Press Releases
Samsung Biologics CDO: Geared towards fusion protein medicines
From cell line development all the way to investigational new drug (IND) submission, Samsung Biologics has a track record of successfully bringing fusion proteins and other complex molecules to preclinical testing. With uncompromised quality serving as a guiding principle during each step of the global CDMO’s development services, deep understanding of a molecule based on a robust in-house database assures clients of timely solutions.
Fusion proteins can bring together two types of cells, a cancer cell and an immune cell for example, boosting the ability of the immune cell to target the cancer cell in close proximity. The molecular bridge in this instance consists of different antibodies fused together. A longer half-life also makes fusion proteins highly sought after in clinical settings for their lasting therapeutic effects in the body.
With the global market estimated at over $55 billion by 2030 compared to $24 billion last year1, fusion protein medicines selectively combine the beneficial parts of what single proteins offer on their own and promise wide-ranging applications. With a fifth of IND submissions at Samsung Biologics dedicated to bispecific antibodies and fusion proteins, every step of the CDMO’s complex molecule biomedicine development is upheld by dual pillars: technological innovation and transparent communication with clients.
For any biologic modality, a molecule’s efficacy in vivo depends on scientific tools that take advantage of cells’ transcription mechanisms. Using the Transposase system, Samsung Biologics’ cell line development (CLD) and upstream processing (USP) teams achieve high titer while maintaining product quality of fusion proteins, including those influenced by glycans, sialic acids, and charge variants – critical quality attributes (CQAs) to be monitored. Using S-TensifyTM, the teams also boost productivity of the cell culture, contributing to titer.
Hand-in-hand with or arguably more important than titer, however, is quality of the product according to senior CLD scientist Byungseok Choi. The CLD team uses a high-throughput lectin assay along with total sialic acid contents (TSAC) analysis to determine sialic acid levels during clone screening, which pave the way for quality-assuring measures. “We are continuously researching novel methods of clone screening and cell culture, including perfusion to remove used media and unwanted byproducts,” said Junyong Park, a lead scientist in USP Development. To enhance and fine-tune product quality throughout the upstream process, the USP team has also established S-GlynTM and S-OptiChargeTM platforms.
Coupled with scientific tools is organic communication with the client providing the molecule for development services. During times when the client needs guidance on better understanding of their molecule, the CLD and USP teams take part in a regular back-and-forth to share resulting timeline changes, according to Sanghyeop Choi, a senior scientist in Next Generation CLD. This is particularly relevant for toxicology studies scheduled in advance.
Following the CLD and USP steps, challenges may arise as subsequent processes unfold to yield the active pharmaceutical ingredient (API). As fusion proteins are prone to fragmentation, they are more likely to aggregate than monoclonal antibodies. This ultimately leads to unwanted entrapment of proteins in the cell’s Golgi apparatus, preventing secretion of naturally folded proteins and causing premature degradation. Therefore, efforts to raise titer have proven to be counterproductive, as they simultaneously compromise purity of the API.
As a means to directly address this challenge, the DSP team has established their working system for removing impurities from extracted proteins. Initial steps of the procedure are facilitated through in silico analyses of different physico-chemical properties, which help to efficiently select more favorable resins from an established library. To address host cell proteins (HCPs) – one example of process-related impurities – the DSP team works side-by-side with the Analytical team, utilizing their capabilities in liquid chromatography-mass spectrometry to track HCPs down to their specific types while screening for various types of chromatography resins.
The CLD and process development (PD) teams as one collaborative entity have been consistent in their approach to on-time communication with clients. The teams make use of a comprehensive in-house analytical capability, from charge variants to reversed-phase hydrophobicity interaction chromatography. “The client may not see the need for removing glycans if glycosylation does not interfere with the molecule’s potency,” said Yoonsik Kim, a senior scientist in Analytical Development. Such decisions can only be made with multiple batches available; with discretion informed by the client’s needs, Samsung Biologics is able to flexibly conduct diverse fusion protein projects especially when the client has extensive experience and requests. “Internal project management teams excel in handling these requests,” said Bongkyu Choi, Associate Director of Downstream Processing. “One client in particular took the time to let us know how satisfied they were with our performance.”
“Alongside customized CLD, USP, and DSP steps, the formulation phase for fusion proteins requires a detailed understanding of the molecules’ solution behavior,” explained lead scientist Derrick Katayama of Formulation Development. The DEVELOPICKTM platform, now enhanced to version 3.0, provides early investigation into the behavior of a client’s fusion protein including hydrophobicity, informing an appropriate formulation strategy. “DEVELOPICKTM gives us a clue into aggregation and solubility problems that may arise,” said Heonchang Lim, Director of Formulation Development. “This helps inform downstream colleagues and saves clients time.”
Such early detection of formulation development risks translates to flexible execution of client requests. For example, when a molecule is especially poorly behaved, the client recommends that the team moves forward with lyophilization immediately.
Close collaboration between the CLD, USP, DSP, formulation development, and CMC (chemistry, manufacturing and control) support teams enable technological innovations and client communication to successfully complement each other at Samsung Biologics. Through its technological expertise and track record of success, the CDMO helps clients navigate through unforeseen hurdles that may arise from the drive toward ensuring quality in the overall development process. The Transposase system used in the beginning helps achieve high quality and titer by bypassing random integration, reducing the CLD timeline by an entire month. Such advances trickle down the development pipeline and are compounded to reach early approval.
As Samsung Biologics looks ahead to the coming decades to meet growing contract manufacturing and development demands, it renews its commitment to scientific insights to inform constructive discussions with clients and ultimately reach more patients worldwide.
1. GlobalData
Related Content
Press Release Samsung Biologics launches high-concentration formulation platform to accelerate high-dose drug development
Press Release Samsung Biologics launches development platforms for enhanced therapeutic efficacy
Whitepaper Mitigating early development risks with Samsung Biologics DEVELOPICKTM platform
From cell line development all the way to investigational new drug (IND) submission, Samsung Biologics has a track record of successfully bringing fusion proteins and other complex molecules to preclinical testing. With uncompromised quality serving as a guiding principle during each step of the global CDMO’s development services, deep understanding of a molecule based on a robust in-house database assures clients of timely solutions.
Fusion proteins can bring together two types of cells, a cancer cell and an immune cell for example, boosting the ability of the immune cell to target the cancer cell in close proximity. The molecular bridge in this instance consists of different antibodies fused together. A longer half-life also makes fusion proteins highly sought after in clinical settings for their lasting therapeutic effects in the body.
With the global market estimated at over $55 billion by 2030 compared to $24 billion last year1, fusion protein medicines selectively combine the beneficial parts of what single proteins offer on their own and promise wide-ranging applications. With a fifth of IND submissions at Samsung Biologics dedicated to bispecific antibodies and fusion proteins, every step of the CDMO’s complex molecule biomedicine development is upheld by dual pillars: technological innovation and transparent communication with clients.
For any biologic modality, a molecule’s efficacy in vivo depends on scientific tools that take advantage of cells’ transcription mechanisms. Using the Transposase system, Samsung Biologics’ cell line development (CLD) and upstream processing (USP) teams achieve high titer while maintaining product quality of fusion proteins, including those influenced by glycans, sialic acids, and charge variants – critical quality attributes (CQAs) to be monitored. Using S-TensifyTM, the teams also boost productivity of the cell culture, contributing to titer.
Hand-in-hand with or arguably more important than titer, however, is quality of the product according to senior CLD scientist Byungseok Choi. The CLD team uses a high-throughput lectin assay along with total sialic acid contents (TSAC) analysis to determine sialic acid levels during clone screening, which pave the way for quality-assuring measures. “We are continuously researching novel methods of clone screening and cell culture, including perfusion to remove used media and unwanted byproducts,” said Junyong Park, a lead scientist in USP Development. To enhance and fine-tune product quality throughout the upstream process, the USP team has also established S-GlynTM and S-OptiChargeTM platforms.
Coupled with scientific tools is organic communication with the client providing the molecule for development services. During times when the client needs guidance on better understanding of their molecule, the CLD and USP teams take part in a regular back-and-forth to share resulting timeline changes, according to Sanghyeop Choi, a senior scientist in Next Generation CLD. This is particularly relevant for toxicology studies scheduled in advance.
Following the CLD and USP steps, challenges may arise as subsequent processes unfold to yield the active pharmaceutical ingredient (API). As fusion proteins are prone to fragmentation, they are more likely to aggregate than monoclonal antibodies. This ultimately leads to unwanted entrapment of proteins in the cell’s Golgi apparatus, preventing secretion of naturally folded proteins and causing premature degradation. Therefore, efforts to raise titer have proven to be counterproductive, as they simultaneously compromise purity of the API.
As a means to directly address this challenge, the DSP team has established their working system for removing impurities from extracted proteins. Initial steps of the procedure are facilitated through in silico analyses of different physico-chemical properties, which help to efficiently select more favorable resins from an established library. To address host cell proteins (HCPs) – one example of process-related impurities – the DSP team works side-by-side with the Analytical team, utilizing their capabilities in liquid chromatography-mass spectrometry to track HCPs down to their specific types while screening for various types of chromatography resins.
The CLD and process development (PD) teams as one collaborative entity have been consistent in their approach to on-time communication with clients. The teams make use of a comprehensive in-house analytical capability, from charge variants to reversed-phase hydrophobicity interaction chromatography. “The client may not see the need for removing glycans if glycosylation does not interfere with the molecule’s potency,” said Yoonsik Kim, a senior scientist in Analytical Development. Such decisions can only be made with multiple batches available; with discretion informed by the client’s needs, Samsung Biologics is able to flexibly conduct diverse fusion protein projects especially when the client has extensive experience and requests. “Internal project management teams excel in handling these requests,” said Bongkyu Choi, Associate Director of Downstream Processing. “One client in particular took the time to let us know how satisfied they were with our performance.”
“Alongside customized CLD, USP, and DSP steps, the formulation phase for fusion proteins requires a detailed understanding of the molecules’ solution behavior,” explained lead scientist Derrick Katayama of Formulation Development. The DEVELOPICKTM platform, now enhanced to version 3.0, provides early investigation into the behavior of a client’s fusion protein including hydrophobicity, informing an appropriate formulation strategy. “DEVELOPICKTM gives us a clue into aggregation and solubility problems that may arise,” said Heonchang Lim, Director of Formulation Development. “This helps inform downstream colleagues and saves clients time.”
Such early detection of formulation development risks translates to flexible execution of client requests. For example, when a molecule is especially poorly behaved, the client recommends that the team moves forward with lyophilization immediately.
Close collaboration between the CLD, USP, DSP, formulation development, and CMC (chemistry, manufacturing and control) support teams enable technological innovations and client communication to successfully complement each other at Samsung Biologics. Through its technological expertise and track record of success, the CDMO helps clients navigate through unforeseen hurdles that may arise from the drive toward ensuring quality in the overall development process. The Transposase system used in the beginning helps achieve high quality and titer by bypassing random integration, reducing the CLD timeline by an entire month. Such advances trickle down the development pipeline and are compounded to reach early approval.
As Samsung Biologics looks ahead to the coming decades to meet growing contract manufacturing and development demands, it renews its commitment to scientific insights to inform constructive discussions with clients and ultimately reach more patients worldwide.
1. GlobalData
Related Content
Press Release Samsung Biologics launches high-concentration formulation platform to accelerate high-dose drug development
Press Release Samsung Biologics launches development platforms for enhanced therapeutic efficacy
Whitepaper Mitigating early development risks with Samsung Biologics DEVELOPICKTMplatform