Intelligent Media Design to Drive Better Therapeutic Outcomes

Introduction

Hi. My name is Brad Taylor. I'm the VP of Marketing at Nucleus Biologics and I would like to give you a little insight into who we are and why we believe custom media can greatly improve your research outcomes and, therefore, should be a focus as you design your studies and perform your research

Our Mission

We are the cell performance company. We strive to expedite the time from discovery to cure through reproducibility and consistency of top-quality cell culture products. We achieve this goal by empowering scientists and clinicians with disruptive innovative products and ecosystems that facilitate manufacturing reproducibility of cGMP products, unmatched personal and timely support, and ultimately introducing practices and products which improve the environmental impact of cell culture.

Our Facilities

we provide a vertically integrated cGMP manufacturing solution for powder processing and complete liquid media manufacturing from two facilities in San Diego, California, and Madison, Wisconsin. Our San Diego facility includes nearly 18,000 square feet of space with a segregated cGMP ACF manufacturing space, including one ISO 8 and two ISO 7 cleanrooms. We have milling and blending capabilities with ambient and cold storage utilizing WFI spec water for solubilization in our 2,000-liter tank and have a capacity currently of around 500,000 liters per year. We are pursuing ISO 13485 certification by the end of 2021. Our Madison, Wisconsin facility has 1,200 square feet of space and performs xeno-free recombinant protein manufacturing.

Common Misconceptions

Before we talk about our products and solutions, let's begin by discussing some common misconceptions about cell culture media in order to demonstrate the critical role that cell culture media can play in your research project. So first, a lot of people think "The specifics of my formulation aren't really that important." This has been disproven in many instances and has been definitively demonstrated that even single component changes can improve aspects such as transfection efficiency, cytotoxicity, and yield. This recent publication out of UPENN highlighted this exact point - one single component change moving from human serum to Physiologix, Nucleus Biologics' xeno-free human serum replacement, resulted in significant therapeutic benefits by increasing potency in a xenograft mouse model of neuroblastoma resulting in a log reduction in tumor burden. So now we know the components are critical, what about the complexity? The configuration and research involved with custom media can be somewhat time-consuming, yes. There are a plethora of publications in the public domain as can be seen in this graph. This is data extracted from PubMed showing the number of publications available using the search term "t-cell." There are currently around 513,000 publications to date and, of course, with research continuing due to the promise of T-cell therapies, there's no reason to believe this will decrease. So how do you quickly find the information you need, and after finding that information, how are you certain it is the best information available for your study? Well certainly, one way is to use our online ordering and formulation platforms - NB-Lux and NB-AIR.

Timelines

Now let's look at the timelines for the different types of media options - traditional custom versus proprietary off-the-shelf versus NB-Lux. The light blue portion of the bar represents the time taken to research your components. Red is for configuration and quotation. Blue is for ordering, manufacturing, and delivery. And orange is media testing. Traditional custom media manufacturing is a slow process and can require more than a year considering there will likely be two iterations of media testing and manufacture. Configuration can require up to four weeks for each instance, and manufacturing, due to the large scale, can be a 20-week process. Using proprietary off-the-shelf certainly is able to reduce manufacturing time - the blue portion of the bar - but ordering components and receipt of those components from multiple vendors can still be time-consuming. NB-Lux reduces configuration times - the red portion of the bar - because of the easy online ordering process. Furthermore, internal process improvements facilitate streamlined manufacturing and quick turnaround roughly equal to off-the-shelf media, thus just by utilizing NB-Lux we can reduce the timeline for custom media production by more than half and provide similar timelines as proprietary off-the-shelf media. Now, just recently, we introduced a counterpart to NB-Lux called NB-AIR, which aims to reduce the time needed for research and formulation by utilizing AI-based algorithms to search and suggest components to produce the desired critical quality attributes or CQAs. This has led to a further reduction in timelines by three weeks, meaning that we can formulate, manufacture, and deliver custom media tailored in volume to your stage of development within approximately a 21-week time frame - less than a third of the 66 weeks required for traditional custom media and three weeks faster than proprietary off-the-shelf media.

Components

So components are critical, and the process has been streamlined, but can you afford it? Small custom volumes do come at a price premium; however the alternative is to research, source, order, and manually mix media using off-the-shelf components from multiple manufacturers. With custom media, you save on labor and materials and simplify quality control as you're sourcing material from one supplier as opposed to multiple vendors, not to mention, there is inherent variability that results from mixing each lot by hand. Furthermore, how much waste will there be? Will you use everything you order? What if your components don't have the desired effects? These are some of the reasons why you incur that price premium. However, with our tools and products, once formulations are identified, scale-up comes with significant price benefits and can quickly become cheaper than proprietary off-the-shelf media. Let's explore that and take an example of a company with high commercial volume for its sole therapy of around 5,000 patients. Considering that a typical patient therapy may require around 14 liters of media per year, we determine an average price using a model for several different off-the-shelf T-cell media with standard supplements, which came to around $300 per liter. Then costed the same media formulation produced using NB-Lux and our proprietary methods, but at higher volumes to facilitate this example. In comparison, the cost per liter of custom media dropped to $189 per liter. This equates to savings of around $8 million per year for this company. Plus, with our custom media, you own the formula, you have less work in terms of qualification and validation of the process - as it is from one source compared to off-the-shelf media where you may not know what exactly is in your media and certainly don't own it. There's also more work and complexity as there are more vendors and products to qualify as well as multiple processes to validate. So, just to summarize, custom media's value is really in the individual ownership that it provides to researchers as well as the transparency in every step of your process. And finally, also consistency of supply which is such a pertinent topic at the moment. We're seeing unprecedented supply shortages due to COVID-19 and the reallocation of supplies to COVID-related research and development, particularly with vaccine production. This means components have become quite difficult to source. We are experts in the sourcing and procurement of components, and again, offer complete transparency on lead time so you have less worry and difficulty in getting the media you need. So I say the question isn't "Can you afford it", it's "Can you afford not to do it."

Solutions

Now that you understand the reasons why we are so passionate about the importance of custom cell culture media, let's talk about the solutions we provide to meet your cell culture needs. Our services range from formulation, both automated and guided, to supplements and recombinant proteins, to customization tools that expedite the ordering process and return ownership back to you. NB-AIR is our AI-based formulation platform that facilitates expedited cell culture media formulation; we also offer wet lab formulation services for more complex projects or process development. Our xeno-free cGMP serum replacement, Phsyiologix, can be added to any of your formulas; and xeno-free Vitronectin ECM promotes superior cell proliferation, maintains pluripotency, and supports normal colony morphology for MSCs and iPSCs. After your formula is finalized, you can easily import it into NB-Lux to define specific testing requirements, volumes, and packaging. Your formulations are stored with your profile and are your property. Later this year, we will be launching a new line of products with the goal of reducing the exceptional amount of waste currently produced by cell culture and also reducing the carbon footprint associated with the delivery of liquid media. So stay tuned to coming exciting announcements at Nucleus Biologics.

Custom Media Formulation

The root of our custom media formulation is NB-AIR, our configuration tool. NB-AIR searches PubMed based on the user's cell type and CQAs chosen to identify compounds that may impact and tailor results to the desired criteria. NB-AIR predicts and suggests formulations for testing, which can be ordered through NB-Lux in quantities that facilitate quick testing and identification of preferred optimal media. So let me show you how quick and easy this process can be. In short, the user enters their cell type, the CQAs, and how they want their media to impact that chosen CQA - increase, maintain, or decrease. The bullseye plot shows components that impact the chosen CQA and exactly how it's impacted. Next, components for the formulation are narrowed based on these selections. To begin, a basal media is chosen. The user can research each component - papers, data quotations, the impact of each component on other CQAs. Nucleus Biologics cell culture supplements, such as Physiologix, can also be added to any formulations as well. After the user's desired component selections are made, the software suggests formulations to facilitate testing and ID of media that promote the desired CQAs. Formulations can be named, saved to your profile, and exported to NB-Lux. Saved formulas show in the user's profile and can be opened for customization, including testing such as sterility and pH. Volume and packaging can also be customized to your desires as well as a final confirmation of the concentrations within your media. Remember, lead time and pricing update real time so the user always has visibility in the specifics of their products. And that's how simple custom media formulation and configuration using NB-Lux and NB-AIR can be.

Complex Media Formulation

For more complicated formulations, we can perform formulation process development and testing for you. We have formulated media for a multitude of immune stem protein expression and cancer cells through a structured process and generated gigabits of growth data utilizing mass spec, Incucyte, and flow cytometry. We have extensive animal and serum-free formulation experience. With in-house manufacturing, we can expedite iteration and testing. Lead times are around 9 to 16 weeks depending on the packaging, and are built for scalability.

Conclusion

So, I hope you've enjoyed our corporate overview and now understand why cell culture media is such a critical component of any study. And secondly, why we are the preferred vendor for custom cell culture media and services. We are proud to offer customizable products and services which improve ordering efficiency and decrease waste and labor for your project. We return individual ownership of cell culture media back to our customers. With consistent processes and highest quality standards, you will realize streamlined QC and validation, consistency of supply, and ready-to-pipette products - no manual mixing, which can introduce variability. We offer volumes that are scalable to transition with you from the bench to the bioreactor. There is transparency in every facet of our process - no hidden ingredients whatsoever. And with Nucleus Biologics media, you will see lower overall costs over the life cycle of your development project, particularly during scaled production. Our solutions as well are AI technology-driven to expedite formulation, customization, and improve outcomes through machine learning. Lastly, I appreciate your time and hope this overview was informative. Please let us know if you have any questions at [email protected], or for sales inquiries, reach out to [email protected]. You can certainly find more educational resources on our website as well. Thank you very much for watching!