The Downstream Column Podcast

In this podcast, we spoke with Nainesh Shah, Senior Application Engineer at Asahi Kasei Bioprocess about buffer management including the benefits of inline buffer formulation, and single use inline buffer formulation systems.   Buffer Management  We started the podcast by talking about how critical buffer management is to bioprocessing. Mr. Shah discussed how buffers are required in large quantities during the biomanufacturing process and that traditionally buffers were made in large tanks, stored, and used as needed. However, now real estate in the bioprocessing industry is at a premium and companies are looking to utilize new technologies that can reduce facility footprint. For buffer management, it makes sense to create buffer on demand to reduce the footprint dedicated to buffer production in the past.   Inline buffer formulation is a hot topic with companies who require a large quantity of buffer because it provides a way to create buffer on demand in a much smaller footprint. The interesting thing is that it is now also a hot topic among small R&D scale buffer users as well. Inline buffer formulation systems are ideal for users who need 200 to 500 liters of buffer at a time. The system takes the concentrate and adds clean water to provide just the right amount of buffer on demand. Another benefit of inline buffer formulation is that you can achieve a quick process changeover and move on to the next buffer formulation without spending valuable time cleaning the tank, taking samples, and readjusting the critical parameters.   Recently, any new manufacturer, whether it's a large scale or small scale tends to move into this field of buffer management and operates one or two Inline Buffer Formulation (IBF) systems like the MOTIV™. They then use these systems to make all sorts of buffers needed for their various processes.  The MOTIV Family of Inline Buffer Formulation Systems Next, I asked Nainesh if he could talk a bit more about the MOTIV family of inline buffer formulation and fluid management systems that Asahi Kasei Bioprocess America (AKBA) offers. He explained how the award-winning MOTIV family has evolved into a series of inline buffer formulation systems designed to help companies move past downstream bottlenecks by driving buffer productivity. The product family includes 3-pump, 5-pump, and custom IBF configurations that can fit most any space, cost, or performance requirements. The MOTIV is a leader in buffer production with a range of scale from 4,500 liters per hour to 10 liters per minute to fit an entire range of volume requirements.  He went on to say that they have added a new feature where MOTIV can fill up bags with buffer and monitor the quantity in the bag to make buffer on demand even easier.   MOTIV SU Then we talked about the new MOTIV SU, a single use inline buffer formulation system, built to produce complex buffers on-demand effectively and efficiently, all from one pump head, and without the need for CIP/SIP procedures between batches. The innovative design modulates flow through control valves while simultaneously integrating buffer solutions and mixing. As with all the MOTIV systems, OCELOT System Control ensures precise blends every time, controlled by pH and conductivity feedback or flow.  The MOTIV SU is perfect for a biomanufacturer who does not want to spend time with cleaning and validation. It is great for one time use as it does not require time spent in cleaning, validation, and making sure that it is free of all the contaminants and all the buffers which may be harmful for the next process. Another benefit would be if a biomanufacturer used a buffer which had a chemical or ingredient which would be problematic for other processes, and they wanted to eliminate any risk of contamination.   Since the MOTIV SU has replaceable parts, which come as a pre-built unit, it is easy to replace the components and then the system is ready to run again. The MOTIV SU is on the same platform as the MOTIV and is an ideal solution for companies that don't want to disrupt their regular production lines, but still want to use the same production criteria that in the future could be added to production lines.   Nainesh went on to talk about why single use is such an important option. He said that because there is so much time, energy, and money being spent to clean and provide the proper validation, which then sometimes needs to be reverified or revalidated later. Single use is a good option, and if the process permits, it can be used for a long duration of time provided you have the backup data that you are not contaminating. If you're using the same material repeatedly, yes, it's a single use, it's a replaceable part, but it doesn't mean that it's a one time use and then it is gone. It is just like the bioprocess industry using 50 liter and 100 liter bags for holding their buffers, which are all single use and this goes along that same line for the bioprocessing industry.  Single use versus stainless steel Next he walked through when you would choose a single use option versus a stainless steel option. He explained that a primary consideration would be if you are using anything that would be considered corrosive. If a company is using something in their process and they are not sure whether it is corrosive and they don't have any documentation or any test reports to show whether it is corrosive or whether stainless steel will hold up and they don't want to damage the stainless steel equipment, it would be good to have a single use option as a fail proof. They can start bioprocessing studies in the single use system and at the same time start doing some studies with stainless steel to see if there is any issue with corrosion. In six months time, if they don't find any corrosion issues, they can switch over to a stainless steel option.  Another reason to go with single use is color. Any chemist or bioprocessing person would know whether it's going to impart coloration or affect the stainless steel from the inside, that is again a quick answer to go for a single use option.   Another area where single use is a good option is if you are considering whether to invest and want to prove that your technology works. You could start with the single use and then when you have a more permanent situation you can move into stainless steel.   I followed up by asking if there are any striking differences between the single use and the stainless steel option. He explained that there are a few things that need to be considered when you're using a single use system. First, because it uses only one pump, which is also a mixer and it creates a suction force to take the concentrates in, there are limitations on the maximum or minimum flow that you can get and the concentrations. It is not good to use very concentrated material and then use a small quantity per minute to do the dilution. So that is a limitation that the user should consider.  The MOTIV SU works on the same principle of mixing feedback control loop for the pH and the conductivity, or the flow and it can control in all the three parameters. It has its own tolerance values that the user can put in of what is acceptable or not acceptable. When it is not acceptable, the system will divert buffer out to a waste outlet and then when it gets back into specification it will revert the buffer back into the product outlet or the designated outlet. Collection of the buffer will start and the system will monitor how much is collected. The user can define and set all these parameters in their method, which are very easy to use and intuitive, just a quick 15-20 minute walk through can get a team up and running.  Set up and operation Next, I asked if he could talk specifically about the operating system for this unit and also answer the question of if an end user wants to create a new buffer, do they need to come to AKBA. He said that the operating system is based on a Windows based PC housed inside the electrical enclosure with Allen Bradley controls for all the control mechanisms. The user does not have to contact AKBA or work with AKBA if they want to add any new buffer or modify a new buffer. They can make their own buffers, but we teach the user how to make methods via a drop down menu with fill in blanks. Then they can run the method and the system is ready to go. Customers can always come to AKBA if they're having any issues with making a buffer and we are always there to help guide them through.   Lastly, I asked what the set up is like for end users who are interested in implementing the system. He explained that the regular MOTIV and the MOTIV SU are all skid units which are mounted on wheels that can be easily wheeled in and out of an area as needed. As he said earlier, real estate is very important in the bioprocessing industry and rooms are being utilized for multiple purposes. The mobility of the MOTIV family means that the user can connect to an electrical power supply that can be 110, 220 or 230 volts, in some instances with a higher flow rate it may need the three-phase power supply, but those are all plug ins. Then they connect the air supply for the valves and everything to open. Then connect the concentrate containers, that can be bags, 1 meter cube totes, drums, etc. Lastly, they direct where they want the buffer to go whether it's going to a container sitting right next to the system, or it could go into a port that can transfer the buffer into another room. That’s it, very easy and no special tools required for starting the system up or shutting it down. The floor size requirement is a typical office table space.  It has a small HMI on top of it to see how the process is moving and all the pertinent data is is displayed there. If there are alarms it will show the user right there what is happening and the operator or the user can take care of it right away  For more information,

In this podcast, we spoke with Emanuel Krobath, Biopurification Specialist and Chiara Pacini, Bioprocess Specialist both with Pall Corporation about gene therapy process development including challenges and resources that are available for support.   I began the discussion by asking Emanuel and Chiara to tell listeners a little bit more about their jobs and how they support gene therapy developers on the bench. Emanuel started by saying that as a bioprocess product specialist, he performs customer bench case studies at the customer site, specifically for the downstream process including vaccines, recombinant proteins, monoclonal antibodies and gene therapy products. He shared that the customers he works with are usually in preclinical or Phase I studies and he supports them from clarification to the final sterilizing grade filtration. This scale up, optimization, and technical support is offered free of charge to help customers succeed in their process development. He said that he also finds new technologies and ideas for the Pall R&D team during these visits. Chiara shared that she supports customers from bench scale studies through the manufacturing process on downstream starting from  clarification to sterile filtration. She spends most of her time traveling to her customers’ laboratories or manufacturing sites to provide general support, conduct optimization studies and technical support training to find the best practice or membrane selection for their process. I then asked if they could share what are the most common questions that they get from their customers. Emanuel said that what size filter do they need for a specific product and what is the best material to use is one of the most common. Chiara said that for her it is how to intensify a process or make it more robust for clarification, TFF, chromatography, and membrane filtration. We also talked about a series of videos on Pall’s website and how these were created to help translational academics who work in gene therapy. Emanuel explained that they wanted to support academia specifically in their scale up and small-scale process development, because often in academia, the user will take the first filter that is available at their site. It is important that they understand and have the support to select the correct filter for their product, so that the process is optimized at manufacturing scale. Chiara agreed that the videos were designed to show we can support the development process not just for manufacturing scale, but also for initial bench scale studies. This and the initial optimization study that Pall performs with the customer ensures scalability to large scale processes and identifies the critical process parameters needed to reach high yield and product productivity. Next, we discussed what they like most about the work that they do. Chiara described how being a bioprocess specialist gives her the opportunity to meet the people in both large and small companies who are working on these therapeutics. She enjoys supporting the development of different molecules and gene therapies and is always updated on the latest techniques used for gene and cell therapy. Emanuel said that he enjoys traveling, which is important because visiting customers in person is a big part of his job. He added that it never gets boring since he is supporting customers as they deal with very diverse processes and challenging problems. His favorite part of the job is that basically they are doing scientific work at the frontline, and he saw this to an even larger extent during the COVID pandemic as they were involved in nearly every vaccine process development. I followed up by asking which projects that they were most proud of. Emanuel said that with the exponential growth of plasmid DNA demand, as it is either used as a template for mRNA vaccines or the molecular function for DNA vaccines, the upstream and downstream processes have not been optimized. Now, a couple of very eager Pall scientists, including Emanuel, are optimizing the plasmid DNA process map, particularly the clarification, as this seems to be the most challenging. Since Pall and Cytiva are two sister companies under the Danaher umbrella, the goal for this project is to provide a complete process map for the upstream and downstream solely using Pall and Cytiva products. Chiara agreed that they are focused on the plasmid platform due to the COVID pandemic. Last year she worked with an Italian customer to develop a COVID vaccine with plasmid DNA to mRNA in a liposome carrier in the clinical stage. She also worked with Pall colleagues and other companies under the Danaher portfolio, Precision Nanosystems and Cytiva, on a global project. I then asked about what they saw as the most difficult aspects of process development, purification, and downstream processing of viral vectors. Chiara said that she feels the most challenging part is to achieve high virus titer and active particles. For example, she said that they work on the AAV viral vector process and it is very robust and established compared to the lentiviral process which is still very challenging due to stability and therefore you have to manage pressure, temperature and shear stress. Over the last 2-3 years the trend is moving to pDNA and mRNA. I closed the podcast by asking if they had anything else that they would like to add for listeners. Emanuel said that filtration is not something redundant and should be carefully thought through, because perhaps the product becomes a game changer along the line. Studies done during academia studies could save a lot of money and time during the process development. Chiara added that she joined Pall to make a contribution to the development of gene therapies and she has worked on covid vaccines, cancer therapy and personalized medicines. She sees that personalized gene therapies for cancer treatments are a huge target for academia and the emerging cell therapy work. Learn from experts and discover how using scalable manufacturing tools can accelerate your gene therapy developments

In this podcast we spoke with Derrick Alig, North American Western Regional Sales Manager for PSG Dover Biotech, Chris Couper, President and Founder of Liquidyne Process Technologies, and Phil Sanders Biotech Chief Innovation Officer at Agilitech about current supply chain challenges, possible solutions, what the future holds, and ways to navigate supply chain shortages to ensure manufacturers meet their timelines. Supply Chain Shortages I began the discussion by asking our panel members if they could discuss challenges that their customers are currently having with sourcing single use consumables and technologies. Derek began by discussing the lack of raw materials to make these products, whether it is polymer-based components where lead times have been extended due to lack of raw materials, or other areas such as chips. As a result, customers are having to purchase larger quantities of product in advance, which ultimately leads to even longer lead times. Chris added that from a distribution perspective and an integrator perspective, many of their primary suppliers have had issues. They have also seen that many manufacturers have been able to ramp up their production with plants that were put in place in 2019-2020. However, it takes one to three years depending upon the complexity and the scope work to create additional manufacturing facilities and production lines. In addition, many manufacturers are using alternate materials. While they may have qualified one product in the past, now they are qualifying additional supply chains, so they have a primary supply chain and also secondary and tertiary chains. Phil discussed bringing an agnostic approach to managing supply chain shortages to alleviate some of the issues of having a single source. He also pointed out that sometimes the focus is on single use supply chain issues, but there are companies using reusable equipment that are having some of the same supply chain issues, especially when it comes to these things like chips and control systems. Supply Chain Solutions Next, I asked the panel how their individual companies are approaching these challenges, specifically how they are working with customers to provide solutions for these challenges. Derek explained that at PSG Dover they are committed to providing quality products to customers in the biotech market. They focus on delivery times for customers by adding more shifts to keep up with demand and in late 2021, they added a second validated cleanroom to provide additional production capacities. They have also acquired companies to provide additional capacity. Chris added that the situation could have been much worse if manufacturers had not stepped up and added capacity like PSG Dover and that they have seen improvements in lead times. He added that for Liquidyne they have a minimum of three supply chains for virtually every component that they offer. They let their customers know that they need to qualify the three components so they can be used interchangeably to meet timelines. Phil added that maintaining flexibility is critical. For example, maybe the entire amount of inventory that is needed isn’t available now, but there is enough to get started while orders are placed for the rest of the material. Instead of trying to provide a customer with inventory for an entire year, provide three months' worth, then another three, and so on. Supply Chain in the Future I followed up by asking what they thought the future looks like for the supply chain over the next three to five years. Does this resolve itself or does it shift to another potential supply chain shortage? Derek said that he thinks that customers will continue to require multiple supply chain solutions and suppliers will also need to continue to add multiple sources for their raw materials and electrical components. Chris said that he thinks companies that are successful will take the time to study what has occurred, how they reacted, what could have been done differently, potentially better, and what missteps should be avoided. One thing that we've learned as an industry is that we must be able to react quickly to the market, science had the ability to react quickly to this pandemic and they moved vaccines and treatments to the market in an incredibly short timeline. They took things that historically take several years to accomplish and did it in a matter of months. Suppliers need to be able to respond quickly to increased demand as well. Ultimately, he thinks that customers will need to communicate about what they need in for one to two years in advance instead of in three to nine months. Phil said that he thinks the biggest issues are what we don't know today, what geopolitical event is going to happen that could cause sanctions on a country where we're getting components from and then having to shift those things. What act of God, tsunami, or earthquake, etc. If we can start figuring out what issues that coming, maybe we can maintain a specific inventory on these components. Maybe Chris keeps some of them, Derek keeps some of them, and I keep some of them so that we're working together to provide solution. He thinks over the next three to five years, the things that we're talking about today are going to be a thing of the past and we're going to be talking about a new supply chain shortage. Chris added that as three companies we look at risk and try and share that risk to create a better overall customer experience. We must work together in order to make that a reality, and we have to make sure that we communicate individually and together as a team with the client base that exists along with the client base that we don't even know about yet. All the panelists agreed that there needs to be excellent communication and partnership with customers to fully understand what their needs are and to help them ask the right questions to ensure that they will have the supply they need to move forward. Navigating the Supply Chain Then the panel discussed the things that they recommend customer related to supply chain, not just for purchasing and production, but also for scientists.  Derek started by saying that what they really want to know from their customers is their timeline so they can match it up with what they can deliver. It allows PSG Dover to review all the different options available for the best solution possible and also to make them aware of what is realistic with the current supply chain. Chris added that it is critical to know what the key components for a process are and what are the risk items or items that have volatile lead times. It is critical for customers to be able to rank these items in terms of risk. Because of volatility in the marketplace in terms of getting the product or volatility in terms of price, we're seeing price adjustments 30 days' notice and it's not only for future orders, but also for orders that haven't shipped. New price increases happen because the raw materials that were used to build the product have escalated in price, and this is what's being passed down the supply chain. It is very important to look at the high-risk items and make sure that the product is secure and that there isn’t an issue in a year or two. Phil explained that customers need to understand that assemblies are different components. So, you can't look at an entire assembly and say that that whole thing is at risk. It's the different components and understanding that sensors or pump heads or connectors or any of these things can be a supply chain issue and having that discussion with the team is important. It is important for customers to think about if there is an issue with one of the components, what is plan B? Is there inventory on the shelf or are there other options that can be explored. Phil then gave an example from one of their customers that had a specific design to be able to maintain their TMP control, but the issue was that the team wasn’t sure that the supply chain for that design could be maintained. Instead Agilitech built the unit with interchangeable parts, so if that a component wasn't available, there were others on the market that could be substituted. He reiterated that it is important to be adaptable and flexible and have those conversations, so you have a plan for managing supply chain issues in advance. Chris added that it is very important to have the entire team present when in discovery meetings with the customers. In order to facilitate quick turnaround times, these meetings need to involve not only the scientists, but ideally project managers, people from automation, and people from quality and documentation so that all the expectations can be addressed and met. This post is sponsored by Liquidyne Process Technologies, Inc.. This post is sponsored by Agilitech.

In this podcast, we spoke to Tom Watson, Group Leader, Product Management – Biotech Division, Gregor Kalinowski, Manager SLS Purification Consultants Europe, and Aude Iwaniec, R&D Bioprocessing Team Leader, all from Pall Corporation, about why high concentration mAbs are an increasingly important part of the biotech landscape, current manufacturing challenges and solutions, and future trends. High concentration drugs offer benefits for patients I began the discussion by asking why high concentration mAbs are an important topic in today’s biotech landscape. Tom explained that high concentration drugs are an important innovation because when a biotech drug can be prepared at high concentration that is administrable, it is usually self-administered in a subcutaneous mode. This method of delivery brings lifestyle benefits to patients and reduces health care costs because it negates the need for an intravenous treatment. Subcutaneous biotech drugs have been available for a while, but recently more companies are developing new drugs or formulating existing ones at high concentration. High concentration mAb manufacturing vs. more traditional mAb production I followed up by asking what some of the differences in terms of manufacturing high concentration mAbs versus more traditional mAb production are. Tom described that a mAb or recombinant protein for subcutaneous delivery is going to be prepared at a high concentration. Starting with the final concentration steps, it is common to have a highly viscous fluid of 10 to 30 centipoise, with a concentration of greater than 100 grams per liter and often higher than 250 grams per liter. He went on to say that the concentration step reduces the volume of the fluid processed across the subsequent unit operations that are typical of a biotech process. What happens then is a reduction in the dosage volume, since you only need 1 to 2 milliliters of a highly concentrated biotech drug for therapeutic effect. So, typically there are small dosage volumes, or in some cases dosage volumes can be several milliliters to permit a slightly longer-term infusion of a subcutaneous drug. However, viscosity makes processing the fluid more challenging across the unit operations including the concentration step itself, but also through filtration, mixing, freeze/thaw, formulation, and dispensing. In addition, the smaller batch volumes that correspond with the increased concentration of the drug raises the cost of the Active Pharmaceutical Ingredient (API) per unit volume and this results in more significant impact with any product loss. Manufacturing challenges with high concentration drugs Next, we discussed some of the main challenges that exist in manufacturing workflows for high concentration mAbs. Tom said that he repeatedly hears from customers about challenges relating to product loss in hold up volume, aggregation of the molecules, limitations with analytical equipment and sampling procedures, and destabilization of filtered fluid due to the stripping out of formulation components. Achieving high product concentrations I then asked Gregor about the specific challenges to achieving high product concentrations. He explained that product viscosity is increasing with increasing product concentration. So, for a given crossflow, the pressures are also increasing with increasing product concentration. He went on to say that the permeate flux is decreasing with increasing product concentrations and therefore the processing times become longer, and the number of pump passes are much higher compared to low concentration processes. This combination of extended recirculation time and the increased concentration carries a significant risk of shear related damage that may impact the product quality. Finally, the high viscosity of the final retentate pools typically results in a poor recovery from TFF systems because of limited drainability. I followed up by asking him which solutions can be applied to overcome these new challenges in the final ultrafiltration/diafiltration (UFD) step? He said that first, an optimization of the TFF cassettes screen type. For example, a coarser screen or suspended screen can be applied, then the resulting cassette pressure drop can be used to process high viscous material. Alternatively, single pass TFF significantly reduces the shear exposure because the entire concentration step is performed in a single pass without a recirculation. This is especially important for sensitive products like sensitive plasma proteins, and plasma derived factors as well as shear sensitive viral particles, as single pass TFF offers a significant reduction in cumulative shear exposure because of the single pass. He went on to say that for high concentrations and high viscosities they have demonstrated concentrations exceeding 250 mg/mL for IgG with single pass TFF technology or even higher concentrations with plasma proteins. The single pass TFF applies a serialized flow path and therefore the feed flow requirement of a single pass TFF system is significantly reduced when compared to a parallel membrane conventional TFF configuration. As a result, the single pass TFF system hold up volume is considerably smaller when compared to a conventional TFF system. The reduced hold up volume of the single pass TFF system also allows for enhanced product recovery, higher step yield, and higher final concentrations. Typical yields at high concentration from single pass TFF systems are equal or greater than 98%, whereas conventional TFF system yields can be as low as 80% or less. High concentration filtration Next, I asked Aude about other types of filtration, including direct flow. She said that higher concentration causes a significant increase in viscosity and that also affects the sterilizing grade filtration after the concentration step for the final formulation and fill. Higher viscosity has a direct impact on the filtration flux and that causes higher processing time. With higher concentration there is a likelihood of having higher aggregate content compared to lower concentration mAbs and this will in turn impacts the sterile filter capacity. It can cause your current filter size to block earlier that you would expect. So again, this means that it will increase your processing time or you might need a larger filter. She then offered her thoughts about solutions. She said that the first approach one might consider in overcoming this challenge would be to use a larger device size for a specific batch size. However, you need to keep in mind that using a larger device size is likely to increase your non-recoverable volume at the end of the sterilizing grade filtration process. She went on to say that that high concentration drugs are highly valuable, so the processing yields in each step is a critical factor to keep in mind. Something else to consider when thinking about larger device size and therefore larger membrane surface area, is that it could impact other product attributes such as excipient concentration. The research shows that polysorbate, which is used as an excipient in mAb formulation, might adsorb to sterilizing grade membrane. Using a larger device, and therefore a larger surface area for the same batch size, might increase the polysorbate adsorption which in turn could decrease your polysorbate concentration; particularly at the beginning of your filtration. High concentration drug production solutions I then asked what else Pall has been working on over the past couple of years to provide solutions suited for high concentration drug production. Tom described a diversity of products well suited to late-stage processing of monoclonals and recombinant proteins, not just direct flow filters or tangential flow filters as discussed. For example, their freeze and go storage and transport solutions, polymeric filling needles, and mixers all have attributes to help sustain critical product quality attributes for a concentrated drug. These products also help minimize costly losses that could be incurred by using technologies that have limited performance with high concentration feeds. In complement to their product offering, Pall also has a validation services team. The team recognizes that generating large sample volumes for process specific validation can be difficult with high concentration feeds, so they offer filter validation studies for fluid volumes in the range of several 100 milliliters rather than a couple of liters that would traditionally be utilized for process specific filter validation. Tom also shared that Pall is proud of their Allegro™ Connect bulk filling system. The recently launched system permits the integration of direct flow filters with high capacity for viscous feeds into a bulk filling manifold. This system automates the critical late stage filtration and dispensing step and has several features designed to maximize recovery of the high value filtered fluid. I then asked how companies can maximize productivity for their high concentration drugs? Tom explained that it is all down to selection, making sure that you've implemented the right equipment in your unit operations. It is important to seek out crossflow tangential flow filtration technologies that reduce shear and permit easy recovery of concentrated fluid. Second generation design, high area sterilizing grade filters with asymmetric PES media can enable smaller footprint filtration systems with less dead volume to occupy non-recoverable/hard to recover hold up. He added that another thing to do is always look towards vendors of single-use systems that are keen to explore your recovery challenge, who when presented with the problem of line loss will try and come up with ideas to minimize them through clever system design, appropriate orientation, or construction of components that help facilitate that fluid recovery and, of course,

In this podcast, we interviewed Katie Keller, Director of Quality and Safety at Asahi Kasei Bioprocess America, about the importance of quality management and how to achieve the best possible results. Topics included the most critical elements of quality management, how to ensure the purchase of high-quality equipment, and future trends. I started the conversation by asking Katie what she thought were the most critical elements of quality management. Katie replied by saying that a holistic approach to quality is best for any organization. It used to be that the quality unit was considered responsible for product quality, making all the decisions, and driving all the improvements and that's not really the case today. She feels the most successful approach is that since quality is so important, everyone should be responsible for it. She went on to say that when all employees understand how they contribute to product and service quality and therefore customer satisfaction, there is more buy in throughout the organization. People are empowered to take responsibility for the improvement of the processes they manage, and this total quality management is achieved by clearly defining the interaction of each process to another, ensuring employees understand that, and then setting the expectation that quality is achieved from every level of the organization with everyone playing a part. I then asked Katie what should bioprocess equipment customers be looking for to ensure that they are purchasing high quality equipment? She told me that across industries, it's common for customers to search for suppliers with robust quality management systems. As a supplier, Asahi Kasei Bioprocess America (AKBA) can minimally prove this by achieving and advertising certification to ISO 9001. This shows that Asahi Kasei meets the minimum expectations for a manufacturing company to provide those quality products and services, but it really doesn't stop there. If they can show their customers that they have well designed, thorough processes that are continually improving, this naturally leads to better quality products and customers gain confidence in their ability to meet ongoing needs. I continued the discussion by asking if she could talk a bit about ISO certification and why it's an important part of their quality management system. Katie explained that ISO 9001 really is the minimum. Their customers in the pharmaceutical industry might stop and look when they see the ISO certification, but what really brings them confidence and satisfaction are the ways Asahi Kasei goes above and beyond this. For AKBA, ISO certification is not just words on a page, there is a reason why every requirement in that standard exists. Katie shared that she believes it is her job to interpret this in a way that means something to her organization, so they can not only live it but improve upon it and take the next step. She elaborated on her point by saying that it is how you build upon those minimum criteria that truly shows a customer who you are and what is important to you as an organization. This is how a company can start to build that quality culture where the employees believe in the message that customer satisfaction, both internal and external, comes first. I asked her about how these quality management systems affect the design and build of their equipment and how they have an impact beyond the quality management systems. Katie said that having ISO as a guideline is helpful for this, especially if they need to create or revamp a process. Asahi Kasei Bioprocess starts by asking what ISO requires to get a baseline and then looks at what their customers’ expectations for safety, quality, and productivity are. She explained that by keeping both these things in mind, they can create robust processes with controls or checkpoints to ensure they are satisfying all the requirements. However, that example is at the front end of creating a new process, a robust quality system also ensures you have a mechanism to continue to learn. AKBA uses the data collected from previous equipment builds or customer facing activities to apply lessons learned to future projects. These lessons can come in the form of data compiled from nonconforming product customer feedback at reflection meetings, which are all incredibly important pieces of their quality system. Lessons provide inputs for future process and product improvements. In this way they are always learning, growing, and therefore continually improving their equipment design as well as the customers' experience with it. Next, I asked her what trends she sees in quality management going forward in the industry and what it might look like in five to ten years. Katie responded by saying that right now she can see a digital transformation, because even less than ten years ago, many companies were working on transitioning from paper-based quality management systems to electronic systems and now everything is in the cloud. Moving forward, she feels we can expect full digitization throughout all different kinds of organizations’ quality systems, both large and small companies, and the new norm could be interacting digitally through cloud-based portals instead of emails. Another example could be that communication will be digitally scanned and accepted rather than receiving paper-based packing lists attached to shipments. Additionally, she thinks the implementation of AI is growing at a rapid pace in manufacturing and this will result in the automation of more quality judgments. She went on to say that there has been lots of talk in the quality sphere about quality 4.0 and whether quality professionals will be out of a job soon, but she strongly believes there will still be a need for quality professionals to advise on ways to grow a business using quality tools and concepts. She said that we must make sure we can evolve with the times, but skills like problem solving and process improvement are still innately human skills that will always be needed. By continuing to keep people connected to each other and engaged in the quality system through the total quality management approach, we can continue to build a culture where everyone is responsible and accountable and motivated to keep improving. To sum up her answer she said, “I believe that when you have everyone in an organization living and breathing a unified message for quality, you can really do some great things, and I can't wait to see how far we'll have come in 10 years”. I closed the interview by asking her if she had anything else to add for listeners. She added that with the rapid pace that everything is changing right now, especially in these certain industries like manufacturing and pharmaceuticals, it's an exciting time. She thinks the more that we can embrace the change, the greater things we can do. At Asahi Kasei Bioprocess, they are always innovating and trying to meet customers' needs for tomorrow. She thinks really getting behind that idea with an open mind and  supporting employees internally so they have the empowerment and the mechanisms to be successful will be critical moving forward. To learn more about Asahi Kasei Bioprocess America’s products and services, please visit: https://fluidmgmt.ak-bio.com/