98 - Quality by Design in Formulation (S7E8)

All right, so today we're diving into the world
of drug formulation. Specifically, something
called quality by design, or QBD. Sounds intriguing.
Yeah, it's basically revolutionizing how medicines
are made. And we've got a ton of cool material
to go through today. We're looking at how drugs
actually work in the body. Ah, the fascinating
world of ADME. Exactly, ADME, all that stuff.
We've also got some insights into the whole regulatory
landscape. FDA, those guys, always important.
Oh, absolutely. And then we even got some sneak
peeks from, get this, organic process research
and development. OPRND. Now that's where the
real magic happens. Yeah, it's a bit of a mouthful,
but OPRND, it's a gold mine of info. And our
big mission today is to really unpack this whole
QBD thing, you know? Yeah. How does this systematic
approach actually improve the way we make the
medicines we all rely on? I'm all ears. Because
what really excites me about QBD is how practical
it is, right? It's not just some theory stuck
in a textbook It's a real hands -on way of doing
things and it affects like every single step
in making a drug product Interesting. Yeah, and
we'll see how it leads to you know drugs being
made more consistently more efficiently Which
ultimately means better medications for patients,
right? Safe reliable high quality stuff and all
while jumping through those regulatory hoops.
Yeah, can't forget those. Oh, absolutely not.
But just a quick point before we get too deep.
Yeah. For today's dive, we're laser focused on
the formulation of the actual drug product. OK.
So we're not going to go into how the active
ingredient, the API, is made. Gotcha. So formulation,
the final product. You got it. Cool. OK, so let's
get down to it. At its core, QBD seems to be
about bringing like a really strong scientific
mindset to this whole process of making drug
formulations. A hundred percent. It's about,
you know, moving beyond just crossing your fingers
and hoping for the best. Right. No more trial
and error. Exactly. The big idea with QBD is
to really understand, deeply understand two things.
The formulation itself, like what goes into it,
the recipe, and also the entire process of how
it's made. start to finish. The goal, the ultimate
goal is to be able to make a product every single
time that has all the qualities, all the characteristics
that it's supposed to have. And so you're saying
that for a long time, drug development was kind
of like a lot of guesswork. Yeah, well, maybe
not guesswork, but definitely lots of trial and
error. You tweak something, see what happens,
tweak it again. QBD is like, okay, let's be more
predictive, more in control. And for our listeners,
you know, who want to understand this complex
stuff, QBD really gives you that clear framework.
It's systematic. It's logical. It's like, here's
how quality is built into the medicine you take.
So if it's this like really systematic way of
doing things, then anticipating problems must
be a big part of it, right? Absolutely. You're
talking about risk management. Exactly. And it's
a core part of QBD. From day one, when you're
just designing the drug, all the way to when
it's being made in a factory, you're constantly
looking for anything that could go wrong. anything
that could affect the quality of the product.
So you're not just trying to dodge major disasters?
No, it's about consistency. Okay. Every single
dose, every pill, every vial needs to be safe
and effective. Right. By finding those potential
weak points early on, we can stop problems before
they even happen. It's a much smarter, safer
way to do things. Makes sense. Now we've been
hearing a lot about these things called CQAs.
Critical quality attributes. What exactly are
they? They sound super important. Oh, they are.
You can think of CQAs as the bridge between the
formula of a drug and how it actually affects
a patient. OK. So basically, there are specific
properties of the drug. It could be physical,
chemical, biological, or even microbiological.
And these properties have to stay within a certain
limit, a certain range, to guarantee that the
drug is good. It's high quality. So they're kind
of like the vital signs of the drug. Exactly.
If the CQAs aren't right, the drug's not healthy.
It's not going to work the way it should. And
how we figure out what these CQAs are is by looking
at how they might affect the safety of the medication
and also how well it works. It's efficacy. Exactly.
It's efficacy. So can you give me some real world
examples of these CQAs and drug formulation?
Well, our sources talk about you know, how a
drug dissolves. Dissolution, yeah. And its stability.
Those seem pretty critical, right? Absolutely
spot on. Now, our sources don't give a straight
up list of, you know, here are all the CQAs for
every formulation. OK. But we can kind of figure
it out. From all the stuff about ADME solubility,
you can start to connect the dots. So, like,
how fast the tablet dissolves in the body? The
dissolution rate, super important CQA. If a drug
doesn't dissolve right, it might not get absorbed
properly, so it won't work as well. Remember
that thing about IV, IVC? Oh, shoot. in vivo
correlation. Yeah, that's the one. It's all about
making sure what we see in the lab matches up
with what happens in a real person, and that's
definitely something we'd monitor as a CQA. So
we're always checking that those lab results
translate to real -life effectiveness. Exactly.
Now think about a drug that's a suspension. Okay.
Like a liquid with little particles floating
around the size of those particles. Yeah. Another
big CQA. Too big, too small, and you've got problems.
Problems like what? could affect how the product
behaves, how long it stays stable on the shelf,
even how easy it is to give to a patient, even
the pH, how acidic or basic a liquid formulation
is. That can be a CQA too, especially if it messes
with the drug's stability or how it gets absorbed.
So it sounds like we're really focusing on these
CQAs, keeping them in check, and that's how QBD
makes sure drug products are consistent. You
got it. by really understanding and controlling
the critical process parameters. The what now?
Oh sorry, the CPPs. CPPs. It's just all the specific
things we do during manufacturing, like how long
we mix something, the temperatures, all that
jazz. And of course the material attributes,
you know, making sure the ingredients themselves
are up to snuff. Gotcha. By controlling all those
things, we can get rid of a lot of the, you know,
unexpected variations in the final product. So...
Every batch of medication is basically identical
each dose a patient gets is consistent and that's
the aha Moment, right? Yeah, that's the science
behind reliable medicine and knowing all that
stuff being so precise Does that make the whole
development process? more efficient. Oh, absolutely.
When you've got a good grasp of your formulation
from the get -go, you know what you're aiming
for. Right. You can design everything so much
better. You're not wasting time with endless
experiments trying to figure things out by changing.
With no more happy accidents. Exactly. Plus,
when you use QBD, your manufacturing process
is just better. More robust, like you said. Yeah,
robust. You've already dealt with all the potential
problems, so there are fewer surprises, fewer
things going wrong, and that means fewer recalls,
which, let's be honest, nobody wants. Definitely
not. Okay, but we're talking about new drugs
here. So how does this all work with getting
approval from the FDA and all those regulations?
Well, this is where QBD really shines. Okay.
Because the FDA, they're actually big fans of
QBD. Really? Yeah. See, when you develop a drug
using QBD... you're showing them a really deep
understanding of the product and how it's made.
You're proving you know your stuff. Exactly.
You're not just saying, oh, trust us, it works.
You're giving them all the data, all the science.
And our sources, particularly those ICH guidelines,
they really highlight this global push towards
QDD. And ICH stands for? Oh, right. It's the
International Council for Harmonization of Technical
Requirements for Pharmaceuticals for Human Use.
A mouthful, but important. Very. They set the
standards. So basically, by using By using QBD,
companies are making better medicines and making
the FDA happy. It's a win -win. It makes the
whole approval process smoother. Way smoother.
Cool. So let's break it down. How are these QBD
principles used in the actual steps of making
a drug? Alright, let's start at the very beginning.
Design phase. You've got your idea for a new
drug. What now? You gotta figure out what to
put in it. Exactly. You gotta choose your active
ingredient, the API. But remember, we're focusing
on formulation. Right, right. So we're talking
about the inactive ingredients, the excipients,
all the other stuff that helps the drug work.
Okay. Now with QBD, you don't just pick whatever's
cheapest or easiest. It had to be piggy. Very
picky. You gotta think about how each ingredient
will affect those CQAs, you know, the critical
quality attributes we talked about. Right. Our
sources on evaluating drug candidates. They stress
how important it is to understand things like
how soluble the drug is, how stable it is, right
from the start. Yeah, that's in the early stages.
Exactly. That's going to determine a lot. Like,
will it be a pill, a capsule, a liquid? What
excipients do you need to make sure it gets to
where it needs to go in the body? And stays good?
Doesn't break down. Exactly. So QBD, it's like
having a super smart guide helping you make the
best decisions right from the start. Sounds pretty
helpful. But what about later on, like when you're
actually making the drug on a big scale? Manufacturing
optimization. That's where QBD gets really hands
-on. It's all about designing the process so
you can crank out those drugs consistently and
make sure they always meet your CQAs. And how
do you do that? By knowing your process inside
and out. You've got to figure out which things
are critical. Critical like? Like, how fast are
you mixing things? What temperature are things
drying at? OK, those specific parameters. Yeah,
those parameters. And you've got to understand
how each one affects those CQAs. Like, our material
on oral drug delivery, it talks about how QBD
can even let you shift those quality checks to
earlier stages. So instead of just checking at
the very end. Right. You can check the raw materials,
you can check during the process, and you know
that if those checks are good, the final product
is going to be good. Because you've controlled
everything from the beginning. Exactly. It's
like a chain reaction of quality. Speaking of
chains, our notes... mentioned looking at real
-world cases from those OPRND sources. Oh, yeah.
But we said they mostly focus on the API, right?
The active ingredient, not the formulation. Right.
But here's the thing. Even though OPRND might
be talking about making the API those QBD principles,
they're everywhere. Because the quality of the
API, it directly affects the quality of the final
formulation. So like, if an article talks about
some new way to make the API with super consistent
particles, even though they're focused on making
the API better, that consistency is huge for
formulation, too. Exactly. Because those particles,
they affect how the API flows, how it mixes with
the excipients. It can even change how fast it
dissolves, which is, remember, a key CQA. Right,
right. So even though those OPRND articles might
be about API, they're full of insights that apply
to formulation, too. Because everything's connected.
Exactly. The whole process, from API to final
drug, it all has to work together. And QBD helps
make sure it does. So to sum it all up, we've
seen how QBD, this whole idea of a systematic
scientific approach, it's changing how drugs
are made. Big time. It's all about understanding
risks. identifying those CQAs and controlling
everything. And that leads to better medicines.
Medicines that are more consistent because you're
not leaving things to chance. And more efficient
to develop because you're not wasting time with
trial and error. And the FDA loves it. Which
makes everyone happy. Absolutely. And we've seen
how QPD is used in every step of the way. from
picking the right ingredients to fine -tuning
the manufacturing process. It's a total game
-changer. So to all our listeners out there,
think about the journey a drug takes from a scientist's
idea to a medicine that helps someone. QBD isn't
just some boring rule. No way. It's about making
sure that journey leads to the best possible
outcome for everyone. Safer, more effective medicines.
It's pretty amazing when you think about it.
It really makes you wonder, like, what other
industries out there, you know, industries that
are super important, could benefit from using
this kind of approach? Food, energy, transportation.
I mean, who wouldn't want things to be safer
and more efficient? It's a big question worth
pondering. And on that note, thanks for joining
us for this deep dive. Thanks for listening,
everyone.