Alphalyse A/S

𝗣𝗥𝗘𝗦𝗦 𝗥𝗘𝗟𝗘𝗔𝗦𝗘: 𝗔𝗹𝗽𝗵𝗮𝗹𝘆𝘀𝗲 𝗵𝗮𝘀 𝗽𝗲𝗿𝗳𝗼𝗿𝗺𝗲𝗱 𝘁𝗵𝗲 𝘄𝗼𝗿𝗹𝗱’𝘀 𝗳𝗶𝗿𝘀𝘁 𝗠𝗦-𝗯𝗮𝘀𝗲𝗱 𝗛𝗖𝗣 𝗮𝗻𝗮𝗹𝘆𝘀𝗶𝘀 𝘂𝗻𝗱𝗲𝗿 𝗚𝗠𝗣 𝗰𝗼𝗻𝗱𝗶𝘁𝗶𝗼𝗻𝘀 𝗳𝗼𝗿 𝗿𝗲𝗹𝗲𝗮𝘀𝗲 𝘁𝗲𝘀𝘁 𝗼𝗳 𝗕𝗮𝘃𝗮𝗿𝗶𝗮𝗻 𝗡𝗼𝗿𝗱𝗶𝗰 𝗔/𝗦 𝗖𝗢𝗩𝗜𝗗-𝟭𝟵 𝗯𝗼𝗼𝘀𝘁𝗲𝗿 𝘃𝗮𝗰𝗰𝗶𝗻𝗲 𝗰𝗮𝗻𝗱𝗶𝗱𝗮𝘁𝗲. We proudly announce the successful performance of the world’s first GMP-certified mass spectrometry (MS)-based Host Cell Protein (HCP) analysis for product release testing for Phase 3 clinical trial. The unique LC-MS-based HCP analysis developed by Alphalyse is significantly faster than traditional methods for product impurity documentation and has the potential to reduce the time required to document new vaccines, from the current industry standard of 12-18 months to as little as 4 months, while being as safe or safer than older methods. This makes the Alphalyse method particularly useful for developing vaccines during a global pandemic when the time to create a process-specific ELISA is limited.   Read the full press release on our website or download the PDF below: https://lnkd.in/erVxz7Ha Or, join our upcoming webinar: LC-MS HCP assay validation and GMP release testing for complex samples → https://lnkd.in/eXwUWPMW #GMP #covid19vaccine #MassSpectrometry #LCMS #drugdevelopment

❓ “Should I worry about ubiquitin in my final drug substance?” We find the host cell protein ubiquitin in many client samples. Ubiquitin is a small (76 amino acid, 8 kDa) protein that exists in all eukaryotic cells – ‘ubique’ is Latin for ‘everywhere.’ Ubiquitin is difficult to purify from drug products since it binds to the therapeutic protein as a post-translational modification. And it can be hard to detect, even with a process-specific ELISA. In this blog entry, Ejvind Mørtz takes a look at ubiquitin – and the challenges it may pose.

Phage therapies might solve a critical global health challenge – but are too complex for traditional impurity analysis. Bacteriophages (phages) are viruses that target bacteria, offering treatment for multidrug-resistant infections. On January 1, 2025, the European Pharmacopoeia Supplement 11.6 will implement a new general chapter (5.31) on phage therapy medicinal products to standardize methods in this rapidly advancing field: https://lnkd.in/d2BrHkKc But even with the new guidelines, the production and control of phage therapies face unique obstacles. Phage products may contain multiple phages, excipients, and host cell proteins from the bacterial host. Characterizing such highly heterogeneous protein profiles is difficult, contributing to the difficulty of getting phage products approved for the general market. At Alphalyse, we have years of experience analyzing phage therapies and can perform product and impurity characterization according to Good Manufacturing Practice (GMP). Learn more about our unique mass spectrometry-based options for advanced therapies and phages: https://lnkd.in/d_PKnk37

Clusterin is classified as a high-risk host cell protein (HCP) found in CHO-produced drugs. Clusterin is often detected in mAb products after Protein A purification, as referenced in several literature reviews. At Alphalyse, we find it in one-third of our client samples, making it one of our most ubiquitous host cell proteins. It is known to interact with antibodies, particularly immunoglobulins. As early as 1992, research identified clusterin as a specific protein that binds to IgG. Its high immunogenicity poses a potential risk to patients, making it an HCP of significant concern to regulatory authorities. Clusterin is a major stress response protein that functions as a chaperone in regulating cell death. Studies have shown that its expression levels correlate with oxidative stress, suggesting clusterin may be a highly sensitive indicator of host cell vitality. 📃 References:  [1] https://lnkd.in/dzqaQ2wP [2] https://lnkd.in/dDjAKsdd [3] https://lnkd.in/dzUtSfK3 [4] https://lnkd.in/dyEWTVUJ Image: proteopedia.org

A Scandinavian study found heat shock proteins in the blood of hibernating bears… 🐻 Proteins we also come across in biopharmaceutical process samples. 🧪 Cells produce heat shock proteins (HSPs) in response to stressful conditions, such as extreme temperatures and other environmental pressures. In bears, HSPs prevent fatal blood clots caused by prolonged immobility during hibernation. During biologics manufacturing processes, host cells are also subjected to changes in temperature, pH, and nutrient availability, just like the cells of a bear hibernating through the winter. This can trigger the production of HSPs. However, if we do not remove these HSPs sufficiently from biologic drugs, they may affect the therapeutic proteins and induce adverse health effects in patients. Therefore, HSPs pose a risk to the quality, safety, and efficacy of biologic drugs, making it important to monitor and control their levels during production – and to document their clearance. Are you curious to learn more about the physiological significance of heat shock proteins? Find the Science article on HSPs in hibernating bears here: https://lnkd.in/g28TkBXH

Outsourcing – a safer choice. Changes to chemistry, manufacturing and controls (CMC) are often very challenging in biologic drug development. Process optimization, transfer to a different production facility, and updates to regulatory requirements all require developers to test the quality and purity of their product using extensive analytical methods. In a Cell & Gene Therapy Insights article (https://lnkd.in/eVkT5WAu) on strategies for reducing risks to licensing approval of gene therapies, the authors recommend outsourcing product and impurity analyses to Contract Research Organizations (CROs) – such as Alphalyse. What can we do for you? 👉 As our client, you will work with a team of mass spectrometry experts headed by an experienced project manager. 👉 We will meet with you to understand your product and offer personal advice and support based on your unique needs. 👉 You will have access to knowledge from our extensive database – based on regulatory guidelines, literature, analyses of commercially released products, and our experience from 10,000+ protein analyses. 👉 You can perform data-driven process optimization without investing in time-consuming training and method development. 👉 You can use our top-of-the-line LC-MS technology to progress your development process faster while saving on expensive equipment. Outsourcing your HCP analysis to a CRO with the experience and expertise to guide your project is more than just a convenience – it's an investment in your product. Contact us to learn more about how we can assist you ✉️ alphalyse.com/contact-us

One-step HCP analysis of your GMO product – we do the inactivation, preparation, and analysis under GMP. Alphalyse is certified to work with Class 1 genetically modified organisms (GMOs). The industry increasingly produces vaccines and advanced therapies with the use of GMOs. However, product characterization and protein impurity analysis can be challenging since not all laboratory facilities can handle these products. Previously, this necessitated additional, time-consuming steps for inactivating the GMO samples before sending them to the lab for analysis. ☀️ Alphalyse can do all these steps for you. By letting us handle the inactivation and preparation of your samples, your results will be: ➡️ Faster – no extra handling steps on your part ➡️ Less work – you only ship your samples to one location ➡️ Higher quality – our GMO inactivation procedures are optimized for our analytical instruments, ensuring precision data ➡️ Performed to GMP specifications at your request Want to learn more about the analysis of your GMO product? Get in touch with Ejvind Mørtz and Martin Rask Johansen for more information 👉 alphalyse.com/contact-us

Mass spectrometry has the potential to transform GMP release testing – soon. We recently invited Dr. Søren Skov Jensen, a former Senior CMC Specialist at Genmab and now employed at Novo Nordisk, to share his insights into developing a holistic control strategy for Host Cell Protein (HCP) impurities in mAb products. An interesting topic of discussion was the possibility of validating a mass spectrometry (MS)-only HCP method for GMP release. Watch this video of Søren’s prediction for the future of MS – or find the full webinar here: alphalyse.com/genmab

Top 20 protein impurities in mAb products – are they problematic? Monoclonal antibodies (mAbs) are increasingly used to treat cancer, autoimmune disorders, and viral infections. Most mAb treatments are administered intravenously in high doses, usually multiple times. ❌ If Host Cell Protein (HCP) impurities remain in a mAb product, there is a risk they may cause harmful effects in patients – especially if significant amounts are repeatedly infused directly into the patient’s bloodstream along with the mAbs. ❌ HCPs may affect the stability of the drug product, reducing its effectiveness against the illness. We used our unique mass spectrometry-based assay to analyze and compare HCPs in more than 50 mAb products, including 16 commercial mAbs already licensed for patient treatment. 👇 Check out the carrousel to discover the top 20 Host Cell Proteins we found – and which are of concern! 👇

A CMC worst-case scenario: A recombinant drug candidate expressed in E. coli contained several Host Cell Proteins, including flagellin. Clinical trials were suspended in Phase 3 after a patient suffered a severe reaction. The developer created a process‐specific ELISA and measured an HCP concentration that was a factor of 3-4 higher than the initial result measured using a commercial, generic E. coli HCP ELISA. Following the failed clinical trials, the developer required more than a decade to eliminate the HCPs and bring the drug to market. This case study highlights the need for improved analytical methods to ensure safe and effective drugs. Failure to identify and monitor problematic HCPs puts patients and projects at risk. You can minimize the risk with proper assay characterization and coverage analysis. https://lnkd.in/d_CQFyVm