sure each batch of the drug is consistently high quality.
OK, this is all fascinating.
(05:19):
This level of detail, I'm guessing
it's not needed in the very early phases of drug
development, right?
Good point.
QBD is about using the appropriate level of detail
at each stage.
In the early phases, like preclinical testing,
we're focused on understanding the drug's basic properties,
you know, how it behaves.
We're gathering information to build a foundation
(05:40):
for our QBD approach.
And looking for any potential safety concerns, of course.
So it's kind of like starting with a rough sketch
or moving on to the detailed blueprint.
Precisely.
Then as we progress into clinical trials,
you know, we learn more and we refine that QBD strategy.
It's an evolving process, always adapting to new information
and challenges.
I'm getting a much clearer picture now.
(06:02):
Now, how does validation fit into this process?
Validation is a crucial step.
It's like the final exam for our manufacturing process.
We need to prove that the process we've developed
consistently delivers a drug that
meets those quality standards.
All those standards we define so carefully.
So it's not just about saying, hey, trust us, this works.
It's about proving it.
(06:23):
Absolutely.
It involves rigorous testing and documenting everything
to demonstrate that it all works as intended.
And what about verification?
How is that different?
I always get those two mixed up.
Think of verification as those ongoing quality checks,
making sure everything is still running smoothly.
Like when you're driving, you're constantly
(06:44):
checking your mirrors, your blind spots.
You're making sure you're still on track.
So validation is like passing your driving test.
And verification is like proving you're still a good driver
every time you get behind the wheel.
Exactly.
Both are super important for making sure the drug is
safe and high quality.
OK, we've covered a lot here.
(07:04):
But I've got to ask, what happens
when you need to make changes to a drug
after it's already been approved?
I mean, that's got to happen sometimes, right?
It does happen, and that's where QBD really shines.
Because we have this deep understanding of the drug
and the process, we can assess the impact of any changes.
Will it affect those CQAs?
Will it push us outside of our design space?
(07:25):
It's like having that detailed map of the city again.
Right.
If you need to reroute traffic, you
can see how it will affect everything else.
Exactly.
QBD gives us that framework for making smart decisions
about post-approval changes.
We can move forward with confidence
knowing we're not messing with the quality or safety.
This is so insightful.
It sounds like QBD is really revolutionizing
(07:45):
the whole pharmaceutical industry.
It's not just about checking boxes.
It's about really understanding the science
and building quality into everything you do.
It really is a paradigm shift.
It's about putting quality and the patient
at the center of drug development.
Absolutely.
I'm eager to hear more about how QBD
works in those different phases of drug development.
We touched on it briefly, but can we go a little deeper?
(08:06):
For sure.
Let's explore how QBD changes and adapts
throughout the whole life cycle of a drug,
from the research lab to the pharmacy shelf.
Awesome.
This deep dive is already blowing my mind.
Can't wait to hear what else you've got for us.
So you're interested in how QBD looks
different at those various stages of drug development.
Yeah.
It's not like you just flip a switch
(08:26):
and suddenly everything's QBD, right?
I imagine there are different levels of, I don't know,
intensity depending on where you are in the process.
Are you doing full-on QBD when you're just
testing a new molecule in a Petri dish?
That's a great point.
In those early preclinical stages,
it's really about building that basic knowledge.
Like, what's this drug?
What's its chemical personality?
(08:47):
How does it behave in the body?
Are there any early signs of toxicity?
Things like that.
It was more exploratory at that point,
kind of like sketching out the rough draft of our quality
blueprint.
Exactly.
We're starting to identify those critical quality attributes,
those CQAs, those must-have features for safety
and efficacy.
(09:08):
And we start to get a feel for that potential design space.
But it's still early.
We're just getting started.
And then things get a lot more serious
when we move into clinical trials, right?
Absolutely.
Because now we're actually testing this drug in people.
Exactly.
And with each phase of clinical trials,
we gather more data about the drug's safety
and effectiveness in actual humans.
(09:31):
Real people, yeah.
This helps us refine our understanding of those CQAs.
What's truly essential for this drug to work well and be safe?
And we can start narrowing down that design space, that safe
zone for manufacturing.
So our blueprint gets more and more detailed as we go.
Exactly.
Adding in the electrical wiring, the plumbing,
making sure everything is up to code.
(09:51):
I love that analogy.
And it doesn't stop there.
Even after a drug is approved and it's out in the market,
QBD is still relevant.
Wait, really?
Yeah.
I thought getting approved was kind of like the finish line
for QBD.
That's a common misconception.
QBD isn't just about getting that stamp of approval.
It's about ensuring quality throughout the entire lifecycle
of the drug.
(10:12):
And that includes those post-approval changes
that might be necessary.
OK, yeah, let's talk about post-approval changes.
OK.
Because I can imagine there are all sorts of reasons why
you might need to tweak things once the drug's on the market.
Absolutely.
Maybe we need to scale up manufacturing
to meet a higher demand.
Or maybe we found a more efficient way
(10:32):
to produce the drug substance.
Makes sense.
Which could lower costs, make the drug more accessible.
Or what if some new safety concerns come up
after the drug's been used by more people?
That's a crucial point.
Monitoring the drug after it's approved
is a key part of that QBD mindset.
And sometimes new technologies come along,
(10:54):
or there are new scientific advancements that
allow us to improve the drug's formulation, or even
the manufacturing process.
So it's about continuous improvement, right?
Absolutely.
Always looking for ways to make a good drug even better.
But how does QBD actually make those post-approval changes
easier?
Isn't it just a ton of paperwork and regulatory hoops
to jump through?
(11:15):
This is where the real power of QBD comes in.
Because we've defined that design space.
And we have a deep understanding of those critical quality
attributes.
We can assess the impact of any proposed changes,
like will this tweak affect the drug's quality?
Will it affect its safety or effectiveness?
QBD gives us the framework to make those informed decisions.
(11:37):
Like that city map analogy again,
if you need to reroute traffic, you
can see how it will affect the entire system.
Precisely.
No surprises, no traffic jams.
And the FDA, they really like this.
They've been big supporters of QBD.
When a company can show they've embraced these principles,
it builds trust.
So they're more likely to be like, OK,
you've clearly done your homework.
(11:58):
You understand the science behind this.
You have our blessing.
Exactly.
It can really streamline the review process
and even lead to faster approvals, which ultimately
benefits everyone, especially the patients who
get access to those improved medications sooner.
You've convinced me on the why of QBD.
Now I'm curious about the how.
(12:19):
What are some of the tools and techniques
that are used in this process?
It all sounds pretty high tech.
One of the foundational tools is risk assessment.
It's about identifying potential sources of variability
in the manufacturing process and figuring out
how those variations might impact those CQAs.
It's all about prioritizing, focusing our efforts
(12:41):
on controlling those factors that are most critical.
So it's kind of like a triage system for a potential problem.
Exactly.
Figure out what could really go wrong
and focus on preventing that.
Another important tool is process modeling.
We can use mathematical models to simulate
the entire manufacturing process.
This allows us to see how different variables might
(13:03):
affect the final product.
So like a flight simulator, but for drug manufacturing.
Exactly.
You can test out different scenarios
and optimize the process before you even
start making the drug.
That's cool.
And then there's statistics, which plays a huge role.
Statistical analysis helps us understand variability
and set those boundaries for our design space.
And techniques like design of experiments or DOE
(13:25):
allow us to test different combinations of variables.
And find that sweet spot for the manufacturing process.
No.
So QBD brings together all of these scientific tools
and extra T's.
It really does.
It's a team effort with chemists, engineers,
statisticians.
Wow.
Even clinicians.
All working together.
To ensure the quality of that final drug product.
(13:45):
It's really impressive how thorough and scientific
this whole process is.
Right.
It's amazing how far we've come from those old trial and error
methods.
That's a really important point.
QBD represents a shift from a reactive approach
to a proactive approach.
We're not just trying to fix problems after they happen.
We're trying to prevent them in the first place.
So it's about building quality in from the beginning,
(14:07):
not just hoping for the best at the end.
Exactly.
That's the heart of QBD.
I'm really starting to appreciate
how much thought and science goes
into making sure these drugs are safe and effective.
It's a continuous process.
It is.
Of learning and improvement.
This deep dive has been so eye opening.
Yeah.
I feel like I've gained a whole new level of understanding
about drug development and the whole importance of quality.
(14:30):
That's great to hear.
But I'm also curious about the real world
impact of all this.
Can we talk about some tangible benefits?
What does QBD really mean for drug manufacturers
and for patients?
So we've talked a lot about the science and the why behind QBD.
But let's get practical here.
What are the actual benefits?
(14:51):
In the real world, is it all about keeping the FDA happy?
Not at all.
Or are there advantages for drug manufacturers?
Right.
And ultimately for patients?
That's the goal.
Yeah.
From a manufacturer standpoint, QBD can actually
lead to fewer batch failures.
OK.
Imagine you have to scrap a whole batch of medication
because it didn't meet the standards.
Yeah, that's a nightmare.
(15:12):
It's a huge waste of time, money, and resources.
Right.
Nobody wants that.
So QBD helps prevent those costly mishaps.
Gotcha.
So less waste.
Exactly.
And that's good for the bottom line.
Absolutely.
By really understanding those critical process parameters
and how they affect quality, manufacturers
can fine tune their processes, reduce variability,
(15:34):
and increase their chances of consistently producing
high quality medications.
Makes sense.
And less waste is also better for the environment, of course.
True, true.
OK, so there's a clear business case for QBD.
Definitely.
But what about the bigger picture?
Yeah.
How does this all benefit the patients who
rely on these medications?
Well, think about it.
(15:55):
When quality is built into every single step,
from the early research to manufacturing,
it ultimately leads to safer and more effective medications.
It just makes sense.
It does.
So it's not just about meeting those minimum requirements.
It's about exceeding them, aiming for that highest
possible level of quality.
I like that.
(16:15):
Striving for excellence.
Exactly.
And by encouraging innovation, as we talked about before,
QBD can lead to new and better treatments for diseases
that don't have good options right now.
So pushing the boundaries while keeping patients safe.
Absolutely.
This is really inspiring stuff.
It seems like QBD has the potential to really, truly
(16:36):
change the pharmaceutical industry for the better.
It does.
It really does.
And as more companies adopt these principles,
I think we're going to see even more benefits in the future.
It's an exciting time to be in this field, for sure.
I guess.
I feel like we've only scratched the surface of this topic.
This deep dive has been incredible.
It has.
I feel so much more knowledgeable
(16:57):
about drug development and just how important quality
is in that whole process.
I'm glad to hear that.
It's always great to see that spark of curiosity.
Absolutely.
Before we wrap up, any final thoughts for our listeners?
I would say keep learning.
Keep digging deeper.
Yeah.
Those ICH guidelines, Q8 and Q11,
they're publicly available.
(17:17):
You can read them for yourself.
Great point.
And there are so many resources online.
Tons of resources.
Through professional organizations
that can give you even more insights
into the world of QBD.
Awesome.
Well, a huge thank you to you, our listeners,
for joining us on this deep dive into the world of quality
by design.
Thanks for listening.
I hope you've come away with a new understanding
(17:38):
of the science and all the hard work that
goes into pronging safe and effective medications
to the people who need them.
It's been a pleasure.
And that's it for this deep dive.
Until next time, stay curious, stay informed,
and keep asking those great questions.
We'll see you next time.
And we'll be back to guide you through the amazing world
of science and tech, one deep dive at a time.
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