55 - What are cGCPs? Foundations and Ethical Principles (S22E1)

Okay, so we all want to feel confident, you know,
in the medications that we use, that they're
safe. Absolutely. And that they're really truly
effective. Right. But have you ever really stopped
to think about, like, all of the work that goes
on behind the scenes to make that possible? Yeah.
To be able to trust those medications? A hundred
percent. Like all of the systems and the regulations?
Yeah. And one of the most important sets of those
standards is current good clinical practices.
Yeah, we call those CGCPs for short. Or CGCPs.
You'll hear us say that a lot. Yeah, you'll hear
us say that a lot. So we're taking a deep dive
into that. Yeah, it's a big one. Into that world
today. Absolutely. So this is really not just
about like... dry rules, regulations. This is
really about the foundation of how we actually
conduct clinical trials and how we test these
new treatments. So we're going to unpack these
core principles of CGCPs and we'll highlight
their really vital role in protecting the people
who volunteer to participate in research. And
also at the same time, making sure that the data
we get from those trials is reliable and robust.
And to do that, We've got kind of a wealth of
information in front of us here. We do. We're
looking at a transcript that's specifically dedicated
to the foundations and the ethical principles
of CGCPs. Very important. We've also got excerpts
from the Code of Federal Regulations. That's
the CFR. And for those of you who are unfamiliar
with the CFR, that's basically like... the rule
book of the federal government. For the US government.
From the US government. That's right. It's where
all the rules and regulations are published.
Exactly. And these cover everything from how
you manage electronic records to the standards
that we use for manufacturing. Yes. And actually
conducting clinical trials. It's all in there.
It's all in there. Yeah. And we've also got some
things from like... books on GMP, good manufacturing
practices. Very important. Quality systems. Yeah.
We've got the ICH guidelines. The internationalists.
The international guidelines. Yeah, so these
are guidelines that countries around the world
use to harmonize drug development. It's really
important for global trade and safety. Yeah,
and then we've got... transcripts from YouTube
videos that kind of break down GMP clinical trials,
FDA regulations. Nice, so we can get the perspective
of people explaining these things. Exactly. That's
really helpful. And then we've even got a report
that analyzes findings from FDA inspections.
That's a good one. Which are known as Form 483
observations. Yeah, those are the things that
the FDA finds when they do an inspection. And
if you have 483 observations, That means you're
in trouble. You're in trouble, potentially. So
we're going to look at all those to understand
CGCPs better. Yeah. So our mission here is pretty
straightforward. Yeah, what is it? We want to
give you a clear understanding of what CGCPs
are all about. Yep. We're going to explain why
they're so important. To everybody. Yeah, to
everybody. And explore these really fundamental
ethical and procedural elements that make them
up. the core of it. Yeah, so let's just start
with the basics. What are CGCPs? So basically,
CGCPs are these internationally recognized standards.
They're ethical and scientific quality standards
that govern how clinical trials are designed,
how they're conducted, how they're recorded,
and how they're reported. Okay, so it's like...
It's the whole thing. It's like the rule book.
It is the rule book. For running a clinical trial.
It's the rule book for anyone involved in testing
new medical treatments in humans. Okay. That's
what it is. So it's not just like a good idea.
No. It's the standard. It's the standard. That
everyone's expected to follow. Exactly. Okay,
so why do we have this? Good question. Like what's
the purpose? So CGCPs serve to really critical
purposes. First and foremost, they're there to
protect people, the people who participate in
the trials, their safety, their well -being,
and their rights. That's the main ethical commitment.
But equally important is the role that they play
in ensuring the quality of the data that comes
out of the trials. Because if we can't trust
the data, we can't trust any of the conclusions
that are made. about whether a treatment's safe
and effective. That makes sense. Right. So it's
all about protecting the participants and making
sure that the science is sound and trustworthy.
Yeah. OK, so we've talked about the GMP regulations
before. Yes, we have. And I feel like that's
probably a good place to start. That's a good
connection. With kind of putting this into a
bigger picture. How did we get here? So GMPs
are all about the quality of drug manufacturing,
making sure that the drugs are made correctly.
But CGCPs are about making sure that the drugs
are actually safe and effective and that we're
testing them in the right way. So the history
of GMPs can really help us understand how we
got to this point where we care so much about
ethics and research. So we've talked about the
thalidomide disaster. back in the 1960s, where
this drug was given to pregnant women. And it
caused really severe birth defects in their children.
Yeah, it was really tragic. It was a huge tragedy.
And it really highlighted that just making sure
that the medicines were manufactured correctly
wasn't enough. We needed to actually make sure
that they were safe and effective. Before you
give them to people. Exactly, before you give
them to people. Especially vulnerable populations
like pregnant women. So this tragedy was a major
driving force behind developing stricter regulations
that focused on patient safety and data integrity.
So GMP ensures that medicine is well made. Right.
CGCP ensures that we prove it actually works.
In humans. In humans. Yeah. And that it's safe.
Ethically and scientifically. OK. So that's a
really good distinction. Yeah, it's a big one.
And it's a good reminder that these aren't just
You know, bureaucratic hoops to jump through.
These regulations exist for a reason. They exist
because of very real and serious consequences
that have happened in the past when we haven't
had these regulations in place. Yeah, and when
we haven't followed them. Exactly. So it's not
just a checklist. No, not a checklist. No, it's
more than that. It's more about like a commitment
to quality and ethics. It's a commitment to...
building quality and ethical considerations into
every single stage of the research process. Yeah,
that's throughout the entire process. From the
beginning, from the design of the study all the
way through to the reporting of the results.
Yeah, okay, so then What are the core ethical
principles that underpin CGCPs? So there are
a few really key ethical principles that guide
all clinical research. And these are things like
respect for persons, beneficence, and justice.
OK, so let's talk about those. Let's bring those
down. A little more. What does respect for persons
actually mean? So respect for persons means that
we recognize the autonomy of individuals and
their right to make their own decisions about
whether or not they want to participate in research
and we also have to protect those. who have diminished
autonomy. Okay, so like people who can't. Yeah,
like children. Yeah. Or people with cognitive
impairments. Right. They might not be able to
make those decisions for themselves. You have
to protect them. Okay. And this principle is
really embodied in the idea of informed consent.
Informed consent. That's a big one. Yeah, it's
a term we hear all the time. It is. When we're
talking about it. All the time. Medical research.
So what is that? Why is that so important? Informed
consent is basically the process of giving potential
participants, all of the essential information
about a clinical trial. So this includes things
like what's the purpose of the trial? What are
the procedures involved? What are the potential
risks and benefits? And what other treatments
might be available? And this information has
to be presented in a way. that the potential
participant can understand. So it has to be in
their language. It has to be at their level of
understanding. And their decision to participate
has to be completely voluntary. They have to
be told that they can withdraw from the study
at any time without penalty. So it's not just
a one -time signature on a form. It's an ongoing
process. It's ongoing. And that's really important.
So it's about really making sure that people
can make informed decisions about their health.
It is about empowering individuals to make choices
about their own health and whether or not they
want to be part of research. Okay, so we've talked
about the participants. What about the actual
design of the study? Yeah, that's a good point.
How does that impact the ethical conduct and
the quality of the data? A well -designed protocol
is super important, not just for the ethics,
but also for the data. So, if the protocol is
not well -designed, it can expose participants
to unnecessary risks. And even if it doesn't
harm them, it can lead to data that's unreliable.
Right, or unusable. Exactly. So then what makes
a protocol well designed? Well, there are a few
key elements that are really important. So first,
you need to have clearly defined objectives and
research questions. Like, what are we trying
to learn? From this study, you need to know that
upfront. Then you need to have criteria for who
can participate in the study. These are called
inclusion and exclusion criteria. And these criteria
have to be scientifically sound, but they also
have to be fair. We need to make sure that the
burdens and benefits of research are distributed
equitably. across different populations. So that's
the ethical principle of justice. Making sure
that everyone has a fair chance to participate.
And then the protocol needs to provide a very
detailed description of all the study procedures.
So that's things like, what are the interventions?
What are the doses? What's the schedule of visits
and treatments? What assessments are we doing?
All of that stuff. needs to be laid out in detail.
And then it needs to include a plan for safety
monitoring. How are we going to identify adverse
events? How are we going to document them? How
are we going to report them? And then finally,
you need to have a plan for the statistics. How
big is the sample size going to be? How are we
going to analyze the data? All of that. So you
need to consider all that before you even start
the trial. Exactly. And if there are flaws, In
the protocol. Yeah, like if the safety monitoring
is not adequate. Yeah, or if there aren't enough
participants Yeah, then it raises ethical concerns
right because you might be putting people at
risk, right? But it also undermines the science.
Yeah, because the data might not be reliable
Okay, so it's both ethical and scientific. It's
both. Yeah, it's all connected. Well, okay So
let's move on to the data itself. Okay How do
CGCPs make sure that the data that we collect
during a trial is high quality. Right. So CGCPs
really emphasize the importance of data quality
and data integrity throughout the whole clinical
trial. So every aspect of how you handle that
data from the very beginning, when you collect
it, to how you analyze it and how you store it.
Has to be done with a lot of attention to detail
right to make sure the findings are trustworthy
Okay, so it's more involved than just like wait
more writing some numbers down Yeah, it's not
just about recording numbers on a piece of paper
or in a spreadsheet No, it's about making sure
that the data is accurate. Yeah, and that it's
reliable Okay, and one of the key things is documentation,
right? So we've talked about good documentation
practices before GDP. Yes. Yeah, right and those
principles apply here as well. Okay So all records
have to be legible. Okay. They have to be contemporaneous.
Yeah. Meaning you have to write them down. Yeah.
At the time that the event happens. Right. They
have to be accurate. Yeah. They have to be original
and they have to be attributable. Meaning you
know who did it. Exactly. Okay. And what about
all the electronic data? Oh yeah. That's a big
one these days. Yeah because I mean that's. Most
data is electronic. Most data is electronic now.
Yeah. So how do CGCPs address that. So the CFR
has a whole section on electronic records and
electronic signatures. It's 21 CFR part 11. And
these regulations are there to make sure that
the data is authentic, that it's reliable, that
it's confidential. So you have to have things
like unique electronic signatures, audit trails,
so you can track any changes to the records,
and you have to validate the computer systems
to make sure that they're working properly. So
it's a whole other layer of complexity. But the
underlying principles are the same. Accuracy,
reliability, trustworthiness. That's the key.
What about lab testing? Oh, yeah. That's a big
one. Yeah, because that's where we're getting
a lot of the data about how the drug is working
in the body. So the integrity of lab testing
is super important because it provides key data
that supports the safety and efficacy of the
investigational product. So here's where GMP
comes in again. Even though GMP is focused on
manufacturing, a lot of those principles apply
to lab testing as well. So things like having
controlled processes and robust quality systems.
and using risk management. All of those things
underpin the quality of the lab work. OK, and
then specifically, what kinds of things are we
looking for? So you need to have really good
quality control procedures in the lab. So that
means things like using check standards to make
sure that your instruments are calibrated correctly,
running blank samples, to make sure there's no
contamination, establishing detection and quantitation
limits so you know how much of the drug you can
actually detect. and then having data review
processes where multiple people look at the data
to make sure it's accurate. So it's all about
making sure that the lab testing is reliable
and accurate. So it's a very interconnected system
where all these different regulations and guidelines
are working together. To ensure quality. But
every step. All of this stuff, it's not just
a Good idea. Right. It's a requirement. It is
a regulatory requirement. Right. So if you're
doing... It's a law. Yeah. If you're doing a
clinical trial... Yeah. You have to follow these
rules. You have to follow the rules. Right. If
you want your data to be accepted... Right. By
the FDA. By the regulatory authorities? Exactly.
Yeah. Okay. So it's not something to mess around
with. Right. You know. And what happens if you
don't? Bad things. Yeah. What are the consequences?
So the FDA does inspections... Right. to check
up on people and make sure they're following
the rules. And if they find that you're not,
there could be some pretty serious consequences.
Like what? Well, they can shut down your trial.
Oh, wow. They could reject your data. Yeah. They
could delay your drug approval. Yeah. And they
could even take other regulatory actions. Like
fines. Yeah, fines, warning letters, all sorts
of stuff. OK. So it's not something you want
to mess with. It's not something to take lightly.
No. Yeah. So understanding CGCPs really gives
you a good look into how medicines are developed.
Exactly. And all the work and the ethical considerations.
Yeah, that's a lot of work. that go into that.
And it's all for good reason. Yeah. Right. So
whether you're like preparing for a meeting or
just trying to get up to speed. Or just curious.
In a certain area or just curious how it all
works. Right. Knowing these principles really
helps you appreciate how complex it all is. It's
very complex. Yeah. And all the safeguards that
are in place. To protect everybody. All about
protecting people. Yeah. OK. So. Just to recap,
CGCPs are a set of international regulations
based on ethical principles and they emphasize
protecting the participants in clinical trials
and ensuring the quality and the integrity of
the data that's collected. It's all about the
data. This is achieved through a lot of hard
work. Yeah. Designing the study protocol. Yes.
Very carefully and ethically. It's sticking to
the standards. And then following the standards
throughout the whole process. From beginning
to end. Yeah. It's a long process. OK. So basically,
every medical breakthrough that we've ever seen
has been built on this foundation. It all relies
on CGCPs. Of CGCPs. Yeah. It's the framework
for advancing health care responsibly. Wow. Yeah.
So if you're interested in learning more about
CGCPs, there is a lot of information out there.
And I would encourage you to look into the CFR
and the ICH guidelines. Those are great resources.
Yeah, there's a lot of detail there. There is.
And it can be a little bit overwhelming. But
it's worth it. What it's worth it. If you want
to really understand this stuff. If you really
want to understand it. Yeah. Okay. Well, thank
you for joining us. Thank you for having me.
On this deep dive. It's been a pleasure. Into
CGCP. I hope you learned something.