Accelerate biotechnology

The good, the bad, and the ugly in biosimilar development

Meet the Expert: Wilfried, Scientific Director

Whether it concerns a biosimilar, a biobetter, a product to treat a rare genetic disorder or a biothreat counter-measure, product yield from mammalian cell lines is a critical economic driver. Naturally, increased specific productivity – microgram product per cell per day – decreases the cost of goods, allowing lower prices while retaining expected product margins (the “good”). That is why expression technologies, like our STEP® technology, that allow the generation of extreme high protein producer mammalian cell lines are highly sought after. However, the “bad” is that we sometimes see that a process providing the highest yield does not deliver a product that adheres to set product quality standards. The outright “ugly” in this story is that sometimes even extensive process development does not result in a substantial improvement in product quality, forcing us to accept lower productivity.

In this article, I would like to show you an example of how we selected a biosimilar producing CHO cell line,  expressing extreme high levels of laronidase and why we compromised about 50% of the productivity in order to guarantee product quality. Laronidase is an enzyme involved in the breakdown of glycosaminoglycans. It is a marketed product used for treatment of lysomal disorders, such as Hurler forms of MPS 1 and Scheie syndrome. Treatment costs are around $400,000 per patient per year as the enzyme is highly glycosylated and very complex to manufacture.

Developing a biosimilar cell line

Using our STEP® technology for cell line development, we ultimately selected a cell clone expressing about 100 mg/L in a generic fed-batch process. We next performed a limited basal media screening study and fed-batch studies resulting in a fed-batch process that provided about 750 mg/L enzyme at day-11. However, careful analysis demonstrated that at day-11 the glycosylation profile of our product substantially deviated from the marketed product and from our own product produced at day-1 through day-8. We then embarked on extensive small scale R&D studies testing a wide range of basal media and feed strategies. Additionally, we optimized the harvest time. Unfortunately, none of these activities allowed us to push the culture beyond day-8 without compromising the product quality. Therefore, we were forced to lock-in the process using a day-8 harvest as starting point for the purification train. The yield at day-8 was about 50% of the yield we generally obtain on day-11.

Laronidase biosimilar project status

The extensive small scale process development activities ultimately resulted in a cell line and production process (day-8 harvest) that enables 12x higher productivity compared to literature. The purified product qualifies as a biosimilar as both biological activity and glycan profile are very close to the marketed product. Even though my team wished to move forward with a process providing the highest productivity while not compromising quality, we are still proud to have successfully developed a promising laronidase biosimilar cell line and process. This cell line and process undoubtedly will lower the ultimate production costs compared to the currently marketed product.

Batavia Biosciences offers a broad range of process development and manufacturing services for all major classes of biopharmaceuticals, i.e., viral vaccines, viral vectors, recombinant proteins and antibodies. As a company dedicated to help bringing biopharmaceuticals to the market at higher speed, with reduced costs, and with a higher success rate, Batavia Biosciences has vast experience in developing cell lines and processes for biosimilars. With our team of experienced scientists and technicians, we are well equipped to take on any challenge associated with biosimilar development.

STEP® technology

SCOUT® technology

Process development