First fruits from Core Biogenesis & Nucleus Biologics Collaboration: Launch of Thermostable FGF-2 in cGMP Grade
Strasbourg, France, and San Diego, California – November 5, 2024 – Core Biogenesis, a leader in sustainable bioproduction of recombinant proteins, and Nucleus Biologics, an expert in GMP-grade cell culture media, are thrilled to announce the launch of their novel thermostable Fibroblast Growth Factor 2 (FGF-2 TOP®) manufactured in cGMP grade -developed to transform stem cell culture processes. By combining the proprietary plant-based bioproduction platform of recombinant proteins from Core Biogenesis with Nucleus Biologics’ GMP expertise, this innovative solution brings unparalleled stability and cost-effectiveness to researchers and biomanufacturers in stem cell science and regenerative medicine.
An answer to what manufacturers demand for successful cell therapy development:
Since the beginning of their collaboration, Core Biogenesis and Nucleus Biologics aim to support the advancement of cell manufacturing technologies and cell therapies, by solving the main problems encountered during raw materials supply. Currently, researchers and manufacturers face common issues including:
- Poor stability, low cell culture efficiency (bioactivity) and lack of consistency of media components -such as growth factors.
- Safety issues related to the materials derived from animal, human or bacterial origin.
- The existing production capacity from material suppliers -typically unable to meet with the scales needed for constant manufacturing and commercialization of cell-based products.
- Prohibitive costs during cell therapy development (from discovery, pre-clinical to the commercialization phases) -especially at the stage of developing full cell dosages for a large number of patients.
- Materials need to come from sources involving better sustainable practices -to ensure human health is improved while our natural ecosystems are preserved in equilibrium.
As the cell therapy field continues making significant progresses and demonstrating their clinical success among multiple disease conditions -mainly in the oncological realm-, the previous challenges become more evident and the need for robust solutions more urgent. All these current issues are even more obvious as the field is shifting towards allogeneic approaches, where cells from a single donor can be expanded, banked, and used across multiple patients with the aim of establishing cell therapies as the new Standard of Care. Allogeneic strategies require robust batch manufacturing processes and scale-up technologies to maintain consistent quality and efficacy, especially in producing the high cell densities necessary for broad patient applications. As illustrative examples, the average cell numbers needed per patient to treat different pathologies ranges from 1 million for Parkinson´s disease, to 10 billion cells for a cardiac infarct -involving large scale manufacturing processes in bioreactors.
Both public researchers and private manufacturers report significant inconsistencies when growing cells at large scales. Cellular behaviours are different between adherent (2D) and suspension (3D) cultures, where the success on manufacturing several batches at the larger volumes with regularity, is still to come. For this, better components are needed to develop high-performance media formulations that provide the nutrients and signalling to the cells at constant rates.
Current landscape of stem cell-based therapies, and main challenges associated at the different stages of development
How FGF-2 TOP® (Thermostability Optimized) in cGMP Grade allows for consistent large scale stem cell manufacturing, while reducing costs?
Thermostable FGF-2 overcomes the typical challenges associated with traditional FGF-2, which is prone to degradation and instability. In stem cell culture, FGF-2 is critical for maintaining cell proliferation, self-renewal, and differentiation, yet its traditional sensitivity to heat and storage conditions has created obstacles to achieving consistent and reproducible cell culture results. Core Biogenesis’ sustainable platform enables production of FGF-2 in the patented thermostable protein sequence version, which enhances stability, delivering sustained bioactivity and reducing the frequency of media supplementation. This improvement directly translates to time savings and a reduced risk of variability in cell culture outcomes.
FGF-2 TOP® bioactivity levels showing improved results in cell proliferation assay with NIH/3T3 fibroblasts compared to both competitor “wild-type” FGF-2 and competitor Heat-Stable FGF-2. The consistent signalling levels over a 7 days period at 37ºC are also shown, and compared against the daily protein decay from the “wild-type” FGF-2 under the same conditions.
Manufactured from Core Biogenesis’ environmentally conscious bioproduction platform, the thermostable FGF-2 is expressed using sustainable agricultural inputs rather than traditional animal, human or bacterial-derived materials. This approach aligns with both companies’ commitments to environmental responsibility, achieving high-purity recombinant proteins with reduced resource consumption.
“By integrating our eco-friendly platform with Nucleus Biologics’ renowned GMP expertise, we’re able to make high-performance recombinant proteins accessible to a wider range of applications.”
FGF-2 TOP® (Thermostability Optimized) performance on iPSCs cultures both in 2D (adherent) and 3D (suspension) cultures forming healthy colonies and embryoid bodies respectively. The capacity to maintain high pluripotency levels when iPSCs are cultured with FGF-2 TOP® under different concentrations (50-100ng/mL) and conditions (daily and every-other-day feeding), are also shown and compared to competitor products.
FGF-2 TOP® (Thermostability Optimized) in cGMP Grade. The key advantages:
1. Animal-derived component free recombinant protein expressed in an endotoxin-free system (plant seeds):
Allowing to eliminate the safety issues coming from human/animal-derived raw materials, and to prevent potential toxicities from the endotoxin lipopolysaccharides present in bacteria (such as e.coli). FGF-2 TOP® is supplied with an ADCF statement and additional manufacturing information on request.
2. High purity (≥ 95%) and bioactivity (0.5-1 ng/mL):
In comparative analysis with other FGF-2 products available both in “wild-type” and thermostable versions, FGF-2 TOP® (Thermostability Optimized) showed the highest performance for cell expansion.
3. Consistent lot-to-lot performance:
Each lot of FGF-2 TOP® in cGMP grade comes with rigorous testing employing scientifically-relevant assays, to ensure stringent quality control specifications. This permits end-users to ensure the efficacy of the product and to guarantee the repeatability of their work.
4. At least 50-70% cost reduction:
By leveraging the benefits of plant-based production of recombinant proteins and the simplicity in the upstream processes, FGF-2 TOP® is commercialized with a price that transforms the cost structure for cell therapy manufacturing. Thanks to the substantial cost reduction of this growth factor, cell therapy developers can now access FGF-2 TOP® in cGMP grade with a price per milligram even lower than the average offered by other vendors for the FGF-2 molecule in RUO grade. This also allows to start working with the end in mind, and to use GMP materials early in the process -without comprising the dedicated budget for cell therapy programs.
5. Stock security:
The large scale biomanufacturing capabilities of Core Biogenesis enables to quickly supply growth factors in gram quantities -like FGF-2 TOP®. More importantly, the plant seeds where the growth factors are expressed and stored, allow to naturally preserve the proteins. This technology disrupts the potential concerns with raw materials supply chains in cell therapy, as manufacturers can make long-term reservations of large quantities of the product preserved in the seeds, request on-demand purification, and select the supply schedules most convenient for their programs.
6. Sustainable manufacturing:
Core Biogenesis´ plants can produce recombinant proteins -as thermostable FGF-2- using sunlight, water, and CO₂, which are renewable and readily available inputs. Precision fermentation using bacteria such as e.coli, on the other hand, requires carefully controlled conditions in bioreactors, using electricity, specialized growth media, and often additional cooling, which can be more resource-intensive.
Illustrative example of costs reduction in cell therapy manufacturing thanks to the use of FGF-2 TOP®. The bar graph compares the average market price per milligram of competitor FGF-2 products to FGF-2 TOP® both at the RUO and GMP grades. The price of FGF-2 TOP® (Thermostability Optimized) in cGMP grade is similar to a non thermostable FGF-2 RUO product from other vendors, and reduces by >50% the costs for this raw material.
Quality attributes to ensure safety and efficacy:
Nucleus Biologics’ extensive GMP experience ensures that the thermostable FGF-2 meets rigorous quality standards, making it ready for translational and clinical research. The GMP-compliant FGF-2 ensures consistent product quality, supporting both research and commercial stem cell production needs.
FGF-2 TOP® (Thermostability Optimized) in cGMP grade is manufactured and supplied under the following certifications, quality testing and guidelines:
- Product manufactured, tested and released under ISO 9001:2015 and ISO 13485:2016 certifications
- Lot-specific Certificate of Analysis (CoA)
- Defined purity and bioactivity specifications
- Endotoxin testing in accordance to USP <85>
- Sterility in accordance to USP 61 – bioburden
- Sample stability testing program
- Regulatory compliance following the guidelines of USP <1043>
FGF-2 TOP® (Thermostability Optimized) in cGMP has been designed for cell therapy and cell manufacturing applications. If you would like to request a quotation for pre-ordering, or test a free sample, please click the button to submit your interest