25 - Laboratory Notebooks and Data Recording (S16E5)

Welcome back everyone for another deep dive.
Today we're going to get into something that
is super important. But it might not seem like
the most exciting topic at first glance. It might
seem more back office than frontline science,
but it's really, really important. And that is
how to keep good records, especially lab notebooks
and analytical data and how all that fits into
the big picture of GMP. Yeah, you got it. If
you care about the quality and the safety of
the things that you're using, especially if you're
someone who works in a field like pharmaceuticals
or dietary supplements or any other field that's
really heavily regulated. You know the GMP is
a huge deal and and keeping really good records
according to those GMP regulations is like it's
the foundation of trust It's how we build trust
in in the products and in each other. That's
a great point I mean when you pick up that bottle
of pills from the pharmacy or a you know a vitamin
or a supplement from the store there's this trust
there, right? You're trusting that what's in
that bottle is exactly what it says it is, and
that it's safe. And all of these processes that
we're gonna talk about today are what make that
trust possible. It's how we go from a bunch of
ingredients to a final product that you can rely
on. Absolutely. So today we're gonna unpack some
of the best practices for doing that, from how
do you record information correctly in the first
place, all the way to... How is that information
stored securely so that it's accurate, it's available
when you need it? And we really want to get across
why each of these steps is so important for data
integrity, which is a fancy way of saying, making
sure that the data is good, basically, reliable,
and trustworthy. Making sure that the information
that you're basing decisions on is the real deal,
the whole truth. and nothing but the truth. Exactly.
So to do this deep dive, we've pulled together
a bunch of different sources. And I think this
will give us a really well -rounded view of this
whole topic. We've got some excerpts from the
Code of Federal Regulations, the CFR. which is
the legal framework for a lot of this stuff.
We've got some industry guidelines from groups
like the International Council for Harmonization,
the ICH, which gives us some best practice recommendations
from experts in the field. And we've also got
some great insights from GMP experts that we
found in YouTube transcripts and books on GMP
and quality auditing. So I think with all of
these different perspectives, we can really get
a good understanding of how to do this right.
Yeah. I think so, too. OK, so let's start with
one of the most fundamental principles in all
of this, and that's contemporaneous recording.
Now that might sound a little bit jargony and
technical, but the idea behind it is actually
pretty simple. And it's really crucial for data
integrity. I think what's so interesting about
contemporaneous recording is that it's both super
simple and super important at the same time.
Basically, it just means that you document things
as they happen right. No waiting, no relying
on your memory later. If something happens at
1045 in the morning, you write it down at 1045
in the morning. Right. You don't go back at the
end of the day and try to remember everything
that happened. Exactly. And this isn't just about
checking boxes for the regulators. It's really
about making sure that the data is as accurate
as possible. Our memories, they're not perfect.
We forget things. We mix things up. Details get
fuzzy over time. But when you document things
in real time, you create this really accurate
time -stamped record of exactly what happened.
It's like taking a snapshot of the moment. And
that real -time documentation really reduces
the chance of errors creaking in. Absolutely,
and the regulations are very clear about this.
Yeah, I remember in one of the YouTube transcripts
we were looking at there was a specific mention
of 21 CFR Part 111, which I think is the part
that covers GMP for dietary supplements. And
they were really emphasizing documenting lab
activities permanently at the time they happen,
whether that's writing it down in a notebook
or entering it into an electronic system. You
got it. It has to be done right then and there.
So yeah, so it's not just a good idea. It's actually
a regulatory requirement. It is. And the reason
for that comes down to minimizing errors and
maximizing accuracy. Like we were saying, human
memory details can get lost or unintentionally
changed over time, but by documenting things
as they happen in real time, you create this.
really solid record of exactly what occurred.
It's like a scientific time capsule. You're capturing
the truth of that moment. I like the scientific
time capsule. So we've talked about why contemporaneous
recording is so important for data integrity,
but how does it actually work in practice? Like
how does this idea of capturing data in the moment
actually play out in a lab setting? Well, if
you think about it, contemporaneous recording
is like the foundation upon which the whole system
of data integrity is built. If you know that
the initial record was made accurately, And at
the moment that something happened, everything
that comes after that, all the analysis, the
interpretation, the decisions that are made based
on that data, it all stands on a much firmer
foundation. You can trust the data because you
know that the very first step was done right.
Yeah, that makes a lot of sense. And it really
drives home the importance of that phrase that
we've seen pop up again and again. in our research.
If it wasn't documented, it wasn't done. Exactly.
It's not just a saying. It's a core principle.
In the world of GMP, if you didn't write it down,
it basically didn't happen. And that might seem
kind of extreme, but it's really important because
it forces people to be diligent about documentation.
Right. And it makes sure that there's this clear,
auditable trail of everything that was done.
Yeah. And I think it also helps to prevent mistakes
and oversights, right? Because if you know that
you have to document everything, you're more
likely to be careful and thorough in the first
place. Exactly. It's all about accountability
and transparency. And that's really what builds
trust in the data. OK. So we've established the
importance of recording things right now in real
time. So let's talk about the where. And that
brings us to that classic image of scientific
work, the lab notebook. It's probably what most
people picture when they think about scientists
working in a lab. You know, it's funny how that
image is really stuck with us the lab notebook
really is like this central hub of information
in a GMP lab. It's the primary, detailed, permanent
record of everything that happens, all the experiments,
the observations, the data that's generated.
It's not just a place to jot down numbers. It's
a complete story of the scientific work that
was performed. Yeah, it's a historical record.
Absolutely. And I remember reading one of the
YouTube transcripts about the importance of finding
the right balance between detail and clarity.
You know, it's not just about writing everything
down. It's about writing it down in a way that's
easy to understand and doesn't leave any room
for misinterpretation. Yeah, that's a really
good point. You have to be thorough, but you
also have to be concise. And the goal is to provide
enough information so that somebody else, even
years later, could pick up that notebook and
understand exactly what was done, how it was
done, and what the results were, all without
having to rely on the memory of the person who
originally did the work. Right, because the person
who did the work might not be around anymore,
or they might not remember all the details. So
the notebook has to be able to stand on its own.
So if we were to open up a lab notebook that's
being maintained to GMP standards, what are some
of the key elements that we should expect to
find in a typical entry? What makes a good notebook
entry? Well, I think there are a few things that
are absolutely essential. First, you need to
be able to tell exactly what experiment or test
or activity is being documented in that entry.
So that might mean giving it a clear descriptive
title or referencing a specific protocol number
or standard operating procedure or SOP, anything
that uniquely identifies what's being done. OK,
so clear identification is key. What else? The
date and time of the entry are super important
too. That goes back to the whole idea of contemporaneous
recording, right? Making sure that everything
is documented as it happens. Right, right, of
course. What about the materials that were used
in the experiment? Yeah, so you'd want to see
a detailed list of all the materials and equipment
that were used. And that should include things
like specific identification numbers for the
equipment so that you can trace it back to its
maintenance records and calibration history.
Actually, 21 CFR 211 .182 even specifically mentions
the need to record the equipment used. Oh, wow.
So they're really specific about that. Oh, yeah.
And in one of those EAS consulting group videos,
they were talking about equipment qualification,
too, making sure that any equipment that's used
is actually suitable for its intended purpose
and that it's working properly. And that's where
you get into those different qualification phases,
the DQ, the IQ, the OQ, the PQ, design qualification,
installation, operational qualification, performance
qualification. You know, making sure that the
equipment is designed right, that it's installed
correctly, that it operates the way it should,
and that it actually performs the tasks it's
supposed to. That makes sense. You want to make
sure that your tools are up to the job. So you've
got your equipment, you've got your materials.
What about the actual procedure that was followed?
Right. So the entry should also clearly describe
the steps that were taken. And a lot of times
that will involve referencing a specific approved
SOP or standard operating procedure. And then
all of the observations and the raw data need
to be recorded directly into the notebook as
they're generated. You don't want people transcribing
from scraps of paper later on because that introduces
the possibility of errors. Yeah, you want that
original data right there in the notebook. Exactly.
And if any calculations are done, those should
be... documented too, not just the final result,
but the actual steps that were taken to get there,
you know, the formulas that were used and the
intermediate calculations. And of course the
final results of the experiment or test have
to be stated very clearly. And sometimes you'll
also see them compared against predefined acceptance
criteria. to make sure that they fall within
the acceptable range. Right, because you want
to make sure that the results are actually meaningful,
that they're not just numbers on a page, but
they actually tell you something about the quality
of the product or whatever it is that you're
testing. Exactly. Now I know that in the real
world, experiments don't always go exactly according
to plans, so what happens when there's a deviation
from the procedure? Yeah, that's a really important
point. A good lab notebook will also include
documentation of any deviations from the standard
procedure. any unexpected observations or any
problems that came up during the work. So that
might be something like an equipment malfunction,
a variation in the materials that were used,
or even just a change that had to be made to
the planned procedure. And when these things
happen, it's super important to record why the
deviation occurred and what steps were taken
to deal with it. Yeah, it's not just about documenting
the hiccups. It's about explaining them and showing
how they were addressed. That makes sense. Exactly.
You want to have that complete picture. And then
finally, every single entry in the lab notebook
needs to be signed and dated by the person who
did the work. That way you know exactly who's
accountable for what. And I think we even saw
on one of the YouTube videos that sometimes companies
will keep a register of specimen signatures to
make sure that the signatures in the notebooks
are authentic. Yeah, that's right. It's all about
maintaining that chain of custody and making
sure that you can trace everything back to the
source. So it's really a comprehensive system.
I mean, the lab notebook is like a diary of the
experiment from start to finish. It's got everything
in it. Now, speaking of things not always going
perfectly about, I know that humans are involved
in all of this and humans make mistakes. So how
do you handle corrections in a GMP environment?
Because you can't just erase something or hit
delete in a paper notebook. Yeah, that's a great
question. And it's really important because the
way that errors are handled, can make or break
data integrity. You absolutely cannot just scribble
something out, use correction fluid, or try to
cover up a mistake. All of those things can raise
red flags because they make it look like you're
trying to hide something. Yeah, that makes sense.
If you see something that's been completely obliterated,
you immediately start to wonder what was under
there. Exactly. So the accepted way to make a
correction in a GMP lab notebook is very specific.
You draw a single line through the incorrect
entry. but you do it in a way that leaves the
original entry legible. You can still read what
was originally written. Then you write the correct
information next to the crossed out part. And
the person who made the correction has to initial
and date the correction. So it's all about transparency.
You're not trying to hide the mistake. You're
just correcting it in a way that's clear and
auditable. Exactly. And the same goes for electronic
records, too. You know, you can't just delete
data or modify it without leaving a trace. There
have to be audit trails that track every change
that's made to the data. Now I remember one of
the YouTube videos had a really strong warning
about falsifying records or signing for another
person Can you talk a little bit more about why
that's such a big deal? Yeah, absolutely Falsifying
records or signing for someone else is a huge
no -no in GMP These records are legal documents
and if you intentionally misrepresent information
it undermines the whole system It's like lying
under oath basically And I imagine that the consequences
for that kind of thing can be pretty severe.
Oh, yeah, for sure. You could face fines, product
recalls, even criminal charges. And on a more
fundamental level, it just destroys trust. If
people can't trust the data, then the whole system
falls apart. So it's really, really important
to be honest and accurate in all of your documentation.
So we've been talking a lot about paper records,
but I know that a lot of data in a modern lab
is generated directly by instruments and stored
electronically. How does all of this fit into
the world of electronic data capture? Yeah, that's
a great question. With electronic data, there
are a whole bunch of other things to consider.
For one thing, the software that you're using
to capture, process, and store that data has
to be validated. Meaning you have to prove that
it's working correctly and that is producing
reliable data. And I think this is where 21 CFR
part 11 comes in, right? The regulations on electronic
records and electronic signatures. Yep, that's
the one. Part 11 lays out all sorts of requirements
for electronic records to make sure that they're
trustworthy. And one of the big things is audit
trails. Those are like electronic footprints
that track every action that's taken within the
system. So if somebody changes the data point
or delete the file or even just tries to access
the system, there's a record of it. It's almost
impossible to mess with the data without leaving
a trace. So it's kind of like having a security
camera for your data. Yeah, exactly. And it's
not just the software either. The instruments
themselves still need to be. properly maintained
and calibrated. You need to have procedures in
place for that and you need to keep records of
all the maintenance activities and calibrations.
And a lot of times that's done electronically
now too. Right. So it's really a whole system.
It's not just about the paper notebooks anymore.
It's about managing all of the data, whether
it's on paper or in a computer system. So we've
talked about how data is captured. Let's talk
about what happens after it's been recorded.
Is it just filed away somewhere? No, not at all.
Once the data has been captured, whether it's
in a notebook or electronically, it has to be
reviewed. And this is a really important step
because it helps to catch errors and make sure
that everything is complete and accurate. And
I think we saw in several of the YouTube videos
that there are often multiple levels of review,
right? Yeah, exactly. The person who did the
work will usually review their own data first.
And then it might be reviewed by a peer or a
colleague. And then a supervisor will look at
it. And sometimes even the quality assurance
department will do a final review. It's like
having multiple sets of eyes on the data to make
sure that nothing slips through the cracks. And
I imagine that preventing transcription errors
is really important too, especially when you're
moving data from one system to another or from
instruments to reports. Oh, yeah, absolutely.
Transcription errors can be a big problem. So
you want to minimize manual data entry as much
as possible. And when you do have to transcribe
data, you need to have procedures in place to
verify that it's been done correctly, like having
a second person check the data against the original
source. So it's all about checks and balances,
making sure that the data is accurate and reliable
every step of the way. Exactly. OK, so let's
talk about what happens to the data long term.
How do you make sure that it's stored securely
and that it's accessible when you need it? Yeah,
secure storage is a really big deal. You know,
you have to protect these records from loss,
damage, unauthorized access and alteration. And
that goes for both paper records and electronic
data. And I know that there are regulations that
specify how long certain records have to be kept
right. Yeah, that's right. The FDA and other
regulatory bodies have very specific requirements
for record retention. So for example, one of
the YouTube transcripts mentioned that data related
to serious adverse events for dietary supplements
might have to be kept for up to six years. Wow,
that's a long time. Yeah, it is. And there are
general GMP regulations, too, that lay out retention
periods for different types of records. So companies
need to have systems in place to make sure that
they're meeting those requirements. So it's not
just about Stuffing things in a filing cabinet
or backing up a hard drive. There's a lot more
to it than that Yeah, you have to have a plan
for how you're gonna archive the data and how
you're gonna make sure that it stays accessible
and readable for however long you're required
to keep it and with the paper records that might
mean storing them in climate controlled environments
and insecure facilities and with electronic records
it means having good backup systems and Data
migration plans so that you can still access
the data even as technology changes Yeah, because
technology changes so quickly these days, you
don't want to end up with a bunch of data that
you can't even read anymore because the software
is obsolete. So there's a lot to think about.
We've covered a lot of ground here, from capturing
data in real time to storing it securely for
years to come. So what are some of the biggest
challenges that companies face in trying to meet
all of these requirements? You know, honestly,
one of the biggest challenges is just human error.
You know, people make mistakes. They forget things.
They transpose numbers. They might not understand
the procedures correctly. And all of those things
can lead to errors in the data. And then there
are challenges related to data management. You
know, making sure that all the data is organized
and labeled properly so that you can find what
you need when you need it. And that can be tricky,
especially when you're dealing with large volumes
of data. And what about electronic systems? I
imagine there are challenges there, too. Yeah,
for sure. Electronic systems can be great for
data management, but they also come with their
own set of challenges, like making sure that
the systems are validated and secure and that
they comply with all the regulations. And then
there's the issue of data integrity, making sure
that the data in this system hasn't been altered
or corrupted in any way. There's a lot to think
about. So given all of those challenges, what
are some strategies that companies can use to
try to overcome them? Well, I think one of the
most important things is training. You know,
making sure that everybody who's involved in
data collection and handling understands the
importance of GMP and the procedures that they
need to follow. And that training needs to be
ongoing. It can't just be a one time thing. Right.
You have to keep people up to date. Exactly.
And then it's also important to have clear SOPs.
standard operating procedures for all of the
key processes, you know, step -by -step instructions
that people can follow. And those SOPs need to
be reviewed and updated regularly to make sure
that they're still accurate and relevant. So
it's about having systems in place to prevent
errors from happening in the first place. Yeah,
that's right. And then you also need to have
systems in place to catch errors if they do happen.
So that means doing regular reviews and audits
of the data and the documentation. Yeah. And
it also means having a culture of quality where
people feel comfortable speaking up if they see
something that's not right. So it's not just
about the rules and the procedures, it's also
about the culture of the company, you know, making
sure that everybody understands the importance
of data integrity and that they're all working
together to achieve it. Yeah, exactly. It has
to be a team effort. Well, I think this has been
a really insightful deep dive into a topic that's
often overlooked, but that's absolutely essential
for making sure that the products we use are
safe and effective. I agree. It's easy to get
caught up in the excitement of scientific discovery
and innovation, but it's really important to
remember that all of that has to be grounded
in solid data. And that means having robust systems
in place for capturing, managing, and protecting
that data. So for our listeners out there, we
hope that this deep dive has given you a better
understanding of the importance of data integrity
and the many steps that go into ensuring it.
Because ultimately, it's all about trust. When
you pick up a bottle of medicine or a jar of
vitamins, you're putting your trust in the company
that made it and in the systems that they have
in place to guarantee its quality and safety.
So as you go about your day, we encourage you
to think about the data that's all around you,
the data that's used to make decisions that affect
your life. and to appreciate the role that GMP
plays in making sure that that data is reliable
and trustworthy. And that's it for this deep
dive. Thanks for joining us. Thanks everybody.