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CQA CPP CMA #QbD #Quality by Design Part 5 — Transcript

by Simplify Pharma · 1,800 words · 370 segments · language en · Watch on YouTube

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0:01Welcome to Simplify Pharma. In this
0:03lecture, we will discuss the difference
0:06between
0:07critical material attributes, critical
0:09process parameters, and how are they
0:12correlated to critical quality
0:14attributes.
0:16An effort has been made to simplify it
0:18further.
0:19Please like and subscribe to my channel
0:22and press the bell icon
0:23to get new video updates.
0:26Let's take a look at the factors that
0:28affect drug product critical quality
0:30attributes. There are two factors that
0:32affect.
0:33One is properties of input material, and
0:36the second one is manufacturing process
0:39parameters.
0:40When we say properties of input
0:42material, over here input materials,
0:45they consist of raw materials, starting
0:48material,
0:49APIs, packaging and labeling material.
0:53So, a key element of drug development
0:56and product or process characterization
0:59is a requirement to identify and control
1:03critical material attributes and
1:05critical process parameters that
1:08influence critical quality
1:11attributes.
1:13So, the two factors that affect critical
1:15quality attributes, it is critical
1:17material attributes and critical process
1:20parameters.
1:22Over here in this diagram, we can see
1:25the critical material attributes, they
1:27are the starting material.
1:30So, that's why we consider them as input
1:32material.
1:34Then critical process parameters, these
1:36are the parameters of the manufacturing
1:38process pharmaceutical unit operations.
1:41And they both affect the critical
1:43quality attributes, that is the
1:46quality of the output material of the
1:48product.
1:49So, we can say a material attribute or a
1:52process parameter,
1:53when can we call it as critical?
1:56When a realistic change in that
1:58attribute or parameter, it impacts it
2:01significantly impacts the quality of the
2:04output material. So, any change in
2:07critical material attribute or critical
2:09process parameters, when it affect or
2:12impact the quality of the output
2:15material,
2:16we call them critical.
2:20Let's take a look in detail one by one
2:23into critical process parameters and
2:25critical material attributes.
2:27A critical process parameter, it is
2:29another category of risk factor that is
2:32associated with manufacturing variables.
2:35So, we can define a process parameter,
2:38it is a measure that indicates the
2:40status of the process or unit operation.
2:44And it can be changed to achieve the
2:46desired product quality.
2:48Now, what are the examples of this
2:51process parameters? pH, cooling rate,
2:55drying rate,
2:56rotation speed, pressure, temperature.
3:00So, these are called as process
3:02parameters.
3:05When are they considered critical? When
3:07any change
3:09within the normal operating ranges that
3:12can affect a CQA, then a process
3:15parameter becomes a critical process
3:18parameter.
3:20Therefore, it should be monitored or
3:21controlled to ensure that the process
3:23produces desired quality.
3:26We can say a critical process parameter,
3:29it is a term used in pharmaceutical
3:32production
3:33for process variables which have an
3:35impact on critical quality attribute.
3:40These critical factors, they are based
3:42on the severity of harm to a patient,
3:45the safety, efficacy of the medicine,
3:48and how it affects the safety
3:51of a patient resulting from failure to
3:53meet the quality attribute.
3:55So,
3:56a a case where the factors, any
3:59variation in the factors, it affects the
4:02uh safety and efficacy
4:04of the patient, then in that case the
4:07factor becomes critical.
4:09So, what we have learned till now, the
4:11critical process parameters, they have
4:13direct impact on critical quality
4:17attributes.
4:18And a process parameter, it can be
4:20changed, there can be variations in it,
4:23it can be measured, it can be
4:24controlled.
4:26And how can we identify a critical
4:28process parameter?
4:30By correlating manufacturing process
4:32data with finished product testing
4:34results. So, this shows which variables
4:37have greatest impact on product quality.
4:41We need to understand when a potential
4:44process parameter becomes a critical
4:46process parameter.
4:48When it has high impact on critical
4:51quality attribute, that is CQA.
4:54This critical process parameters, they
4:56identified from a list of potential
4:59process parameters using risk assessment
5:02and experimental work. So, on the basis
5:05of risk
5:06risk assessment and experimental work,
5:09there's a list of potential process
5:11parameters, and then from that list we
5:14identify critical process parameters.
5:18So, what are critical process parameters
5:20which have high impact on
5:22CQA, that is critical quality attribute.
5:27Any process is considered to be well
5:30understood when all sources of
5:32variability they have been identified,
5:35explained,
5:37and managed. Therefore, allowing better
5:39prediction of CQAs.
5:42A better process understanding
5:45could be established by identifying all
5:48potential process parameters that could
5:51affect the CQAs.
5:54Now, in this case, screening out the
5:58high-risk process parameters, we need to
6:01screen out the high-risk process
6:03parameters based on
6:06prior knowledge and risk assessment.
6:09Thus, linking process parameters with
6:12CQAs by designing and conducting
6:15experiments,
6:16determining the criticality of process
6:19parameters based on experimental
6:22results.
6:23And thus, defining acceptable ranges for
6:26critical process parameters. Like this,
6:29we can link critical process parameters
6:31to CQA.
6:34Here is a case study wherein we can see
6:37uh example of process parameters.
6:40Now, in this case study, uh potential
6:43critical process parameters, uh
6:46and how which critical quality
6:49attributes they impact for a
6:52lyophilization operation, it is given.
6:55Now, see, uh for a lyophilization
6:57operation, what are the process
6:58parameters? Drying temperature, uh
7:00drying pressure, chamber pressure,
7:02chamber pressure,
7:04then freezing rate, freezing duration,
7:06primary drying duration, secondary
7:08drying duration. These are the stages of
7:10lyophilization.
7:12And which quality attributes they
7:14impact?
7:15Stability, size, reconstitution time.
7:20So, this is how process parameters
7:22impact quality attribute. This is how it
7:25looks like, the document looks like.
7:29This is one more case study I have
7:30pulled from the internet wherein we can
7:32see potential process parameters that
7:34are related to wet granulation.
7:37Now, over here we can see
7:40uh
7:40for example, high or low shear
7:42granulation, for that fill level,
7:45granulation mix time,
7:48then fluid fluid bed granulation, type
7:51of fluid bed, spray nozzle,
7:53then fill level.
7:56So, these are the potential process
7:58parameters.
8:01Coming to the second factor that affects
8:03critical quality attribute, that is CMA,
8:06critical material attribute.
8:09A material attribute, it is physical,
8:11chemical, or biological property or
8:14characteristic.
8:15Again, when it is considered critical?
8:18When any variation within the normal
8:20operating range, it can affect the CQA,
8:23that is critical quality attribute.
8:25Therefore, it should be monitored,
8:27controlled to ensure that the material
8:29produces the desired quality.
8:32When we say
8:34material in critical material attribute,
8:37it means raw material, starting
8:39material, reagent, solvent,
8:42intermediate.
8:43Well, attribute means physical,
8:45chemical, biological, microbiological
8:48property or character characteristic of
8:50this material that can be measured.
8:53It could be particle morphology,
8:55then ingredient ratio, drug loading,
8:58surfactant concentration,
9:00aqueous solubility.
9:03A material attribute is critical when
9:06any change, any variation in it
9:08significantly impact a CQA, that is
9:11critical quality attribute.
9:15Then there's this case study I pulled
9:18from the internet.
9:20A critical assessment of properties of
9:23the excipients, input material.
9:26It is desirable.
9:28Why? To identify what impact it will
9:31have on critical quality attributes of
9:33the product.
9:34Now, CMA, they considered for input
9:37material including drug substance,
9:40excipients,
9:41granulating fluid. Now, uh please
9:44understand over here the case study that
9:46we are taking, it is of wet granulation
9:48process. That's why in wet granulation
9:51process, CMAs, uh the critical material
9:54attributes, what all is considered under
9:56that? Input material, drug, excipient,
10:00granulating fluid.
10:02And CQAs, that is critical quality
10:04attribute. This is for output material.
10:07What is the output of wet granulation?
10:09We obtain granules after the process of
10:12wet granulation. So, these granules,
10:14they are the output material.
10:17So, such properties, they would qualify
10:19to be the critical material attributes
10:21for the product. And they would demand
10:24establishment of a decision space.
10:26Uh sorry, design space as a part of
10:29control strategy for the
10:32development process.
10:34Now, over here, we can see the potential
10:37critical material attributes. They are
10:39particle size,
10:40degree of crystallinity, surface area,
10:43moisture content, solubility,
10:46then binder, diluent type, grade,
10:49disintegrant type, grade.
10:53Then, this is the granulation process.
10:55And
10:57uh which all critical quality attribute
10:59it can affect the CMAs? Granule size
11:02distribution, granule flow,
11:05granule strength,
11:07then porosity, compactability.
11:10Now, after understanding what is a
11:12critical quality attribute, what is
11:15critical process parameters, what is a
11:17critical material attribute, we need to
11:19understand how are these three
11:21correlated. What is the correlation
11:23between them?
11:25Now, in this diagram, we'll try and
11:27understand how are CMAs, CPPs, and CQAs
11:31interrelated or correlated with each
11:32other.
11:34CMA, that is the input material
11:36attributes.
11:38So, once we are using input material in
11:41the form of API, excipients, those
11:44attributes of those material,
11:47then CPP, this is the process
11:50parameters. For example, let's take a
11:51simple example of tableting.
11:54So, in tableting, what are the different
11:56process that are used?
11:58Like granulation, drying, compression,
12:03coating. So, these are the different
12:04process and the parameters associated
12:07with those process. How
12:10these both affect the quality of the
12:13output material.
12:15So, CMA, CPP, any variation in these two
12:19factors, they affect the quality of the
12:21output material. That's why these three
12:24are correlated with each other.
12:27Now, this is a case study where we can
12:30see
12:31the correlation between
12:34the process parameters,
12:36then the quality attributes, and the
12:39material attributes.
12:41This we have taken example of tableting
12:43process.
12:45We can see
12:46uh during the operation of tableting,
12:48what are the different stages?
12:49Granulation, drying, milling, mixing,
12:52compression, and coating.
12:55So, what is the CMA during the
12:58granulation process?
13:00Particle size distribution, particle
13:02shape, elasticity,
13:04density, hardness, moisture content.
13:07What are the process parameters? Mixing
13:09time,
13:10then uh binder fluid addition rate and
13:13time,
13:14method of binder addition, temperature.
13:17And what is the quality attribute?
13:19The granule size and distribution. What
13:22is the moisture content of the granules
13:24that we have achieved? Similar manner,
13:28we will see for drying. These are the
13:31CMAs for drying.
13:33Then, these are the CMAs for
13:36milling.
13:38This is for mixing.
13:40Let's take a look at compression. Again,
13:43we'll try and understand. In
13:44compression,
13:46the CMAs are part granule or particle
13:49size, depending upon whether we're using
13:51granule or if it is direct compression,
13:54in that case, particle size.
13:56Then, granule or particle size
13:58distribution, cohesive adhesive
14:00property, because it is a compression.
14:02Elasticity, brittleness,
14:05then hardness, moisture content,
14:08density, porosity.
14:10Then, process parameters involved?
14:12Compression force,
14:14hopper design,
14:16roller type, ejection force. What are
14:19the quality attributes? Weight
14:21variation, hardness, friability, content
14:23uniformity, assay, dissolution,
14:25disintegration. So, these are If you
14:27remember, these are all the tests that
14:29we perform once we have manufactured
14:31tablet in pharmaceutical lab.
14:35So, this is how all three are correlated
14:37with each other.
14:39So, if you like my video, please do
14:41like, subscribe, and share.
14:45In our next video, we will discuss about
14:47the risk assessment stage of quality by
14:50design.
14:52Please do like, subscribe, and share my
14:53videos so that you can keep me motivated
14:57to keep posting more and more videos.
14:59Let's keep the learning happening and
15:02keep growing and learning.
15:04Thank you.

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