Welcome to the BioPharma and Downstream Process Simulation using ANSYS

Hello, welcome to the BioPharma Downstream Process Simulation using ANSYS. My name is Jesus Ramirez, I am part of the Technical Staff of OSINIC operation. We are a coalition partner from ANSYS.

We are experts in the simulation of different phases of structural stress by fluid and electromagnetic fields.

We have been the main communication partner of G-ART by ANSYS in 2016, 2018, and 2021. We offer our customers best-in-class software tools, consulting services, training, mentorship, and technical support.

When we look at our portfolio, we can see that ANSYS offers different tools for virtual physics, including tools for structures, fluids, electronics, photonics, and semiconductors. The digital twin for Industry 4.0 provides real-time solutions.

We are located in the United States, in California, Nevada, Oregon, Washington, Maryland, Virginia, South Carolina, North Carolina, Idaho, and Montana. We have two offices, our headquarters in Sunnyvale, California, and an office in Doncaster, UK. I am a mechanical engineer with a Ph.D.

in mechanical engineering, focusing on the CFD side. I have been working with CFD for 12 years and am always willing to help and solve our customers' issues, develop nice models, and answer any questions you may have.

Today, I will give a brief introduction about how bio-pharma processes work and discuss some downstream processes such as sterilization, chromatography, spray drying, filtration, tablet coating, and tablet compaction.

These are common downstream processes you will find in bio-processing and bio-pharma. In the bio-pharma bio-processing industry, simulation has helped in the area of drug manufacturing, bioreactor efficacy, regulatory approvals, and drug delivery.

For example, Biogen was able to reduce its technology transfer time for a suburban area in Terminus using ANSYS.

In the drug delivery industry, Oklahoma State University used ANSYS to prove the targeted drug delivery on long-term to 90% efficiency when compared to the 20% efficiency of conventional methods. Let me talk to you about some of the ANSYS solutions we have for pharmaceutical processes.

Pharmaceutical processes start with process development and manufacturing. In the chempharma industry, this is called DPI and has several stations, including upstream and downstream processes. We have a webinar focused on upstream processes, but today we will talk about downstream processes.

Upstream processes include packaging, cold chain, and drug delivery, for which we have solutions. Let's start with some applications, such as lyophilization, also called freeze-drying. This is a process where DPI is sublimated from a frozen drug product in a high vacuum at low heating conditions.

This process offers several advantages for biologists, including low air shelf life, a gentle dry process for heat-sensitive active, and low particulate B contamination.

The numerical modeling of the sublimation process can provide detailed insights that experiments cannot provide and help optimize operating conditions and equipment for reduced costs. This numerical simulation offers an option for accelerated testing of biophilization processes.

Now let's talk about chromatography, a process of separation of a mixture by passing it through a medium, where each of the components moves at different rates. The different components of the mixture travel to the stationary phase at different speeds, causing them to separate from each other.

In this picture, we are focusing on liquid chromatography, where the mixture of interest is dissolved in a liquid and passes through a solid stationary phase. The nature of the specific mobile and stationary phases determines which substance will travel more quickly or slowly.

A parametric study focused on the variation of one of these parameters or properties can be studied using different ANSYS tools. For example, SpaceClaim, a CAD tool, can be used to create parametric geometries.

ANSYS Fluid can be used to study the flow rates, specific positions, and velocity of the bed. The post-processing can be done using CFD-Post or EnSight to visualize the separation of the species.

In the figure on the lower side, we can see the movement of dye flowing through the column and identify how the medium would flow to the back bed and what side of the fluid exits the bed. This simulation was done using ANSYS Fluid, but it can also be done using CFX, another CFD tool.

This simulation is the starting point for studying scale-up of the column. We can start with a small-scale simulation and then do the escalation process. If you want to know more about subplots for doing escalation, you can go to our webinar of biofarming upstream processes to see more of this.

In the upper right side, we can see an arrow pointing to the analytical scale simulation, which is an analytical simulation. However, we can observe that there are two additional curves that are data taken from a production scale.

The production scales results are much wider or show a much wider pattern of separation than the analytical solution. Using simulation has become an important step for avoiding mistakes in this kind of designs. Now let's move to another application, spray drying.

The process of spray drying is very common in different industries, such as consumer goods, farm products, food, and water. In this process, liquid is sprayed into a controlled environment where some components of the spray are evaporated, leaving other components behind and hence creating a powder.

One of the main problems that customers mention when it comes to us is that depending on the liquid formulation they are using, the processes require constant changes in operating conditions. The goal is to get a specified particle size solution of certain composition.

The drying needs to be performed correctly. For helping them to resolve this problem, we build a computational model that allows us to simulate the nozzle, the primary jet break cup model, to see if the jet break cup is what we want.

We can also observe the temperature distribution of the fluid inside the spray dryer. If the pattern of injection is not the desired one, we can do a detailed analysis of the nozzle to modify the design and try to match the requirements of our process.

Now let's move to something that is also common downstream processes, handling granular flow. We have a dedicated tool that is called ANSYS Rocky, which handles particles of filling size and helps us to analyze these different processes.

ANSYS Rocky uses the discrete element model and has many features, such as the ability to capture the motion of particles, handle different shapes, and use GPUs for acceleration. For example, the double comb blender is an efficient and versatile machine for mixing dry powders and granules.

The simulation shows how the app can be used to ensure an homogeneous mixture by understanding the drop RPM and the tilt angle to rotate the drum to avoid the segregation of particles. Another application is the sensitivity of the final homogeneity, which depends on how the filling is done.

With this software, you can see directly what happens with the mixing, depending on the emission injection. We can also use ANSYS Rocky for evaluating sharp flow patterns, eliminating stagnant sources, and mitigating gradient material problems.

We can do optimization processes and prove the design if required. Now let's move to another application, tablet coating. The efficiency of the coating process depends on several parameters, such as drum rotational speed, feed level, number of sprays, tablet shape, and airflow.

To evaluate and increase the efficiency of the coating process, output quantities, such as inter tablet quality variability, number of sprays guns, velocity distributions in spray guns, risk in tight distribution, spray gun collision statistics to reduce breakage of final tablets, should be analyzed.

We can use ANSYS Rocky to simulate the drying process after the coating is done. We can couple the particle motion with a CFD analysis to simulate the drying process. Finally, we have a filling system that is faster than the general one.

When filling millions of buyers as fast as possible, a stable filling without splashing, mashing is required, while ensuring that the liquid does not slosh out of the buyer.

For doing that, they do simulation, extend under sterilization of buyers, simulate the droplet during embouchure, and simulate the buyer sterilization process. We can do all of these relations using ANSYS tools and have a complete solution for our needs.

Thank you for your attention, and if you have any questions, please contact us. We will be happy to answer.