Optimizing cell culture performance

Brandon Pence talks to NGP about achieving maximum output from process optimization collaborations.

In your opinion, what are the main challenges currently facing biopharmaceutical drug development?
Brandon Pence. Moving products to market quickly remains the challenge of any company, in particular those developing biotherapeutics and vaccines. Additionally, as new biologics are developed for more specialized applications, the demand for yesterday's large manufacturing plants with tens of thousands of liters in bioreactor capacity is diminishing. The ability to quickly manufacture products in a cost-effective manner, and in many cases locate the manufacturing facility in the region where the end-product will be supplied, is becoming key to the market performance of the biologic. To accomplish this, more biopharmaceutical manufacturers are turning to single-use systems for liquid preparation and handling, cell culture manufacturing and bulk intermediate storage.

The advantages of single-use systems have been widely documented over the past few years and include manufacturing cost reduction, rapid production turnaround timelines and maintaining a consistent contact surface throughout the manufacturing process flow. With the expanded range of applications for single-use systems, ease of implementation is another critical factor. At Thermo Fisher Scientific, we are placing technology experts in the field capable of working directly with our clients on identifying opportunities to utilize single-use systems all the way from the development of initial application protocols through their integration and qualification.

How can biopharmaceutical companies increase the productivity of their protein-based drug production?
BP. Matching cell expression systems with the raw materials consumed and the equipment used in the bioproduction process can significantly improve titers, elevating overall efficiencies for manufacturers. However, achieving this productivity improvement requires a balance between providing the right nutritional components in the form of complete cell culture media and feed supplements for the cell platform selected with the optimization of the bioreactor production process. In many cases, titer improvements are a function of customizing the nutritional components for the specific cell clone and then developing the right strategies for delivering those nutrients.

We believe that having subject-matter experts with the right process monitoring technologies enables us to analyze the complete cell culture process and provide customized responses to our clients needs. In many cases, these customized responses influence the type of cell culture media and supplements used, as well as the protocols for operating production bioreactors. Through practical application of this approach, we've been successful in partnering with biopharmaceutical manufacturers to achieve productivity improvements greater than two-fold compared to traditional production systems.

What should companies look for when choosing an external partner to help optimize cell culture performance and achieve maximum results from their research?
BP. Having the right technologies and applications resources is obviously important. We have taken a leadership position in the bioprocessing industry by integrating cell culture nutrients (sera, media and supplements) with single-use handling and production systems, including the Thermo Scientific HyClone Single-Use Bioreactor. This enables us to partner with companies in developing complete cell culture systems.

Another critical factor to be considered for achieving maximum output from process optimization collaborations is the ability to take results and implement them globally. This includes selecting a partner with global manufacturing sites and a history of providing and supporting products placed into various regions. One important element that is often overlooked is identifying a partner capable of providing the right degree of collaborative activity. This activity may involve onsite technical discussions and support, project management and communication, and coordinating studies at research facilities located at the partner's headquarters. 

How do you see the area of cell culture-based biotherapeutics developing over then next few years?
BP. An emerging trend in cell culture science will be the development of more personalized biotherapeutics instead of large blockbuster drugs. These will require smaller productions systems as they will take advantage of existing cell culture productivity improvement technologies as well as have refined dosing requirements for a smaller patient population. As such, personalized biotherapeutics manufacturers will require an ability to customize the delivery of key raw materials and production systems to ensure robust and efficient processes.

Additionally, the emergence of biosimilars as patents expire on existing blockbuster biotherapeutics could have a profound impact on the biopharmaceutical industry. Utilizing strategic partners capable of providing the right technologies will enable both biosimilar manufacturers and novel biotherapeutics developers the ability to constantly be at the forefront of their respective domains.

Brandon Pence is the Associate Director of Market Management for Thermo Scientific Cell Culture and BioProcessing. In his current role, Pence is responsible for global strategic business efforts primarily aimed at improving the tools utilized in bioprocessing systems, biotherapeutics and vaccines manufacturing.