Culture media is fast becoming a limiting factor for intensified drug production. Overcoming this hurdle will require a combination of novel feed designs and innovative technologies.
The observation comes from Dong-Yup Lee, PhD, director of the White Bioinnovation Research Center at Sungkyunkwan University in Seoul, South Korea, who says the media industry is working to develop solutions.
“Biopharma’s push for process intensification, like high-density cell cultures and continuous production, is raising the bar for what culture media need to deliver. Traditional media, designed for simpler fed-batch processes, often can’t provide enough nutrients or stability for these intensified conditions.
“That’s why companies are rethinking media design to better support high-performance, long-duration cultures, especially by improving nutrient balance and reducing stress on cells,” he tells GEN.
One major media design issue is poor nutrient solubility. CHO cells, like all cells, need a steady supply of amino acids to grow, multiply and—crucially from a drug industry perspective—synthesize proteins. The challenge for media developers is that many amino acids are hard to dissolve. L-cysteine, for example, contains a thiol group that is poorly soluble in aqueous environments, particularly in concentrated formulations.
Dipeptides—molecules made of two amino acids—are a potential solution, according to Lee, who says, “They offer an exciting and synergistic solution to long-standing challenges in media design. By pairing two amino acids into a single molecule, dipeptides may dramatically improve solubility and stability, especially for problematic amino acids like cysteine and tyrosine.
“What makes this strategy particularly interesting is that the two amino acids in a dipeptide can work together in ways that free amino acids can’t, enhancing nutrient uptake and reducing metabolic stress. For biopharma manufacturers, this means better cell health, higher productivity, and greater process control. However, designing them is quite challenging!”
One of the major challenges—which was discussed in research published by Lee and colleagues earlier this year—is determining how each pair will behave in culture.
Lee says, “Not all dipeptides behave the same way. Manufacturers must carefully evaluate how efficiently a given dipeptide is transported into cells and metabolized, as well as its compatibility with regulatory requirements and interactions with other media components.”
Cost-effective, scalable production methods will also be needed, according to Lee, who adds, “In this context, I am currently trying to develop an ‘off-the-shelf’ dipeptide toolkit comprising well-characterized, pre-validated options, which could offer a practical and flexible solution for streamlined media optimization.”
The impact intensification is having on the media sector goes beyond amino acids. Changing biopharmaceutical expectations are driving the adoption of new technologies and design strategies, points out Lee.
“Tools like metabolic modeling and data-driven AI/machine learning enable researchers to simulate how cells respond to different nutrient inputs, thereby helping optimize dipeptide choices faster and more accurately,” he says. “As far as I know, some media companies are already exploring these approaches, and I’m currently in discussions with one of them who is particularly interested in applying these strategies to their next-generation media platforms. These collaborative efforts are pointing toward a future where media design is faster, smarter, and more customized than ever before.”
The post Process Intensification Driving Innovation in Media Design appeared first on GEN - Genetic Engineering and Biotechnology News.
The observation comes from Dong-Yup Lee, PhD, director of the White Bioinnovation Research Center at Sungkyunkwan University in Seoul, South Korea, who says the media industry is working to develop solutions.
“Biopharma’s push for process intensification, like high-density cell cultures and continuous production, is raising the bar for what culture media need to deliver. Traditional media, designed for simpler fed-batch processes, often can’t provide enough nutrients or stability for these intensified conditions.
“That’s why companies are rethinking media design to better support high-performance, long-duration cultures, especially by improving nutrient balance and reducing stress on cells,” he tells GEN.
Dipeptides
One major media design issue is poor nutrient solubility. CHO cells, like all cells, need a steady supply of amino acids to grow, multiply and—crucially from a drug industry perspective—synthesize proteins. The challenge for media developers is that many amino acids are hard to dissolve. L-cysteine, for example, contains a thiol group that is poorly soluble in aqueous environments, particularly in concentrated formulations.
Dipeptides—molecules made of two amino acids—are a potential solution, according to Lee, who says, “They offer an exciting and synergistic solution to long-standing challenges in media design. By pairing two amino acids into a single molecule, dipeptides may dramatically improve solubility and stability, especially for problematic amino acids like cysteine and tyrosine.
“What makes this strategy particularly interesting is that the two amino acids in a dipeptide can work together in ways that free amino acids can’t, enhancing nutrient uptake and reducing metabolic stress. For biopharma manufacturers, this means better cell health, higher productivity, and greater process control. However, designing them is quite challenging!”
One of the major challenges—which was discussed in research published by Lee and colleagues earlier this year—is determining how each pair will behave in culture.
Lee says, “Not all dipeptides behave the same way. Manufacturers must carefully evaluate how efficiently a given dipeptide is transported into cells and metabolized, as well as its compatibility with regulatory requirements and interactions with other media components.”
Cost-effective, scalable production methods will also be needed, according to Lee, who adds, “In this context, I am currently trying to develop an ‘off-the-shelf’ dipeptide toolkit comprising well-characterized, pre-validated options, which could offer a practical and flexible solution for streamlined media optimization.”
Innovation
The impact intensification is having on the media sector goes beyond amino acids. Changing biopharmaceutical expectations are driving the adoption of new technologies and design strategies, points out Lee.
“Tools like metabolic modeling and data-driven AI/machine learning enable researchers to simulate how cells respond to different nutrient inputs, thereby helping optimize dipeptide choices faster and more accurately,” he says. “As far as I know, some media companies are already exploring these approaches, and I’m currently in discussions with one of them who is particularly interested in applying these strategies to their next-generation media platforms. These collaborative efforts are pointing toward a future where media design is faster, smarter, and more customized than ever before.”
The post Process Intensification Driving Innovation in Media Design appeared first on GEN - Genetic Engineering and Biotechnology News.