How Efficient Scale-Up Can Make Chemical Projects Profitable & Sustainable

You are in a dilemma.

You are not sure how to go about it.

You’re a chemical industry professional and are working for a large chemical conglomerate. Your major responsibility is to take the manufacturing processes from the laboratory scale to the commercial scale. And recently you’ve been entrusted with the commercialization of a fine chemical molecule. In technical language you call it Scale-Up.

It’s not that you’ve not done this type of Scale-Up projects earlier. You’ve done many successful projects. But this time it’s a bit different. Two aspects connected with this particular product is making it difficult for you to choose the approach.

High Profit Margin

It’s a high volume product having high profit margin. In fact, it’s an import substitute. There’s huge demand for this product in the country. And your organization wants to be the world leader in this product.

Normally most of the large manufacturers prefer this type of products. Why?

Because if you are able to successfully manufacture the product in tons and capture the major market share, you needn’t concentrate on many products. This single product can add tremendous value to the bottom line. So far so good. But you were concerned about one point…

Your competitors might have evaluated this product. Why there’s no news in the market that someone is going for it? In addition to it, the market demand for this product has gone up recently. Of course you know the reason why the market price is in an increasing trend.

Because, though it’s an existing product, a new application has been developed recently. And because of this new high volume application the demand is going up. The supply is not able to cope up with the demand.

Though the situation is not very clear, you’re sure of one thing. Many companies must be trying to develop this technology. But it’s the complexity of the manufacturing process, which is making it difficult to develop the process and subsequent commercialization.

The process technology is exactly the second aspect which is bothering you the most.

Complex Process Technology

The process has been developed in one of the laboratory of your company. Much piloting has not been done. You were told that the process has not been fully optimized.

Normally process engineers are involved in the laboratory process development. You are not sure whether the process has been checked for the scalability or not.?You know it very well that some of the laboratory processes are not scalable to the plant scale. Normally process engineering intervention rectify this issue by modifying the process a little bit. But that part you’ll know, once you get into the details.

But here the point is different…

Your organization wants to commercialize this product as early as possible. Of course you have got free hand to follow your own way and there’s no resource constraint. That’s precisely the reason why you want to follow efficient procedure for Successful Scale-Up.

We shall discuss about what you did for Scale-Up of the Fine Chemical Molecule later…

First of all, let’s get into the details of Successful Scale-Up of Chemical Products in general from the beginning. Right?

Let’s start…

Before getting into the details of the Scale-Up, let’s know a little about the Chemical Products.

Chemical Products

There’re thousands of commercially important chemical products in use. They can be categorized in many ways.

As for example based on the types of molecules they can be classified into Inorganic Chemical Products and Organic Chemical Products.

Major categories based on the applications are:

• Bulk Chemicals : These are high volume low value products?like Petrochemicals, Acids and Alkalis.
• Specialty Chemicals : These high volume chemicals having special applications like Dyes & Pigments, Agrochemicals, Polymer & Lubricant Additives and others.
• Fine Chemicals : These are high value low volume chemicals having applications in Pharmaceutical, Specialized Agrochemicals and Specialty Chemical Industry. In fact Pharmaceutical Industry consumes maximum percentage of Fine Chemicals.
• Chemical Formulations : Chemical Formulations are essential to make the Chemicals useful to the society. Leaving aside the Industrial Chemicals, most of the chemical products are made by Chemical Formulation. One way the Chemical Formulation process is different from other chemical processes. The process doesn’t involve molecular conversion. Only physical processes are used.

If you look at the world around you, you’ll find most of the man-made things are made directly or indirectly based on the chemical products. That’s precisely the reason why Chemical, Pharmaceutical, and other Process Industries are important.

But the most important thing here is: Manufacturing the chemical products. Why? Because unless they’re made in large scale, they won’t be useful to the society. And it’s equally important to make them available to the people who want them at a price they can afford. Right?

But how will you be able to make them at large scale?

For manufacturing them successfully at commercial scale, you’ll need two important things:

• Efficient Process Technology
• Well-Designed Manufacturing Facility

Let’s talk about Efficient Process Technology…

Efficient Process Technology

Process Technology is essential to make any product. But how to have Efficient Process Technology?

You’ve got two options:

• Procure the Technology from the Technology Providers
• Develop your own Process Technology

If you select the second option, you need to develop the process technology from the scratch. But how to start the development process?

You need to go for Process Development.?

Process Development

Process Development starts with laboratory experimentations. It’s necessary to develop and optimize the process at small scale before going for large scale operation. Why? Because thereby you’re able to check the process without the risks involved in large scale manufacturing.

Process Development is aimed at meeting many critical business aspects like:

• Manufacturing the product with quality as per the customer requirements.
• It’s important that the manufacturing process meets the requirement of ?technically feasibility and economically viability.
• The most important aspect is to comply with all the requirements of ?health, safety and environment aspects.

Do you think developing successful manufacturing process in the laboratory is enough?

No, it’s not.

Commercialization of the Manufacturing Process

If you want to make the products at large scale, the manufacturing process you have developed in the laboratory must meet the requirements of large scale operation.

But how to evaluate the manufacturing process for its suitability at commercial scale?

For that, you need to find the answers to the critical questions like:

• At what cost will you be able to manufacturing the product? How does the manufacturing cost compare with the selling price of the product. Will you be making decent profit?
• What about the safety aspects when you operate at large scale?
• Is the process environment friendly? What about the waste generation? Will you be able to treat the waste streams economically and comply with the pollution control requirements?
• It’s very important to consider the product quality, when you manufacture them in large scale? Will you be able to achieve the product quality the customers want?

None of the above questions is easy to answer. Right?

It’s one thing to make the product in the laboratory. But making them at large scale is entirely different. That’s why the transition from laboratory scale to plant scale is challenging.

That’s what is nothing but Scale Up.

Efficient Scale-Up

An Efficient Scale-Up is very critical to business growth. But it calls for technical expertise and tremendous industrial experience.

If you want to make the Scale Up successful, you need to know more about chemical products manufacturing. Let’s see why…

As we’ve seen there’re thousands of chemical products. But if you study the processes by which they’re manufactured, you’ll observe an interesting fact…

Though a wide variety of chemical products are made industrially, the manufacturing processes used to make them are limited. In fact, many products are made by using similar manufacturing processes.

So it’s the manufacturing processes which make all the difference. That’s precisely the reason why the major focus of Process Engineering approach of Scale-Up is on the manufacturing process. Why?

Because the Scale-Up doesn’t depend upon the type of products. It depends on the manufacturing processes.

That’s why Process Engineering approach is very effective for successful Scale-Up in Chemical, Pharmaceutical, and other Process Industries.?

What is Process Engineering Approach

It’s based on the understanding of the manufacturing process at the basic level. You need to know precisely what is happening in the processes at the molecular level. And that too not in qualitative terms but in a quantitative way.

If you study the manufacturing processes closely considering the molecular movements, you’ll observe an important fact.

Some operations involve molecular changes, whereas in some operation there’s no change in the molecules.

Unit Process

In these processes, the molecular transformation is taking place due to the molecular conversion. Of course, molecular conversion can be accomplished by using various processes like Chemical Reaction, Fermentation, Biochemical Processes and so on.

Irrespective of the type of molecular conversions you use, the processes at moleculr level remain same. Right?

Here, though the total number of atoms is fixed, the molecules are getting changed.. The raw material molecule is getting changed to form new product molecule. We call them Unit Processes.

Unit Operation

In those operations, there’s no molecular transformation, only physical phenomena are taking place. Though the number of different molecules is constant, the compositions in different processes streams are changing.

These processes are mostly used for separation and purification of the chemical products. In addition to it these processes are used in Chemical Formulation processes without involving any molecular conversions. We call them Unit Operations.

In fact both these operations – Unit Processes and Unit Operations - are equally important. Why?

Because only getting the raw material molecule transformed to the product molecule is not enough. The product is still in the reactor along with impurities and byproducts as reaction mass.

It’s of no use unless the product is separated, purified, and processes to make it suitable for the customer.?And the separation and purification processes can’t be carried out without using the Unit Operations.

When you talk about taking the manufacturing process you’ve developed in the laboratory to the plant scale the most important question comes up is: Is the processes you’re using to make the product in the laboratory suitable for large scale operation?

Because your major goal is to successfully commercialize the product.

The answer to the above question is very important because the equipments and manufacturing systems used in the commercial plant are entirely different from that of the laboratory.

So if you’re interested in successful manufacturing at commercial scale, you must ensure the Scalability of the Process.

Scalability of the Manufacturing Process

For Business Growth, introduction of new products or new processes are essential.?More important is their successful implementation. Right?

But how to develop and test the New Product or new Process Idea?

The laboratory experimentation is the only way to develop and test the process or product idea. But the question here is: Can the laboratory process be performed in the equipments and systems used in large scale manufacturing?

So what is the solution?

The only solution is to ensure the scalability of the manufacturing process at the laboratory experimentation stage itself. But how to do that?

You can check the suitability to a great extent by evaluating the laboratory process and the experimental results using process engineering approach.

That’s precisely the reason why you need to involve the process engineers with the research scientists from the beginning.

Because the Process Engineering intervention at the laboratory development stage has got many advantages like:

• Compiling the laboratory experimentation Data;
• Analyze the process information based on experimentation as well as estimated physico-chemical information.
• Evaluate the technical feasibility of the laboratory process at commercial scale;
• Start working on the Plant Design in order to Minimize the Capital Investment and maximize the Output
• Evaluating the Safety and Environmental aspects at commercial scale operation.

As far as Efficient Scale-Up is concerned it’s necessary to understand and optimize the process as much as possible. So it will be necessary to do a huge number of laboratory experimentations.

Statistical Design of Experiments

The normal practice in the laboratory experimentation is to use classical optimization. Procedures using classical optimization take one parameter at a time. Naturally it calls for more experiments. So it becomes difficult to optimize the process.

Let’s take an example. You are optimizing a process having critical parameters like pressure, temperature, and concentration. At first, you’re optimizing the pressure keeping other two parameters at a constant level. Right? ?

So you are not doing complete optimization. You’re only optimizing the variables partially. Why? Because when you repeat the procedure with say temperature the optimum will change.

When you talk about the Design of Experiment approach, it’s different. It’s a software based statistical procedure. And you are optimizing multiple parameters simultaneously using statistical models. So, you’re achieving complete optimization.

And it results in minimizing the number of experiments and optimizing the process in a far better way.

Scale-Up Approach

Now you’re ready for Scale-Up. You’ve already developed an optimized laboratory process. So, you have completed the first step. It’s better, if you have already evaluated the scalability aspects. Right? Now you are sure of smooth Scale-Up.

But the question here is: Is it right to go for commercial scale directly or use an intermediate pilot stage? It’s a difficult question to answer. Why?

Because both the approaches have their own plus and minus points.

It’s quite economical and faster to go for Direct Scale-Up. But it involves huge risk. When you’re taking the process from a 2 L Flask to a 20000 L Reactor the Scale-Up Factor is 10000. So you know to what kind of risk is involved.

On the other hand when you take the process from a 2 L Flask to a 200 L Pilot Reactor the Scale-Up Factor is 100. And when you take the process from a 200 L Pilot Reactor to a 20000 L Reactor the Scale-Up Factor is again 100.

Now you know the risk is minimized. Right?

But what’s the disadvantage? Yes, you’re right. It calls for time and money. And both are expensive.

So what’ll you prefer?

It depends on the products and processes. Let me explain…

When you deal with simple processes and especially where efficient process engineering methods exist you can safely go for direct Scale-Up. Why?

It’s because enough process information and efficient mathematical models are available.?But in case of complex and sensitive processes it’s better to go for Piloting.

Let’s take an example. When you’re planning for separating simple chemical compounds by distillation you can go for Direct Scale-Up. Because sufficient process engineering information and effective mathematical models along with industrial experience are available.

In case you are planning for Scale-Up of the complex reaction processes especially ?those involving sensitive and hazardous molecules, Piloting becomes necessary. Because sufficient information and mathematical models are not available. A lot of things are no known.

Let’s take the case of the processes involving extensive solid handling. Here with solid handling the piloting becomes a necessity. Why? Because unlike the fluids – liquid and gases - the solids behave in a very unpredictable way and it’s very difficult to mathematically model the solid handling processes.

Why Piloting?

When you make your products in the laboratory, you make them at gram scale. But when you make them in commercial plant, it’s in tons. The equipments and the systems used are entirely different.

So, when you compare the processes used in a laboratory to that of commercial plant you will find a number of major differences.

Because of the differences, the Scale Up is so challenging. And that’s why Process Understanding is of utmost importance. Why?

Because when you don’t understand the process very well and don’t have sufficient information the situation becomes full of uncertainties. In those situations, Piloting helps a lot.

But where to do the Piloting?

You need an well designed Pilot Plant so that you can carry out the pilot trials in a controlled environment. But just taking pilot trials are not enough. You need to measure all the process parameters, observe the process thoroughly and analyze the information using mathematical models. Why?

Because unless you understand how the process is behaving, especially compared to the laboratory experimentation, you’ll not be able to judge how will it behave in the commercial plant.

In fact you need to know about the process with respect to the scale difference and it’s essential to build the confidence. That’s necessary for taking the process to the commercial scale because the stakes are high. Right?

But what about the Pilot plant?

If you study the Pilots Plant Designs, you’ll find in most of the cases the design is similar to that of the commercial plant. And of course, the pilot plants are well instrumented for collection and recording of vital information.

In short, piloting is useful for two main reasons:

• It’s essential for optimization of the processes so that the manufacturing performance - cost, product quality, productivity – along with safety and environmental aspects are taken care of in the commercial plant.
• You know, efficient plant design is essential to minimize the capital investment and achieve the business objectives. And for that you not only need accurate and useful process information but also understand the process to the fullest extent. An well designed piloting protocol can only do justice to this important function.

Successful Scale-Up

We’ve already discussed the Scale Up is important. Right? Now we shall discuss how to do that. ?We need to discuss how to do efficient Scale-Up and achieve successful commercial manufacturing.

We’ve already classified the manufacturing processes into well defined categories in order to make the Scale Up procedure systematic. That’s to help us develop specific Scale Up procedures independent of the type of the products.

And to do that we need to get into the details of specific manufacturing processes. Before discussing specific Scale-Up procedures, let’s focus on those unit operations which are used in almost all manufacturing processes. And you’ve to design the systems to meet the process requirements.

Three of the most important unit operations are:

• Heat Transfer,
• Mass Transfer
• Mixing.

Heat Transfer System

If you study the manufacturing processes carried out in chemical, pharmaceutical, and other process industries, you’ll observe an interesting thing. Irrespective of the type of processes, most of the steps happens at certain temperature. In fact the temperature is so important that the process performance depends on it.??????

Now, the question is: How to achieve the temperature?

One way of achieving it is by changing the temperatures. In case you need lower temperature than that of the existing, you have to cool the materials. And if you’re interested in higher temperature, you have to heat the materials from their existing temperatures.

In short, what you’ve to do is to either cool down or heat up. Right? So, for cooling you have to take out some heat energy from the materials. Whereas for heating, you need to add up some heat to the materials.

Here what you’re doing is nothing but transferring heat. That’s what is Heat Transfer.

In most of the manufacturing processes, Heat transfer plays a very important role. When you’re dealing with Scale-Up, this unit operation becomes critical. Why?

Because you need to carry out the manufacturing processes at their optimum temperatures both in the laboratory scale as well as commercial plant. You need to ensure in that the equipments and systems employed in the commercial manufacturing plant have the required heat transfer capabilities.

Mass Transfer System

When you talk about Scale-Up, you need to know what is mass transfer. Right?

It has got to do with the movement of molecules from one area to another. But there must be some reason why it happens. It happens where there’s a difference in the chemical potential. In that case there’ll be the movement of mass from higher potential to the lower potential to bring the system to equilibrium.

But it is important. Why?

Because Mass transfer controls most of the manufacturing processes whether it’s?molecular conversion or separation. In fact, most of the chemical manufacturing processes involve Mass Transfer.

And when you’re dealing with Scale-Up, this unit operation becomes critical. Why?

Because you need to carry out the manufacturing processes at their optimum conditions both in the laboratory scale as well as commercial plant. You need to ensure in that the equipments and systems employed in the commercial manufacturing plant have the required mass transfer capabilities.

Mixing System

Mixing is very important in the manufacturing processes. Why?

Because it makes non uniform systems uniform. Unless there’s uniform condition in the systems, the manufacturing processes can’t perform optimally.

The Mixing processes and the type of the systems used in the industries vary widely. They depend on what you want to mix and to what extent.

The Mixing processes are different like liquid-liquid, liquid-solid, liquid-gas, solid-solid, solid-gas, gas-gas, and multiphase mixing.

If you study the manufacturing processes, you’ll see hardly any manufacturing process where mixing is not required.?In fact, mixing is essential for heat transfer as well as mass transfer between different components or streams in any manufacturing process.

You need to carry out the manufacturing processes at their optimum conditions both in the laboratory scale as well as commercial plant. So, it’s essential to ensure that the proper mixing systems are in place.?

Scale Up of Molecular Conversion Systems

For achieving molecular conversion, you need to use specific manufacturing processes like chemical reaction, biochemical processes like fermentation and enzymatic reactions and others. As?we’ve discussed earlier, these specific processes have many subcategories. Right?

But when you talk about these manufacturing processes, the basic requirements remain the same. All the processes are governed by chemical thermodynamics, chemical kinetics, heat transfer, mass transfer, mixing and so on.

When you’re involved in Scale-Up, you need to carry out the manufacturing processes at their optimum conditions both in the laboratory scale as well as commercial plant. So, it’s essential to ensure that the equipments and systems are based on the specific molecular conversion processes you’re using.

Scale Up of Separation Systems

Earlier we’ve already discussed that achieving molecular conversion is not enough. Proper Isolation and Purification of the product is essential. ?That’s the only way, your products will meet the customer requirements. So you need powerful Separation Processes to do that.

For achieving product separation and purification, you need to use specific separation processes like Crystallization, Distillation, Liquid-Liquid Extraction, Solid-Liquid Extraction, Filtration, Drying, Absorption, Adsorption, Evaporation, and others.

When you’re involved in Scale-Up, you need to carry out the manufacturing processes at their optimum conditions both in the laboratory scale as well as commercial plant. So, it’s essential to ensure that the equipments and systems are based on the specific separation processes you’re using.

Your Fine Chemical Scale-Up Assignment

Now that we’ve discussed a lot about successful Scale-Up, let’s see what you did with your Fine Chemical Scale-Up assignment.

By following proper Scale-Up procedure you could successfully take up the product from the laboratory scale to the commercial scale plant. And you could commission the plant before schedule.

The most satisfying aspect for you was that you could achieve better Output - Product Quality, Plant Capacity and Manufacturing Cost - in the commercial plant compared to the laboratory batches.?

In short, you’ve helped a lot in taking your organization to the Next Level. Nothing can be more satisfying. Right?

Let’s Conclude

As we’ve discussed, no business can sustain without growth. And when it comes to Chemical, Pharmaceutical, and other Process Industries, business growth becomes more important.

Day by day New Products are getting added to the existing long list. Newer, more efficient processes are being developed. More and more advanced technologies are getting developed. Efficient machines and equipments along with powerful systems are being designed.

In this business environment, putting up new projects and expansion of the existing manufacturing facilities have become a necessity.

If you want exponential business growth, you must have well-designed Research & Development Facility. And you need a powerful Scale-Up function to translate the developments from the laboratory to the commercial scale. Preferably the Development Function should be Centralized for better focus.

Efficient Scale-Up is very important for Business Growth. An Integrated Process Engineering based Scale-Up approach can help you achieve Business Excellence.

Let’s join hands in using innovations in achieving Efficient Scale-Up and developing them further to add tremendous value to chemicals industry.

I'm curious to hear your thoughts on this exciting topic. Share your insights in the comments below!

If you’re interested in more in-depth exploration, perhaps you can refer to my other articles on fine chemicals manufacturing. You can follow my LinkedIn page for regular updates and insights on process industry.

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