33 – The Role of GMP Audits in Ensuring Compliance (S18E1)

You ever think about like all the stuff we just
kind of assume is going to be safe? Like you
grab a bottle of vitamins. You don't even think
twice about whether what's on the label is actually
in that or if that pill to stop your headache
is actually going to do the trick. It's so true.
We put a lot of faith in the products we use
every day, especially when it comes to our health,
like with medicines or supplements. Yeah, exactly.
And I think sometimes we forget about the huge
amount of work that goes on behind the scenes
to make sure that trust we have isn't misplaced
and a really key part of that system that guarantees
the quality of those products. medicines and
supplements you were talking about is something
called GMP audits. GMP audits. GMP stands for
good manufacturing practice and these audits
are super important in the pharmaceutical and
dietary supplement industries. Okay so today
we are going behind the scenes pulling back the
curtain on these GMP audits, these good manufacturing
practice audits. That's right. Consider this
your crash course, your deep dive into how these
audits work to make sure the products you use
are safe, and actually do what they say they're
going to do. All right, so we're talking about
GMP audits. We're talking about these practices
that are used to verify that these manufacturers
are following regulations like CGMP, so current
good manufacturing practice. Exactly. We're going
to be looking at how those regulations are actually
put into practice. And this is about ultimately
protecting the consumer, right? It's about giving
us a clear picture of how the safety and quality
of the products we use are protected. Absolutely.
That's the whole point. So to do this deep dive,
we've been looking at a bunch of different sources.
Yeah, we've been digging into some pretty heavy
stuff to really understand all the ins and outs
of GMP audits. Okay, like what? We've got excerpts
from the actual Code of Federal Regulations,
parts 110 and 111 to be exact, that spell out
all the legal requirements that manufacturers
have to follow. So straight from the source,
the official rules. Yep, and to get a more practical
perspective, we've also watched YouTube videos
from experts at the FDA and some industry pros.
Oh, that's cool, getting the inside scoop from
the people who are actually doing this work.
Yeah, it's been super helpful. And to round things
out, we've also incorporated some detailed handbooks
and analogies that really break down the specifics
of how audits are conducted. OK, so we've got
the laws, the expert opinions and the how to
guide. Sounds like we're well equipped for this
deep dive. I think so. So what exactly are we
setting out to do today? What's our mission?
Well, first off, we want to break down the different
kinds of GMP audits that exist because it's not
just one size fits all. Makes sense. Different
audits for different purposes. Exactly. And then
we'll look at how these audits are specifically
designed to uncover any weak spots in the manufacturing
process or the overall quality system. So kind
of like a detective searching for clues of where
things could go. Exactly. It's about finding
those potential problems before they become big
problems. Okay, makes sense. And what else are
we going to be exploring? Well, we'll also look
at how audits help companies continuously improve.
It's not just about catching mistakes. It's about
learning from them and getting better all the
time. OK, so that's like the positive side of
audits, using them as a tool for growth. Right.
And lastly, we'll dive into the crucial role
of documentation and follow up in the whole audit
process. Yeah, I imagine that's really important,
keeping track of everything and making sure any
problems that are found actually get fixed. You
got it. Documentation is key in this whole world.
OK, so let's get down to business. We keep hearing
about these internal audits. What exactly are
they? Internal audits are kind of like when a
company checks its own homework. They grade themselves.
In a way, yeah. They assess their own operations,
their own practices, and make sure everything
is lining up with those CGMP standards we were
talking about, current trick manufacturing practices.
Okay, so it's like an internal checkup to make
sure they're following the rules. That's a good
way to put it. And the important thing is that
it's proactive. They're doing this on their own,
regularly, not just waiting for an outside inspection.
So they're staying ahead of the game, finding
potential problems before someone else does.
Exactly. It's all about minimizing risk and ensuring
consistent quality. Okay, so let's say a company
is doing an internal audit. What are some of
the things they're going to be focusing on? Well,
one of the biggest things is sanitation. They're
going to be looking really closely at the facilities
themselves. Just like is the place clean? Well,
it goes beyond just basic cleanliness. They're
checking things like the water systems, making
absolutely sure there's no chance of contamination.
Like what kind of contamination? Think backflow
prevention or cross -contamination between wastewater
and clean water lines. All that stuff's laid
out in 21 CFR Part 110. It's super important
to prevent any kind of contamination from the
get -go. Yeah, you don't want something like
a plumbing issue to mess up a whole batch of
medicine. Exactly. They'll also look at the sewage
disposal system and even the condition of the
restrooms to make sure everything is up to code.
Wow, so it's really a thorough look at the entire
facility. Yep, and then they'll move on to equipment.
Like the machines they use to make the product?
All the equipment, yeah. The manufacturing equipment,
the testing equipment, the packaging equipment.
Everything has to be in tip -top scape. So they're
just making sure it's all there, right? Not just
that it's there, but that it's properly maintained,
cleaned regularly, and calibrated correctly.
Calibrated? Yeah, so that the equipment is producing
accurate and consistent results. Okay, that makes
sense. If your tools aren't working right, your
product might not be right either. Exactly. And
there's a huge emphasis on documentation here.
The video by Devon Edwards and the EAS Consulting
Group video both talked about this. You got to
have detailed log books to keep track of all
the maintenance, cleaning, and calibration. So
you can prove that everything was done correctly.
Proof is key. And EAS Consulting Group pointed
out that even moving a piece of equipment can
affect its qualified status. You mean like if
you move a machine to a different spot in the
factory? Yep. They have to re -verify that it's
still working properly in its new location. Wow.
So every little detail matters. Absolutely. You
have to think about every potential point where
something could go wrong and have a system in
place to prevent that. Okay. So we've talked
about sanitation, equipment. What else do these
internal audits cover? Well, of course they're
going to look at the actual manufacturing processes
themselves. Are they sticking to their standard
operating procedures? So are they following the
recipe, so to speak? Exactly. Those SOPs, those
standard operating procedures, are like the rulebook
for making the product. Everything from start
to finish manufacturing, testing, packaging,
even distribution, needs to be clearly documented
and consistently followed. No going rogue in
the factory. Right. If you don't have clear procedures
and everyone's doing their own thing, you're
just asking for trouble. Inconsistency can lead
to mistakes and potentially unsafe products.
And we're back to documentation again? Always.
Remember, if it isn't documented, it didn't happen.
We heard that over and over in our research,
including that season four transcript. Okay,
so documentation is crucial for showing that
everyone is following the SOPs. It is. It's the
proof that everything is being done according
to plan. Alright, what about the lab side of
things, where they test the product? Yeah, the
lab is super important. Internal audits will
definitely scrutinize the lab controls and testing
procedures. So they're checking to make sure
the lab is doing their job right. Exactly. They
need to be using scientifically sound methods,
methods that have been validated. The EAS Consulting
Group video talked about that, and so did Kim
Honba's book. So you got to make sure the tests
themselves are reliable. Absolutely. Otherwise,
the results are meaningless. It's like if your
measuring stick is broken, you can't really measure
anything accurately. That's a great analogy.
The tests have to be accurate in order to get
a true picture of the quality of the product.
OK, so they look at the facilities, the equipment,
the processes, the lab. What about the actual
materials, the stuff they use to make the product?
Oh, yeah, absolutely. Material handling and storage
are huge. They need to prevent any kind of contamination
there as well. So it's not just about keeping
the factory clean, but also how they store and
handle everything. The raw materials that come
in, the finished products that are ready to ship
out, everything needs to be stored properly to
protect it from contamination. It's kind of like
even if you have the best ingredients, if you
leave them out on the counter, they're going
to go bad. Exactly. And there are regulations
about this, too. Part 110 of the CFR specifically
talks about it. It's not just common sense. It's
the law. So it sounds like these internal audits
are really comprehensive. They cover pretty much
every aspect of the operation. What are the main
benefits for a company to do these internal audits?
Well, first off, they're going to uncover weaknesses
that the company might not even know about. It's
kind of like getting a second opinion, a fresh
set of eyes on your operations. So it's like
finding those blind spots, the things you might
miss if you're too close to it. Yep. And by finding
them early, they can prevent them from becoming
big problems later on. Like preventing a product
recall or something like that. Exactly. That's
a huge benefit. And second, it helps ensure that
their quality management system is actually working
as intended. It's one thing to have a plan on
paper, but it's another to make sure it's actually
being followed in practice. Right. Internal audits
help bridge that gap between theory and reality.
Okay, so that's kind of like checking that the
system itself is working. And what's the third
big benefit? Internal audits really foster a
culture of continuous improvement within the
company. So it's not just about passing the test.
It's about always striving to do better. Yes.
By identifying areas where they can improve,
companies can refine their processes, enhance
their quality, and ultimately produce even better
products. Okay, so it's like constantly raising
the bar. Exactly. It's about making good even
better. That's great. OK, so we've got the inside
perspective with internal audits. What about
when someone from outside the company comes in
to do an audit? What's the purpose of that? So
these are called external audits, and they're
typically conducted by regulatory bodies like
the FDA, by customers, or by third party organizations.
OK, so different groups with different motivations
for auditing a company. Right. But the main objective
is always the same. To assess the company's compliance
with the relevant regulations and standards.
It's an independent check to make sure everything's
on the up and up. So it's like having an impartial
judge come in and give their verdict. That's
a good way to put it. Let's talk specifically
about the FDA inspections. What exactly do those
involve? Well, the FDA's role is to monitor compliance
with regulations and to ensure the safety and
integrity of everything from the research data
into the finished products. So they're really
overseeing the entire process from the initial
research to the products that end up in our hands.
That's right. They're looking to make sure companies
are following all the rules and that those medicines
and supplements we rely on are actually safe
and effective. And what happens if they find
something during an inspection that's not quite
right? Well, that's when they issue a Form FDA
483. A 483? What's that? It's a formal notification
that the FDA gives to the company's management
at the end of an inspection. It basically lists
out any observations, any potential deviations
from the regulations that the investigator has
identified. So it's kind of like a warning, a
heads up that they've found some issues. It's
more like, hey, we noticed this and you need
to address it. And does that automatically mean
the company is in trouble? Not necessarily. The
important thing to remember here, and this was
emphasized in the FDA CITC Day 3 transcript,
is that these are observations, not automatic
violations. So it's not a guilty verdict right
away? No. The FDA will review the observations
more carefully before deciding if any further
action is necessary. OK. So the FDA points out
these potential issues. What does the company
do next? They have to respond to the 483 in writing,
usually within 15 business days. So they get
a chance to explain themselves. Right. It's their
opportunity to show that they understand the
observations and to outline how they're going
to fix them. The FDA takes their response into
consideration when making a final determination.
So it's like a back and forth process, not just
a one -way street. Exactly. The company gets
to have their say and the FDA considers that
before making any decisions. What happens if
the FDA isn't satisfied with the company's response
or if the issues are really serious? Well, in
more serious cases, the FDA might designate the
facility as OAI, which stands for Official Action
Indicated. Official action indicated. That sounds
pretty serious. It is. It means the FDA has serious
concerns about the facility's compliance with
CGMP, and they're likely to take further action.
Like what kind of action? They might do follow
-up inspections to make sure the companies actually
fix the problems or they might take more drastic
measures depending on the situation. Okay, so
OAI is definitely something companies want to
avoid. We also came across something called remote
regulatory assessments. What are those all about?
Yeah, those are getting more common now. It's
a way for the FDA to assess compliance without
actually having to physically visit the facility
every time. So, kind of like a virtual inspection.
In a way, yeah. They might request documents
electronically or have virtual meetings to evaluate
the company's practices. And this is something
new that the FDA is doing. Relatively new, and
it's becoming an increasingly important part
of their toolkit. Emily Jeba talked about this
in her presentation transcript. It could be mandatory,
where the FDA has the legal authority to demand
information remotely, or it could be voluntary,
where the company agrees to participate. So it
gives the FDA more flexibility in how they conduct
their oversight. Exactly. It's a way to be more
efficient and cover more ground. OK, so the FDA
has a few different ways of keeping tabs on things.
What about those customer or third party audits
we mentioned earlier? Why would those be done?
Well, those are often done when a company wants
to evaluate their suppliers or any contract manufacturers
they might be using. So it's like checking up
on the companies they're doing business with.
Right. It's about making sure that everyone in
their supply chain is meeting the required standards.
So if I'm a pharmaceutical company and I'm buying
raw materials from a supplier, I might want to
audit them to make sure they're following all
the right procedures. Exactly. And those audits
often use standardized checklists, sometimes
based on ISO standards or specific regulatory
requirements. So it's like having a common set
of criteria to evaluate against. Yeah, it provides
a consistent framework for assessing quality
and compliance across the board. Makes sense.
And that brings us specifically to supplier audits.
What's the main goal of those? Supplier audits
are all about ensuring the quality and reliability
of all the ingredients that go into a product.
Not just the raw materials, but everything. Everything,
yeah. Raw materials, packaging components, even
services that are outsourced, if it comes from
a supplier, it needs to be vetted. So it's like
a chain. You're only as strong as your weakest
link. Exactly. If you're using subpar materials
or relying on a supplier with poor practices,
it's going to affect the quality of your final
product. No matter how good your own manufacturing
process is. Right. You can't make a perfect product
from imperfect ingredients. So what do these
supplier audits typically focus on? What are
they looking at? They really delve into the supplier's
entire quality system, their processes, their
controls, their documentation. So it's like a
mini audit of the supplier themselves. Pretty
much. They're looking at how the supplier manages
their own incoming materials, how they test things,
their overall approach to quality management.
And this all ties back to that idea of ensuring
the quality of the final product, right? Absolutely.
Even tiny impurities in the raw materials, for
example, can have a big impact on the quality
of the final drug or supplement. We saw that
in the ICH Q11 Q &A's transcript. It's all connected.
So it's about managing risks and ensuring quality
every step of the way. That's the goal. Okay,
we've covered the different types of audits,
internal, external, and supplier. Now let's talk
about the audit process itself. What are some
of the common elements across all these different
audits? Well, one of the most important things
is that they all follow a systematic approach.
It's not just random checking, it's a structured
and planned evaluation. So there's a method to
the madness. Definitely. They use a very deliberate
methodology to make sure they're covering all
the bases and getting a complete picture of the
company's operations and compliance. OK. So it's
not just showing up and poking around. It's a
much more organized process. Exactly. And the
whole point of this systematic approach is to
uncover any weaknesses or vulnerabilities in
the processes. So they're looking for potential
problems. They're looking for anything that doesn't
meet the standards, anything that could compromise
the quality of the product. Okay, so they're
identifying problems, but it's not just about
finding problems, right? It's about fixing them
and preventing them from happening again. You
got it. And that's where CAPA comes in, corrective
and preventive actions. So it's not just about
pointing out what's wrong. It's about figuring
out why it's wrong and how to make it right.
Exactly. And it's a continuous process. You identify
an issue, you fix it, and then you put measures
in place to prevent it from happening again.
Okay, so audits are really driving this continuous
improvement cycle. They are a key driver, yeah.
They force companies to take a hard look at them.
and make changes for the better. Now we've talked
about the importance of documentation throughout
this deep dive. What role does documentation
play in the audit process itself? Documentation
is absolutely essential to the entire audit process.
It's the proof, the evidence, that everything
is being done correctly. So if it's not written
down, it didn't happen? Pretty much. You need
records of everything. Audit plans, schedules,
checklists, observations, findings. It all has
to be meticulously documented. And why is all
this documentation so important? Well, for one
thing, it provides a clear record of what was
audited, what was found, and what actions were
taken. It creates accountability. So it's like
a trail of breadcrumbs showing exactly what happened
during the audit. Exactly. And it's also important
for follow -up. You need to be able to track
the progress of any corrective actions and make
sure the problems are actually being addressed.
So the documentation doesn't end when the audit
is over? No, it continues as the company works
to implement those corrective actions and verify
that they've been effective. Okay, so documentation
is a key part of the whole process from start
to finish. And speaking of finishing, what happens
after the audit? What's the next crucial step?
The most important thing is the follow -up on
those corrective actions. It's not enough to
just identify the problems. You have to actually
fix them. It's kind of like going to the doctor,
getting a diagnosis, but then not taking the
medicine they prescribe. That's a good analogy.
The audit is like the diagnosis and the corrective
actions are the treatment. You've got to follow
through with the treatment to get better. OK,
so the company needs to actually implement those
changes, those fixes. Yes, and then they need
to verify that those changes have actually worked.
This is all about closing the loop and ensuring
that the issues don't come up again. So it's
not just about checking boxes. It's about actually
making things better. Exactly. Continuous improvement
is the goal. OK, so we've covered the different
types of GMP audits and the overall process.
Now let's tie it all together. What's the ultimate
purpose of all this? What role do these GMP audits
play in ensuring compliance within these industries.
At their heart, GMP audits are about verifying
compliance with CGMP standards. That's their
primary role. They're the mechanism for making
sure companies are following those good manufacturing
practices that we've been talking about. So it's
about checking that they're playing by the rules.
That's part of it. But it's more than just checking
boxes. They're looking to see if the company
truly understands the principles behind the regulations
and if they're applying those principles in a
meaningful way. That's about the spirit of the
law, not just the letter of the law. Exactly.
And they're also looking at the big picture,
evaluating the effectiveness of the entire quality
management system. Not just isolated processes,
but the whole system that's in place to ensure
quality. Right. They're asking, is this system
actually capable of consistently producing safe
and effective products? And they're also looking
ahead, trying to identify potential risks before
they become problems. Absolutely. That's the
proactive element of audits. They help companies
identify areas where they might be vulnerable
and implement controls to mitigate those risks.
So audits are really playing a crucial role in
ensuring the quality and safety of the products
we use. They are. And they're a big part of why
we can trust those products, why we can have
confidence that they'll do what they're supposed
to do. Okay, let's do a quick recap of what we've
learned about GMP audits. We started with internal
audits, those self -checks that companies do
to make sure they're on track. Right, those are
all about proactive identification of problems
and continuous improvement. Then we looked at
external audits, those independent assessments
conducted by the FDA, customers, or third -party
organizations. External audits provide that crucial
outside perspective, making sure companies are
meeting those broader regulatory requirements
and industry standards. And we also talked about
supplier audits, which specifically on ensuring
the quality and reliability of all the materials
and services that go into the manufacturing process.
Because the quality of the final product depends
on the quality of every ingredient and every
process along the way. And regardless of the
type of audit, they all share that systematic
approach designed to uncover any weaknesses and
drive those corrective and preventive actions
that lead to better products. And of course none
of it would be possible without meticulous documentation
and thorough follow -up to ensure those problems
are truly fixed. So it's a complex system with
a lot of moving parts, but ultimately it's all
about protecting the consumer. Absolutely. It's
about ensuring that the medicines and supplements
we use are safe, effective, and meet the highest
quality standards. It really makes you appreciate
the work that goes into making sure the products
we use every day are reliable. It does. And it
makes you think, what other unseen processes
are out there working behind the scenes to keep
us safe and healthy? That's a great question.
It's like a whole hidden world that most of us
never even think about. Exactly. And it's a testament
to the importance of regulations, of good manufacturing
practices, and of those dedicated professionals
who are constantly working to ensure the quality
of the products we depend on. Well said.