In recent years there has been a change in the ingredients used to optimize cell culture media for applications in biopharmaceutical production. Animal-derived substances are now being replaced by well-defined chemical compositions. This evolution is helping to increase the overall safety, consistency and performance of cell culture processes - and of the drug products derived from them. Biopharmaceutical companies are looking for high purity, stability and supply security for their cell culture ingredients. 

Amino acids are essential ingredients in cell culture media as they function as protein building blocks. Low stability and solubility of some amino acids like L-Glutamine, L-Tyrosine and L-Cystine impose limits to media formulations, storage stability, process intensification and ultimately overall productivity.  However, these challenges can be overcome with the replacement of such amino acids with our highly stable and soluble cQrex® peptides.

L-Glutamine is a well-known example of an amino acid that exhibits limited chemical stability in cell culture media. It's degradation leads to elevated levels of ammonia and glutamic acid or pyroglutamate, which have a detrimental impact on cell culture performance and product quality. As cell culture media containing L-Glutamine cannot be stored for extended periods of time. L-Glutamine is usually added to culture media shortly before starting the cell culture process. To simplify the process and reduce risk of contamination, Evonik offers glutamine peptides:

• cQrex® AQ (L-Alanyl-L-Glutamine)
• cQrex® GQ (Glycyl-L-Glutamine hydrate)

The glutamine peptides are chemically stable forms of L-Glutamine which can be used to prepare storage-stable basal media and feeds. These highly bioavailable peptides have a long and successful history across a range of cell culture applications. They are metabolized at different rates, which allows fine-tuning of the L-Glutamine supply depending on the cell types and requirements.

L-Tyrosine is an important amino acid for protein synthesis and cellular metabolism. However, it is poorly soluble in cell culture media and cannot be dissolved at the desired concentrations at neutral pH. While extreme pH values are often used to increase solubility, this process can face many drawbacks. To solve this challenge, Evonik has developed a selection of peptides:

• cQrex® GY (Glycyl-L-Tyrosine dihydrate)
• cQrex® AY (L-Alanyl-L-Tyrosine dihydrate)

The tyrosine peptides increase the solubility at neutral pH by up to 50 times compared to free L-Tyrosine. Full replacement of L-Tyrosine is possible because the peptides are efficiently taken up and metabolized by the cell.

L-Cysteine plays an important role in the protection of cells from oxidative stress because it is a building block for glutathione. However, it is highly reactive and readily forms the dimeric L-Cystine which is hardly soluble at neutral pH and often precipitates in the media. Evonik has developed a solution to overcome this issue:

• cQrex® AC (N,N'-di-L-Alanyl-L-Cystine) 
• cQrex® KC (N,N-di-L-Lysyl-L-Cystine dihydrochloride) 

The cystine peptides are highly soluble, stable and bioavailable forms of L-Cystine. With a thousand times higher solubility than the free amino acid, cQrex® KC allows the formulation of concentrated basal, feed and perfusion media at neutral pH. Hence, the peptides can be used to intensify and simplify complex production processes. By increasing the cell proliferation, viability and cell-specific productivity, cQrex® KC also contributes to higher antibody titers and increased overall productivity of biological drugs.  

Using the cQrex® peptides to partially or fully replace amino acids in basal, feed and perfusion media helps to increase yields and generate more stable and robust processes. In addition to these peptides, Evonik also offers a range of ingredients which further help to enhance media processes and cell culture performance:

• cQrex® AKG (α-Ketoglutaric acid)

cQrex® AKG is a titer-enhancing additive that can improve energy supply and protect cells against oxidative damage.

• PhytoChol® Biopharma

PhytoChol® Biopharma is an animal-origin free cholesterol that helps improve cell culture outcomes.

• D-Mannose

Specialty carbohydrates like D-Mannose can be used as alternative energy sources and building blocks for intracellular protein glycosylation.