The Pharmaceutical Post: CDMO strategies for disrupting the biomanufacturing scale-up paradigm

Biopharmaceutical advancements are pivotal in the growth of our market. In the latest edition of The Pharmaceutical Post, Dr Parviz Shamlou, SVP, Technical and Scientific Leader at Abzena shares his thoughts on CDMO strategies for biomanufacturing scale-up.

Monoclonal antibodies dominate the biopharmaceutical market. This is due to their highly targeted therapeutic capabilities and broad applicability across a range of diseases. Scale-up and tech-transfer in biomanufacturing are distinctly challenging compared to traditional pharmaceutical manufacturing due to the complexity of biological drugs.

“The translation of these discoveries into commercial products requires scalable manufacturing processes,” says Parviz. “Success often depends on speed-to-market, and the ability to establish scalable manufacturing processes that are cost-effective, efficient and robust.”

With rising costs and smaller budgets, one area where the CDMO industry has made strides in fine tuning is in scaling up monoclonal antibodies (mAbs) saving time and money, especially for smaller biotechs. All companies are looking to increase titers and yields and reduce the cost of manufacturing biologics.

Parviz agrees, one of the major challenges with first-generation platforms for monoclonal antibodies (mAbs) was the relatively low product titers, typically 2-3g/L. Low titers require large production bioreactors, typically stainless-steel, which translates directly into higher production costs. Stainless steel bioreactors require steam-in-place (SIP) and clean-in-place (CIP) technologies after each batch, adding to bioreactor down-time, costs and resources in comparison to more flexible single use bioreactors.

“Abzena’s new cell line development (CLD) platform, AbZelectPRO™, improves the process by rapidly providing high-producing cell lines with consistent quality, helping to ease scale-up and manufacturing efforts,” says Parviz.

The cell line development (CLD) platform has been developed with a focus on optimizing three key areas: the vector, the host cell line and the process. These optimizations enable the rapid generation of stable CHO cell lines for antibodies and more difficult-to-express proteins, such as fusion proteins, bispecifics and other novel modalities, with high titers over 8g/L, in just 10 weeks.

“This allows us to use smaller upstream production bioreactors in an accelerated timeline. Abzena has combined the high-producing cell lines with single-use bioreactors, achieving significant gains for our customers. This includes lower overall production costs and faster speed to market, as well as a lower environmental impact”.

AbZelectPRO™ utilizes ProteoNic’s 2G UNic premium vector technology® to boost expression levels and generate higher-producing, stable cell lines.

Parviz says: “The flexibility of the AbZelectPRO™ platform allows for the efficient and parallel generation of multiple fast stable pools, allowing the in-depth characterization of multiple candidates. Material from stable pools allows an in-depth assessment of developability and enables manufacturability risks to be mitigated as early in the process as possible.”

The industry-standard three-column AbZelectPro™ platform process includes dedicated viral clearance strategy, buffer exchange and a concentration step, as well as bulk drug substance presentation and storage. Abzena can adjust the platform process to meet the specific needs of the molecule under investigation, full analytical support and stability studies are provided throughout the process at each intermediate step and with the final drug substance.

“AbZelectPRO™ provides a solution to rapidly progress new molecules to IND by streamlining the CLD process and de-risking upstream and downstream processes for improved efficiency,” Parviz explains.

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Going forward, developed biomanufacturing processes will require specific technologies. For instance, Abzena’s vision for scale-up of next generation biologic manufacturing processes for the next five years and beyond is towards continuous bioprocessing, combining single-use technologies with process analytical technology (PAT). Currently, fed-batch bioreactors are the technology of choice in industry while perfusion bioreactors continue to gain acceptance, explains Parviz.

“Combining perfusion bioreactors with single-use technologies provides the next major step in scale-up,” he says. “For this to happen, the industry needs to adopt PAT, including on-line, in-line and at-line measurement and monitoring of all relevant operational parameters and process control. Abzena sees the development of PAT as an important component of adoption of perfusion bioreactors and continuous downstream processing. While much development work is taking place in continuous downstream processing, additional work is progressing across multiple unit operations, including chromatography, viral inactivation and buffer exchange and concentration. Progress in these areas in the next decade – and – beyond will make it possible to create the first generation of an end-to-end continuous manufacturing platform for monoclonal antibodies and associated products.”

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