It is well recognized that the cost of Protein A resins is substantial, especially if the cost of Protein A can’t be amortized over a large number of purification cycles. When monoclonal antibodies in development don’t pass the clinical trial stage, the money and resin are spent, raising the overall cost of bringing a successful therapeutic to market. So what can be done?
One solution is to use a less expensive Protein A resin designed specifically for early phase clinical trials, then switch to a resin designed for manufacturing.
This ebook, published in the November issue of BioProcess International, details a comparability study conducted in high-throughput format to support the strategy of switching resin between phase 2 and 3. The three resins evaluated are based on the same base matrix and immobilization chemistry and differ only in the type and amount of immobilized Protein A.
The study consisted of 20 purification cycles under identical conditions for each of the three resins studied. Comparability data for yield, product purity, host cell proteins, DNA, and leaked Protein A were assayed. The feedstock was a clarified CHO cell culture supernatant containing an IgG of subclass 1. All the resins passed the 20 cycles without changes in product or contaminant profiles. No significant difference was observed in performance or product quality among the three resins under the conditions used. Thus, from a scientific point of view, the three resins could be exchanged for each other without negative impact on the quality of the purified product.
The following three agarose-based resins were packed in 600-μL RoboColumn® units (Atoll, Germany) and used for the cycling study:
Praesto AC resin: recombinant Protein A, 35–50 g/L (native sequence, good binding to antibody fragments (Fabs) belonging to the VH3 family)
Praesto AP resin: alkaline stabilized Protein A, high capacity, 50–65 g/L
Praesto APc resin: alkaline stabilized Protein A, 35–55 g/L.
The feed stock (clarified CHO cell culture supernatant) was provided by Alvotech.