January 28, 2025 • 26 mins
Explore the fascinating world of drug safety with a deep dive into ICH S7 guidelines. Discover how rigorous testing, from animal models to cutting-edge tech like in vitro methods and computer simulations, ensures medications are safe for human use. Learn how researchers assess effects on vital systems like the heart, lungs, and nervous system, and how post-market surveillance continues to protect patients after approval. A compelling look at the science, ethics, and collaboration driving safer, more effective treatments!
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
All right, so we've got this mountain of FDA documents you sent in all about drug safety.
(00:04):
Yeah, you seem pretty fascinated by all the rigorous testing that happens before a medication even gets close to a human, huh?
We're talking safety pharmacology, right?
The science of making sure new drugs aren't going to cause, you know, nasty side effects, especially on your vital organs, like the stuff that keeps you going.
And these guidelines, ICHS-7, they're all about protecting you from potential harm.
(00:28):
Yeah, that's right.
Before a drug even gets to human trials, researchers really need to make sure that it's not going to mess with your heart, lungs, nervous system, you know, all the important things.
And ICHS-7 or the International Council for Harmonization Guidelines for Safety Pharmacology Studies provide the framework for these assessments.
It's really crucial.
(00:49):
Yeah, like a safety checklist, huh?
Exactly.
Making sure scientists have thoroughly investigated a drug's potential effects.
Yeah.
One thing that jumps out from these FDA documents is the reliance on animal models in these early stages.
It's a complex and obviously often debated topic.
Oh, for sure.
Animal models are definitely like a cornerstone of safety pharmacology.
(01:09):
Right.
But they also raise those really important ethical considerations.
Of course, yeah.
But, you know, they often provide the best and most comprehensive way to initially assess the drug's safety before it's even considered for human testing.
So it's a balancing act.
Yeah.
Between gaining this crucial information but also ensuring the ethical treatment of animals.
(01:30):
Mm-hmm.
Can you dig a little deeper into the reasons why researchers rely on animal models in the first place?
Yeah, sure.
What makes them so valuable in this context?
Well, I think the key is in the biological similarities between animals and humans.
You know, their organs function in very similar ways.
They have comparable metabolic pathways.
Right.
And often their responses to drugs mirror how humans might react.
(01:54):
So it's almost like having a preview of how the drug might behave in a human body.
But in this, like, controlled setting where scientists can kind of adjust the dosage, the environment?
Yeah, precisely.
That level of control is one of the big advantages of animal models.
Researchers can manipulate all those different factors in ways that just wouldn't be possible in human studies.
(02:17):
Makes sense.
Yeah.
And it lets them isolate certain specific effects and gain a deeper understanding of the drugs mechanisms.
Yeah, that makes a lot of sense.
These FDA documents also highlight the limitations of animal models.
Mm-hmm.
And the push for alternatives.
Yeah.
Because, I mean, no animal perfectly replicates a human system, right?
(02:37):
Right.
You're absolutely right.
There are always species-specific differences.
Of course, yeah.
And that can complicate predictions.
I mean, something that's safe in a rat might not be safe in a human.
Yeah.
So that's where the limitations become pretty apparent.
Yeah.
And it's why the scientific community is very actively pursuing alternatives, you know, to try to minimize that reliance on animal models.
(02:59):
From what I see here, there's a lot of exciting research happening.
Yeah.
Like in in vitro testing.
Mm-hmm.
And computer simulation.
Exactly.
In vitro testing, so using human cells in Petri dishes.
Right.
That allows scientists to actually study those effects directly on human tissues.
Mm-hmm.
It's a really powerful tool to see how a drug interacts with specific cells and pathways.
(03:21):
OK.
So it's a way to kind of zoom in on those cellular interactions.
Yeah.
Without having to use a whole organism.
Exactly.
And what about computer simulations?
Yeah.
So those are revolutionizing the field.
They allow researchers to model those complex biological processes.
They can virtually test a drug's effects.
Oh, wow.
On different organs and systems and predict potential side effects and even interactions.
(03:44):
Mm-hmm.
Before even, you know, stepping foot in a lab.
So it's almost like having this virtual laboratory where you can run a bunch of experiments.
Yeah.
Without any ethical considerations.
Exactly.
Or limitations of animal models.
You got it.
Although those technologies are still evolving.
They can't fully replace animal models just yet.
Right.
But they definitely hold immense promise for reducing our reliance on them in the future.
(04:06):
It's like we're standing at the cusp of a new era in drug safety testing, where technology
is letting us be both more efficient and more ethical.
Precisely.
And, you know, speaking of efficiency, one thing that really struck me in these FDA
documents is the sheer volume of testing required.
Mm-hmm.
It's not just about the active drug itself.
(04:27):
It's every single component, you know?
Like on drug labels, you see inactive ingredients.
Oh, yeah.
I always wondered about those.
Yeah.
They sound so boring.
Right.
But they're not so inactive when it comes to safety.
So even seemingly harmless ingredients can interact with the active drug.
Yeah.
Or even have like unforeseen effects on the body.
Exactly.
The FDA scrutinizes everything.
(04:49):
Wow.
And any change to the formulation can trigger a whole new wave of safety testing.
So it's not just about the star of the show, the drug itself.
Yeah.
But also the supporting cast of all the inactive ingredients.
Right.
They all have to go through this rigorous testing.
Yep.
To make sure they're playing their part safely.
Absolutely.
And it doesn't even stop there.
(05:10):
The manufacturing process itself is under the microscope.
So like imagine a company.
They want to tweak how a drug is made, maybe to improve efficiency or the yield.
Even if the product seems identical in the end, the FDA requires them to prove that change
hasn't introduced any new risks.
That's incredibly thorough.
Yeah.
(05:30):
It really underscores, you know, the importance of consistency and transparency in this world
of drug development.
Yeah.
Everything has to be like meticulously documented and validated.
Exactly.
Leaving no room for doubt when it comes to patient safety.
Absolutely.
And all of this is guided by those ICHS7 principles.
(05:51):
It's not just about will this drug kill you.
Yeah.
You know, it's about understanding all the subtle effects it has on your vital organs.
OK.
So let's dive into the nitty gritty then.
How do researchers actually assess a drug's impact?
Sure.
We're talking the heart, lungs, nervous system.
You know, the silent workhorses that keep us alive.
Exactly.
So a drug might not be lethal, but it could subtly disrupt these systems, and that would
(06:15):
lead to problems down the line.
Right.
So ICHS7 outlines a whole bunch of tests to evaluate these potential effects.
So what does that actually look like?
I'm picturing like a scene from a sci-fi movie with all these scientists huddled over blinking
monitors.
Yeah.
But what's the reality?
Well, it's not quite as dramatic as Hollywood portrays it.
Right.
But it's definitely meticulous, and it involves a wide range of tests.
(06:39):
So let's start with the cardiovascular system.
OK.
One of the most common assessments is the electrocardiogram, or EKG.
Right.
And that measures the heart's electrical activity.
Oh, OK.
So it allows researchers to identify irregularities in the heart rhythm or potential signs of damage
from the drug.
So they're basically like listening to the heart's electrical chatter.
(07:00):
Exactly.
Making sure the drug isn't like throwing off the beat.
Exactly.
And beyond just the electrical activity, researchers also look at blood pressure cause.
Some drugs can cause dangerous fluctuations in blood pressure.
So it's really important to see how a new drug might affect that.
So it's like giving the heart a complete checkup, just making sure it's functioning properly
(07:21):
under the influence of this new drug.
Exactly.
And what about the respiratory system?
How do they make sure a drug isn't going to mess with our breathing?
Right.
So for the respiratory system, a key focus is breathing rate.
OK.
And the volume of air inhaled and exhaled.
This reveals any signs of respiratory distress, like shortness of breath or shallow breathing.
(07:44):
So they're really monitoring the mechanics of breathing.
Exactly.
Making sure the lungs are working properly.
Yeah.
And the drug isn't causing any restriction.
Exactly.
They're also analyzing blood gases to see how well the lungs are absorbing oxygen and
removing carbon dioxide.
So it's a comprehensive pulmonary evaluation.
Yes.
Making sure the drug isn't interfering with our ability to breathe.
(08:04):
Exactly.
What about the nervous system?
Yeah.
That seems particularly challenging just because it's so complex.
Right.
And a drug could have all kinds of effects on it.
Yeah, you're right.
The nervous system is incredibly intricate.
And assessing neurotoxicity can be quite complex.
But ICHS7 outlines a bunch of tests to cover all those different potential effects.
(08:25):
So walk us through them.
What are some of the key things researchers are looking for when it comes to the nervous
system?
Well, one of the most, I guess, fundamental but crucial assessments is simply observing
the animal's behavior.
OK.
So researchers will look for changes in activity level, their coordination, gait, reflexes,
even things like their social interactions.
(08:48):
Any deviation from that normal behavior could be a sign that the drug is affecting the nervous
system.
Interesting.
So they're looking for any behavioral clues that might indicate a problem.
It's amazing how much you can tell just by observing.
It really is.
But beyond just simple observation, they also use more specialized techniques to assess
those specific aspects of nervous system function.
(09:08):
One common tool is electroencephalography.
EEG.
Exactly.
EEG, which measures the brain's electrical activity.
Oh, I've heard of that.
Yeah.
So it's like attaching electrodes to the brain to listen to its electrical conversations.
Wow.
And by analyzing those brainwave patterns, they can actually detect any abnormalities
that might be caused by the drug.
(09:29):
So it's a way to kind of peer into the electrical workings of the brain.
Yeah.
Make sure the drug isn't disrupting things.
Precisely.
And beyond these core assessments, researchers can delve even deeper.
You know, using specialized tests to evaluate things like cognitive ability, sensory perception,
the scope of that neurotoxicity testing can be really extensive depending on the drug
(09:53):
and its potential targets in the nervous system.
It's mind boggling to think about all the different ways a drug could affect the nervous
system.
Yeah.
But it's reassuring to know that researchers are equipped with so many different tools
to assess the risks.
Exactly.
And as technology keeps advancing, we're probably going to see even more sophisticated ways to
assess neurotoxicity.
Wow.
(10:13):
Allowing for a much deeper understanding of those things.
Understanding of those drug effects on the nervous system.
It's incredible how science is constantly pushing boundaries, giving us new insights
into how the human body works and the drugs we use to treat it.
Yeah, it really is remarkable how far we've come in understanding the nervous system and
(10:33):
how drugs can impact that delicate balance.
But let's maybe shift gears for a second and delve into another fascinating aspect of safety
pharmacology.
You highlighted this with all those FDA documents.
Lead the way.
What other intriguing corners of drug safety are we exploring today?
Well, we've talked a lot about animal models and their crucial role in these early safety
(10:56):
assessments.
But within that realm, there's this whole world of specific model organisms.
Right.
Each one is chosen for its unique characteristics and the insights that it can provide.
Yes, the model organisms.
It's like a cast a call for human standard.
Yeah.
Researchers selecting the best actor based on the specific question they're trying to
answer.
(11:16):
That's a fantastic analogy.
And just like in Hollywood, you know each organism brings its own talents to the set.
So like if researchers are concerned about a drugs effects on the cardiovascular system,
they might choose a dog or a pig because their cardiovascular systems are pretty similar to
humans.
So it's about finding the best match.
Yeah.
The organism that can most accurately mimic the human response and provide the most reliable
(11:41):
data.
Exactly.
But what about those species that seem, I don't know, less obviously related to us?
Yeah.
Like zebrafish or fruit flies.
I mean, they pop up in research sometimes.
Yeah.
What can those possibly tell us?
Right.
What could they tell us about human biology?
It might seem a little counterintuitive, but even those organisms that seem very distantly
(12:02):
related to humans can offer valuable insights.
Okay.
So like zebrafish, for example, surprisingly useful for studying developmental processes.
Their embryos are actually transparent.
So scientists can actually observe organ development in real time.
Wow.
That's incredible.
So it's not just about anatomical similarity then.
It's also about leveraging those unique characteristics of certain species.
(12:26):
Yeah.
Each organism has its own superpower.
Exactly.
And as technology keeps advancing, we're finding even more creative ways to use these organisms.
Right.
So scientists can now genetically modify mice, for example, to make them more susceptible
to certain diseases.
Oh, wow.
Which then allows for targeted drug testing.
So it's like tailoring the organism to fit the research question, creating this
(12:50):
more precise and efficient system.
Exactly.
But with those advancements come ethical considerations as well, right?
Of course.
The more we can manipulate these organisms, the more carefully we need to consider our actions.
Right.
The implications of our actions.
Exactly.
So the ability to modify these organisms raises those ethical questions about their
welfare and our responsibility as researchers.
(13:12):
Right.
So it's a constant dialogue within the scientific community, making sure that we're using these
models responsibly and ethically.
And speaking of responsibility, those FDA documents emphasize minimizing animal use
whenever possible.
It seems like a core principle guiding this whole field.
Oh, yeah.
Absolutely.
That's a top priority.
(13:33):
The three Rs, so replacement, reduction, and refinement, are guiding principles in animal research.
OK.
So scientists are constantly trying to find alternatives to animal models whenever they can.
And when animal studies are necessary, the aim is to use the fewest number of animals possible
while still making sure they're doing OK.
So it's not just about replacing animals then.
(13:55):
Right.
It's also about reducing the number and refining those studies to minimize any potential distress.
Exactly.
So it's this multi-pronged approach to ensure ethical research.
Right.
And this commitment to the three Rs is woven into the fabric of ICHS7.
Yeah.
So those guidelines prioritize both the scientific rigor and the animal welfare.
(14:19):
It's heartening to see that ethical considerations are such a big part of drug development.
Yeah, definitely.
It's about finding that balance between advancing scientific knowledge, but also respecting the
lives of these animals.
Well said.
And that's a balance that's constantly being refined.
As our understanding of both science and ethics evolves.
But beyond just the ethical considerations, there's also a practical aspect to minimizing animal use.
(14:44):
Oh, interesting.
So it's not just about doing the right thing.
There's also practical benefits to reducing reliance on animal models.
Oh, absolutely.
So animal studies, they can be really expensive.
Right.
And time consuming.
Right.
So just from a purely practical standpoint, there's a strong incentive to find alternatives
that are more efficient and cost effective.
(15:05):
Right.
And as technology progresses, we're seeing those alternatives emerge.
So it's this perfect storm of ethical and practical drivers kind of pushing the field toward these new approaches.
Exactly.
It's a win-win for both science and animal welfare.
Yeah.
But as we transition to these new methods, we need to be mindful of the challenges as well.
OK, what kinds of challenges?
It seems like a positive shift overall.
(15:27):
It is, but I think there's always going to be hurdles.
Right.
Whenever you're adopting new technologies.
Of course, yeah.
So one challenge is simply that validation process.
No.
Before we can rely on these new methods, we have to demonstrate that they're as good as traditional models.
Right.
And that takes time and research and a lot of careful comparison.
(15:49):
So it's not just about developing the technology itself.
Yeah.
You also have to prove that it works.
Yeah.
And the results are trustworthy.
Exactly.
Like a trust but verify thing in the scientific world.
Yeah.
And that verification is so important because, I mean, ultimately, the goal is to protect patients.
Therefore?
We need to be absolutely certain that these new methods are giving us the right information about a drug safety.
(16:13):
Speaking of patient safety, let's circle back to ICHS-7 and those vital organ systems we talked about.
You mentioned that researchers use a mix of in vivo and in vitro approaches to assess drug effects.
Mm-hmm.
Can you maybe give us some specific examples of the types of tests used?
Yeah, of course.
Let's go back to the cardiovascular system.
(16:34):
One of the most common tests is the electrocardiogram or EKG, which measures the electrical activity of the heart.
Right.
So this can reveal irregularities in the heart rhythm, like arrhythmias, which can be a side effect of some drugs.
So it's like listening to the heart's electrical signals.
Yeah.
Looking for any unusual patterns.
Right.
(16:55):
And what other tests are used to assess cardiovascular safety?
Well, another important one is blood pressure monitoring.
Okay.
Some drugs can cause blood pressure to like rise or fall dangerously.
Yeah.
So it's important to see how a new drug might affect that.
Right.
And then in some cases, they might even look at the heart tissue under a microscope.
(17:16):
Wow.
To check for any structural changes that might show damage from the drug.
So it's a really multifaceted approach.
Mm-hmm.
Looking at the electrical activity, the blood pressure, and even the microscopic structure of the tissue.
Exactly.
Like a detective at a crime scene.
Gathering clues from every angle.
Exactly.
And that attention to detail is really important because the cardiovascular system is so central to our overall health.
(17:41):
Any disruption to that can have effects throughout the whole body.
Right.
Yeah.
Okay.
So we've covered the heart.
Mm-hmm.
What about the lungs?
How do they assess a drug's impact on the respiratory system?
Right. So one common method is to actually measure the animal's breathing rate.
Okay.
And the volume of air they inhale and exhale.
(18:01):
So this can show any signs of respiratory distress, like shortness of breath or really rapid shallow breathing.
So they're monitoring the mechanics of breathing basically?
Yeah, exactly.
Just making sure the lungs are functioning okay?
Uh-huh.
And I imagine they also look at blood gases, right?
Yeah.
To see how well the oxygen is being absorbed.
There you go.
Yes, you're absolutely right.
So analyzing the blood gases can tell us a lot about how well the lungs are oxygenating the blood
(18:26):
and removing carbon dioxide.
And then sometimes they might also examine the lung tissue under a microscope
to look for signs of inflammation or damage.
It's like they're putting a puzzle together using all these different pieces of information
to get this full picture of what the drug is doing to the respiratory system.
Exactly.
And just like with the cardiovascular system, any disruption there can be serious.
(18:49):
Yeah.
So this really thorough assessment is super important.
Okay, so we've got the heart, the lungs.
Now, what about the nervous system?
Right.
That seems like a particularly challenging one to assess given how complex it is.
It is incredibly complex.
And because the nervous system controls so many different bodily functions,
any kind of disruption to it can have a whole range of effects.
(19:11):
So researchers use a bunch of approaches to assess that neurotoxicity.
Okay, so walk us through some of those.
What kinds of tests do they do for the nervous system?
So one of the most basic methods, but still important, is just observing the animal's behavior.
Oh, no.
So researchers look for any changes in their activity level, their coordination, gait, reflexes,
(19:33):
even things like their social interactions.
Interesting.
So any change from normal behavior could be a sign that the drug is affecting the nervous system.
So it's like looking for any little behavioral quirks that might indicate a problem.
It's amazing how much you can learn just by watching.
Yeah.
But they also use more specialized techniques to actually assess that nervous system function.
(19:54):
One of the most common ones is electroencephalography, or EEG.
EEG, yeah.
Which measures the electrical activity of the brain.
So they're basically attaching electrodes to the animal's head to listen to the brain's signals.
Oh, wow. I've heard of that before.
Yeah. And by analyzing those brainwave patterns, they can detect abnormalities
(20:16):
that might be caused by the drug.
Wow.
And they can also use it to look at things like sleep-wake cycles
and even cognitive functions sometimes.
So they're not just looking at basic movement.
Right.
They're looking at brain activity, too.
Exactly.
It's incredible how sophisticated these techniques have become.
It is. And as technology keeps advancing,
(20:36):
we're likely to see even more refined methods for assessing neurotoxicity.
Wow.
So there's a growing interest in using imaging techniques like fMRI to actually visualize brain
activity happening.
Wow.
And that can give us a much more detailed understanding of the drug's effects.
It's like we're constantly pushing the boundaries to get a deeper understanding
(20:59):
of the nervous system and how drugs impact that.
Absolutely. But even with all these advancements, there are always challenges
when it comes to predicting how a drug will behave in a human being.
Right, of course, because the human body is so complex.
Yeah.
You can't always predict everything.
You're absolutely right. The human body is incredibly complex.
Yeah.
And there's always individual variation that makes it difficult to predict every single side effect.
(21:24):
But the goal of safety pharmacology is to really minimize those risks as much as possible.
Right.
And the guidelines in ICHS-7 are like constantly evolving to reflect the latest science.
It's a constant quest for knowledge, then.
Refining our understanding of the body and the drugs we use.
Exactly. And it's a quest that needs constant vigilance.
(21:46):
Yeah.
Even after a drug is deemed safe and is on the market.
You've hit a crucial point there.
Yeah.
The journey doesn't end with those initial studies.
Right.
And the approvals. There's a whole world of post-market surveillance.
Mm-hmm.
That continues to monitor the drug's performance.
Exactly. You know, making sure it lives up to its promises and doesn't have any unexpected risks.
(22:07):
Okay. Let's unpack that a bit. What does post-market surveillance actually entail?
What's in place to make sure a drug is still safe and effective once it's out there?
Being used by millions of people. So we know the journey doesn't end when a drug is approved.
Right. There's this whole system of post-market surveillance.
Right.
But what does that actually look like? Is the FDA sending out spies to watch people take their pills?
(22:32):
Well, it's not quite a spy movie.
Right.
But there's definitely like a system for monitoring. So companies have to report any adverse events.
Okay.
That come up after a drug is approved.
So if someone has like a weird side effect.
Yeah.
That wasn't caught in the trials, that gets reported to the FDA.
Exactly. And the FDA takes all those reports and analyzes them.
(22:55):
Wow.
Looking for patterns or anything that might suggest a problem. They actually have a whole division for this kind of post-market surveillance.
That's good to know.
Yeah.
So it's not like a see-y'all later situation once the drug is approved.
Right.
There's still this commitment to making sure it's safe out in the real world.
Yeah.
With all its complexities.
Absolutely. And it's not just about collecting data. The FDA can take action based on those findings.
(23:18):
So they might update the drugs label with new warnings or require more studies.
They can even take a drug off the market completely if it turns out to be riskier than they thought.
Wow. So it's pretty serious business.
Yeah, it is.
So those initial ICHS7 studies, they're just the beginning, kind of laying the groundwork for this long-term assessment.
Exactly. Those early studies give us this baseline understanding of the drug's safety.
(23:43):
But the real test is when it's out there being used by lots of different people with different medical histories and lifestyle.
It really makes you realize how complex this whole thing is. It's not just about science. It's about being vigilant and data analysis.
And just this constant commitment to protecting public health.
(24:03):
Yeah. And it highlights the collaborative nature of all of it. It's scientists and regulators, health care providers, and even patients.
They all play a role in making sure medications are used safely.
Speaking of patients, I'm curious about their role. I mean, beyond just taking the medication, how do they contribute to this ongoing assessment?
That's a great question. So patients are really important through something called pharmacovigilance.
(24:26):
OK.
Which is basically collecting and monitoring information about the effects of medicines.
Right.
And a lot of that comes from patients themselves reporting side effects or anything unusual they experience while taking a drug.
So it's almost like a citizen science project.
Yeah, exactly.
Patients are contributing data to this safety assessment.
That's a great way to put it. And there are a lot of ways for them to report these things.
(24:49):
They can talk to their doctors or contact the company that makes the drug directly or even use online reports to report the drug.
They can use online reporting systems from like the FDA.
So they really have a voice in this and can contribute to the safety of meds.
Yeah. And it sort of closes the loop. It creates a feedback system where real world experiences help shape the evaluation of a drug's safety.
(25:13):
It's really amazing how all these pieces fit together from those early ICHS7 studies through the approvals and into this post-market surveillance.
It's science and regulation and patient engagement all working together to keep the medications we use safe.
It really is. It's a testament to the work of so many people behind the scenes, you know, to protect public health.
(25:34):
Absolutely. And it really shows why it's so important to stay informed.
The more we all understand about this process, the better we can be about our own health and well-being.
Absolutely. Knowledge is power, right?
Yeah.
The more we know about our medications, the more we can advocate for our health.
Exactly.
And contribute to finding those safer and more effective treatments.
Well, there you have it. A deep dive into ICHS7.
(25:58):
We explored the intricacies of animal models and those assessments of vital organs.
And we've seen how post-market surveillance works.
Hopefully, you've gained a new appreciation for the complexities of drug safety and the dedication of everyone working to make sure our meds are safe and effective.
Until next time, stay curious and keep those questions coming.
All right, so we've got this mountain of FDA documents you sent in all about drug safety.
(00:04):
Yeah, you seem pretty fascinated by all the rigorous testing that happens before a medication even gets close to a human, huh?
We're talking safety pharmacology, right?
The science of making sure new drugs aren't going to cause, you know, nasty side effects, especially on your vital organs, like the stuff that keeps you going.
And these guidelines, ICHS-7, they're all about protecting you from potential harm.
(00:28):
Yeah, that's right.
Before a drug even gets to human trials, researchers really need to make sure that it's not going to mess with your heart, lungs, nervous system, you know, all the important things.
And ICHS-7 or the International Council for Harmonization Guidelines for Safety Pharmacology Studies provide the framework for these assessments.
It's really crucial.
(00:49):
Yeah, like a safety checklist, huh?
Exactly.
Making sure scientists have thoroughly investigated a drug's potential effects.
Yeah.
One thing that jumps out from these FDA documents is the reliance on animal models in these early stages.
It's a complex and obviously often debated topic.
Oh, for sure.
Animal models are definitely like a cornerstone of safety pharmacology.
(01:09):
Right.
But they also raise those really important ethical considerations.
Of course, yeah.
But, you know, they often provide the best and most comprehensive way to initially assess the drug's safety before it's even considered for human testing.
So it's a balancing act.
Yeah.
Between gaining this crucial information but also ensuring the ethical treatment of animals.
(01:30):
Mm-hmm.
Can you dig a little deeper into the reasons why researchers rely on animal models in the first place?
Yeah, sure.
What makes them so valuable in this context?
Well, I think the key is in the biological similarities between animals and humans.
You know, their organs function in very similar ways.
They have comparable metabolic pathways.
Right.
And often their responses to drugs mirror how humans might react.
(01:54):
So it's almost like having a preview of how the drug might behave in a human body.
But in this, like, controlled setting where scientists can kind of adjust the dosage, the environment?
Yeah, precisely.
That level of control is one of the big advantages of animal models.
Researchers can manipulate all those different factors in ways that just wouldn't be possible in human studies.
(02:17):
Makes sense.
Yeah.
And it lets them isolate certain specific effects and gain a deeper understanding of the drugs mechanisms.
Yeah, that makes a lot of sense.
These FDA documents also highlight the limitations of animal models.
Mm-hmm.
And the push for alternatives.
Yeah.
Because, I mean, no animal perfectly replicates a human system, right?
(02:37):
Right.
You're absolutely right.
There are always species-specific differences.
Of course, yeah.
And that can complicate predictions.
I mean, something that's safe in a rat might not be safe in a human.
Yeah.
So that's where the limitations become pretty apparent.
Yeah.
And it's why the scientific community is very actively pursuing alternatives, you know, to try to minimize that reliance on animal models.
(02:59):
From what I see here, there's a lot of exciting research happening.
Yeah.
Like in in vitro testing.
Mm-hmm.
And computer simulation.
Exactly.
In vitro testing, so using human cells in Petri dishes.
Right.
That allows scientists to actually study those effects directly on human tissues.
Mm-hmm.
It's a really powerful tool to see how a drug interacts with specific cells and pathways.
(03:21):
OK.
So it's a way to kind of zoom in on those cellular interactions.
Yeah.
Without having to use a whole organism.
Exactly.
And what about computer simulations?
Yeah.
So those are revolutionizing the field.
They allow researchers to model those complex biological processes.
They can virtually test a drug's effects.
Oh, wow.
On different organs and systems and predict potential side effects and even interactions.
(03:44):
Mm-hmm.
Before even, you know, stepping foot in a lab.
So it's almost like having this virtual laboratory where you can run a bunch of experiments.
Yeah.
Without any ethical considerations.
Exactly.
Or limitations of animal models.
You got it.
Although those technologies are still evolving.
They can't fully replace animal models just yet.
Right.
But they definitely hold immense promise for reducing our reliance on them in the future.
(04:06):
It's like we're standing at the cusp of a new era in drug safety testing, where technology
is letting us be both more efficient and more ethical.
Precisely.
And, you know, speaking of efficiency, one thing that really struck me in these FDA
documents is the sheer volume of testing required.
Mm-hmm.
It's not just about the active drug itself.
(04:27):
It's every single component, you know?
Like on drug labels, you see inactive ingredients.
Oh, yeah.
I always wondered about those.
Yeah.
They sound so boring.
Right.
But they're not so inactive when it comes to safety.
So even seemingly harmless ingredients can interact with the active drug.
Yeah.
Or even have like unforeseen effects on the body.
Exactly.
The FDA scrutinizes everything.
(04:49):
Wow.
And any change to the formulation can trigger a whole new wave of safety testing.
So it's not just about the star of the show, the drug itself.
Yeah.
But also the supporting cast of all the inactive ingredients.
Right.
They all have to go through this rigorous testing.
Yep.
To make sure they're playing their part safely.
Absolutely.
And it doesn't even stop there.
(05:10):
The manufacturing process itself is under the microscope.
So like imagine a company.
They want to tweak how a drug is made, maybe to improve efficiency or the yield.
Even if the product seems identical in the end, the FDA requires them to prove that change
hasn't introduced any new risks.
That's incredibly thorough.
Yeah.
(05:30):
It really underscores, you know, the importance of consistency and transparency in this world
of drug development.
Yeah.
Everything has to be like meticulously documented and validated.
Exactly.
Leaving no room for doubt when it comes to patient safety.
Absolutely.
And all of this is guided by those ICHS7 principles.
(05:51):
It's not just about will this drug kill you.
Yeah.
You know, it's about understanding all the subtle effects it has on your vital organs.
OK.
So let's dive into the nitty gritty then.
How do researchers actually assess a drug's impact?
Sure.
We're talking the heart, lungs, nervous system.
You know, the silent workhorses that keep us alive.
Exactly.
So a drug might not be lethal, but it could subtly disrupt these systems, and that would
(06:15):
lead to problems down the line.
Right.
So ICHS7 outlines a whole bunch of tests to evaluate these potential effects.
So what does that actually look like?
I'm picturing like a scene from a sci-fi movie with all these scientists huddled over blinking
monitors.
Yeah.
But what's the reality?
Well, it's not quite as dramatic as Hollywood portrays it.
Right.
But it's definitely meticulous, and it involves a wide range of tests.
(06:39):
So let's start with the cardiovascular system.
OK.
One of the most common assessments is the electrocardiogram, or EKG.
Right.
And that measures the heart's electrical activity.
Oh, OK.
So it allows researchers to identify irregularities in the heart rhythm or potential signs of damage
from the drug.
So they're basically like listening to the heart's electrical chatter.
(07:00):
Exactly.
Making sure the drug isn't like throwing off the beat.
Exactly.
And beyond just the electrical activity, researchers also look at blood pressure cause.
Some drugs can cause dangerous fluctuations in blood pressure.
So it's really important to see how a new drug might affect that.
So it's like giving the heart a complete checkup, just making sure it's functioning properly
(07:21):
under the influence of this new drug.
Exactly.
And what about the respiratory system?
How do they make sure a drug isn't going to mess with our breathing?
Right.
So for the respiratory system, a key focus is breathing rate.
OK.
And the volume of air inhaled and exhaled.
This reveals any signs of respiratory distress, like shortness of breath or shallow breathing.
(07:44):
So they're really monitoring the mechanics of breathing.
Exactly.
Making sure the lungs are working properly.
Yeah.
And the drug isn't causing any restriction.
Exactly.
They're also analyzing blood gases to see how well the lungs are absorbing oxygen and
removing carbon dioxide.
So it's a comprehensive pulmonary evaluation.
Yes.
Making sure the drug isn't interfering with our ability to breathe.
(08:04):
Exactly.
What about the nervous system?
Yeah.
That seems particularly challenging just because it's so complex.
Right.
And a drug could have all kinds of effects on it.
Yeah, you're right.
The nervous system is incredibly intricate.
And assessing neurotoxicity can be quite complex.
But ICHS7 outlines a bunch of tests to cover all those different potential effects.
(08:25):
So walk us through them.
What are some of the key things researchers are looking for when it comes to the nervous
system?
Well, one of the most, I guess, fundamental but crucial assessments is simply observing
the animal's behavior.
OK.
So researchers will look for changes in activity level, their coordination, gait, reflexes,
even things like their social interactions.
(08:48):
Any deviation from that normal behavior could be a sign that the drug is affecting the nervous
system.
Interesting.
So they're looking for any behavioral clues that might indicate a problem.
It's amazing how much you can tell just by observing.
It really is.
But beyond just simple observation, they also use more specialized techniques to assess
those specific aspects of nervous system function.
(09:08):
One common tool is electroencephalography.
EEG.
Exactly.
EEG, which measures the brain's electrical activity.
Oh, I've heard of that.
Yeah.
So it's like attaching electrodes to the brain to listen to its electrical conversations.
Wow.
And by analyzing those brainwave patterns, they can actually detect any abnormalities
that might be caused by the drug.
(09:29):
So it's a way to kind of peer into the electrical workings of the brain.
Yeah.
Make sure the drug isn't disrupting things.
Precisely.
And beyond these core assessments, researchers can delve even deeper.
You know, using specialized tests to evaluate things like cognitive ability, sensory perception,
the scope of that neurotoxicity testing can be really extensive depending on the drug
(09:53):
and its potential targets in the nervous system.
It's mind boggling to think about all the different ways a drug could affect the nervous
system.
Yeah.
But it's reassuring to know that researchers are equipped with so many different tools
to assess the risks.
Exactly.
And as technology keeps advancing, we're probably going to see even more sophisticated ways to
assess neurotoxicity.
Wow.
(10:13):
Allowing for a much deeper understanding of those things.
Understanding of those drug effects on the nervous system.
It's incredible how science is constantly pushing boundaries, giving us new insights
into how the human body works and the drugs we use to treat it.
Yeah, it really is remarkable how far we've come in understanding the nervous system and
(10:33):
how drugs can impact that delicate balance.
But let's maybe shift gears for a second and delve into another fascinating aspect of safety
pharmacology.
You highlighted this with all those FDA documents.
Lead the way.
What other intriguing corners of drug safety are we exploring today?
Well, we've talked a lot about animal models and their crucial role in these early safety
(10:56):
assessments.
But within that realm, there's this whole world of specific model organisms.
Right.
Each one is chosen for its unique characteristics and the insights that it can provide.
Yes, the model organisms.
It's like a cast a call for human standard.
Yeah.
Researchers selecting the best actor based on the specific question they're trying to
answer.
(11:16):
That's a fantastic analogy.
And just like in Hollywood, you know each organism brings its own talents to the set.
So like if researchers are concerned about a drugs effects on the cardiovascular system,
they might choose a dog or a pig because their cardiovascular systems are pretty similar to
humans.
So it's about finding the best match.
Yeah.
The organism that can most accurately mimic the human response and provide the most reliable
(11:41):
data.
Exactly.
But what about those species that seem, I don't know, less obviously related to us?
Yeah.
Like zebrafish or fruit flies.
I mean, they pop up in research sometimes.
Yeah.
What can those possibly tell us?
Right.
What could they tell us about human biology?
It might seem a little counterintuitive, but even those organisms that seem very distantly
(12:02):
related to humans can offer valuable insights.
Okay.
So like zebrafish, for example, surprisingly useful for studying developmental processes.
Their embryos are actually transparent.
So scientists can actually observe organ development in real time.
Wow.
That's incredible.
So it's not just about anatomical similarity then.
It's also about leveraging those unique characteristics of certain species.
(12:26):
Yeah.
Each organism has its own superpower.
Exactly.
And as technology keeps advancing, we're finding even more creative ways to use these organisms.
Right.
So scientists can now genetically modify mice, for example, to make them more susceptible
to certain diseases.
Oh, wow.
Which then allows for targeted drug testing.
So it's like tailoring the organism to fit the research question, creating this
(12:50):
more precise and efficient system.
Exactly.
But with those advancements come ethical considerations as well, right?
Of course.
The more we can manipulate these organisms, the more carefully we need to consider our actions.
Right.
The implications of our actions.
Exactly.
So the ability to modify these organisms raises those ethical questions about their
welfare and our responsibility as researchers.
(13:12):
Right.
So it's a constant dialogue within the scientific community, making sure that we're using these
models responsibly and ethically.
And speaking of responsibility, those FDA documents emphasize minimizing animal use
whenever possible.
It seems like a core principle guiding this whole field.
Oh, yeah.
Absolutely.
That's a top priority.
(13:33):
The three Rs, so replacement, reduction, and refinement, are guiding principles in animal research.
OK.
So scientists are constantly trying to find alternatives to animal models whenever they can.
And when animal studies are necessary, the aim is to use the fewest number of animals possible
while still making sure they're doing OK.
So it's not just about replacing animals then.
(13:55):
Right.
It's also about reducing the number and refining those studies to minimize any potential distress.
Exactly.
So it's this multi-pronged approach to ensure ethical research.
Right.
And this commitment to the three Rs is woven into the fabric of ICHS7.
Yeah.
So those guidelines prioritize both the scientific rigor and the animal welfare.
(14:19):
It's heartening to see that ethical considerations are such a big part of drug development.
Yeah, definitely.
It's about finding that balance between advancing scientific knowledge, but also respecting the
lives of these animals.
Well said.
And that's a balance that's constantly being refined.
As our understanding of both science and ethics evolves.
But beyond just the ethical considerations, there's also a practical aspect to minimizing animal use.
(14:44):
Oh, interesting.
So it's not just about doing the right thing.
There's also practical benefits to reducing reliance on animal models.
Oh, absolutely.
So animal studies, they can be really expensive.
Right.
And time consuming.
Right.
So just from a purely practical standpoint, there's a strong incentive to find alternatives
that are more efficient and cost effective.
(15:05):
Right.
And as technology progresses, we're seeing those alternatives emerge.
So it's this perfect storm of ethical and practical drivers kind of pushing the field toward these new approaches.
Exactly.
It's a win-win for both science and animal welfare.
Yeah.
But as we transition to these new methods, we need to be mindful of the challenges as well.
OK, what kinds of challenges?
It seems like a positive shift overall.
(15:27):
It is, but I think there's always going to be hurdles.
Right.
Whenever you're adopting new technologies.
Of course, yeah.
So one challenge is simply that validation process.
No.
Before we can rely on these new methods, we have to demonstrate that they're as good as traditional models.
Right.
And that takes time and research and a lot of careful comparison.
(15:49):
So it's not just about developing the technology itself.
Yeah.
You also have to prove that it works.
Yeah.
And the results are trustworthy.
Exactly.
Like a trust but verify thing in the scientific world.
Yeah.
And that verification is so important because, I mean, ultimately, the goal is to protect patients.
Therefore?
We need to be absolutely certain that these new methods are giving us the right information about a drug safety.
(16:13):
Speaking of patient safety, let's circle back to ICHS-7 and those vital organ systems we talked about.
You mentioned that researchers use a mix of in vivo and in vitro approaches to assess drug effects.
Mm-hmm.
Can you maybe give us some specific examples of the types of tests used?
Yeah, of course.
Let's go back to the cardiovascular system.
(16:34):
One of the most common tests is the electrocardiogram or EKG, which measures the electrical activity of the heart.
Right.
So this can reveal irregularities in the heart rhythm, like arrhythmias, which can be a side effect of some drugs.
So it's like listening to the heart's electrical signals.
Yeah.
Looking for any unusual patterns.
Right.
(16:55):
And what other tests are used to assess cardiovascular safety?
Well, another important one is blood pressure monitoring.
Okay.
Some drugs can cause blood pressure to like rise or fall dangerously.
Yeah.
So it's important to see how a new drug might affect that.
Right.
And then in some cases, they might even look at the heart tissue under a microscope.
(17:16):
Wow.
To check for any structural changes that might show damage from the drug.
So it's a really multifaceted approach.
Mm-hmm.
Looking at the electrical activity, the blood pressure, and even the microscopic structure of the tissue.
Exactly.
Like a detective at a crime scene.
Gathering clues from every angle.
Exactly.
And that attention to detail is really important because the cardiovascular system is so central to our overall health.
(17:41):
Any disruption to that can have effects throughout the whole body.
Right.
Yeah.
Okay.
So we've covered the heart.
Mm-hmm.
What about the lungs?
How do they assess a drug's impact on the respiratory system?
Right. So one common method is to actually measure the animal's breathing rate.
Okay.
And the volume of air they inhale and exhale.
(18:01):
So this can show any signs of respiratory distress, like shortness of breath or really rapid shallow breathing.
So they're monitoring the mechanics of breathing basically?
Yeah, exactly.
Just making sure the lungs are functioning okay?
Uh-huh.
And I imagine they also look at blood gases, right?
Yeah.
To see how well the oxygen is being absorbed.
There you go.
Yes, you're absolutely right.
So analyzing the blood gases can tell us a lot about how well the lungs are oxygenating the blood
(18:26):
and removing carbon dioxide.
And then sometimes they might also examine the lung tissue under a microscope
to look for signs of inflammation or damage.
It's like they're putting a puzzle together using all these different pieces of information
to get this full picture of what the drug is doing to the respiratory system.
Exactly.
And just like with the cardiovascular system, any disruption there can be serious.
(18:49):
Yeah.
So this really thorough assessment is super important.
Okay, so we've got the heart, the lungs.
Now, what about the nervous system?
Right.
That seems like a particularly challenging one to assess given how complex it is.
It is incredibly complex.
And because the nervous system controls so many different bodily functions,
any kind of disruption to it can have a whole range of effects.
(19:11):
So researchers use a bunch of approaches to assess that neurotoxicity.
Okay, so walk us through some of those.
What kinds of tests do they do for the nervous system?
So one of the most basic methods, but still important, is just observing the animal's behavior.
Oh, no.
So researchers look for any changes in their activity level, their coordination, gait, reflexes,
(19:33):
even things like their social interactions.
Interesting.
So any change from normal behavior could be a sign that the drug is affecting the nervous system.
So it's like looking for any little behavioral quirks that might indicate a problem.
It's amazing how much you can learn just by watching.
Yeah.
But they also use more specialized techniques to actually assess that nervous system function.
(19:54):
One of the most common ones is electroencephalography, or EEG.
EEG, yeah.
Which measures the electrical activity of the brain.
So they're basically attaching electrodes to the animal's head to listen to the brain's signals.
Oh, wow. I've heard of that before.
Yeah. And by analyzing those brainwave patterns, they can detect abnormalities
(20:16):
that might be caused by the drug.
Wow.
And they can also use it to look at things like sleep-wake cycles
and even cognitive functions sometimes.
So they're not just looking at basic movement.
Right.
They're looking at brain activity, too.
Exactly.
It's incredible how sophisticated these techniques have become.
It is. And as technology keeps advancing,
(20:36):
we're likely to see even more refined methods for assessing neurotoxicity.
Wow.
So there's a growing interest in using imaging techniques like fMRI to actually visualize brain
activity happening.
Wow.
And that can give us a much more detailed understanding of the drug's effects.
It's like we're constantly pushing the boundaries to get a deeper understanding
(20:59):
of the nervous system and how drugs impact that.
Absolutely. But even with all these advancements, there are always challenges
when it comes to predicting how a drug will behave in a human being.
Right, of course, because the human body is so complex.
Yeah.
You can't always predict everything.
You're absolutely right. The human body is incredibly complex.
Yeah.
And there's always individual variation that makes it difficult to predict every single side effect.
(21:24):
But the goal of safety pharmacology is to really minimize those risks as much as possible.
Right.
And the guidelines in ICHS-7 are like constantly evolving to reflect the latest science.
It's a constant quest for knowledge, then.
Refining our understanding of the body and the drugs we use.
Exactly. And it's a quest that needs constant vigilance.
(21:46):
Yeah.
Even after a drug is deemed safe and is on the market.
You've hit a crucial point there.
Yeah.
The journey doesn't end with those initial studies.
Right.
And the approvals. There's a whole world of post-market surveillance.
Mm-hmm.
That continues to monitor the drug's performance.
Exactly. You know, making sure it lives up to its promises and doesn't have any unexpected risks.
(22:07):
Okay. Let's unpack that a bit. What does post-market surveillance actually entail?
What's in place to make sure a drug is still safe and effective once it's out there?
Being used by millions of people. So we know the journey doesn't end when a drug is approved.
Right. There's this whole system of post-market surveillance.
Right.
But what does that actually look like? Is the FDA sending out spies to watch people take their pills?
(22:32):
Well, it's not quite a spy movie.
Right.
But there's definitely like a system for monitoring. So companies have to report any adverse events.
Okay.
That come up after a drug is approved.
So if someone has like a weird side effect.
Yeah.
That wasn't caught in the trials, that gets reported to the FDA.
Exactly. And the FDA takes all those reports and analyzes them.
(22:55):
Wow.
Looking for patterns or anything that might suggest a problem. They actually have a whole division for this kind of post-market surveillance.
That's good to know.
Yeah.
So it's not like a see-y'all later situation once the drug is approved.
Right.
There's still this commitment to making sure it's safe out in the real world.
Yeah.
With all its complexities.
Absolutely. And it's not just about collecting data. The FDA can take action based on those findings.
(23:18):
So they might update the drugs label with new warnings or require more studies.
They can even take a drug off the market completely if it turns out to be riskier than they thought.
Wow. So it's pretty serious business.
Yeah, it is.
So those initial ICHS7 studies, they're just the beginning, kind of laying the groundwork for this long-term assessment.
Exactly. Those early studies give us this baseline understanding of the drug's safety.
(23:43):
But the real test is when it's out there being used by lots of different people with different medical histories and lifestyle.
It really makes you realize how complex this whole thing is. It's not just about science. It's about being vigilant and data analysis.
And just this constant commitment to protecting public health.
(24:03):
Yeah. And it highlights the collaborative nature of all of it. It's scientists and regulators, health care providers, and even patients.
They all play a role in making sure medications are used safely.
Speaking of patients, I'm curious about their role. I mean, beyond just taking the medication, how do they contribute to this ongoing assessment?
That's a great question. So patients are really important through something called pharmacovigilance.
(24:26):
OK.
Which is basically collecting and monitoring information about the effects of medicines.
Right.
And a lot of that comes from patients themselves reporting side effects or anything unusual they experience while taking a drug.
So it's almost like a citizen science project.
Yeah, exactly.
Patients are contributing data to this safety assessment.
That's a great way to put it. And there are a lot of ways for them to report these things.
(24:49):
They can talk to their doctors or contact the company that makes the drug directly or even use online reports to report the drug.
They can use online reporting systems from like the FDA.
So they really have a voice in this and can contribute to the safety of meds.
Yeah. And it sort of closes the loop. It creates a feedback system where real world experiences help shape the evaluation of a drug's safety.
(25:13):
It's really amazing how all these pieces fit together from those early ICHS7 studies through the approvals and into this post-market surveillance.
It's science and regulation and patient engagement all working together to keep the medications we use safe.
It really is. It's a testament to the work of so many people behind the scenes, you know, to protect public health.
(25:34):
Absolutely. And it really shows why it's so important to stay informed.
The more we all understand about this process, the better we can be about our own health and well-being.
Absolutely. Knowledge is power, right?
Yeah.
The more we know about our medications, the more we can advocate for our health.
Exactly.
And contribute to finding those safer and more effective treatments.
Well, there you have it. A deep dive into ICHS7.
(25:58):
We explored the intricacies of animal models and those assessments of vital organs.
And we've seen how post-market surveillance works.
Hopefully, you've gained a new appreciation for the complexities of drug safety and the dedication of everyone working to make sure our meds are safe and effective.
Until next time, stay curious and keep those questions coming.
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