Scaling Spray Drying: From R&D to Commercial Production

TL;DR

Successfully scaling spray drying operations from R&D to full commercial production demands a meticulously planned and executed process. It begins with a deep understanding of customer objectives, focusing on precise particle properties and characteristics, supported by in-process evaluation in a fully equipped lab. The journey involves a complex, multidisciplinary approach, integrating R&D, engineering, and quality teams to meticulously define requirements for cleaning, sanitation, and labor. Optimization trials are critical, extending run times to assess process stability, powder conveyance, and product consistency, while also refining batch sizes and formulation specifics. The transition to commercial viability hinges on finalizing contract manufacturing or tolling agreements, establishing clear SOPs for critical parameters like solubility, moisture content, and flowability, and ensuring optimized yields. Acknowledging that pilot-scale success doesn’t guarantee full production efficacy, expertise in dynamic atomization technology is crucial to mitigate unforeseen issues, allowing for operation within narrow parameters to consistently achieve in-specification product.

From Concept to Commercial: The Spray Drying Development Pathway

Hendrik: What is that next step? It’s what we refer to pilot scale dryer trials. Two important notes that I do want to mention here. The first one is APD do not use desktop dryers for the initial drying trials. That requires, translation from the specific desktop dryer to our technology or to conventional spray drying technology or to scaled units. We have a pilot scale dynamic atomization dryer that represents our own unique drying and atomization technology. We can scale dryer settings and run conditions up directly from this pilot scale drying trials to the next level dryer without making any assumptions towards settings, pressures, temperatures and so forth. The second thing that’s also very important for customers to know is that we are very transparent in the way that we handle these dryer trials.

Hendrik: We always invite customers to attend these pilot scale dryer trials. It gives them the opportunity to see how we conduct these trials, how we achieve their specific objectives and they learn the technology and they get to know the team and that they are going to work with in future and that’s that includes our whole team so whether it’s logistics or the r&t department or quality we involve everybody so that they know the team and that so that they know who they’re going to deal with going forward so these trials are focused on a couple of things. First it is the liquid handling side. We look at the equipment required for the liquid, we look at viscosities, we look at the formulation required, we look at the sequence of the formulation.

Hendrik: We’re in the process now of developing the procedures and the processes for batching, for formulation and for creating a stable and homogenous feed product. From a dryer perspective, we would look at the feed solids concentration and how we feed that into the dryer and how that would atomize.

Viscosities are very important And then because our dynamic atomization technology allows us to handle higher salts concentration than, in general from conventional spray drying, we start looking at feed solids optimization also. And then depending on the specific customer requirements with regards to flowability, solubility, density requirements, what are the delivery systems ? Are there specific requirements with regards to particle size distribution, handling of fines? So when we start with the dryer itself, we look at their own settings, we look at their own conditions, and we look at the basic process parameters that we are going to evaluate for the next steps.

Hendrik: And that is the inlet temperatures, the outlet temperatures, and then atomization pressures and atomization, the kinetic energy that we put into the atomization. We look at different nozzle configurations, spray patterns, and then specifically we start evaluating particle size or particle engineering in general. What is required from different nozzle configurations, different type of nozzles the spray patterns the droplet size that we have to create so it is it’s it’s an it’s an intense exercise but very focused and very objective focused we won’t do anything unless we know exactly what the customer objectives are with regards to every single particle property and particle characteristic requirements i can also add that we have a full equipped lab right next to our R&D facility, which gives us the ability to do in process or in the real time evaluation.

Hendrik: We can do on the fly adjustments. If we run the product in the dryer and we see that the moisture specification is out of spec or the particle size distribution is not in specification, we can immediately evaluate that in the lab, and look at the particle characteristics and then do on-the-fly adjustments on the dryer to achieve these specific objectives.

And then the last thing is that we would create powder samples for the customer for their own evaluation. We not only send the customer a full report on the powder characteristics and properties that we achieved, We don’t only give them information with regards to challenges that we experienced and how we’ve overcome these challenges, whether it’s fines or conveyance of the product or yields, maybe I would say minor formulation adjustments.

Hendrik: We also give them powder samples for their own evaluation. And then we have really good communication with the customer. There would be a back and forth before we go to the next step where we evaluate, what we have achieved and what their evaluation from the powder property and characteristic size are. And then we would discuss, okay, what are we going to do for the next step?

Ulli: I’m going to try something here, Stephen. I have a chart that outlines this development process that Hendrick just spoke about. I’m going to share this and see if it works. Yeah. Hold on. Hendrick, maybe you can go back and just, or I can do it in terms of. This process begins with very clear requirement definition in step one, including all the details that Hendrick just mentioned. And then the product goes onto the Dynamic Atomization 5 spray dryer, which is a R&D slash small scale unit where all these real-time changes can be made. Once that’s validated and approved from the customer, it goes on to our next size dryer, which is the DA50 dryer to confirm consistent particle size, flowability, morphology, all the elements that Hendrick just mentioned.

Optimizing for Scale: Stability, Yield, and Quality Assurance

Ulli: And once that is passed and approved by the internal team as well as by the customer, this project will then go into scale up, which is a large scale dryer. It’s 100 times bigger than our R&D and little pilot dryer. Then it’s ready for full scale production. And you see here steps five and six, which really go into final quality assurance testing. We confirm all the requirements and then it’s implemented with custom packaging and documentation and goes to the customer.

Will: Yeah, that’s a really helpful graph there. What’s interesting about this, Stephen, is I think two key points. First of all, what Hendrick and Uli have outlined here is the stages in the process, but also that it’s very well defined. And as you point out, there are a lot of questions. People want to know exactly how does this work? How does it flow through from the lab or the bench top all the way through to commercialization, which is one of the most, I would say, common questions we get. People always want to know what are the steps, what’s it going to be like, because they want to project through all the way to the finish line, which is a logical thing to try to understand.

Will: One of the most important questions that’s on everyone’s mind, but they’re a little sometimes shy to ask, is when is the right time to come to APD, to start this discussion? And embedded in that is what’s the competition doing? Well, they come to us because we’ve done hundreds of projects. We’re the experts. We’ve done projects in virtually every industry with all sorts of challenges and all sorts of ingredients, et cetera.

Your question was about, if a company has a powder formulation that works in their lab, but 80 to 90% of the time, that’s not how things start. They don’t have a powder formulation that works in their lab. 80 to 90% of the time, they might have an idea or they might have a liquid or they might have a challenge.

Will: Something’s broken, but there is no powder formulation that works in their lab. And that’s exactly why they’re coming to us. And so maybe they have an extract or they just have a concept or they see an opportunity in the market, but it’s at a much earlier stage, which is why our process is so well defined, even pre-bingetop, pre-lab work, helping understand what objective are they trying to meet. And there’s no bad ideas. And that’s particularly working with a business like ours, which has executed hundreds of engagements with hundreds of clients. We have the absolute best context to engage as a partner with these prospective clients and help them through the situation.

Will: But we often hear this product is broken or our process is broken or can your equipment do this because it seems like an insurmountable challenge or no one has done it in their industry or any industry before. But that’s precisely why we are almost always having even our first discussion under NDA, because it’s a very sensitive discussion. It’s something that they absolutely want to know what the competition is doing or if something is feasible. But it’s a very sensitive discussion that we’re having, maybe about something that they’re already working on or failed in their efforts to work on it.

But they see a great opportunity in the market if they can only find the right partner to help them get it out there.

Ulli: Yeah, that makes total sense. I’m glad that you brought that up because I remember, I think semi-recently, we were even talking about a client where, without any real specifics, you’re talking with people while their raw material is still on the ground while you’re even talking to them about the development of what you’re going to be doing with that and how you’re going to be putting that out there and what that’s going to be going into. I think it’s important for the people to know that, yeah, they can come to you guys pretty much at any point.

Hendrik: It would be beneficial for, potential customers that listen to this to just take one step backwards and, dig into the details of each step a little bit more so that they understand what the intensity are and how we achieve specific objectives. The customers that we deal with 99% of the time has very specific objectives with regards to their product. It’s high value products with these specific requirements. And how do we achieve that for customers at different scales? Uli mentioned the D50 dryer as the second step, which is 100% correct. I want to just discuss that in a little more detail. Customers know what our focus areas are with every step. The second step is where we start optimization and process engineering. And this is where R&D meets the engineers. And we start looking at scalable process conditions.

Mitigating Risk in Large-Scale Powder Processing

Hendrik: We look at different equipment requirements that directly resembles commercial scale equipment. We look at the explosion risk and mitigation, powder recovery systems and processes. It’s important to not only look at the powder properties and characteristics that customers want. We want to focus on yield. How does the product convey through the system? And how does it behave over longer times? There’s a difference between running one hour on a small scale dryer and running six hours on a mid scale dryer or running, 16 to 24 hours on a full commercial dryer. We start looking at all of these aspects and what the influence that would have on the bigger scale. At the same time, we would start looking at auxiliary equipment that’s going to be required, in the liquid handling phase. We look at quality reviews and quality requirements, sanitation and cleaning strategies, and how we’re going to deal with that on commercial level.

Hendrik: And then basic things like testing requirements, sampling requirements, line clearums, regulatory requirements, raw material requirements, for example. Is it non-GMO? Is it kosher? Is it halal? and then we look at the batch sizes and the procedures required is the sequence for the batching, heating, cooling requirements, viscosity influences and so forth. It’s a very complex process that we go through where we involve not only the R&D team but we bring in the engineers, we bring in the technical team to look at the equipment and we start bringing in quality also to look at quality requirements with regards to cleaning and sanitation laboring requires and so forth so it’s it’s a very complex and very detailed process that we go through and the objective is to ensure that when we get to this the full commercial level that we do not run into any unforeseen issues or problems and then the is a pre-commercial demonstration trial run and that is where we take what we’ve learned on the optimization trials and now we run just for longer time so we have extended the run times to determine process stability powder conveyance through extended run times look at the consistency of the product and we look at process optimizations we look at batch sizes we look at the runtime optimization formulation requirements are very specific and needs to be done in a very specific sequence otherwise you’re not going to have the same an homogenous sheet material every time and then we also look at final validation of all the processes with the customer we look at commercial viability and then we start looking at pricing with regards batching involved is there any raw material requirements from our site?

Hendrik: There’s a customer going supply in the raw materials and packaging requirements and so forth. We focus on making sure that we are prepared for full commercialization before we go into that process. And like Uli mentioned, the final process is then full commercial campaigns. And at this stage, we have finalized, the contract manufacturing agreement or the tolling agreements we had the final agreements on the specifications and procedures in place the customer understands 100 percent what are the specifications what are the procedures we are now implementing the sops that we have defined and during the optimization trial so whether that is about properties like solubility how do we measure solubility that we agree on that SOP and the procedure for solubility so that we have that and we agreed on that the same with things like moisture content in the powder flowability how do you measure flowability solubility how do we deal with fines how do we focus on yields and how do we optimize yields so the i think the final thing that i can mention is that this is a never-ending process.

Hendrik: It’s not that we went through step one through four and now we’re at full commercialization and now we just run the product for the customer every single time.

We always have to improve. We always have to improve efficiency, consistency. We will always attempt to optimize yield and to ensure better throughput. We assess things like seasonable variability, is there humility constraints? We look at the raw material variability and consistency and there is a consistent communication process that we have with the customer before every campaign to review what we’ve achieved the previous time, were there any challenges and how can we improve with regards to all of these things that I’ve mentioned. Optimizing yield every time, optimizing product performance, reviewing product performance, how can we improve the product? And then maybe we can go back to step four or step three, if the customer has some powder property requirement changes or, hey, I have a different application for this product, how can we address that? Maybe slight density changement or moisture content changement. We continuously go through the process to ensure that we always optimize and always focus on achieving better results.

Ulli: Yeah, that makes sense. Even just the combination of all of your guys’ answers, it really shows how thorough the process is. But no, I think those were really, really great distinctions. Moving on to the next question, And I think that some of this was answered, I think, within your specific process. But I think going to the whole industry, if you could speak on what are the most common things that break when you try to scale to spray drying process to us?

Ulli: Excuse me. What are the most common things that break when you try to scale to a spray drying process from a small R&D batch to a full production run? And again, I think you guys talked about it a little bit quite in depth in terms of how you mitigate that. But maybe if you could go into some of the pitfalls that may happen if you weren’t quite so thorough with your process.

Hendrik: Yeah, I had to think about this a little bit., what can break?, when you deal with processes and equipment, there’s always the possibility that something can break from an equipment perspective. The unfortunate truth is that not everything that works on pilot scale or scaled up scales works on full production scale This is where experience and expertise are required to mitigate the unknown and unforeseen factors Typically it a size and time issues It easy to run a small batch in a small vessel with a small mixer than running a 10x scale-up a version of that batch with bigger equipment, bigger mixers. And now that material sits in that same feed vessel, not for two or three hours, but for 16 to 24 hours. And what can happen with that material?

Hendrik: Bigger batches, it’s longer heating time, longer cooling time, larger batches, longer holding time. What happens with that material over that 8 to 16 hours or even to 24 hours while it’s sitting in that batch waiting to be dried?

What are the shear factor influences of the mixers that you’re using? What are the thickening potential of the material and the viscosity changes in the material over that extended period of time? and how would that viscosity changes influence the product, from the first hour that you started running the material and you achieve in-spec material, but after 16 hours you are feeding a different viscosity material or the material settled out because it was not proper mixing and now you have different powder or particle size.

Hendrik: These are the things that you learn through experience and through proper scale-up procedures and processes so that you can mitigate these unforeseen things that it’s not always possible to know, but you have to be able to foresee that these things could happen and then how you’re going to address that. We have experienced more than 20 years experience with scale-up demonstrations. We have already completed three successful scale-up demonstrations just in Q1 of this year. Important is real-time data collection and evaluation, keeping record of any variables and creating operating parameters. If the operator have parameters that he can operate within and he knows that yes there is variability in viscosity there’s variability in a particle size distribution how do you operate within those parameters and our dynamic atomization technology that we have allows for that we can operate within very narrow parameters and achieve in specification product without the concern that these unknown factors could influence the process and I think that is that is what’s really important is that you should always have the parameters that you can work within you should always have the information that you can evaluate and go back to.

Hendrik: I would say a typical example is if you have a low soils concentration feed material and that it’s going to take time. If you have say 10% feed soils concentration material, it’s going to take a longer time for you to produce powder and then you can evaluate that powder.