Scaling Powder Processes: From Pilot to Commercial Production

TL;DR

Successfully transitioning a powder product from pilot to commercial scale requires meticulous attention to detail, particularly concerning particle behavior and material properties under extended run times. As discussed by Will West, Ulli Lindauer, and Hendrik Grobler, issues like high salt concentration materials yielding low recovery rates highlight the importance of thorough pre-commercialization and optimization trials. Understanding how particle characteristics, such as size and density, evolve at different production scales is critical for engineering a robust powder. Furthermore, ensuring supply chain resilience through the qualification of multiple material suppliers during the pilot phase is paramount. This not only mitigates risks during potential crises but also provides leverage for cost optimization. The overall development timeline is heavily influenced by a client’s internal decision-making processes and sample approval cycles, emphasizing the need for collaborative planning. Addressing post-drying challenges and ensuring material compatibility with downstream equipment are essential steps to avoid costly delays and re-evaluations in the product development lifecycle. Our expertise in contract powder processing and spray drying servicess, including dynamic atomization, is designed to navigate these complexities efficiently, whether for pharmaceutical spray drying or nutraceutical powder processing.

Navigating Particle Behavior Across Production Scales

Will: That makes total sense. That’s a really, really interesting aspect. Even just the financials being able to more accurately fully project out on the financial scale, the whole cash flow plan of what that exact product line product scaling is going to look like is just so valuable. That’s interesting. It also, I think part of this case study you were just bringing up with specifically calculating out, even just misunderstanding the molecule versus the particle, goes in really well to the next question, which is how does particle behavior change at different production scales, and how do you account for that when you’re engineering a powder?

Hendrik: Yeah, that’s also a very interesting question. And I would like to answer that by first starting with our technology. And as by now that APD uses a unique atomization and drying technology that’s different from conventional spray drying. We technically flash dry the particle in less than a second. And that means 100% of the particle is dried within that second. And in conventional spray drying, you would dry maybe 80% or 90% of the particle in that first, two to three seconds. And then the rest of the drying would happen while the particle is flowing through the drying chamber and exits the drying chamber. There are different hotspots, different temperatures inside the drying chamber.

Hendrik: Our drying chamber has two temperatures in. The first is the inlet temperature and the second one is the outlet temperature. And the outlet temperature represents the temperature inside the drain chamber other than that inlet temperature where we atomize and dry the product. That means that the particle is not exposed to extended heat during the drying process or while it’s traveling through the drain chamber. However, in a large drain chamber that’s maybe, 40 to 60 feet tall, the particle does take longer to exit the drain chamber than when you have a drain chamber that is, 10 feet tall. How do we address that? Our technology gives us an additional airflow that we introduce into the drain chamber that is not supporting atomization, but supports only humidity control inside the drying chamber and conveyance outside of the drying chamber.

Hendrik: We typically don’t have these challenges that conventional spray drying have with regards to how do you account for, a particle behavior on different scales.

We know that if we have addressed the basic parameters which is the inlet temperature, the outlet temperature, and atomization energy that we put into that into the drain that particle that we would achieve the same value properties whatever scale we use or dry that particle at.

Will: That makes that makes sense. That was a really interesting question that I think, funnily enough, there was so many parts of it, I think that were almost touched on previously. We’ll go straight on to the next question then. What role does pilot scale testing play and what specific data should a company be looking for from a pilot run before committing to a full production investment? So if you could almost think of even like specific key data points, obviously with you guys, they’ll get a full rundown and they’ll get all the information that they need.

Will: But when somebody is going with somebody, what specific things should they be making sure that they check from a pilot run to make sure that it’s able to scale up? It’s very important that a customer understands what those questions are that they should ask. They do not always know that.

Hendrik: We support and we help the customer to determine what questions should be important and what questions they should ask. We deal with customers, anything from startups to mid-sized companies that wants to create a new product or a new product line or a new formulation for a different application or with well-established huge companies that understand exactly what they need and what they want and they know how to answer the questions. We have to help and support to make sure what are those questions to be asked. And it’s related to the product itself, every particle characteristic or power property requirements that is involved based on the delivery system and the application of the product. Is it moisture content?

Hendrik: Is it water activity? Is it density, flowability, solubility, bioavailability? So there’s a whole range of questions that needs to be addressed. What are the specific requirements and how are you going to achieve that. Then it is the equipment itself and it’s the ability of the technology to achieve that and not only achieve that on pilot scale, but how do you scale that up to the next level?

So what we have developed at APD is a questionnaire for the customer that they complete before we even start with these lab tests or lab evaluations, or we go to a pilot scale testing where we have listed all the questions that they should ask and that they should expect answers to.

Hendrik: And if they don’t know the answer yet, then APD has the experience and the expertise to help them to address these questions. If you have a product that you want to use in a beverage application, solubility is important. How are we going to achieve that? If you want to put a powder in a capsule, for example, flowability and density is important. Particle size distribution is important. Consistency is important. And I think that is what we do at APD is we ensure that both the customer and ourselves ask the questions that’s supposed to be asked so that we can achieve the objectives for the customer.

Will: Yeah, one of the things I’d like to add here, Stephen, is that the pilot work plays an important role, not just at the piloting stage for the purposes of things you would typically think of when you’re at that stage, but it foreshadows things that are going to come later and should be used to protect the business during commercialization. And I’ll give you a couple of examples. First of all, it’s much more costly to have a problem during the commercialization stage when you’re ramping up or when you’re at full scale or when you’re in a time a business crisis at full scale in particular, rather than it is to envision how to build flexibility into the business when you’re working at the pilot scale. And many companies don’t take the opportunity at little or no cost to explore these things when they’re piloting.

The Critical Role of Pilot-Phase Supplier Qualification

Will: That’s one of the things we help clients do. A great example of that is for companies who are in the food and the beverage and nutraceutical space. Ingredients, for example, might be the same type of ingredient. Curcumin, quercetin, many others. They might even have spec sheets that look identical or nearly identical from their suppliers. But that does not mean that they’re going to run the same, convey the same in the production plant. And so it’s extremely important when choosing ingredients to look at multiple potential suppliers and run them on the equipment at the pilot phase to qualify not just the one supplier that you think is going to be your main supplier, but look at multiple suppliers, qualify multiple suppliers for the sake of redundancy, for the sake of insurance, so how they’re going to perform and make sure that the business is insulated for a time of crisis.

Will: One very concrete example, quercetin. Quercetin, for multiple suppliers, runs very differently on most equipment. During COVID, quercetin became extremely hard to source. For those providers who had qualified multiple quercetin suppliers, they had multiple vendors to turn to very quickly, knowing quite well, which ones were going to give them not only a source of quercetin, but from those who still had quercetin available for their products, which ones were going to give them the best yield in the manufacturing environment. Those who never bothered to qualify multiple vendors and run them on the equipment at the pilot phase had no idea whether or not the question they were going to source and run would give them anything more than 60 70 percent yield where they might have been used to 95 97 percent yield in the manufacturing environment so they might have been able to get the product but they were going to be paying two or three times as much for it and then they might have found out that their yield was going to drop 30 or 40 percent as well.

Will: That can be catastrophic financially just to try to keep product in the market.

The piloting phase is not just important to move through to commercialization. It gives you flexibility at commercialization to avoid troubleshooting retroactively, but it also gives you the visibility to make the right decision in times of crisis.

Ulli: Yeah, no, that foresight, I think, is, as you said, it’s not even just of utmost importance. Sometimes it could be the cause for dire situations if you don’t do that. That’s a really, really great thing to point out, I think, for a lot of companies.

Will: Yeah, so just real, I’m sorry, real quick, one of the things that I should express here is, I mentioned, and so people are going to ask me to justify this after the fact, I should I should put it in the recording now. How do you do that cost effectively? Well, if we’re doing, one shift, evaluating things in a pilot run, we’ll simply batch multiple ingredients and run each one for, 90 minutes. We can run several over the course of one shift. It’s as easy to run several ingredients over the course of one shift during the pilot phase to test suppliers as it is to dedicate that shift to one supplier., we’re going to set aside the time for the partner anyhow. We prefer to run and test multiple suppliers for them when we’re testing ingredients on the platform.

Ulli: That’s really interesting because I do think that is a really important aspect to include because even in other industries, even in other vending situations, the idea of having redundancies almost does seem like a luxury for a lot of people. The idea of having backups or the idea of having redundancy or the idea of having an extra vendor here or there just in case seems like a luxury.

That a lot of people would assume would be very costly to make sure of So that really awesome that you guys are able to do that What that does as well is give you multiple suppliers that you can assure have good products and then make sure that they’re bidding against each other if that’s feasible for the financial benefits long term.

Ulli: Yeah, no, that makes total sense. That’s a really cool thing you guys are able to do. Moving forward to the next question. How long does a typical scale up engagement take from first conversation to delivering commercial product? And what are the biggest factors that speed it up or slow it down?

Hendrik: From my experience, Stephen, I can tell you that we have seen anything recently, six weeks from the first lab evaluation through to optimization, the four steps that we just explained that we go through to the first production run, a minimum of six weeks. And then the longest was three years. And we accommodate each customer and each customer’s objectives and timeframe requirements. Although we have a very robust process, we can do that in six weeks. It is possible. From APD’s perspective, we work with the customer and we look at their objectives and their requirements. What are the biggest factors that speed this up or slow this down?

Addressing Post-Drying Challenges and Customer Timelines

Hendrik: Is it a brand new product? Is there market development involved? Is there shelf life studies that needs to be done? Is there additional post-drying development work that needs to be done? Like does this, what is the delivery system? Does this need to go into capsules? Does it need to go into gummy stick packs? And then what are the challenges, the post drying challenges that the customer have to go through and these things can slow down a product and then if there are issues with any of the particle property requirements like density or particle size and it does not behave very well with the post drying equipment then do we have to review that and do we have to make adjustments to the other properties so those things can influence that.

Hendrik: Most of the times we know that if we have determined the objectives and we know what the power of properties should be and we know what the delivery system is going to be, then we can mitigate these factors that will slow down the process. But there are always challenges and from APD’s side we have the ability to accommodate these things and help the customer to get the product do full commercialization at the time that they require.

Ulli: I’ll add something here, Stephen, because for many, many years, I was on the customer side of various manufacturing companies.

And I think one of the things I’d like to point out here is the flip side of this particular timeline. When a customer approaches us with a project or we take on a project, it’s important that the customer keep in mind that the time that their company needs internally for sample approval, decision making, that all in some way, shape or form plays into not the APD timeline, but into the total development timeline for this product.

Ulli: For example, if a turnaround, a powder evaluation and a approval can happen within 48 to 72 hours, six weeks is absolutely doable. If it requires an executive committee approval, if it involves potential focus groups on the customer side to have their ultimate user input, then it will take longer. That’s very important to keep in mind because these timelines are fantastic until you deal with the reality of corporation schedules, corporations traveling, their teams might not be available.