36 – Audit Findings and Corrective and Preventive Actions (CAPA) (S18E4)

Okay, so you've been sending in, you've sent
us a bunch of materials about audits and all
this stuff about quality and it really makes
you think about all the work that goes on behind
the scenes. All this work that we never even
think about to make sure that the products we
use every day actually meet the standards. So
today I thought it'd be really cool to sort of
zero in on what happens after an audit. You know,
like, what are those, like, essential next steps?
Yeah. And specifically, we're going to talk about
how organizations look at the audit findings
and then put those corrective and preventative
actions into place. Or, you know, CAPRA, as we
all know and love it, it's like detective work,
but for quality assurance. Exactly. You've given
us... You've given us so much information, like
a huge amount from all those regulations, like
21 CFR parts, 110 and 111 to practical guides
on GMPs. And I think what we really want to do
in this deep dive is uncover those core principles,
right? How do companies actually analyze those
audit results? And then how do they implement
an effective CAPA? I mean, I think we want to
shed light on the whole process, you know, how
they... they figure out what the problems are,
why those problems happen in the first place,
and then, most importantly, how they make sure
that those problems don't ever happen again.
Right, right. And we don't want to get too bobbed
down in all the regulatory jargon. No, no, absolutely
not. Okay, so let's start unpacking all of this,
right? We hear about audits all the time, but
why are they like... the cornerstone of ensuring
quality. What makes them so important? It sounds
like a really intense process. Yeah, well, I
think you can really think of audits, whether
they're internal reviews or inspections by the
big regulatory bodies, as vital checkups. That's
what they are. They're these checkups to make
sure that an organization is really following
the established standards and regulations. And
this is something we see, this recurring theme
that pops up in the sources, particularly when
we're talking about CGMP. Yeah, the CGMPs. And,
you know, these aren't just random rules that
someone come up with. They're in place to make
sure that especially those critical products
like pharmaceuticals and food, that those products,
they reliably meet all the expectations for safety,
efficacy, quality. everything, right? You just
have to. So, you know, I'm picturing like these
inspectors showing up at a facility, right? What
are they actually looking for? It can't just
be like a general, like, you know, look around,
can it? No, no, no, not at all. And like some
of the GMP training materials highlight. inspectors
are really focused. They have specific checkpoints.
Right. Right. And they are looking at adherence
to best practices. And this is for the entire
manufacturing journey. I mean, we're talking
everything from the very basic design and how
clean a facility is, which, of course, ties back
into regulations like 21 CFR, Part 211, Subpart
C, which that outlines requirements for the physical
plant, the grounds, all that, to make sure that
contamination doesn't happen. to the maintenance
and calibration of equipment, which we see emphasized
in 21 CFR part 111 and tons of other guidelines.
They're essentially verifying that all those
documented procedures intended to guarantee product
quality are actually being followed in practice.
Okay, so let's say they're going through, they're
doing their thing, they spot something that isn't
quite right, it's not quite up to par. That's
where these findings come into play. Precisely.
I imagine, right? But after an audit, any observation
where you know, there might be a deviation from
regulations, or maybe the organization's own
established procedures, those get documented
as findings. And it's really important to remember
that a finding isn't a declaration of, oh my
gosh, you violated something. It's really, I
think it's really best understood as the... auditor's
professional observation. Just saying, hey, this
thing might not actually be meeting the required
standards. This needs a little bit closer attention.
We saw in the annual GMP training 2022 materials,
they also mentioned how not following procedures
can lead to those deviations that require follow
up. Right. Right. That makes sense. So a finding
is like a signal. Right? Saying, hey, this needs
a closer look. Exactly. What's that next step?
Like how did these organizations make sense of
all these findings once they have them? Yeah.
So that's where the analysis begins. So, you
know, once those audit findings are documented,
the organization has to take a really close look
at each and every one of them. And the main goal
here, the primary goal is to really understand
what does this finding actually mean? And then
how could this impact the product quality? How
could it affect our compliance with the regulations?
And we didn't really see a rigid categorization
system, but we can kind of infer that they're
going to relate to the different aspects that
GMPs cover. Right. So let's break that down a
little bit. What are those areas that these findings
might touch on? So thinking about the scope of
GMPs, you know, we've got the physical facility,
we've talked about the design, then there's,
you know, equipment, a huge, huge part. Our instruments
calibrated, maintained, like we saw in 21 CFR
Part 111. And then, of course, there's documentation,
which, I mean... Everyone's heard this, right?
If it wasn't documented, it wasn't done. Which
we heard in the annual GMP refresher training
2022, findings oftentimes highlight those gaps
or inconsistencies in record keeping. And then
we've got things that you might not even think
about right away, like pest control, which we
saw mentioned in 21 CFR part 110. So if pest
control isn't managed properly, that can lead
to findings as well. Really, the key takeaway
here is that Each finding needs to be super carefully
examined to determine what exactly went wrong
and why it matters. And the FDA clinical investigator
training course materials you shared, they really
emphasize the importance of taking the time to
do this detailed review. OK. So we've had our
audit. We've got our findings, which are kind
of like clues, right? Yeah. And now we get to
CAPA. So what exactly is CAPA? And how does it
address all these clues? So CAPA stands for for
collective and preventive action. Right. And
it's this process that organizations use to address
those audit findings that we've been discussing.
Right. But more importantly, it's to stop those
problems from happening again in the future.
It's not just about putting on a band -aid. It's
about saying, OK, what is the fundamental reason
behind this problem? Right. And how do you build
better systems? Yeah. Yeah. OK. So systematic
process, that sounds kind of, you know, Official
can we break that down a little bit like what
are the steps that are typically involved in
a kappa process? Absolutely. So the first step
and it's the most important step is root cause
analysis. Okay, and this is where we dig deep
We want to understand why something happened.
You can't just treat the symptoms, right? You've
got to figure out the underlying cause right
and you know the observations, decisions, and
actions in current good manufacturing practices
material and also in FDA regulatory affairs by
Pisano. They both highlight this, you know, effective
solutions. They hinge on understanding that.
why, sometimes what looks like the obvious cause,
it's really just a symptom of something deeper.
Oh wow, that's interesting. So once you figure
out that why, then what? I mean that's where
the corrective action part of CAPO kicks in.
Right, so corrective actions are those immediate
steps that you take to fix the problem that was
found during the audit. Right, right. You know,
these are about putting things right now. Okay.
So for instance, you know, an audit... uncovers
a documentation error. The corrective action
is to go back, you correct that error, you make
sure the record is accurate. We saw that in the
Tales Lunch and Learn. Or, you know, what if
a piece of equipment was found to be outside
of its calibration limits? Right. The corrective
action is to recalibrate it. That's right in
line with 21 CFR Part 111. Right. And, you know,
verification in that case would be making sure,
you know, after you recalibrate it, you go back,
you check those calibration records, you know,
make sure that it's within the acceptable range
now. It's kind of like, you know, you repair
a flat tire. You want to make sure that it holds
air. Yeah. Yeah, that totally makes sense. Address
that immediate issue. But CAPA also has preventive
action in the name. So how is that different
than just fixing what's broken? Right, so preventive
actions, those are the ones that are looking
ahead. They're proactive, they're designed to
stop that issue from happening again. Not just
in the specific instance that you found it, but
in other places too, right? That's right. And
that's where continuous improvement comes into
play. And that's something that we see in ICH
Q914. Right. and Pasano's FDA regulatory affairs.
It's all about learning from those past experiences
and then changing the systems or maybe the procedures
to avoid it happening again. You know, validation
in this case would be like you repair the tire,
you'd bring the car for a week. Right. You want
to make sure the problem doesn't come back. Yeah,
that makes sense. Could you give me like a concrete
example, you know, like a preventive action that
might come after a corrective action? Sure. So
let's say an audit uncovers a bunch of incomplete
batch records. OK. So the corrective action,
you'd go back and complete all those records.
But a preventive action might be to update the
training program for the staff on how to accurately
fill out batch records, or maybe you implement
a checklist, or even like a digital system with
prompts that guide users and make sure that all
the necessary information is recorded correctly
every time. That's really smart. The goal here
is to address the systemic weakness in the process.
That led to the errors in the first place, not
just to fix those individual errors. Okay, so
we've identified the root cause, we took corrective
action to fix the immediate problem, and we put
in place preventive measures so it doesn't happen
again. What are those like last steps in the
whole capital process to make sure it's all effective?
Yeah, so implementing those actions and documenting
everything is key. Okay. All the analysis that
you did, the actions you decided on, who's responsible,
timelines, you've got to document all of that.
Right. I mean, remember we talked about this,
you know, in the annual GMP refresher training.
The key principle in GMP, if it wasn't documented,
it wasn't done. This documentation is like a
record of the entire CAPA process. And you know,
subpart J of 21 CFR, part 211, they emphasize
this too. Keep detailed records of all those
corruptive and preventative actions. And it's
not just about checking a box for compliance.
It's also super helpful for trend analysis. You
know, you can figure out if there are recurring
systemic issues and you can like share that knowledge
within the organization. You've got to show your
work. But it sounds like it's more than just
showing off, right? So what comes after you've
implemented the actions and documented everything?
How do you know if they've actually been successful?
Right, and that's where verification and sometimes
validation come in. So verification is about
making sure that the corrective action actually
solved the problem. So if a piece of equipment
was recalibrated, you go back and look at those
calibration records. You might do some tests
to confirm that the equipment is working within
the specifications now. goes a little bit further.
It's about showing that the preventive action
works consistently over time, even under different
conditions. So that might involve really closely
monitoring the process after you implement the
preventive action, and collecting data to show
that it's effective. And Blassner's establishing
a CGMP laboratory audit system and derivatives
the certified pharmaceutical GMP professional
handbook. They provide a ton of insight on these
follow -up steps. It's not just about reacting
to problems. It's a whole cycle of identifying,
analyzing, fixing, preventing, and then making
sure those actions are actually working. Exactly.
And having a strong CAPA system, I mean, it's
so important. And it's not just about looking
at audit findings like they're isolated incidents.
It's about continuous improvement, which we saw
in ICH Q914 and a bunch of the other sources.
When you get to the root causes of issues and
then you prevent them from happening again, CAPA
directly enhances product quality. Wow. Think
of it as this learning process. system, right,
where problems become opportunities to get better.
Yeah, yeah, I like that. And it's also super
important for, you know, keeping those regulatory
agencies happy, right? Absolutely. A strong CAPA
system, it's not just a good thing to have, it's
essential for staying compliant with the regulations,
you know, like CGMPs. And we talked about the
goal of GMPs at the beginning, it's to make sure
that products are consistently safe, effective,
and high quality. Right, right. A good CAPA system
shows those regulatory bodies that the organization
is serious about quality management. Yeah. That
they have these mechanisms in place to not only
fix problems, but also prevent them from happening
in the first place. So it's not just a separate
thing, it's part of a bigger... Exactly. CAPA
is a key part of the quality management system,
you know, the QMS. Right, the QMS. That's all
the policies, SOPs, processes, everything that
an organization uses to make sure that products
are consistently high quality. And, you know,
like the annual GMP training 2022 materials mentioned,
the QMS is the framework and CAPA is the ender.
Wow, I like that. Okay, so this has been a really
insightful deep dive into analyzing audit findings
and implementing CAPA. So before we wrap up,
let's recap those key takeaways for our listeners.
Sure, so we talked about how audit findings,
even though they might seem negative at first,
are actually super valuable opportunities for
improvement. Right. And the most important thing
to do after any audit is to analyze each finding.
Right. You know, figure out what it means and
how it could impact the product. Right. Root
cause analysis is essential. Yeah. You can't
find good solutions until you know why the problem
happened. Right. CAPIT itself includes both corrective
actions, which fix the immediate problem, and
preventive actions, which stop. it from happening
again. And documentation, so important. Got to
document everything. And a strong campus system,
it's not just about reacting to mistakes, it's
about continuous improvement. It helps improve
product quality and make sure you're compliant
with those essential regulations like CGMPs.
Yeah, so for our listener, you know, you've gotten
this look behind the scenes into how we ensure
the quality of so many products that you use
every day. And it's more than just checking boxes,
it's about making things better. Exactly, and
here's something to think about. Okay. We've
been talking about, you know, highly regulated
industries like pharmaceuticals, food, but think
about those principles. Okay. Identifying issue,
understanding the root causes, you know, implementing
those corrective and preventive actions. Yeah.
Could you apply those in other areas? Oh, interesting.
You know, maybe in your own work. Right, yeah.
I mean, having a structured approach to solving
problems, that's valuable in any field. Yeah,
yeah, I totally agree. It's about progress and
quality. Awesome. Well, thanks so much for taking
this deep dive with us today. Yeah, thank you.
Until next time, keep those sources coming. We're
excited to see what we uncover together. Yeah,
definitely.