February 21, 2023 • 24 mins
How well does it work and how can you illustrate that? Diana Colleluori explains potency assays and best practices with them.
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James C. Taylor (00:02):
How can you quantify and illustrate how well
what you're developing works?
We talk with Diana Colleluoriabout potency assays.
I'm James C.
Taylor, and this is Insight at Biologics.
And joining me now is Diana.
(00:23):
Diana.
Why don't you tell 'em alittle bit about yourself?
Diana Colleluori (00:26):
I'm happy to.
I have a PhD in biochemistry and an MBAin pharmaceutical and healthcare business.
I have been in the industry for over20 years now, mostly with varying small
to large pharmaceutical companies,innovator companies, and I would say
(00:49):
the first half of my career was probablymore focused in large molecules like
monoclonal antibodies, but the latter halfof my career has been primarily focused
in the cell and gene therapy space.
I've joined Biologics Consulting just overa year ago and am happy to share my wisdom
(01:14):
and knowledge in the potency assay space.
James C. Taylor (01:19):
Awesome.
So let's start with that.
What actually is a potency assay?
Diana Colleluori (01:25):
So that is a bit of a loaded question.
There are several FDA guidances.
There is of course the USCode of Federal Regulations.
I would say as far as regulationsare concerned, the most important one
(01:46):
that I have seen referenced and usedis the potency test for cellular and
gene therapy products and the potencyassay, I'll give you the formal
definition and we can talk a littlebit about what that actually means.
But potency is really defined asthe specific ability or capacity
(02:09):
of the product, drug productas, as indicated by lab test, is
going to affect a given result.
And that is the definition, «laughs».
So what, what that actually means isthat the potency method is usually an
(02:32):
in vitro assessment of the cellularat the cellular level of the specific
activity of your drug product.
James C. Taylor (02:41):
Mm-hmm.
Diana Colleluori (02:41):
So, so that you are measuring the intended downstream
biological effect of what you want yourproduct to do in vivo and that that is
essentially, what a potency assay is.
James C. Taylor (03:00):
Okay.
Diana Colleluori (03:01):
I-- and, and I would, I would add too, James, that
unfortunately, more often than notfor cell and gene therapies, a single
assay is not typically satisfactory.
There are several reasons for this.
I would say the two biggest reasons that asingle potency assay is not satisfactory,
(03:25):
is that cell and gene therapies arecomplex products and often have more
than one mechanism of action, and, andsometimes even more than one active
ingredient, which makes measurement ofpotency of your product very difficult.
James C. Taylor (03:45):
Mm-hmm.
Diana Colleluori (03:45):
The, the second reason is that a lot of times the cell
and gene therapy space, those productshave poorly characterized and poorly or
poorly understood mechanisms of action.
So there may be, you know, a, a celltherapy, for example, that isn't
(04:06):
gene modified, that is exerting abiological effect that is so complicated
and not quite un well understood.
So that the measurement of potency of yourdrug product becomes very complicated.
So using more than one potency assaytends to be the favored approach
(04:32):
by the FDA, and, and this isconsidered a matrix approach, okay?
Where, where you're using multiplecomplimentary assays that measure
different product attributes,but they each contribute to
the quality, consistency, andstability of the drug product.
(04:53):
So, so when you ask what a potency assayis, it really is a loaded question.
Unless you, unless you have a, a verywell defined mechanism of action.
James C. Taylor (05:05):
Okay.
All right.
Fair enough.
Diana Colleluori (05:07):
Yep.
James C. Taylor (05:08):
So you were talking a little bit about the
regulations for potency assays.
What are the current regulations,especially where the, where gene
and cell therapy are concerned?
Diana Colleluori (05:19):
Yeah.
As I mentioned, the, the FDA guidance forindustry on potency tests for cellular
and gene therapy products is probablythe, the most important one, aside
from the Code of Federal Regulations.
And they, they sort ofcompliment each other.
The, the regulations in the CFR,whether it's 210, 211, or 600 and
(05:46):
610, uh, give more explanation anddetails around what potency is, but
also what your potency assay has to do.
So those are the the regulations thatI would look toward if I was trying to
gain a better understanding of what'sbeing expected of a potency assay.
James C. Taylor (06:10):
Okay.
Fair enough.
So what is the most appropriatetime during product development to
begin developing your potency assay?
Diana Colleluori (06:23):
Yesterday.
«laughter» I'll say it is never too early.
And this goes all the way back to yourpreclinical development stages, that
once the mechanism of action of yourproduct is known or you have an idea
(06:45):
of what it is or what your productis supposed to do, that's when the
development of a true potency assayor a matrix of assays should begin.
Um, it's, it's important to understand,and I think a lot of, a lot of folks
developing products get tripped up inthis, is that they're using maybe a
(07:11):
pseudo potency assay in the beginningof the development of a potential
product, and the expectations really haveshifted to needing potency assessments
earlier than phase two / phase three.
The expectation is that theseassays are at, at a minimum being
(07:34):
developed in the preclinical stages.
And I'll say that the, there arelots of reasons to do this and
I'll, I'll go through a few, but.
What is really vital to understand isthat the ability to measure potency
is fundamental to understanding yourdrug product and therefore using the
(08:00):
early product development time tofully characterize and understand
your product is, is critical.
And as I said, it is more ofan expectation today that--
James C. Taylor (08:14):
Mm-hmm.
Diana Colleluori (08:14):
--this is, that this is happening and as I, so, as I noted,
there are, there are lots of reasonsto start measuring potency early.
I'll give you a few that I've seen.
One is the ability to demonstrateyour product's activity,
quality and consistencythroughout product development.
(08:35):
So you're starting in the preclinicalstages, getting ready for filing an
IND and making a clinical batch ortwo or more, and you want that, that
consistency from pre-IND all the waythrough the development of your product.
(08:56):
. The other important reason is thatgenerating and collecting data for
potency of product lots will supportsetting your specifications for
your product with regard to potency.
So those, those are two big, big reasonsin the beginning to get this started.
(09:21):
Don't wait.
You really should begin to think aboutand develop prob-- probably a battery
of, of different potency measuresthat you have in your back pocket.
You, you're going to need potencyfor so many, so many things.
(09:44):
Aside from lot release, changes inmanufacturing process, the stability
and setting your shelf life, and,and I could go on and on, but the,
the development has to start early.
That, that is really critical and thedata that you're going to collect as early
(10:06):
as possible will be extremely importantfor the future development of your
product through throughout its lifetime.
James C. Taylor (10:17):
Now we, we've kind of been discussing the beginning
of the life cycle of an assay.
So what is the progression ofthe life cycle of the assay?
Diana Colleluori (10:30):
That is a great question.
So the first thing is the appropriatepotency assay design, right?
So some examples are you need tounderstand the sources of method
variability, and be able to work onreducing or eliminating those sources of
(10:56):
variability that are just in your assayso that you can continue to develop and
basically have continuous improvementaround the development of your assay.
So appropriate assay design,understanding your method.
(11:17):
I would say also, as you arebeginning to design your assay and
put it online for use, you have toconsider a lot of other variables,
critical assay reagents, for example.
James C. Taylor (11:31):
Mm-hmm.
Diana Colleluori (11:31):
This should be thought about pretty early because
you don't wanna get locked into usinga single source reagent or something
that's custom, that is expensive orperhaps critical reagents that are
not of the appropriate grade for use.
(11:51):
Do you need to qualify a cellbank for the cells that you need
in your, in your potency assay?
Do you have redundant equipment?
What, you know, what equipment are yougoing to use for the output of your assay?
Or, or even multiple labsites, do they have the same
equipment across multiple sites?
(12:13):
Those are some of the, some of thethings that need to be thought about
first and then of course, development.
And you know, that continuousimprovement and optimization of
the method can continue right and--
James C. Taylor (12:28):
Right.
Diana Colleluori (12:29):
And you, as you continue to understand your product and
you continue learning about your method,you can continue to do improvements.
So I'm sure a lot of people are,are wondering, you know, when, when
should they start doing qualificationsand and validation activities.
(12:53):
Once you have a, a solid methoddeveloped, even if you know, there
may be changes down the road for,usually for phase one, now you need to
have a, a what, what everybody callsa phase appropriate qualification.
This means you have a,a fairly solid method.
(13:17):
It's generally expected that thismethod is quantitative and that you
do have acceptance criteria in placefor, for that method, for example, for
lot release of batches for phase one.
The, the idea of a phase appropriatequalification generally is like
(13:40):
a light version of a validation.
May-- maybe not as many runs.
Definitely not really looking ataspects of robustness at this point.
It's usually once you get to phasetwo that it gets a little bit closer
to a validation state where you maynot be doing robustness at that point
(14:05):
either, but you're definitely going towant to satisfy the ICH requirements
for validation around the otherparameters like precision and accuracy.
The full validation is now generallyexpected to be in place to test
your pivotal drug product samples.
(14:28):
And I don't say phase three here becausea lot of cell and gene therapy products
are moving through clinical development atlightning speed and often what would be a
phase two may turn into your pivotal data.
(14:49):
So, so not only do you need a validatedmethod in place to be able to test your
pivotal drug product samples, but the ideathat the timeline of development of your
product has shortened so much because somany of these products are fast tracked
(15:12):
and, and just like I said, lightningspeed through clinical development.
That it, it puts a lot more pressureon being able to develop your potency
assay sooner and validating it sooner.
So starting it yesterday, and also, andalso validating it sooner is, is sort
(15:35):
of what is being expected, you know.
And then of course, commercial andbeyond is, is the, the same idea.
Um, you know, maintaining that validatedstate, trending the performance of
your assay, re-validating the assayif significant changes occur, whether
it's to the method or to reagents or toyour manufacturing process, et cetera.
(16:02):
But that's generally what I havebeen seeing with the progression
of a potency assay life cycle andwhen the, not only the development
begins, but also the phase appropriatequalification and validation activities.
James C. Taylor (16:22):
Now, what are some of the pitfalls of an
assay that should be avoided?
Diana Colleluori (16:28):
I will give you three.
The first one is probably obviousis waiting too long to develop your
potency assay and, and not onlywaiting too long, but also perhaps
not realizing how long it takes todevelop and qualify a potency ass.
(16:52):
This can be a months long process.
I mean, some of these cell-based bioassaysthat are being used for potency take
several days just to run one assay.
And if you are in, you know, thethroes of trying to develop and
understand the method and optimizethe method, this could be weeks to
(17:16):
months long before you can even havea method that is satisfactory enough
to be able to, to do a qualification.
Would it, would it even passin precision, for example?
So waiting too long isprobably the first pitfall.
(17:36):
The second I would say isactually having an open and
honest dialogue with the agency.
I have seen in several instances whereinformation about how the progression
and development of the potencyassay is going is not being shared
(17:59):
openly and honestly with the agency.
And it's actually more beneficialto you to be upfront with them
because ultimately the agencywants to see you succeed as well.
So every opportunity that you haveto interact with the agency to share
(18:22):
with them the progress of your potencyassay is, is extremely important.
I, I would, I would actually say every,every meeting, every briefing book or
question should always have a potencyrelated question, answer in there,
(18:42):
because it, it, it's happening so fastand, and you may have more information
and data and you want to get feedbackfrom them on what are their thoughts.
Is this going to be, uh, asatisfactory enough potency method
for, say, pivotal-- pivotal studies?
And if you don't communicate withthem, you could get to that point in
(19:05):
your product development with an assaywithout having any feedback from the
agency and be told, you know, at the 11thhour that it's, it's not good enough.
So it, it is really importantto be open and honest with them.
I would also as a, as a footnote to this, to this pitfall, also note that when you
(19:28):
do get feedback regarding potency methods,it's important to read between the lines.
I think we all know that the agency is notgoing to come out and tell you what to do.
That, that just doesn't happen.
You are proposing to them what you wantto do, what you think you should do,
and they're giving you feedback on, onwhat they think, how your approach is.
(19:53):
If, if they ever recommend an approachor recommend a, a change to the
method or recommend that you havea second potency assay, I recommend
that you follow their recommendations.
It, it's, it's almost the, therecommendation is almost saying
(20:17):
"You really should do this."
«laughs»
James C. Taylor (20:20):
Right.
Diana Colleluori (20:20):
And so, so I'll stop there for that one.
But the final pitfall that I have seen isnot having enough product routines and.
I, I hope people that are listeningwill understand what I mean when I say
that because the potency method oftenchanges throughout the development
(20:46):
and, and the life cycle of not only theassay, but the, the product that if you
have from phase one to say phase three,made some pretty significant changes
to your method, for example, you mayneed to go back and retest samples that
(21:08):
have already been tested and releasedto gain the data of the, the potency
of those batches using your newlyqualified or newly validated method.
And, and I've even seen this inphase three pivotal studies where the
method is, is still being optimizedand trying to get it validated.
(21:32):
So you may be in the throes ofyour pivotal study, but you still
need retains from that study to beable to go back and, and test your
product lots in, in that method.
And it's really important becauseit's not just for, well, of
(21:52):
course, for specification settingof the product moving forward.
But, you know, all of the statisticalanalysis in relation to the clinical
data, it, it's all tied together.
So product retains is, is another pitfall.
That, I would say, make sure youare putting aside enough retains
(22:16):
for things that you can't evenfathom that you might need it
for at that at that point in time.
So be prepared for the unexpected.
James C. Taylor (22:28):
So we're just about out of time here.
So first of all, people can come toyou for more information, correct?
Diana Colleluori (22:38):
Absolutely.
James C. Taylor (22:40):
Yes.
And I'm sure you'd welcome it.
But what key takeaways would you likepeople to leave this conversation with?
Diana Colleluori (22:49):
I would say the, the key takeaways will be
assay development as early as possible.
It is a dynamic and progressive process.
Second, I would say use all of your FDAinteractions to communicate and discuss
the progress of your potency assay.
(23:11):
And finally, retains, retains, retains.
There are so many reasons that youmay need to go backwards to test lots.
Potency assays tend to be a, abig reason for having to do that.
Those are the, the three mainthings that I think are important
(23:32):
for the community to know.
James C. Taylor (23:34):
Thank you, Diana.
If you'd like to talk to heror any of us here at Biologics
Consulting, just send us an emailat insight@biologicsconsulting.com.
That's Insight at BiologicsConsulting all one word dot com.
The Executive producer of Insightat Biologics is Kris Kraihanzel.
This episode was producedand edited by James C.
Taylor.
(23:54):
The technical supervisor is Jeff Wease.
The Insight at Biologicstheme is by Tom Rory Parsons.
I'm James C.
Taylor.
Please come back for moreInsight at Biologics.
How can you quantify and illustrate how well
what you're developing works?
We talk with Diana Colleluoriabout potency assays.
I'm James C.
Taylor, and this is Insight at Biologics.
And joining me now is Diana.
(00:23):
Diana.
Why don't you tell 'em alittle bit about yourself?
Diana Colleluori (00:26):
I'm happy to.
I have a PhD in biochemistry and an MBAin pharmaceutical and healthcare business.
I have been in the industry for over20 years now, mostly with varying small
to large pharmaceutical companies,innovator companies, and I would say
(00:49):
the first half of my career was probablymore focused in large molecules like
monoclonal antibodies, but the latter halfof my career has been primarily focused
in the cell and gene therapy space.
I've joined Biologics Consulting just overa year ago and am happy to share my wisdom
(01:14):
and knowledge in the potency assay space.
James C. Taylor (01:19):
Awesome.
So let's start with that.
What actually is a potency assay?
Diana Colleluori (01:25):
So that is a bit of a loaded question.
There are several FDA guidances.
There is of course the USCode of Federal Regulations.
I would say as far as regulationsare concerned, the most important one
(01:46):
that I have seen referenced and usedis the potency test for cellular and
gene therapy products and the potencyassay, I'll give you the formal
definition and we can talk a littlebit about what that actually means.
But potency is really defined asthe specific ability or capacity
(02:09):
of the product, drug productas, as indicated by lab test, is
going to affect a given result.
And that is the definition, «laughs».
So what, what that actually means isthat the potency method is usually an
(02:32):
in vitro assessment of the cellularat the cellular level of the specific
activity of your drug product.
James C. Taylor (02:41):
Mm-hmm.
Diana Colleluori (02:41):
So, so that you are measuring the intended downstream
biological effect of what you want yourproduct to do in vivo and that that is
essentially, what a potency assay is.
James C. Taylor (03:00):
Okay.
Diana Colleluori (03:01):
I-- and, and I would, I would add too, James, that
unfortunately, more often than notfor cell and gene therapies, a single
assay is not typically satisfactory.
There are several reasons for this.
I would say the two biggest reasons that asingle potency assay is not satisfactory,
(03:25):
is that cell and gene therapies arecomplex products and often have more
than one mechanism of action, and, andsometimes even more than one active
ingredient, which makes measurement ofpotency of your product very difficult.
James C. Taylor (03:45):
Mm-hmm.
Diana Colleluori (03:45):
The, the second reason is that a lot of times the cell
and gene therapy space, those productshave poorly characterized and poorly or
poorly understood mechanisms of action.
So there may be, you know, a, a celltherapy, for example, that isn't
(04:06):
gene modified, that is exerting abiological effect that is so complicated
and not quite un well understood.
So that the measurement of potency of yourdrug product becomes very complicated.
So using more than one potency assaytends to be the favored approach
(04:32):
by the FDA, and, and this isconsidered a matrix approach, okay?
Where, where you're using multiplecomplimentary assays that measure
different product attributes,but they each contribute to
the quality, consistency, andstability of the drug product.
(04:53):
So, so when you ask what a potency assayis, it really is a loaded question.
Unless you, unless you have a, a verywell defined mechanism of action.
James C. Taylor (05:05):
Okay.
All right.
Fair enough.
Diana Colleluori (05:07):
Yep.
James C. Taylor (05:08):
So you were talking a little bit about the
regulations for potency assays.
What are the current regulations,especially where the, where gene
and cell therapy are concerned?
Diana Colleluori (05:19):
Yeah.
As I mentioned, the, the FDA guidance forindustry on potency tests for cellular
and gene therapy products is probablythe, the most important one, aside
from the Code of Federal Regulations.
And they, they sort ofcompliment each other.
The, the regulations in the CFR,whether it's 210, 211, or 600 and
(05:46):
610, uh, give more explanation anddetails around what potency is, but
also what your potency assay has to do.
So those are the the regulations thatI would look toward if I was trying to
gain a better understanding of what'sbeing expected of a potency assay.
James C. Taylor (06:10):
Okay.
Fair enough.
So what is the most appropriatetime during product development to
begin developing your potency assay?
Diana Colleluori (06:23):
Yesterday.
«laughter» I'll say it is never too early.
And this goes all the way back to yourpreclinical development stages, that
once the mechanism of action of yourproduct is known or you have an idea
(06:45):
of what it is or what your productis supposed to do, that's when the
development of a true potency assayor a matrix of assays should begin.
Um, it's, it's important to understand,and I think a lot of, a lot of folks
developing products get tripped up inthis, is that they're using maybe a
(07:11):
pseudo potency assay in the beginningof the development of a potential
product, and the expectations really haveshifted to needing potency assessments
earlier than phase two / phase three.
The expectation is that theseassays are at, at a minimum being
(07:34):
developed in the preclinical stages.
And I'll say that the, there arelots of reasons to do this and
I'll, I'll go through a few, but.
What is really vital to understand isthat the ability to measure potency
is fundamental to understanding yourdrug product and therefore using the
(08:00):
early product development time tofully characterize and understand
your product is, is critical.
And as I said, it is more ofan expectation today that--
James C. Taylor (08:14):
Mm-hmm.
Diana Colleluori (08:14):
--this is, that this is happening and as I, so, as I noted,
there are, there are lots of reasonsto start measuring potency early.
I'll give you a few that I've seen.
One is the ability to demonstrateyour product's activity,
quality and consistencythroughout product development.
(08:35):
So you're starting in the preclinicalstages, getting ready for filing an
IND and making a clinical batch ortwo or more, and you want that, that
consistency from pre-IND all the waythrough the development of your product.
(08:56):
. The other important reason is thatgenerating and collecting data for
potency of product lots will supportsetting your specifications for
your product with regard to potency.
So those, those are two big, big reasonsin the beginning to get this started.
(09:21):
Don't wait.
You really should begin to think aboutand develop prob-- probably a battery
of, of different potency measuresthat you have in your back pocket.
You, you're going to need potencyfor so many, so many things.
(09:44):
Aside from lot release, changes inmanufacturing process, the stability
and setting your shelf life, and,and I could go on and on, but the,
the development has to start early.
That, that is really critical and thedata that you're going to collect as early
(10:06):
as possible will be extremely importantfor the future development of your
product through throughout its lifetime.
James C. Taylor (10:17):
Now we, we've kind of been discussing the beginning
of the life cycle of an assay.
So what is the progression ofthe life cycle of the assay?
Diana Colleluori (10:30):
That is a great question.
So the first thing is the appropriatepotency assay design, right?
So some examples are you need tounderstand the sources of method
variability, and be able to work onreducing or eliminating those sources of
(10:56):
variability that are just in your assayso that you can continue to develop and
basically have continuous improvementaround the development of your assay.
So appropriate assay design,understanding your method.
(11:17):
I would say also, as you arebeginning to design your assay and
put it online for use, you have toconsider a lot of other variables,
critical assay reagents, for example.
James C. Taylor (11:31):
Mm-hmm.
Diana Colleluori (11:31):
This should be thought about pretty early because
you don't wanna get locked into usinga single source reagent or something
that's custom, that is expensive orperhaps critical reagents that are
not of the appropriate grade for use.
(11:51):
Do you need to qualify a cellbank for the cells that you need
in your, in your potency assay?
Do you have redundant equipment?
What, you know, what equipment are yougoing to use for the output of your assay?
Or, or even multiple labsites, do they have the same
equipment across multiple sites?
(12:13):
Those are some of the, some of thethings that need to be thought about
first and then of course, development.
And you know, that continuousimprovement and optimization of
the method can continue right and--
James C. Taylor (12:28):
Right.
Diana Colleluori (12:29):
And you, as you continue to understand your product and
you continue learning about your method,you can continue to do improvements.
So I'm sure a lot of people are,are wondering, you know, when, when
should they start doing qualificationsand and validation activities.
(12:53):
Once you have a, a solid methoddeveloped, even if you know, there
may be changes down the road for,usually for phase one, now you need to
have a, a what, what everybody callsa phase appropriate qualification.
This means you have a,a fairly solid method.
(13:17):
It's generally expected that thismethod is quantitative and that you
do have acceptance criteria in placefor, for that method, for example, for
lot release of batches for phase one.
The, the idea of a phase appropriatequalification generally is like
(13:40):
a light version of a validation.
May-- maybe not as many runs.
Definitely not really looking ataspects of robustness at this point.
It's usually once you get to phasetwo that it gets a little bit closer
to a validation state where you maynot be doing robustness at that point
(14:05):
either, but you're definitely going towant to satisfy the ICH requirements
for validation around the otherparameters like precision and accuracy.
The full validation is now generallyexpected to be in place to test
your pivotal drug product samples.
(14:28):
And I don't say phase three here becausea lot of cell and gene therapy products
are moving through clinical development atlightning speed and often what would be a
phase two may turn into your pivotal data.
(14:49):
So, so not only do you need a validatedmethod in place to be able to test your
pivotal drug product samples, but the ideathat the timeline of development of your
product has shortened so much because somany of these products are fast tracked
(15:12):
and, and just like I said, lightningspeed through clinical development.
That it, it puts a lot more pressureon being able to develop your potency
assay sooner and validating it sooner.
So starting it yesterday, and also, andalso validating it sooner is, is sort
(15:35):
of what is being expected, you know.
And then of course, commercial andbeyond is, is the, the same idea.
Um, you know, maintaining that validatedstate, trending the performance of
your assay, re-validating the assayif significant changes occur, whether
it's to the method or to reagents or toyour manufacturing process, et cetera.
(16:02):
But that's generally what I havebeen seeing with the progression
of a potency assay life cycle andwhen the, not only the development
begins, but also the phase appropriatequalification and validation activities.
James C. Taylor (16:22):
Now, what are some of the pitfalls of an
assay that should be avoided?
Diana Colleluori (16:28):
I will give you three.
The first one is probably obviousis waiting too long to develop your
potency assay and, and not onlywaiting too long, but also perhaps
not realizing how long it takes todevelop and qualify a potency ass.
(16:52):
This can be a months long process.
I mean, some of these cell-based bioassaysthat are being used for potency take
several days just to run one assay.
And if you are in, you know, thethroes of trying to develop and
understand the method and optimizethe method, this could be weeks to
(17:16):
months long before you can even havea method that is satisfactory enough
to be able to, to do a qualification.
Would it, would it even passin precision, for example?
So waiting too long isprobably the first pitfall.
(17:36):
The second I would say isactually having an open and
honest dialogue with the agency.
I have seen in several instances whereinformation about how the progression
and development of the potencyassay is going is not being shared
(17:59):
openly and honestly with the agency.
And it's actually more beneficialto you to be upfront with them
because ultimately the agencywants to see you succeed as well.
So every opportunity that you haveto interact with the agency to share
(18:22):
with them the progress of your potencyassay is, is extremely important.
I, I would, I would actually say every,every meeting, every briefing book or
question should always have a potencyrelated question, answer in there,
(18:42):
because it, it, it's happening so fastand, and you may have more information
and data and you want to get feedbackfrom them on what are their thoughts.
Is this going to be, uh, asatisfactory enough potency method
for, say, pivotal-- pivotal studies?
And if you don't communicate withthem, you could get to that point in
(19:05):
your product development with an assaywithout having any feedback from the
agency and be told, you know, at the 11thhour that it's, it's not good enough.
So it, it is really importantto be open and honest with them.
I would also as a, as a footnote to this, to this pitfall, also note that when you
(19:28):
do get feedback regarding potency methods,it's important to read between the lines.
I think we all know that the agency is notgoing to come out and tell you what to do.
That, that just doesn't happen.
You are proposing to them what you wantto do, what you think you should do,
and they're giving you feedback on, onwhat they think, how your approach is.
(19:53):
If, if they ever recommend an approachor recommend a, a change to the
method or recommend that you havea second potency assay, I recommend
that you follow their recommendations.
It, it's, it's almost the, therecommendation is almost saying
(20:17):
"You really should do this."
«laughs»
James C. Taylor (20:20):
Right.
Diana Colleluori (20:20):
And so, so I'll stop there for that one.
But the final pitfall that I have seen isnot having enough product routines and.
I, I hope people that are listeningwill understand what I mean when I say
that because the potency method oftenchanges throughout the development
(20:46):
and, and the life cycle of not only theassay, but the, the product that if you
have from phase one to say phase three,made some pretty significant changes
to your method, for example, you mayneed to go back and retest samples that
(21:08):
have already been tested and releasedto gain the data of the, the potency
of those batches using your newlyqualified or newly validated method.
And, and I've even seen this inphase three pivotal studies where the
method is, is still being optimizedand trying to get it validated.
(21:32):
So you may be in the throes ofyour pivotal study, but you still
need retains from that study to beable to go back and, and test your
product lots in, in that method.
And it's really important becauseit's not just for, well, of
(21:52):
course, for specification settingof the product moving forward.
But, you know, all of the statisticalanalysis in relation to the clinical
data, it, it's all tied together.
So product retains is, is another pitfall.
That, I would say, make sure youare putting aside enough retains
(22:16):
for things that you can't evenfathom that you might need it
for at that at that point in time.
So be prepared for the unexpected.
James C. Taylor (22:28):
So we're just about out of time here.
So first of all, people can come toyou for more information, correct?
Diana Colleluori (22:38):
Absolutely.
James C. Taylor (22:40):
Yes.
And I'm sure you'd welcome it.
But what key takeaways would you likepeople to leave this conversation with?
Diana Colleluori (22:49):
I would say the, the key takeaways will be
assay development as early as possible.
It is a dynamic and progressive process.
Second, I would say use all of your FDAinteractions to communicate and discuss
the progress of your potency assay.
(23:11):
And finally, retains, retains, retains.
There are so many reasons that youmay need to go backwards to test lots.
Potency assays tend to be a, abig reason for having to do that.
Those are the, the three mainthings that I think are important
(23:32):
for the community to know.
James C. Taylor (23:34):
Thank you, Diana.
If you'd like to talk to heror any of us here at Biologics
Consulting, just send us an emailat insight@biologicsconsulting.com.
That's Insight at BiologicsConsulting all one word dot com.
The Executive producer of Insightat Biologics is Kris Kraihanzel.
This episode was producedand edited by James C.
Taylor.
(23:54):
The technical supervisor is Jeff Wease.
The Insight at Biologicstheme is by Tom Rory Parsons.
I'm James C.
Taylor.
Please come back for moreInsight at Biologics.
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