Feliza Mirasol is the science editor for 

Feliza Mirasol

FDA has approved Netherlands-based immunology company argenx's VYVGART Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) for treating adult patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This is the third indication for the biologic approved by FDA, making it the first and only neonatal Fc receptor (FcRn) blocker that has been approved for treating CIDP, the company announced on June 21, 2024. The approval is for a once weekly 30-to-90 second subcutaneous injection.

FDA’s approval is based on a clinical study (ADHERE) in which it was demonstrated that 69% of patients treated with VYVGART Hytrulo showed evidence of clinical improvement, regardless of whether or not they had had prior treatment. Improvements in mobility, function, and strength were demonstrated. The clinical trial, which the company stated is the largest clinical trial to date studying CIDP, met its primary endpoint in demonstrating a 61% reduction in the risk of relapse versus placebo.

“argenx continues to pursue our ambition to turn science into solutions for patients with severe autoimmunity,” said Luc Truyen, MD, PhD, chief medical officer, argenx, in the press release. “Patients have been waiting, and today argenx is delivering the first innovative treatment for CIDP in more than 30 years. VYVGART Hytrulo is a precision tool that has been shown to drive meaningful benefits for patients. Today’s FDA approval means that CIDP patients have a transformational new treatment option and further affirms the therapeutic profile of VYVGART Hytrulo and the potential of FcRn blockade in IgG [immunoglobulin G]-mediated autoimmune diseases.”

CIDP is a progressive immune-mediated neuromuscular disorder of the peripheral nervous system (1). It is a rare and debilitating condition in which patients experience a range of disabling mobility and sensory issues, including trouble standing from a seated position, pain and fatigue, and frequent tripping or falling. Currently, 85% of patients with CIDP require ongoing treatment, and nearly 88% of treated patients continue to experience residual impairment and disability.

“While CIDP patients face many daily concerns and challenges, fear of disease progression should not be one of them. CIDP can be debilitating and have significant impact on quality of life, and many patients with CIDP require treatments that may be burdensome. The approval of this promising new treatment option for CIDP may provide hope to patients that they can treat their disease beyond just managing symptoms. CIDP patients deserve treatment options, and we look forward to a future of choices for optimal and individualized care,” said Lisa Butler, executive director, GBS|CIDP Foundation, in the press release.

“Today marks a groundbreaking day for the treatment of CIDP. Existing treatments have been limited to corticosteroids and plasma-derived therapies. These treatments, while effective for many patients, can be challenging for some patients to receive,” Jeffrey Allen, MD, professor, Department of Neurology, University of Minnesota, and principal investigator in the ADHERE trial, added. “Today’s approval of VYVGART Hytrulo gives doctors and patients a new, safe, and effective treatment option that may lessen the burden of treatment that some patients experience.”

VYVGART Hytrulo is also approved in the United States for treating generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor antibody positive.

For access to the treatment, argenx has established a patient support program, called My VYVGART Path, to help patients and health care providers navigate access. The program resources include disease and product education, access support and benefits verification, and financial assistance programs for eligible patients.

1. Gogia, B.; Rocha Cabrero, F.; Khan Suheb, M. Z.; et al. Chronic Inflammatory Demyelinating Polyradiculoneuropathy. (Updated March 4, 2024). In 

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FDA has approved argenx's VYVGART Hytrulo for a new indication, treating chronic inflammatory demyelinating polyneuropathy.

argenx Gets FDA Nod for VYVGART Hytrulo in CIDP Indication

Purolite, Ecolab’s resins business, and Repligen launched a new protein A chromatography resin, DurA Cycle, for large-scale purification processes in June 2024. The companies introduced the new product at BIO 2024, which occurred on June 3–6 in San Diego, Calif.

The new resin is designed for the large-scale commercial manufacturing of monoclonal antibodies (mAbs) and represents the latest addition to Purolite's toolbox. In the past 18 months, Purolite launched two other new resins that address purification challenges related to the increasingly complex drugs progressing through the industry pipeline.

“The launch of DurA Cycle chromatography resin underscores Ecolab’s 100-year heritage of innovation and ongoing investment in Purolite, reaffirming our commitment to the bioprocessing industry. This new resin enables biologic developers to increase manufacturing efficiencies, reduce their cost of goods, and accelerate the delivery of innovation to the clinic,” said Srini Paluri, senior vice-president and general manager at Purolite, in a June 3, 2024, company press release.

This latest resin launch follows Purolite’s earlier investment in a new bioprocessing production facility in Landenberg, Pa. The Landenberg expansion includes the construction of resin production facilities, cleanrooms, laboratories, and new office space. There is also additional space available at the site for future expansion. This site will be Purolite’s fourth location in Pennsylvania and its sixth manufacturing facility globally. The Landenberg site is expected to significantly expand production capacity and to add more than 150 skilled jobs in the area over the next five years (1).

The Landenberg facility will produce high-quality agarose chromatography resin for the downstream purification of mAbs and recombinant proteins. It will also support the purification of new modalities such as cell therapy, gene therapy, and messenger RNA-based therapeutics. With the expanded production capacity offered by the Landenberg site, Purolite expects to better support innovators worldwide with purification resin capabilities that increase yield, optimize productivity, and reduce time-to-market (1).

The Landenberg facility complements Purolite’s Wales, UK-based facility by providing manufacturing capabilities across two world regions. The earlier manufacturing expansion in the UK site is expected to triple Purolite’s production capacity of innovative resins (2).

“The bioprocessing industry is seeking partnerships that can effectively address the most complex challenges in biologic manufacturing. Our collaboration with Purolite, an Ecolab Company, advances industry progress by delivering cutting-edge solutions that meet these demands. Together, we are paving the way for the future of bioprocessing,” said Ralf Kuriyel, vice-president of R&D, Repligen, in the press release.

1. Purolite. Purolite Grows Bioprocessing Production Capacity with New US Manufacturing Facility. Press Release, June 6, 2023.
2. Purolite. Purolite's New State-of-the-Art Facility Marks Innovative Bioprocessing Manufacturing Expansion. Press Release, Oct. 13, 2022.

Ecolab Life Sciences and Repligen have launched a new affinity resin, DurA Cycle, for large-scale biologics manufacturing.

New Affinity Resin Launched by Ecolab Life Sciences and Repligen for Biologics Manufacturing

A new production platform from Syngene International, a contract research, development, and manufacturing organization (CRDMO), offers rapid protein synthesis using a cell line and transposon-based technology that Syngene licensed from ExcellGene, a Switzerland-based service provider specializing in mammalian cell line development. ExcellGene's technology combined with Syngene’s clone selection and development processes means that the new platform provides a significant improvement in efficiency and precision, according to Syngene in a June 4, 2024 company press release.

With enhanced protein production, the platform offers faster preclinical and clinical development and shorter timelines to product launches, reducing the time to market. The platform’s advantages include:

Up to 10 weeks reduction in time versus traditional cell line development methods

Better predictability and protein yields, with high-titer levels of up to 10 g/L achieved

Monoclonal antibodies, biosimilars, bispecific antibodies, antibody drug conjugates, and other recombinant proteins are all supported on the platform.

"By combining the cell line and transposon-based platform from ExcellGene with our proprietary processes, we are pushing the boundaries in cell line development. This innovative approach will not only accelerate development timelines but also enhance the overall reliability and efficiency of the process, delivering substantial benefits to our clients," said Sridevi Khambhampaty, vice-president, Biopharmaceutical Development, Syngene International, in the press release.

"Syngene sees biologics as a key driver of future growth, and we are committed to investing in cutting-edge technology to achieve reliability, precision, and speed for clients. By combining Syngene’s skills and experience with ExcellGene’s best-in-class cell line development technology, we can expedite getting molecules to market for the people and patients who need them," added Alex Del Priore, senior vice-president, Manufacturing Services, Syngene International, in the release.

According to Syngene, the versatility of the platform facilitates integration with perfusion and fed-batch manufacturing processes. “By combining this technology with Syngene’s existing capabilities, the [c]ompany now offers a full range of end-to-end cell line development options, using the latest technology to deliver tangible benefits to customers,” the company stated in its release.

“High yield manufacturing is a multifactorial exercise that starts with transfections and an optimized cell host. We are obviously delighted to partner with and to contribute to Syngene’s process development and manufacturing capabilities. This will leverage our technology and our cells (CHOExpress) for the benefit of their extensive client base. At ExcellGene, we pride ourselves in having studied the profound challenges in DNA transfer to cultivated cells for decades and linked insights from such studies to their phenotypes and use in manufacturing. We are delighted that our work, combined with the talent and expertise of the Syngene team, will directly benefit patients around the world,” said Maria J. and Florian M. Wurm, co-founders and managers, ExcellGene, in the release.

Syngene's new production platform offers rapid protein synthesis with lower risk.

New Syngene Platform Aims for Rapid Protein Production

CordenPharma, a Switzerland-based contract development and manufacturing organization, has entered into a collaboration with Certest, a Spain-based company specializing in lipid nanoparticle (LNP)-based drug delivery and API synthesis, to develop a portfolio of ionizable lipids for LNP formulations.

CordenPharma specializes in the manufacture of drug substances for complex modalities, such as peptides, 

-acetylgalactosamine (GalNAc), and lipids, among others; LNPs containing xRNA/xDNA; and injectable drug products. According to a June 6, 2024 press release, Certest will provide CordenPharma with access to its ionizable lipids platform, which, when combined with CordenPharma’s complex LNP formulation services, is expected to boost CordenPharma’s ability to support the development, discovery, and manufacturing of xRNA/xDNA therapeutic candidates from early clinical phase to commercial.

“The world of lipid nanoparticles is revolutionizing the pharmaceutical industry today. The results have been overwhelmingly positive, and advancements in the formulation of LNPs, along with the development of a robust library of ionizable lipids, are set to redefine the paradigm of the current situation. At Certest, we offer a powerful delivery platform, thanks to our ionizable lipids, that will enable clients to overcome nearly all therapeutic challenges. This collaboration is going to be a significant advancement for our clients,” said Nelson Fernandes, CEO of Certest, in a company press release.

Certest’s ionizable lipids platform is supported by 

 and toxicology data. Through the partnership, CordenPharma will apply its current good manufacturing practice (CGMP) capacities, regulatory know-how, and market access with the aim of ensuring a high-quality GMP supply.

“Many therapeutic domains can benefit from the newly introduced LNP formulation that proved to be successful during the pandemic. At CordenPharma, we aim to consider independently each of the four pillars of an LNP formulation, namely the lipid functional excipients, to provide our customers with the most effective support in solving their therapeutic formulation challenges,” said Matthieu Giraud, senior director, Global Lipids & Carbohydrates Platform, CordenPharma, in a company press release. “This partnership augments our offer with a lean and attractive approach to LNP formulation that also reduces the growing IP [intellectual property] challenges in the market.”

The partnership complements CordenPharma’s strategy to enhance a therapeutic’s targeting mechanism using peptide-decorated LNPs as well as opportunities to enhance messenger RNA transfection using β-sitosterol (1). In February 2024, the company also launched new 

 for the formulation of mRNA-based therapeutics (2).

1. CordenPharma. Launch of Innovative LNP β-sitosterol Process Supports Sustainable Emission Reduction Targets. Press Release, April 17, 2024.
2. CordenPharm. CordenPharma Launches LNP Starter Kits to Mitigate Loss of High-value Payloads During the Gene Editing Journey to Market. Press Release, Feb. 28, 2024.

CordenPharma has partnered with Spain-based Certest to develop ionizable lipids for LNP formulations.

CordenPharma and Certest Team Up on Ionizable Lipids to Develop LNP Formulations

With the completion of a new manufacturing building at its Copenhagen, Denmark, campus, AGC Biologics doubles its single-use bioreactor capacity for mammalian-based services at the site, the company announced in early June 2024. The increased capacity allows the company to produce an additional 150 batches of drug product per year.

 of space, including a large manufacturing floor, expanded quality control and process development lab space, utilities for supporting all operations and preventing outages caused by natural disasters, and a fully dedicated warehouse, according to a June 4, 2024 press release.

The company first announced this planned expansion project in November 2020, into which it is investing approximately $200 million (1). Production in the new building has already begun with a Phase II/III clinical product.

“AGC Biologics Copenhagen site continues to be one of the most active in our network with all the necessary commercial approvals—FDA, EMA [European Medicines Agency], HCA, PMDA [Pharmaceuticals and Medical Devices Agency], ANVISA [Brazilian Health Regulatory Agency], etc.—and we are more than happy to offer the capacity and capabilities our current and future customers will look for with this completed expansion,” said Christoph Winterhalter, chief business officer, AGC Biologics, in the company press release. “The expansion, combined with our new drug product alliance, demonstrates AGC Biologics’ agility to meet all the needs developers may have, from pre-clinical through commercial.”

The manufacturing expansion comprises eight 2000-L single-use bioreactors with two seed trains and two independent downstream suites, making the Copenhagen site one of the few sites globally that houses multiple single-use bioreactor systems at this magnitude and that is capable of high-level production of clinical and commercial batches. For developers that need to tech-transfer in an existing process for products entering the facility, the site also houses multiple single-use suites to offer that flexibility, allowing the site to perform like-for-like process and knowledge activities, according to the press release.

The announcement of this completed expansion follows on the heels of AGC Biologics’ earlier end-to-end protein biologics drug product partnership with 

 (2). The partnership with BioConnection aims to offer “gene-to-vial” services, including drug substance development, manufacturing, and aseptic fill/finish capabilities for drug products.

“I am extremely proud of the work and collaboration of everyone at our site over the last several years, it is truly remarkable to see what we can accomplish by working together. We are eager to offer more of the important capabilities the industry is looking for to support patients in need,” said Andrea C. Porchia, general manager, AGC Biologics Copenhagen, in the press release.

1. AGC Biologics. AGC Biologics to Expand Biopharmaceutical CDMO Capacity. Press Release, Nov. 30, 2020.
2. AGC Biologics. AGC Biologics and BioConnection Partner to Offer New End-to-End Biopharmaceutical Drug Substance and Drug Product Development and Manufacturing Offering. Press Release, May 22, 2024.

The completed expansion at AGC Biologics'Copenhagen, Denmark, site, doubles the company's single-use bioreactor capacity for mammalian-based services.

AGC Biologics Completes Denmark Expansion to Double Single-Use Bioreactor Capacity

Continuous processes continue to advance in bioprocessing. In downstream processing, continuous chromatography is gaining traction in the purification of protein therapeutics. As the biopharmaceutical industry strives to demonstrate, continuous manufacturing offers the benefits of higher productivity and better product quality than traditional batch manufacturing. In addition, continuous processing intensifies production and lowers capital costs, while enabling better control (1). 

Editor’s note: this article was published in the Pharmaceutical Technology Europe June 2024 issue.

Although significant strides have been made to advance continuous upstream processing, downstream processing has not advanced at the same pace. However, according to Gerstweiler et al., “Research on continuous chromatographic purification for antibodies is maturing, and work has commenced on other unit operations and on process system integration” (1).

Somasundaram et al. had earlier noted that “Rapid advances in intensifying upstream processes for biologics production have left downstream processing as a bottleneck in the manufacturing scheme” (2). But to increase efficiency and promote flexibility, biomanufacturers are looking to implement continuous downstream process development. However, despite successful laboratory trials, it has remained difficult to achieve continuous downstream processing at commercial manufacturing scale.

Perhaps another challenging aspect with continuous downstream processing is the ability to implement process control strategies. Advances in process analytical technologies and modeling techniques, however, may provide solutions to improving chromatography control for industrial-scale manufacturing (3). These advances offer opportunities to enhance process robustness, increase productivity and move towards real-time release testing.

It has been previously noted that process optimization and controlling the steps in downstream chromatography contributes to increased consistency of product quality as well as better management of process variability. In addition, control of the downstream processing steps can lead to cost reductions (3). However, the biopharma industry needs to enhance monitoring and control strategies to realize these benefits as current chromatography control strategies remain limited, leading to sub-optimal processing operations. Ultimately, this limitation in control strategies leads to delays in purification for new therapeutic molecules (3).

In speaking with Pharmaceutical Technology EuropeTM, Christine Rozanas, PhD, global product marketing manager at Cytiva, discussed the advantages and persistent challenges with implementing continuous downstream chromatography.

 What is continuous chromatography, and how has it improved downstream bioprocessing?

 Continuous chromatography differs from traditional ‘batch’ chromatography in two key ways: the chromatography system can be loaded continuously, which is a useful approach when the purification step is connected to an upstream perfusion or fed-batch bioreactor, and, by having two or more columns in the loading zone, you can overload the first column [because] any product/target molecule that is breaking through is being captured by the second column in the loading zone. When used with a perfusion or fed-batch bioreactor, continuous chromatography can help reduce the amount of resins and buffers needed. It also provides greater flexibility for processes and uses a smaller footprint in a manufacturing facility.

 What are the benefits of using a continuous chromatography process in downstream bioprocessing?

 Compared with batch operations, continuous chromatography can offer significant productivity gains and increased production capacity, for example, through increased utilization of chromatography resin binding capacity, reduced buffer usage, and smaller column size.

 What have been the major drawbacks or challenges to using continuous chromatography in downstream bioprocessing?

 Despite the benefits, the industry has been to slow to adopt continuous chromatography in downstream bioprocessing for a number of reasons. It can be a more complicated set up compared to a traditional batch process, and, while batch chromatography is done over a single shift or sometimes over 24 hours, the larger volumes processed continuously from perfusion or fed-batch bioreactors must be processed over several weeks or up to a month. [This] can make it more difficult to trace any potential issues that might occur. While regulatory agencies express interest in supporting the use of continuous processing, many companies continue to develop batch purifications first, before evaluating whether a continuous chromatography process would significantly reduce production costs or increase productivity and output.

 How does multi-column continuous chromatography work, and in what scenarios would a biomanufacturer opt to implement this?

 For multi-column chromatography, the large capture column is split into multiple smaller columns that alternate in binding and elution operations in multiple cycles to process the feed from the upstream bioreactor. It can be a great option when working with sensitive molecules, where continuously removing the molecule from a potentially harmful environment into the first purification step can be the only viable option. In scenarios where there is a limited product demand (in kg), continuous chromatography can also allow significant reduction of the needed resin volume through running a higher number of cycles in the available time and thus reducing the column size.

 What key innovations have been instrumental in promoting the use or adoption of continuous chromatography?

 [Some] continuous chromatography systems use controls (e.g., dynamic ultraviolet control, as with Cytiva’s systems) that enable real-time monitoring and control of the process. In Cytiva’s case, its system can adjust accordingly to changes in feed concentration, for example, to optimize processing of the perfusion output. Also, pre-packed columns have provided greater consistency and quality of the internal conditions of each column so that the feed is processed in the exact same way in the alternating columns during the continuous run.

1. Gerstweiler,L.; Bi, J.; Middelberg, A. P. J. Continuous Downstream Bioprocessing for Intensified Manufacture of Biopharmaceuticals and Antibodies. 

, 116272. DOI: 10.1016/j.ces.2020.116272
2. Somasundaram, B.; Pleitt, K.; Shave, E.; Baker, K.; Lua, L. H. L. Progression of Continuous Downstream Processing of Monoclonal Antibodies: Current Trends and Challenges. 

 (12), 2893–2907. DOI: 10.1002/bit.26812
3. Armstrong, A.; Horry, K.; Cui, T.; et al. Advanced Control Strategies for Bioprocess Chromatography: Challenges and Opportunities for Intensified Processes and Next Generation Products. 

, 461914. DOI: 10.1016/j.chroma.2021.461914

ope®
Vol. 36, No. 6
June 2024
Pages: 30–31

When referring to this article, please cite it as Mirasol, F. Evaluating the Use of Continuous Chromatography. 

The biopharma industry is looking at continuous chromatography for sensitive molecules.