The range of applications for twin-screw extruders as pharmaceutical manufacturing equipment—either as a stand-alone, continuous unit operation or integrated into a continuous manufacturing line—is growing. Hot-melt extrusion (HME), which involves melting and mixing polymeric excipients with APIs in a twin-screw extruder to produce an amorphous solid dispersion, is used commercially in multiple applications, including drug-loaded devices or as a solvent-free alternative to spray drying. Twin-screw granulation (TSG) uses a twin-screw extruder to make granules using dry granulation, wet granulation followed by drying either continuously or in a separate fluid-bed batch process, or melt granulation using a highly viscous binder.TSG was used in early powder-to-tablet continuous manufacturing lines, and commercial use continues to grow. Although direct compression can be used for some formulas in continuous manufacturing lines, TSG is important for others where direct compression isn’t suitable.

“In recent years, TSG processes have been advancing rapidly, particularly towards continuous manufacturing processes becoming standard in the pharmaceutical industry because of the potential benefits TSG offers,” says Hemlata Patil, senior manager for hot melt extrusion technology at Catalent. “Consequently, a thorough understanding of the impact of formulation and process variables on granule quality has become crucial.”

Researchers continue to create new process analytical technology (PAT) for TSG that provides process insight and helps advance the science needed for product and process development using quality by design (QbD). QbD techniques will be especially helpful because the modular design of twin-screw extruders widens the range of possible variables.

“TSG and HME technologies provide a lot of promise for formulations, such as controlled release or poorly soluble drugs,” says Doug Hausner, senior manager of business development for continuous manufacturing at Thermo Fisher Scientific. “There is a large knowledge base in twin-screw granulation, but there is also a large design space. There are many options for screw configuration in the equipment, along with other input variables such as liquid-to-solid ratio. Process design requires know-how as well as statistical analysis for optimization.”

This knowledge is important for both individual and integrated operations. Hausner adds that while Thermo does not currently use TSG or HME in its integrated continuous process for final dosage forms, the continuous manufacturing team provides expertise in feeding and PAT for individual TSG and HME operations. “A multi-step continuous process will require a good stand-alone development activity on the TSG or HME step,” Hausner says.

Patil points out that Catalent can use TSG to create granules with various profiles, such as immediate release, sustained release, delayed release, and taste masking. Twin-screw dry granulation (TSDG) is effective for moisture-sensitive materials and useful for APIs that are not suitable for roller compaction, such as molecules that require higher shear for mixing and agglomeration, she adds. “In addition, TSDG has a unique application for APIs with needle-shaped crystal habit, which have low flow rate and bulk density. These poor physical and mechanical properties make them difficult to process via conventional methods such as roller compaction and slugging. The kneading action of the twin-screw extruder enhances consolidation of powders with needle-shaped API, resulting in better flow and compressibility. For high drug-loading products, this process yields superior granule quality and bulk density.”

TSG is beneficial for both high- and low-dose APIs. “In low-dose products, it is feasible to increase the uniformity by forming granules and preventing demixing,” explains Robin Meier, scientific director at equipment maker L.B. Bohle. In high-dose APIs, TSG offers the ability to improve compressibility. Meier says that a stable and compressible granule can be formed with minimal amounts of binder, in the range of 5%. He reports that compressible granules could be produced with all APIs tested so far on the company’s equipment, once a suitable binder was identified, depending on API solubility, particle size distribution, and partition coefficient.

To build the knowledge base regarding the behavior of materials in twin-screw extrusion equipment, Leistritz Extrusion Technology formed a consortium in 2019 of pharma companies, the University of Texas at Austin, and McMaster University.

“Equipment variables include the ratio of the outer diameter of the screw to the inner diameter, the length-to-diameter ratio, and the screw design,” says Stephen Post, product manager for Life Sciences at Leistritz. “We’re working on gaining more knowledge of the fundamental behaviors of materials and equipment, and we’re looking for trends in material behavior that can be extrapolated to similar formulations.”

For example, consortium researchers have investigated how screw design affects particle size distribution (PSD). Researchers are also performing scale-up experiments to replicate the PSD obtained from an 18-mm diameter screw on a 27-mm diameter screw. Although some drug manufacturers may choose to scale-out by using multiple 18-mm extruders, there are advantages to using a larger extruder to scale-up, such as lower facility footprint and lower utilities cost, explains Post. Better scale-up data are needed, he says.

“We are also developing material-sparing methodologies to assess the feasibility of TSG using various screening tools without running the twin-screw extruder” says Feng Zhang, associate professor in the College of Pharmacy at the University of Texas. “One of the key challenges in TSG is the process-induced chemical degradation and physicochemical transformation during processing.We have developed an in-depth understanding of how these undesired changes can be inhibited via rational selection of formulation composition and process design.”

PAT is being used in TSG processes to measure critical parameters in real-time. Moisture content and PSD, for example, are critical quality attributes (CQAs) of the intermediate product that affect CQAs of the final product.

Near-infrared (NIR) PAT has been evaluated to replace time-consuming loss-on-drying measurements to quantify moisture content in granules, says Patil. “NIR analysis allows for the adjustment of process parameters in real-time, resulting in significantly less material waste and improved process optimization within a shorter timeframe, even during the same extrusion run,” she says.

For PSD, direct imaging is well established, but other PAT types are also being investigated.

“The discrete nature of moving particles makes it harder to understand what’s going on in the machine, because standard monitoring techniques like pressure and temperature monitoring are unreliable as indicators of deviating product specifications,” says Michael Thompson, associate dean and professor of Chemical Engineering at McMaster University, whose research group has studied twin-screw granulation for more than a decade. He adds that while batch granulation often produces a Gaussian PSD, twin-screw granulation typically has a bimodal PSD, which makes real-time analysis even more important. Thompson’s lab has developed an inline particle size analysis PAT using acoustic emissions (AE). The researchers created a digital signal filter to ensure that particles of any size would be represented (1). Next, they created a filter that would also account for inelastic forces by training an artificial intelligence model with an elastoplastic (Walton-Braun) contact force model and a dataset of acoustic emission spectra collected from a broad range of granulated pharmaceutical formulations. The prediction error was as low as 2%, demonstrating its applicability to monitoring particle size distributions in continuous twin-screw granulation (2).“I see the existing optical [imaging] methods and this acoustic method as complementary approaches to particle size analysis,” concludes Thompson. “Both have their strengths and weaknesses in a dusty production environment like the exit chute of a twin-screw granulator.”

In a continuous granulation and drying set-up, such as L.B. Bohle’s QbCon 1, Meier indicates it is most meaningful to measure the residual moisture after the drying process (rather than after granulation) to be able to control and feedback the dryer process parameters. “In this case, we usually apply NIR or microwave resonance measurements. The latter allows univariate calibration,” he says. In the granulation step, Meier explains that solid feeding rate and liquid feeding rate are the crucial parameters used to control mean granule size. He suggests that controlling these rates is more reliable than a method that measures in-line PSD and adjusts liquid addition. Meier reports that the QbCon 1 equipment, as part of a complete continuous manufacturing line, was recently delivered to a large German pharma company for clinical supply of new entities. This line is designed for small-scale throughputs up to 4 kg/h and is capable of handling APIs in occupational exposure band 5.

Twin-screw extrusion aids complex formulation

Researchers at Rutgers University are using a twin-screw extruder as a hot-melt coater and granulator in a unique, patent-pending solution to the ongoing challenge of manufacturing drug products with high doses of poorly soluble APIs. “Poorly soluble drugs are poorly soluble because they dissolve less, but this also is often because they are hydrophobic; they are difficult to wet and so they dissolve more slowly,” says Fernando Muzzio, distinguished professor of Chemical and Biochemical Engineering at Rutgers University. “We solved this problem by using a twin- screw extruder to coat the drug substance particles with a surfactant, which improves solubility. The particles are mixed with a low-melting point surfactant and fed into a twin-screw extruder operating at a temperature low enough to avoid decomposing the API but high enough to partially melt the surfactant and allow it to coat the API particles. The resulting granules flow and compress well, allowing us to make a high-dose (approximately 80% API), immediate release tablet.”

Muzzio says that this twin-screw granulation process is potentially less expensive to operate than more complex processes for high-dose, poorly soluble APIs, such as HME, nanomilling, or spray drying. The innovation is a result of understanding what happens to materials when their surface is modified, combined with an understanding of the twin-screw granulation process that allows accurate control of mechanical and thermal variables, says Muzzio.

Abdulhussain, H.A. and Thompson, M.R. Predicting the Particle Size Distribution in Twin Screw Granulation through Acoustic Emissions. 

Jennifer Markarian is manufacturing reporter for 

Articles

Features

As new analytical technologies advance, insight into the twin-screw granulation process is growing.

Exploring Advances in Twin-Screw Extrusion for Solid-Dosage Drugs

In the continued quest for truly personalized medicine, biomarker discovery has expanded far beyond genomics and proteomics. Scientists are increasingly interested in glycans, the carbohydrates that link to proteins and lipids in a process known as glycosylation. Glycosylation is a fundamental regulator of countless biological activities, including immune cell function in health and disease. Research seeking to characterize dysregulated glycosylation and its effects on immune regulation will be vital to the development of new diagnostics and therapeutics. Despite progress in recent years, research has only begun to scratch the surface of this broad topic.

Glycosylation analysis can provide a deeper and more nuanced understanding of immune cell function, going beyond typical biomarkers to establish more detailed phenotypic subcategories of B and T cells and offer insight into disease etiology and progression. The continued study of immune cell glycosylation will undoubtedly drive progress in the identification of methods for early detection and characterization of disease states. However, further advances in analytical technology will be instrumental in helping this field reach its full potential.

The diverse assortment of cell surface glycans, known collectively as the glycome, offers a rich and dynamic tapestry of insights into biological processes. Glycosylation is a ubiquitous post-translational modification (PTM), with approximately 50–70% of all proteins bearing glycans (1). As cell types, including immune cells, become more extensively characterized and subdivided into categories based on biomarkers, glycosylation status has become an increasingly important variable within these analyses. Glycosylation is incredibly dynamic—unlike proteins, the structures of glycans are not coded by a set genetic template. Rather, it is regulated by the milieu of enzymes surrounding the glycoform, meaning that the population of glycans found on any given cell is highly diverse and constantly changing (2). This dynamic diversity, coupled with the powerful role of glycans in regulating downstream functions, means that the glycosylation profile of a cell may provide a deeper insight into real-time functionality than biomarker expression can.

Interactions between glycans and glycan-binding proteins play a vital role in controlling and fine-tuning immune cell development, activation, and function. For example, the presence of specific O-glycan modifications to P-selectin binding ligands dictates the migration of T cell precursors to the thymus. Further glycosylation also mediates the maturation of thymocytes into CD4+ and CD8+ T cells (3). O-glycan remodeling is also an important feature of B cell development, such that distinct glycoforms can serve as markers of different phases of differentiation (4).

The glycan signatures on healthy, dysregulated, or malignant cells, as well as those on pathogens, serve as signals for immune recognition of “self” vs. “other.” The glycome is thus indispensable in regulating immunity vs. tolerance. Changes in immune cell glycosylation are a useful indicator of the cells’ activity throughout cell differentiation, activation, and apoptosis that can be used to characterize subsets of B and T cells in various disease states. These alterations have been associated with various immune cell functions, such as immune cell trafficking, antigen and cytokine receptor activation, cellular signaling, and more.

For example, glycosylation plays a key role in modulating tumor immunogenicity and immune evasion. Tumor cells secrete galectins that can bind to glycans present on effector T cells and attenuate their activity, leading to an immunosuppressive effect. Specific tumor-associated galectins restrain T cell activation, limit cytokine production, or even induce apoptosis (5). Growing evidence also implicates dysregulated glycosylation in autoimmunity. One study examined B cell markers in samples from individuals with primary Sjögren’s syndrome and systemic lupus erythematosus, two chronic autoimmune conditions (6). Researchers discovered notable changes in glycosylation within specific B cell subsets that were altered in both diseases, as well as similar alterations in certain serum immunoglobulins. These and other findings suggest that any dysfunction in normal B and T cell glycosylation can result in the development of pathogenic autoinflammation and contribute to a general perturbation of immune system homeostasis (7).

Lectin-based flow cytometry is among the most important tools for profiling glycosylation in heterogeneous cell populations. Using fluorophore-conjugated lectins that bind to specific glycan structures, researchers can analyze and quantify glycans present throughout a sample of cells in suspension. Flow cytometry offers a number of advantages that make it ideal for profiling immune cell glycosylation, including its high throughput. Researchers can quickly analyze hundreds of thousands of cells for multiple glycan biomarkers within phenotypic subsets identified by more traditional surface markers. Flow cytometry is ideal for assessing liquid samples such as serum; cells extracted from tissue samples such as the thymus, spleen, and lymph nodes; or bone marrow. However, the nature of the flow cytometry method precludes the ability to gain useful spatial information about the distribution of glycans in solid tumors or tissues using this method alone.

Nonetheless, using flow cytometry to profile glycosylation can still help healthcare providers and researchers characterize important immune mechanisms in hematological malignancies. An example of the utility of flow cytometry was shown in a 2023 study that assessed glycan markers on leukocytes in patients with myelodysplastic neoplasms (MDS) (8). MDS are age-related disorders of white blood cell overproliferation, the course of which can range from relatively benign conditions to acute myeloid leukemia (AML). In the study, the researchers identified distinct glycosylation profiles associated with cell maturation and lineage differentiation. They also characterized unique cellular glycosignatures associated with disease course, differentiating low-risk MDS from AML. These findings suggest that lectin-based flow cytometry of leukocytes could be used to identify distinct glycosylation profiles for MDS risk stratification.

Liquid chromatography and mass spectrometry are two methods used separately and in tandem to characterize glycans on a more specific level. Liquid chromatography separates distinct compounds contained within a liquid sample by running it through a solid column. The different components within the sample are then separated based on their speed passing through the column. Mass spectrometry measures the mass-to-charge ratio of ions in an analyte of interest to create a mass spectrum that can be used to determine the mass or chemical composition of the analytes.

When used together, liquid chromatography–mass spectrometry (LC–MS) allows researchers to separate and identify the components of a complex biological mixture. This combination is particularly useful in instances where liquid chromatography would not provide sufficient resolution or when analyte masses would overlap when assessed with mass spectrometry alone. Liquid chromatography, mass spectrometry, and LC–MS are valuable methods for profiling immune cell glycosylation in many applications.

Researchers have leveraged liquid chromatography and mass spectrometry to examine the relationship between immunoglobulin glycosylation status and aging, cancer, autoimmune disorders, and more. A 2020 study of inflammatory biomarkers in multiple sclerosis used hydrophilic interaction liquid chromatography with mass spectrometry to characterize glycans on immunoglobulin G (IgG) (9). When comparing serum IgG from multiple sclerosis patients to age- and sex-matched controls, the researchers identified significant differences in four of 24 measured IgG glycan traits. Additionally, the specific structural alterations observed in IgG glycans were associated with increased proinflammatory potential, suggesting the utility of glycomic changes as possible biomarkers in multiple sclerosis. The results of this study illustrate the ability of LC–MS to provide detailed structural information about glycans in a sample.

Another approach to simultaneously analyzing multiple glycan biomarkers is through lectin microarrays, which use a panel of assorted lectins immobilized on a substrate. By incubating a fluorescently tagged liquid sample with the panel, researchers can use fluorescence detection to assess binding events and thus characterize the glycans present in the sample. Lectin microarrays offer a number of benefits, including relative technical simplicity and high specificity for glycoforms. Additionally, while LC–MS analysis often requires the chemical or enzymatic release of glycans from associated proteins, lectin microarrays can be used to study intact glycans without a demanding sample preparation process (10). However, this method is not quantitative and precludes the complete determination of glycan structures allowed by mass spectrometry.

Lectin microarrays are utilized in a variety of research applications, including biomarker discovery. They are especially promising for studies of immune cell glycosylation, as they allow researchers to observe lectin binding to intact glycoforms rather than separated glycans. For example, one study leveraged lectin microarrays to identify changes in serum immunoglobulin glycosylation in hepatocellular carcinoma (11). Researchers used these findings to construct a model that could distinguish diagnostic markers of hepatocellular carcinoma from other hepatic diseases and healthy controls, potentially improving diagnostic accuracy for the disease.

While glycomics research has gained momentum in recent years, the field still has a way to go in developing tools and methods for fully characterizing and understanding the implications of glycosylation in health and disease. Several well-established approaches are available to characterize glycans present within a sample or on a specific subset of cells. However, most current methods preclude a higher level of resolution that can identify distinct glycans on specific proteins. Advances in methods such as proximity labeling, which can identify biomolecules close to a protein of interest, are beginning to surmount these limitations. Researchers can tag glycan-protein interactions present on cells for later enrichment and analysis using mass spectrometry-based proteomics. Proximity labeling can also be used in conjunction with flow cytometry to characterize select glycan–protein interactions on intact cells (12).

Further innovation and research are needed to establish a more complete understanding of protein-specific glycosylation patterns. As technological developments continue to expand scientists’ understanding of the role of cell- and protein-specific glycosylation in health and disease, these discoveries could be leveraged to identify more precise and relevant biomarkers and therapies than ever before.

1. Apweiler, R.; Hermjakob, H.; Sharon, N. On the Frequency of Protein Glycosylation, as Deduced from Analysis of the SWISS-PROT Database. 

Biochimica et Biophysica Acta (BBA)-General Subjects

 (1), 4–8. DOI: 10.1016/S0304-4165(99)00165-8
2. An, H. J.; Froehlich, J. W.; Lebrilla, C. Determination of Glycosylation Sites and Site-Specific Heterogeneity in Glycoproteins. 

 (4), 421–426.
3. De Bousser, E.; Meuris, L.; Callewaert, N.; Festjens, N. Human T-cell Glycosylation and Implications on Immune Therapy for Cancer. 

 (10), 2374–2388. DOI: 10.1080/21645515.2020.1730658
4. Giovannone, N.; Antonopoulos, A.; Liang, J.; et al. Human B Cell Differentiation Is Characterized by Progressive Remodeling of O-Linked Glycans. 

, 2857. DOI: 10.3389/fimmu.2018.02857
5. Nardy, A. F.; Freire-de-Lima, L.; Freire-de-Lima, C. G.; Morrot, A. The Sweet Side of Immune Evasion: Role of Glycans in the Mechanisms of Cancer Progression. 

, 54. DOI: 10.3389/fonc.2016.00054
6. Morel, M.; Pochard, P.; Echchih, W.; et al. Abnormal B Cell Glycosylation in Autoimmunity: A New Potential Treatment Strategy. 

, 975963. DOI: 10.3389/fimmu.2022.975963
7. Ramos-Martínez, I.; Ramos-Martínez, E.; Cerbón, M.; et al. The Role of B Cell and T Cell Glycosylation in Systemic Lupus Erythematosus. 

 (1), 863. DOI: 10.3390/ijms24010863
8. van Spronsen, M. F.; Horrevorts, S.; Cali, C.; et al. Dysregulation of Developmental and Cell Type-Specific Expression of Glycoconjugates on Hematopoietic Cells: A New Characteristic of Myelodysplastic Neoplasms (MDS). 

 (3), 702–707. DOI: 10.1038/s41375-022-01784-x
9. Cvetko, A.; Kifer, D.; Gornik, O.; et al. Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential. 

 (10), 410. DOI: 10.3390/biomedicines8100410
10. Dang, K.; Zhang, W.; Jiang, S.; Lin, X.; Qian, A. Application of Lectin Microarrays for Biomarker Discovery. 

 (3), 285–300. DOI: 10.1002/open.201900326
11. Zhang, Y.; Zhang, S.; Liu, J.; et al. Identification of Serum Glycobiomarkers for Hepatocellular Carcinoma Using Lectin Microarrays. 

, 973993. DOI: 10.3389/fimmu.2022.973993
12. Vilen, Z.; Joeh, E.; Critcher, M.; Parker, C. G.; Huang, M. L. Proximity Tagging Identifies the Glycan-Mediated Glycoprotein Interactors of Galectin-1 in Muscle Stem Cells. 

 (10), 1994–2003. DOI: 10.1021/acschembio.1c00313.

Pamela James, PhD, is vice-president, Product, Vector Laboratories.

Capturing the nuances of immune cell phenotype and function can be achieved using glycosylation analysis. 

Using Glycobiology to Study the Nuances of Immune Cells

On Oct. 25, 2023, the winners of the 2023 CPHI Pharma Awards were announced at the 

 event. The awards are given out for outstanding achievements and contributions to the pharma industry in 12 categories. This year’s winners include:

CEO of Procos, Enrico Zodio, won CEO of the Year as recognition for the company’s development and growth, which exceeds €200 million and includes capacity to further increase production.

Snapdragon Chemistry (a Cambrex company) topped the API Development & Innovation category for its ultra-high temperature (>300 °C) continuous flow manufacturing process for racemization of sotorsib (LUMAKRASTM) P-dione, which harnessed greener technology that resulted in a 58% reduction of process mass intensity.

Lubrizol Life Science Health took home the prize in the Finished Formulation category for its solubility-enhancing excipient designed for parenteral use. Apisolex is a poly(amino acid)-based excipient that provides formulators with methods to enhance the solubility of hydrophobic BCS Class II and IV APIs, by up to 50,000-fold.

The Manufacturing Excellence category went to Luminary Therapeutics for its manufacturing platform, Gamma Delta 2.0+, that brings allogeneic cell therapies to market for less than 10,000 without sacrificing function.

Gasporox took the honors in the Packaging & Machinery section for its AutoMAP Pharma gas measurement system for high or low concentrations of O2 in modified atmosphere packaging.

Catalent won the Supply Chain Excellence category for its Case Management Services, which provides end-to-end supply chain management for autologous and allogeneic cell and gene therapies.

The Regulatory Compliance category went to Lambda Therapeutic Research for their EDC solution that enhances research and data management. The software suite, including IMPTrack, KnowledgeNET, and Biolyte, enables real-time, accurate data capture through advanced functionalities like barcode scanning and retina-based verification. It also manages and retrieves study-related data to improve compliance with regulatory guidelines.

Medicsen took the Drug Delivery & Device Innovation category for its SMARTPATCH. The wearable patch uses ultrasounds to deliver drugs subcutaneously and combines the main benefits of current patch pumps with the upside of eliminating invasive and painful components.

The Accelerating Innovation category went to React4Life’s MIVO (Multi In Vitro Organ), a patented organ-on-a-chip that can host and culture 3D human biological cells or tissues under fluid dynamic conditions as 

Schneider Electric won the Sustainability category for its Energize program. The program leverages the scale of the global supply chain in a pre-competitive fashion to drive system-level change. 

The new Start-Up Initiative category went to InSyBio for its ability to revolutionize the medical ﬁeld, clinical trials, and food/nutrition industries through its targeted biomarker discovery. The company’s highly accurate predictive analytics enables personalization of tests for drugs, nutraceuticals, and nutrition products.

The ‘Heart of Pharma’ award, also new this year, went to Merck KGaA for its Embracing Carers initiative that recognizes the role of family carers.

“CPHI aims to position itself at the ‘heart of pharma’ by creating an environment where everyone in our industry can come together to exchange ideas and build productive new alliances for the ultimate benefit of patients. I whole-heartedly congratulate all winners of this 20th edition of the CPHI Pharma Awards. Those committed to driving innovation across the key disciplines that shape the success of our industry. I’d also like to thank all those who submitted an entry this year, and the members of our jury who so diligently reviewed them,” commented Tara Dougal, Content Director–Pharma at Informa Markets, in a press release.

News

The winners of the 2023 CPHI Pharma Awards were announced on October 25 at the CPHI Barcelona event.

Winners of the 2023 CPHI Pharma Awards Announced

Bettersize US announced on Oct. 22, 2023 that it is showcasing three of its instruments—the BeNano Series, Bettersizer 2600, and BetterPyc 380—at the AAPS 2023 PharmSci 360 event. The company is also highlighting its FLOW MODE coupled with high-performance liquid chromatography (HPLC), “which enables high-resolution nanoparticle size testing tailored to the precise needs of pharmaceutical professionals,” according to the company.

The BeNano Series features nanoparticle size and zeta potential analysis by three light scattering techniques. The Bettersizer 2600 offers particle size analysis by laser diffraction, with wet/dry dispersions, and the BetterPyc 380 features powder analysis by gas displacement method.

Bettersize Instruments is a provider of analytical instruments for material characterization, comprehensive solutions, and exceptional customer service. In August 2023, the company opened a new facility in Costa Mesa, Calif. to support North American material scientists, researchers, and engineers.

Visit Bettersize at PharmSci 360 at booth number 2135.

New Technology

Bettersize US showcases their BeNano Series, Bettersizer 2600, and BetterPyc 380 instruments at the AAPS 2023 PharmSci 360 event. 

Bettersize Unveils New Capabilities at AAPS 2023 PharmSci 360

On Oct. 19, 2023, Waters Corporation announced that it has launched OligoWorks solid phase extraction (SPE) Kits and components, which are meant to improve sample preparation for liquid chromatography (LC)–mass spectrometry (MS)-based bioanalytical quantitation of therapeutic oligonucleotides.

The kits are designed to deliver up to 2x higher oligonucleotide recovery from biofluids, according to a company press release. The kits’ design also delivers improved LC­MS sensitivity and reproducibility for supporting robust quantitation. Because these capabilities enable lower limits of quantitation, the kits can reduce the need for repeat experiments.

The kits also use an innovative, enzyme-enhanced, and detergent-free sample pre-treatment that, according to Waters in the press release, reduces washing steps and improves mass spectrometer compatibility. This design enables for direct injection LC–MS analysis and is also what allows for the lower limits of quantitation. The kits can also be fully automated, which can improve productivity or simply help scientists gain back time via the reduction of manual steps and oversight.

The OligoWorks SPE Kits are available immediately and complement other Waters tools, including MaxPeak Premier Columns, ACQUITY Premier LC System and Arc Premier LC System, Andrew+ Pipetting Robot. The new kits also support the sensitivity of the Waters Xevo TQ Absolute Mass Spectrometer.

" … Waters is committed to solving customer pain points and enabling greater analytical performance and productivity. Our new OligoWorks SPE Kits directly address oligonucleotide bioanalysis sample prep challenges across diverse oligo therapeutics," said Erin Chambers, vice-president, Consumables and Lab Automation, Waters Corporation. "The science and societal effects of these therapies are exploding given their ability to address human health issues. Our workflow and kits will drive an acceleration of oligo bioanalysis projects and drug development timelines; ultimately improving the experience for drug candidates."

Waters has launched OligoWorks SPE Workflow and Kits, which is aimed at accelerating the bioanalysis of oligonucleotides.

Waters Launches New Oligonucleotide Bioanalysis Kits

On Oct. 18, 2023, SCHOTT announced that it has launched a new component for biopharmaceutical process analysis, the ViewCell flow cell. The purpose of this new component is to optimize downstream processes in the biopharmaceutical industry by enabling safe, continuous process control directly in the production line.

The introduction of the ViewCell flow cell follows the company’s launch of its ViewPort sensor port for bioreactors. Through a sterile-safe optical window, the flow cell allows for 

 measurements of biological and physical parameters in downstream processing. The flow cell can be used during purification and filtration as well as during subsequent formulation. This capability thus reduces the need for both physical sampling and storage tanks, according to a company press release.

According to the press release, optical sensors or spectrometers are connected to the flow cell for monitoring, which means that the measuring instruments do not come into contact with the medium, and thus do not penetrate the sterile barrier. This allows for the sensors or spectrometers to be easily replaced during ongoing production, which the company states in its press release is a major advancement compared to fixed probes. In addition, a glass-to-metal connection allows for a sterile-safe design, which also increases the safety and efficiency of process analysis, contributing to an overall optimized yield.

The company stated in the press release that ViewCell allows biomanufacturers to quickly build and test small-scale flow systems for Raman analysis, which are used to mimic real-world industrial processes. The compact design of the device reduces the overall volume of sample material required, which cuts down on waste and costs—key considerations in the handling of expensive or difficult-to-obtain test materials.

SCHOTT now offers ViewCell, a new component meant to add flexibility to biopharmaceutical process control.

SCHOTT Launches ViewCell Flow Cell for Biopharma Process Control

Sweden-based Salipro Biotech and Estonia-based Icosagen, a contract research, development, and manufacturing organization, announced on Oct. 10, 2023 that they have entered into a multi-target antibody research agreement to advance drug discovery programs. The companies intend to discover and characterize monoclonal antibodies (mAbs) against several challenging membrane proteins, including G protein-coupled receptors (GPCRs) and solute carrier (SLC) transporters.

Under the agreement, Icosagen will leverage its expertise in protein production and analytics. The company’s knowledge in antibody discovery encompasses high-throughput antibody screening and a variety of lead optimization techniques that the company expects will support the collaboration and form a solid basis for future biologic drug development, according to a company press release.

The partnership between the companies aims to build on Salipro's strength in establishing multiple collaboration and licensing agreements with leading pharma and biotech companies that enable drug discovery against complex membrane protein targets. The company’s experience includes small-molecule drug discovery programs as well as structural biology and antibody discovery.

“Our Salipro technology provides an enabling platform for the discovery of therapeutics against challenging drug targets. We are excited to unlock the potential of these targets with Icosagen and develop novel drugs that can improve patient outcomes," said Jens Frauenfeld, CEO of Salipro Biotech, in the press release.

"We are delighted to apply our QMCF technology and protein analytics capabilities in this project. Both teams in Icosagen and Salipro Biotech are always finding ways to push the boundaries in novel technologies of biologics development. It will be interesting to see what we’ll be able to achieve as we put our heads together for this project,” said Mart Ustav Jr., chief scientific officer, Icosagen, in the release.

Salipro Biotech and Icosagen have entered into a multi-target collaboration to discover and characterize monoclonal antibodies.

Salipro Biotech and Icosagen to Collaborate on Antibody Discovery

Particle Measuring Systems Inc. announced the acquisition of Environmental Monitoring Services and EMS Particle Solutions and their parent company on Oct. 2, 2023. According to the press release, EMS is a leader in the cleanroom industry, delivering complete cleanroom monitoring and control solutions, services to customers, and ensuring quality by design from inception to process control.

Particle Measuring Systems has experience in contamination monitoring and control for cleanrooms and aseptic manufacturing environments. Additionally, the acquisition aligns with Particle Measuring Systems’ strategy to be direct in every major geographical market to best support and service customers with advanced contamination monitoring and control solutions. Their partnership with EMS will last approximately 30 years as an exclusive sales and service channel for customers in these strategic territories.

“It has been gratifying to grow EMS over the last 30 years,” said Dave Nolan, managing director at EMS, in a press release. “This is an exciting and natural next step for our organization and I’m looking forward to continuing as part of this great team.”

“We are always looking for ways to provide our customers with better solutions while maintaining our strong growth trajectory and being recognized as an employer of choice by our employees,” said interim Particle Measuring Systems, Inc. President, Mark Fleiner, in a press release. “Acquiring EMS helps us achieve these goals while also preparing for continuity of service and solutions in this strategic geography.”

Source: Particle Measuring Systems (PDF press release)

EMS is a leader in the cleanroom industry, delivering complete cleanroom monitoring and control solutions, services to customers, and ensuring quality by design from inception to process control.

Particle Measuring Systems Announce Acquisition of Environmental Monitoring Services Limited and EMS Particle Solutions 

On Sept. 28, 2023, Sartorius and UK-based startup SPARTA Biodiscovery (SPARTA) announced that they have entered into a partnership for SPARTA’s analysis platform. The platform helps speed the development, manufacture, and quality control of nanoparticles (small polymer or lipid capsules that act as carriers to deliver active agents to target cells) for biopharmaceutical drugs, including gene therapies, vaccines, and cancer drugs.

Under the agreement, Sartorius will invest up to £3.5 million (US$4.3 million) in a minority shareholding in SPARTA through Sartorius Ventures, its corporate investment unit. SPARTA, which was spun off from Imperial College London, developed its core technology, the single particle automated Raman trapping analysis, and developed a prototype for the platform at the college. The technology was established in the group of co-founder Professor Molly Stevens Fellow of the Royal Society, Fellow of the Royal Academy of Engineering. Single particle automated Raman trapping analysis uses spectroscopy to quickly and automatically analyze populations of individual nanoparticles at high throughput. Its mode of action helps accelerate nanoparticle development and optimize quality control during production, according to a company press release.

“The SPARTA platform will help customers optimize the design of nanoparticles at an early stage, even before the drug candidates move on to the clinic. We have teamed up to bring additional product commercialization and application expertise to the table to facilitate a swift transitioning from prototype to launch,” said Oscar-Werner Reif, head of corporate research and chief technology officer at Sartorius, in the press release.

“Often the challenge in bringing new therapies to life is not the development of new active agents, but safe and robust delivery of such agents into the body, e.g., through nanoparticles. We see an unmet need in R&D, manufacturing, and quality control in analyzing the composition of these nanoformulations. Together with Sartorius, we will be able to bring this technology to customers faster,” said Jelle Penders, CEO and co-founder of SPARTA Biodiscovery, in the release.

Under the partnership, Sartorius will leverage SPARTA Biodiscovery’s technology to accelerate development of nanoparticles used for drug delivery.

Pharmaceutical Technology's In the Lab eNewsletter, November 2023