Alphalyse

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

Many mAb developers have struggled to reduce the host cell protein PLBL2 – unaware of the real culprit causing polysorbate degradation. Phospholipase B-like 2 (PLBL2) is one of the most frequent protein impurities we measure in mAb samples from our clients. Researchers first described it as a host cell protein (HCP) of concern in 2015, believing it could degrade polysorbate (PS) excipients. PS is important for protecting the stability of protein drugs. PS degradation by enzymatic HCPs can significantly shorten a drug’s shelf-life and cause adverse patient reactions. However, more recent studies have found no correlation between the amount of PLBL2 and the level of PS degradation. Newer studies indicate a different culprit – another HCP that often co-purifies alongside PLBL2 and is the actual cause of the PS-degradation. Find out which one – and learn about other sneaky HCPs that degrade polysorbate – in our next CMC webinar. Ejvind Mørtz, PhD, will take you through ICH and USP guidelines, best practices for HCP control, and client cases focusing on PS-degradation problems. ⭐ Join us on November 26 to learn how to protect your mAb product from polysorbate-degrading HCPs. Read more and sign up here: alphalyse.com/cmc-webinars

“I would like to know which protein impurities are present in my product, especially if some are problematic, as early as possible. I need to know how my ELISA reagents and my process perform over time and after process changes.” * How do CMC managers handle impurity control in a time of technological and regulatory changes? Thomas Kofoed has asked 3 senior CMC managers about their strategies and experiences with mass spectrometry (LC-MS) as a tool for host cell protein analysis. In this Q&A article, CMC experts Bryant McLaughlin, Margarita Sabater, and Søren Skov Jensen offer a practical look at how LC-MS is reshaping impurity management and regulatory interactions. Learn more about: 🔍 Challenges with ELISA and where LC-MS adds value 🔍 Regulatory feedback on LC-MS data in submissions 🔍 The impact of the latest USP guidelines 🔍 Innovative solutions for impurity control * Read the full article here and see how these approaches might apply to your CMC strategies. 👇

Many mAb developers struggle with polysorbate-degrading host cell proteins – causing costly and time-consuming late-stage changes to the manufacturing process. Polysorbate (PS) 80 and 20 are excipients used to increase the solubility and stability of mAb molecules. However, PS degradation can cause formation of visible and subvisible particles – a critical quality attribute – or immune reactions in patients. Moreover, even trace amounts of enzymatically active host cell proteins (HCPs) are enough to degrade PS dangerously. These HCPs, undetectable by conventional ELISA assays, are often not discovered until late in development – months or years after the manufacturing process has already been finalized. PS-degrading HCPs are, therefore, an increasing focus within the biopharmaceutical industry, with several new host cell lipases and esterases described in the literature within the last 2 years. * Our next CMC webinar will focus on polysorbate-degrading HCPs –  and how to meet regulatory requirements for their control and documentation. In this presentation by Ejvind Mørtz, PhD, you will get insights into: 🔎 New and upcoming regulations affecting HCP control, including ICH guideline Q14 on analytical procedure development and US Pharmacopeia General Chapter <1132.1> on residual host cell protein measurement in biopharmaceuticals by mass spectrometry. 🔎 Examples of PS-degrading HCPs. 🔎 Client cases – how mAb developers use mass spectrometry (LC-MS)-based HCP analysis for process development and documentation for regulatory applications. Join us on November 26 to learn how to protect your mAb product from polysorbate-degrading HCPs. Read more and sign up here: alphalyse.com/cmc-webinars

“Before mass spectrometry, we were blind.” Margarita Sabater, senior CMC specialist at Genmab, recently highlighted the limitations of ELISA for effective problem-solving in mAb development. She described immunoassays as a ‘black box’ unable to identify the root cause of issues such as immunogenicity or polysorbate degradation. However, despite the increasing focus on host cell proteins (HCPs) in both research and regulatory legislation, it is still not uncommon to hear the following statements from biopharmaceutical developers: “We have never seen HCPs in our final drug samples, so this seems more like a theoretical issue.” Or, “Our ELISA does detect HCPs, but the levels are too low to be concerning.” As Margarita pointed out in her webinar on Genmab’s HCP control strategy for mAbs, ELISA alone can’t differentiate between harmless and potentially harmful HCPs – and may not detect all HCPs in a sample. This is why Genmab uses mass spectrometry (LC-MS) to optimize processes and ensure product consistency, saving time and other resources. Discover more about Genmab’s HCP control strategy in our CMC webinar series: alphalyse.com/genmab

👻🦇 Do spooky proteins lurk in your biologic? 🦇👻 Host Cell Proteins (HCPs) are inevitable byproducts when developing vaccines, monoclonal antibodies (mAbs), therapeutic proteins, and viral vector therapies. Some problematic HCPs, such as flagellin, ubiquitin, and the infamous PLBL2, have put clinical trials on hold and wreaked havoc in biologics development. Join Ejvind Mørtz for a spine-chilling webinar on demand this Halloween and learn about: 🎃 Examples of bad actor HCPs that have resulted in clinical hold – and even shut down drug development programs 🎃 Descriptions of the main groups of harmful impurities you should watch out for 🎃 LC-MS-based techniques for identification and quantification of HCPs of concern. Don’t let HCPs haunt your biologics program! Watch the webinar (30 minutes + Q&A) here: https://lnkd.in/ddvMfaRq

Science first – this has been one of the guiding principles at Alphalyse for more than 20 years. Alphalyse is the world’s leading expert in host cell protein (HCP) analysis by mass spectrometry (LC-MS), thanks to our close collaborations with clients, non-profit organizations, and academic institutions. Our research is focused on solving real-world analytical needs in the biopharmaceutical industry: ✅ We developed the world’s first LC-MS-based HCP analysis in 2008 ✅ And the world’s first quantitative LC-MS-based HCP analysis in 2016 ✅ Provided data for the first FDA-approved IND using only LC-MS-based HCP data in 2021. ✅ And performed the world's first GMP-compliant LC-MS-based HCP analysis for release testing in 2022. We also work closely with leading universities to bridge the gap between academic research and industry applications. Together with the Syddansk Universitet - University of Southern Denmark, we offer student internships, BSc and MSc thesis projects, and PhD programs, giving researchers and students hands-on experience with advanced protein analysis techniques. This way, we can drive scientific breakthroughs and help educate the next generation of proteomics experts. Read more about our research on our brand new webpage: https://lnkd.in/dfzBibDb

📢 Don’t let polysorbate-degrading host cell proteins delay your mAb project! Degradation of polysorbate (PS) excipients is a significant risk to mAb product stability and efficacy – and may be caused by host cell proteins. Host cell proteins (HCPs) such as phospholipase B-like 2 (PLBL2) and lipoprotein lipase (LPL) can co-elude through all standard mAb purification steps and cause project delays if they are not sufficiently removed – and classical impurity assays (HCP ELISA) cannot detect them individually. In this webinar, Ejvind Mørtz, PhD, COO and co-founder of Alphalyse, will present the latest research on PS-degrading HCPs, along with key industry developments and recent regulatory updates impacting mAb drug products. The webinar will include: 👉 New and upcoming regulations affecting HCP control, including ICH guideline Q14 on analytical procedure development and US Pharmacopeia General Chapter <1132.1> on residual host cell protein measurement in biopharmaceuticals by mass spectrometry. 👉 Examples of PS-degrading HCPs. 👉 Client cases – learn how mAb developers use mass spectrometry (LC-MS)-based HCP analysis for process development and documentation for regulatory applications. Join us to find out how you can protect your mAb stability: 📅 Date: 26 November 2024 🕒 Time: 16.30 CEST | 10.30am EST | 7.30am PST 📧 Registration: alphalyse.com/cmc-webinars

The enzyme-linked immunosorbent assay (ELISA) has significant limitations, as outlined in the US Pharmacopeia General Chapters <1132> and <1132.1>: 👉 Limited coverage of non- or weakly-immunogenic host cell proteins (HCPs) 👉 Only reports a total HCP content value 👉 Cannot distinguish or quantify specific HCPs of concern 👉 Product-specific assays depend on proprietary reagents that cannot be standardized across the industry. A key advantage of mass spectrometry (MS)-based HCP analysis over ELISA is its ability to identify and quantify individual residual impurities. And with the new USP General Chapter <1132.1>, combined with HCP reference materials provided by the USP, it will now be possible to standardize the analysis across the industry. This will enable comparison of results and knowledge-based risk assessment for developing safer and more efficient biologics. Learn more about the USP’s guidelines to HCP identification and quantitation by MS: alphalyse.com/usp-webinar

For plant-based expression systems, mass spectrometry-based analysis is often the best – and sometimes the only – choice. Plants, such as Nicotiana benthamiana (tobacco), have been used for large-scale production of recombinant proteins for more than 20 years. However, while plant-based expression systems offer scalability and the ability to produce complex therapeutic proteins, they cause significant challenges in downstream processing. Plants typically produce more debris than other expression systems, complicating purification and impurity control. ELISA has been the traditional choice for host cell protein (HCP) monitoring, but commercial kits are limited for plant systems, necessitating expensive and time-consuming custom development. LC-MS is a powerful alternative to ELISA. It provides in-depth HCP profiling, enabling data-driven process optimization for increased product purity and higher patient safety. At Alphalyse, we have performed LC-MS-based product characterization and impurity analysis of 15+ different plant-based expression systems, including Nicotiana tabacum and Physcomitrium patens. Learn more about our analyses for advanced therapies and uncommon expression systems here: https://lnkd.in/d_PKnk37 References [1] https://lnkd.in/dAsx58ri