The perception of regulators, the requirements for supporting evidence and understanding the risks involved are critical considerations when selecting the correct expression system and strain for a given biopharmaceutical.
Regulators must ensure the final manufacturing process produces your biopharmaceutical within acceptable bioanalytical limits. It is essential to ensure that the product performs consistently in terms of efficacy and safety. Behind this lies the production strain, which influences many aspects of the bioanalytical data, including its consistency between batches. The regulators will seek bioanalytical and clinical performance data from multiple cGMP batches with evidence of adequate performance consistency.
The host cell selection and the immunogenicity risks of host cell proteins (HCPs) also strongly influence the downstream processing/purification requirements. In this respect, expression platforms already established and proven for biopharmaceutical manufacture carry a distinct advantage for simpler regulatory approval. Their capabilities and risks are already well known, and the track records of existing products with regulatory approvals have already established acceptable levels of the host cell proteins. The immunogenicity risk of their host cell proteins is also better understood, providing valuable insight into the levels of purification required.
E. coli, Saccharomyces cerevisiae, and Chinese Ovary Hamster cells are all GRAS (Generally Regarded as Safe) and considered well-established expression systems for biologics manufacturing. The alternative yeast Pichia pastoris (Komagataella pastoris) is also becoming more widely accepted.
