Importance of cell and growth factor selection and how this can affect the future regulatory approval and future commercialization of academic research.

The panel discussion offered perspectives from companies working to bring cultivated meat, fish, fat and dairy to consumers. The aim was to inspire early career researchers and demystify research in this industry to highlight and encourage transitions in both directions between academia and industry. The ultimate goal was to aid in shortening the timeframe to impact on sustainability and science and increase the success of the CARMA project by widening the consultative network.

The panel discussion focused on key issues in the cultured meat sector; the current regulatory framework, cell and growth factor selection and academic-industrial relationships.

This blog focuses on the importance of cell and growth factor selection and how this can affect the future regulatory approvals and future commercialization of academic research. Read the other blogs for more insights.

The panel was led by Catherine Elton, CEO of Qkine who was joined by Jon Dempsey, expert in biological medicines process development and regulation, Yennifer Cortes Araya, Head of Cultivated R&D at Uncommon and Prithvi Kodialbail, Chief Technology Officer at Extracellular.

Cell selection and documentation is an important consideration when a food product is being developed. The future regulatory implications of the cell line and anything used to culture the cell, for example growth factors in media need to be considered early in the research program. Full documentation and traceability in the supply chain is essential. Top tip from the panel: integrating great record keeping early in a research project could have a transformative impact on your research translation.

‘We can simplify regulation to two key aspects, firstly the source of your cell line, its history and testing. Testing is not enough so its history has to be documented. Secondly food safety, for example if using stem cells there are compounds added to stem cells to keep their pluripotency. These can’t be added to food because they are pharmaceuticals, we don’t want to give people drugs they don’t need, and they may also not have toxicology profile, so we don’t know what the safe limit is.’ Jon Dempsey.

What should the benchmark cell line be?

A lot of work in the industry is benchmarked with C2C12 cells, a myoblast cell line.

‘Ultimately the cell is your product. If you’re using a surrogate cell line, then it will impact the data generated. Ideally work should be done on the cell line you’re going to use but it can be difficult for academic laboratories to obtain industry-relevant cell lines. C2C12 is a mouse cell line, it’s immortalized, and, in my experience, it has no real comparability with induced pluripotent stem cells. So, I would advise trying to get as close to the final cell line as you can and be careful to interpret data appropriately.’ Jon Dempsey.

‘As an industry we need standardized cell lines that we can use to benchmark data, or else we end up with different research, happening in different places. We can’t really get any benchmark comparable data, even within the UK, never mind all the other countries, if we don’t have a standard cell line. How are we going to solve that, and which way do we go? Ideally in my mind, we need a standard porcine, bovine and other species that are industrially relevant and banked so they are freely available for research. Can we get there?’ Catherine Elton.

‘Achieving this is challenging because, in industry, cell lines are often created in-house and are considered part of a company’s intellectual property. Access to these cells for academic research is generally only possible through industry collaborations. Each cell line yields unique results, so maintaining traceability and complete data for cell banks is crucial. Early on, we learned to ensure that all generated data is directly linked to the specific cell line, making it inseparable from that line. When considering scalability, placing cells in a bioreactor presents additional challenges, as each cell line could behave differently. Processes must maintain complete traceability to ensure that final products are consistent. ’ Yennifer Cortes Araya.

‘I would recommend building collaborations with companies which have cell line, companies want their cell lines to be widely used and want to generate data on them, as this all adds to the bank of knowledge. Bear in mind each regulatory application is made with a different cell line, so it’s beneficial for them to be well characterized.’ Jon Dempsey.

‘In the cell therapy field there are very good guidelines for cell quality, a set of standard markers and growth rates. There is no standard legacy cell line, but groups can derive a cell line and characterize them according to a panel of characteristics. This may be something that could be done in the cellular agriculture field, so cell lines could be created to meet a set of quality criteria and ensure they are within safety guidelines.’ Audience.

Primary or immortalized cells?

Primary cells are harder to grow and slow but most likely to be the first to be used in Europe. Immortalized or otherwise engineered cell line which grow more quickly and more easily but may not lead to a product in the first instance due to regulatory concerns.

‘Some products are from immortalized cell lines, trail blazers. But what we’re trying to produce is, is cultivating meat and meat is composed of muscle cells and fat cells, and they provide sensory effect, flavor effect and so on. What we’re moving towards is more complex products, immortalized cell line products were paving the way, and the push from consumers is for products which are more like meat.’ Jon Dempsey.

‘Some consumers will be open to trying new types of products, while others may prefer options with more focus on fat or meat textures. Personally, I’m a fan of using stem cells for this purpose, but achieving the necessary scale is key—and that’s where immortalised cells maybe can make a difference. Each approach offers unique opportunities, and there’s room to explore different options to meet diverse consumer preferences .’ Yennifer Cortes Araya.

‘If we’re looking for future market entry, I do think that the starting point should be a cell which is from the actual line which will go into product development. This is most effective from a resource perspective and for the R&D which will follow on.’ Prithvi Kodialbail.

‘What we’re starting to see across the industry is that early dossier submissions are primarily avian because they are easier cells to immortalize with low growth factor requirements. However, more recently more activity seems to be in the stem cell area, particularly bovine embryonic stem cells. There seems to be a trajectory from avian, porcine and bovine with fish being particularly relevant in APAC, so it seems that the industry is diversifying in its cell source.’ Catherine Elton

Growth factor selection for regulatory approval

‘Recently the regulators had said they’re unhappy with the use of human recombinant growth factors with animal cell lines due to potential immunogenicity. As scientists we know this is a very small risk, but regulators are now saying if you’re using a porcine cell line you cannot use a human growth factor. These kinds of changes happen frequently, and we have to adapt.’ Jon Dempsey.

Species-specific growth factors for agriculturally relevant species such as bovine, porcine and for fish and seafood (tuna, salmon, eel) can be hard to source. At Qkine we’ve been frustrated by the lack of commercial availability of reliable growth factors as it is holding back the sector so we have invested in R&D to develop food grade animal-type proteins specifically for the cellular agriculture market.

‘We have seen food companies launch food grade growth factors, but when evaluated this means low quality, bulk and lost cost rather than food safe or food grade. We need to be aware of our supplier chain and the supplier chain needs to evolve along with this sector. It something we need to be aware of in study design and we need to build in redundancy and security in the supply chain without compromising on quality.’ Catherine Elton.

‘Low cost shouldn’t mean low quality and there’s a huge focus on cost in cultivated meat. But actual costs are much lower than for sectors such as pharma. We need to be careful about cutting costs and compromising on quality, ultimately the supply chain will grow with the industry and as the scale of production increases the cost goes down, so cutting initial costs and compromising on quality may not be necessary.’ Jon Dempsey.

Panelists

• Catherine Elton – CEO, Qkine
• Jon Dempsey – Roslin Technologies and independent consultant
• Prithvi Kodialbail – CTO, Extracellular
• Yennifer Cortes – Head of Cultivated R&D, Uncommon

The future of cellular agriculture looks bright, CARMA is bringing together industry leaders and academics in a transdisciplinary approach to deliver sustainable food manufacturing in the UK and beyond.

Qkine, which is partnered with CARMA is a specialist recombinant protein manufacturer has recently launched a range of exceptionally pure, agriculturally relevant species-matched food grade growth factors specifically for use in cellular agriculture. These have been developed with future regulatory novel food dossier preparation in mind under a HACCP food regime in an allergen-free process. Full documentation is available for these products including full raw materials traceability, protein allergen analysis, CoO, CoA, beta-lactam-free and animal origin-free certification.

View high quality food grade growth factors