Blood-Free Fetal Bovine Serum Alternatives in Cell Culture Media

Published on 10 October 2021

An Interview with Marcus Curl, Director of Product Applications

Can you start by providing a quick introduction to InVitria and how you provide value to biopharmaceutical manufacturing?

InVitria provides an alternative to serum and serum-proteins in the production and formulation of therapeutics. We specialize in creating completely blood component-free manufacturing environments for gene therapy, cell therapy, diagnostics, medical devices, and vaccine production. Our goal is to remove the supply chain and safety risks associated with serum and serum-proteins while improving the productivity and consistency of these manufacturing processes.

What are the concerns with serum and the proteins derived from serum? Why would InVitria target this specifically?

 

Animal- and blood-derived components pose risk in many ways. They may contain adventitious pathogenic agents such as prions and viruses that can affect product yield or even patient safety. It is also well known that the supply of human serum, fetal bovine serum, calf serum, and the protein components isolated from serum are susceptible to supply chain risk—these are not limitless resources.  Finally, the performance of serum and serum-derived components are highly variable, leading to processes that have limited reproducibility.

COVID-19 serves as an eye-opening example of the manifestation of these risks as it relates to serum and serum-derived proteins such as albumin. COVID-19 adds to the list of viruses that has the potential to exist in serum supply that must be screened for. It has also resulted in drastic decreases in human serum supply due to lack of blood donation as well as beef processing restrictions leading to scarcity in bovine-derived products. Human serum has also been allocated specifically for the research of COVID-19 treatments and vaccines, making this critical raw material unavailable for research and manufacture of other technologies, further slowing the development of life-saving therapeutics for other conditions, cancers, and diseases. InVitria provides an alternative to these raw materials to create a robust supply chain capable of supporting the future growth and safety of biopharmaceuticals, even in times of crisis.

If serum is such an obvious risk, why aren’t there alternatives?

The cell culture media companies responded to the risks of serum by creating what they call “serum-free” and “xeno-free” media and components. When someone first reads these terms, it may seem as though the products associated would eliminate the concerns previously discussed. Unfortunately, they do not. Serum-free does remove complete serum, but it includes serum-derived proteins such as bovine serum albumin which are susceptible to variable performance and adventitious agent risk. Xeno-free means that the proteins and components are derived from the same source as the intended subject. So, for therapeutics intended for humans, a xeno-free product would contain only proteins and compounds derived from human serum.  Xeno-free eliminated animal-derived products, but that doesn’t even approximate a solution to the challenges and concerns from blood- and serum-derived components.

Concerned that biopharmaceutical researchers and product developers would become confused, we wanted to eliminate any ambiguity and declare a truly Blood-Free source of products.  This clearly distinguishes our proteins, components, and media as being entirely free of any blood- or serum-derived sources, whether that be from animals or humans … or insects, for that matter.

How exactly does InVitria accomplish completely removing serum and serum-proteins when creating Blood-Free products?

InVitria specializes in the production of the key proteinaceous components responsible for the function of serum. We leverage a non-mammalian expression system here in the United States where cGMP proteins and media formulations are manufactured. All manufacturing is operated in facilities that are animal-free at the tertiary level. This means all starting materials, processing technologies, and final packaging is free of any mammalian components. These proteins and complete media are infinitely scalable to meet the increasing demand of biotechnology applications, and unparalleled in their performance in real-world applications. InVitria’s non-mammalian manufacturing technology provides quality by design as risks for adventitious agents are controlled at the upmost level.

How are these “Blood-Free” products applied and do you offer any guidance or research on how they’re best used?

Our products are used the same way that you might use equivalent products that were previously animal- or human-derived. These types of applications include processing buffers, coatings, cell culture media, final formulation, and cryopreservation. We also have the only regulatory approved recombinant albumin excipient on the market, which serves as a testament to the quality and scalability of our technology.

We spend a considerable amount of time testing our products across a wide range of applications, often at the request of our customers. My colleague, Dr. Randy Alfano has developed several of our Blood-Free, chemically defined media products and just completed a study using our products using the Gas Permeable Rapid Expansion (G-Rex®) to demonstrate the performance of our media relative to human serum to produce T-Cell therapies. Another colleague, Dr. Sofia Pezoa recently published a white paper on using recombinant transferrin to enhance the efficiency of transient transfection and subsequent vector yield in HEK293 cells.  They also presented, along with Pall Biotech, a poster at the American Society of Gene and Cell Therapy annual meeting titled, “Application of Aber Biomass Probes to Inform Transfection Timing in Chemically Defined ICELLis-Based Viral Vector Manufacturing.”  And I could go on about the activity our team has in helping customers deploy these solutions.

Is the utility of InVitria’s products entirely in cell culture applications?

Not exactly. While cell culture media for biopharmaceutical manufacturing is a common area where replacing serum and serum components is a priority, there is use of our recombinant serum proteins in final formularies of vaccines and cell therapies, as well as medical devices and tissue preservation. For one specific example, Merck’s ERVEBO® vaccine for Ebola includes our recombinant albumin in the final formulation as an excipient. The ERVEBO vaccine has been used in hundreds of thousands of patients as an FDA- and EMA-approved therapeutic.

To summarize, our products are instrumental in the next generation of cell culture performance, particularly as they apply to biopharmaceutical manufacturing.  But they are also tried and true cGMP-grade components for formulations, coatings, buffers, and anywhere else serum proteins are used.