“Adoption of Computational Fluid Dynamics (CFD) simulation is emerging as a game changer for continuous manufacturing applied to Active Pharmaceutical Ingredients (APIs),” says CD-adapco, a supplier of CFD and computer-aided engineering software.
CFD simulation software helps to predict the impact of fluid flows on a given product throughout design and manufacturing as well as during end use.
According to CD-adapco, CFD has the potential to “foster simulation-driven processes and designs” that will:
- Shorten product-process development cycles
- Reduce energy requirements
- Result in a shorter time-to-market
Kristian Debus, Director of Life Sciences for CD-adapco, participated in an exclusive Q&A on the potential impact of CFD simulation on the pharmaceutical industry.
Q: To start, could you describe your company’s involvement in the life sciences and pharmaceutical industries?
Debus: CD-adapco is heavily involved in the life sciences and pharmaceutical industries, specifically with manufacturing processes as we are addressing the challenges of scale up for API batch processes. We provide means to reduce the total development costs by deploying a simulation bench and creating better designs. Through our processes and work with regulatory agencies or consortia (such as CSOPS, MDIC), our customers are seeing consistent cost and time savings.
Q: How does CFD simulation work?
Debus: CFD simulation allows customers to view a problem from a new perspective, adding to the analytical and experimental view.
- It can help analyze the non-ideal condition in manufacturing operations.
- It can address those non-ideal conditions by testing various possible solutions at a much rapid pace than trial and error.
- For existing processes with bottlenecks, it can help troubleshoot problems by carrying out ‘what if’ analysis.
- It can create robust scale-up procedures by simulating production scales, something that is not possible with experimentation.
Therefore, by deploying CFD and modeling, it is much faster to design new equipment and overcome competitive pressure and stringent quality requirements. Our work with CSOPS specifically addresses the challenge of continuous manufacturing and solid particle transport.
Q: Could CFD simulation be applicable to continuous manufacturing in other areas of pharmaceuticals (in addition to APIs)?
Debus: Manufacturing consists of numerous processes involving flow of fluids or flow of particles. CFD can be applied to all those fluid flow processes and DEM for particle transport and powder transport process. In reality, there is no limit to which operation it can be applied. All the way from mixing and filling, to drying, coating, centrifuge, and so forth can benefit from using simulation. Its ubiquitousness makes it a solution for preventing unpredictable outcomes after scale up or for design changes hamstrung by time-consuming and costly experimental setups. CFD validates the design or at the very least assists the customer to have a better understanding of the complexity of the design for continuous manufacturing.
For an example of one of the processes that impacts the pharmaceutical sector, when we analyzed the particle transport and tablet coating processes, we wanted to design the coating tumbler to ensure a minimal breakage of tablets and reduce operating time. With the use of CFD simulation, we were able to achieve consistent coating thickness and optimized the design iteration process by reducing the variations of experiments to be run and, in turn, realized a significant savings on costs.
Q: How will CFD simulation impact the timeframe a product gets to market?
Debus: It serves to reduce the trial and error in experiments. CFD simulation can be used to accelerate the prototyping process, to bring their product to market while still enjoying higher quality designs. For example, we recently worked with AM Technology in the UK on a mixing device that uses vibration instead of traditional approaches: a novel concept. CFD simulation gave us valuable insight on the importance of product design and how the physics worked.
Q: How will CFD simulation impact product-process development cycles?
Debus: In the face of mandatory quality benchmarks, CFD simulation can reduce the number of experiments performed, while offering the flexibility needed to create new designs in a timely manner. CFD simulation impacts the product-process development cycles by accelerating the design cycle while providing a higher quality design. Discover better designs, faster. For examples in the case of the AM Technology project and their powder mixing device, one can quickly vary the powder type with simulation. In the case of the coating tumbler, we found that CFD simulation allowed for fast changing of the tablet’s size, coating thickness, and tumbler design.
Q: How will CFD simulation reduce energy requirements for the manufacturing of APIs?
Debus: Many of the manufacturing unit operations such as drying or mixing are energy intensive. CFD simulation will reduce the energy requirements for the manufacturing of APIs by providing more efficient designs by reducing the unnecessarily high amount of safety factors or overdesign. If you have to rerun batches or dispose of poorly-mixed API, not only do high material costs occur, but additional energy costs are related to that. Increasing efficiency will greatly reduce revenue, time and energy burdens, which is increasingly important in this economic environment.
Q: How does CFD simulation impact medical device designs?
Debus: CFD simulation helps to make better designs, faster. CFD simulation also reduces the risk of failure in medical device design. Through benchtop testing, CFD simulation can be used to test a heart valve or stent design, provide great insight on respiratory analysis, and have a major impact in analyzing the blood flow in implanted blood pumps. Clinical trials on animals and human beings is something everyone wants to see reduced not only from a humanitarian standpoint, but also from a financial and time-to-market perspective. You can run a simulation of devices to help with benchtop tests. CFD simulation of medical device designs optimizes the design and will reduce the need for animal and/or human testing.
Q: What would you say are some of the key components in continuous manufacturing?
Debus: There are several aspects to this. As you convert from batch to continuous, one has to include continuous monitoring of key variables of the process. This is the process control and instrumentation aspect. But from a design perspective, one needs to satisfy the process needs of the operation: residence times, sufficient heat transfer or mass transfer. It is difficult to fully understand all of it. CFD, or modeling in general, will help you to peer into the depth of those processes and understand the functionality of the devices you want to use, improve and optimize. One of the key components in continuous manufacturing includes particle and transport modeling to understand and optimize the throughput for the API to assure product quality. A good example is again the powder mixer from AM Technology, or mixing in general, as it aids the scale up process not just for powders but also liquids or multiphase mixtures, which can all be simulated with CFD.
Q: What are some of the areas relating to continuous manufacturing that you think companies have room to improve?
Debus: In reality, all areas relating to continuous manufacturing have the capacity to absorb improvement. Simulation can help assess new concepts and ideas faster. A good example of this is in the development of new monitoring systems or process analytical technologies (PAT). CFD simulation can be very useful to tell users how to position them as well as how to read them to validate their measurements. This is a great opportunity for the industry to make better designs now for a better way of manufacturing and will be particularly effective for better quality of device design in particle transport and mixing.
Q: What do you see for the future of API manufacturing? (Or pharmaceutical manufacturing in general?)
Debus: I see the increased use of simulation as an enabling tool resulting in a faster response time to API changes, more targeted medications on smaller batches. Simulation puts all the necessary expertise of a process together in one carriage to pull it towards the optimum. Currently, the major issue is the lack of flexibility to change processes because they are in a rigid setup due to the constraints of batch processing. An excellent example of taking the initial steps to overcoming this obstacle is our design of the coating tumbler. By optimizing the design iteration process to reduce the variations of experiments (and save costs), we ensured a minimal breakage of tablets while reducing operating time to achieve consistent coating thickness.
Q: What do you foresee for the upcoming advances in the medical device market?
Debus: Among the upcoming advances for medical device design, I foresee more support of benchtop testing and in-vivo clinical trials through simulation. On the simulation side, the expertise of users is certainly growing. Our research and commercial partners work on validation cases to assure our tools get used for practical applications and are validated against real-case scenarios. Short-term advances will be seen on the benchtop testing side, while we should see long-term gains on clinical trial support.