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

October 10 is World Mental Health Day – and the official 2024 theme is: It is Time to Prioritize Mental Health in the Workplace. To safeguard mental health at work, the World Health Organization recommends making employee wellbeing a core company value, training and empowering supervisors to create a healthy work environment, and providing employees with purpose, connection, and stability. At Alphalyse, we believe that a healthy work environment and a good work-life balance are essential for the wellbeing of everyone working here. And when we are at our best, we can also provide the best service for our biopharmaceutical clients. Our efforts to create a healthy work environment include: 👉 Flexible work hours 👉 Remote working options 👉 Regular check-ins focusing on employee wellbeing 👉 Tools for recognizing and proactively addressing stress Stress can affect all of us. Alphalyse employs highly educated professionals who have exacting standards for their own performance and often work with tight project deadlines. Research shows that such high-performing people are particularly vulnerable to stress. For this reason, we have introduced several tools for stress prevention. One tool is the Stress Ladder diagram, which helps evaluate our workload and identify colleagues needing support. In the words of our CEO, Thomas Kofoed: ”Work should be a place where we feel happy and fulfilled. When thriving, we’re in the best place to think creatively, develop new research ideas, and provide innovative solutions to our clients’ challenges.” Feel free to borrow our Stress Ladder for your workplace – and let us support each other in prioritizing mental health at work, so we can all feel our best and do our best. 🤝 #WorldMentalHealthDay #MentalHealthMatters #WorkLifeBalance #StressAwareness #LifeAtAlphalyse

Immunoassays cannot simultaneously quantify AAV proteins from the host cell line and the expression vector system. Adeno-Associated Virus (AAV)-based products are challenging to analyze due to the complexity of their impurity profiles, which contain proteins from both eucaryotic host cells and virus vectors. One of our clients wished to compare and document the batch consistency of their gene therapy product. They needed to monitor problematic Sf9 and AcMNPV host cell proteins, but their product was too complex for traditional ELISA analysis. Here is how we quantified residual impurities in their batches – and what we found that might have prevented a successful scale-up: https://lnkd.in/e_CXMSh2

Y-mAbs Therapeutics used our monoclonal antibody (mAb) analysis services to examine batch variations in their antibody products. The results helped them optimize the manufacturing of antibody-based cancer treatments and strengthened their regulatory submissions. *********** When you choose Alphalyse as your CRO, you receive robust and reproducible analytical data, allowing you to compare results between batches and across projects — and you access 20+ years of expertise with protein analysis by mass spectrometry to help you drive your projects forward. Discover how our mAb analysis services can support your therapeutic development: alphalyse.com/services

Peptide mapping is essential for ensuring a biologic’s quality and consistency, confirming the therapeutic protein’s identity, and detecting potential sequence variants. Sequence variants are commonly post-translational modifications (PTMs) of the therapeutic protein, which may affect the stability or bioactivity of the drug product. However, in rare cases, variants may be co-purifying homologs from the host cells used in manufacturing. A homolog host cell protein (HCP) shares a common evolutionary origin and/or sequence, structure, or function similarities with bioactive proteins in humans. In biologics, co-purifying homologs often closely resemble the recombinant therapeutic protein expressed by the host cells. Due to this similarity, homologs can be challenging to separate from the desired therapeutic protein during purification and often go undetected by immunoassays. It is problematic for several reasons: 👉 Homologs may interfere with endogenous protein activity, causing unwanted physiological effects 👉 Homologs may compete with the therapeutic protein for receptor binding, reducing the effectiveness of the drug 👉 Homologs may trigger a harmful immune response in patients In one case [1], peptide mapping of a recombinant human tissue plasminogen activator (tPA) revealed the presence of a co-purifying hamster plasminogen activator (PA) from the Chinese Hamster Ovary (CHO) host cells. The two proteins share ~80% of their sequence, raising concerns about the potential effects of the hamster homolog on drug efficiency and patient safety. In addition, the hamster PA was also highly homologous with goat PA, causing this HCP to go undetected by immunoassays based on goat antisera. Peptide mapping by mass spectrometry (MS) was necessary to detect the homolog, enabling process optimization to remove it. The case above illustrates the importance of orthogonal analytical techniques for detecting homologs and other impurities that may co-purify during production. Peptide mapping by mass spectrometry is not just a quality check—it is a safeguard for drug purity, patient safety, and regulatory compliance 👉 https://lnkd.in/dCh64CMG References: [1] https://lnkd.in/dyEWTVUJ Image: tPA, proteopedia.org

A number of key publications show the importance of the US Pharmacopeia’s best practices for host cell protein (HCP) analysis by mass spectrometry. These papers have contributed to the shift in focus from the total HCP level in a drug sample to individual high-risk HCPs known to degrade the drug product or cause adverse effects in patients. In line with these publications, regulatory authorities increasingly demand that biopharmaceutical developers monitor HCPs of concern to ensure product quality and patient safety. Did you miss our webinar on the upcoming USP General Chapter <1132.1>? Watch it here: alphalyse.com/usp-webinar – or have a look at the papers that preceded it: [1] https://lnkd.in/e2mXytDY [2] https://lnkd.in/eRx9UWmS [3] https://lnkd.in/eqTShrSH

Where does ELISA fall short? The ELISA (enzyme-linked immunosorbent assay) is the most common method for measuring and controlling host cell proteins (HCPs) in biologic drugs. However, ELISA has significant limitations that have caused project delays and even project terminations. In the upcoming US Pharmacopeia General Chapter <1132.1> Residual Host Cell Protein Measurement in Biopharmaceuticals by Mass Spectrometry, a USP expert panel has summarized the shortcomings of ELISA: [1] 👉 Polyclonal antibodies used in the immunoassay often have no or limited coverage to particular HCPs that are non-immunogenic or weakly immunogenic in the animals used to raise antibodies. 👉 The immunoassay may underestimate or overestimate levels of HCPs when individual HCP levels are very high and the antibody is limiting their detection or when an HCP is highly immunogenic in the immunized species dominating the ELISA signal. 👉 An ELISA assay generates a single value for total HCPs and does not distinguish the contribution of individual HCPs. 👉 The lack of specific identification prevents a knowledge-based risk assessment of particular HCPs. In addition, ELISA results depend on proprietary reagents that are tied to a product or production system, precluding industry-wide standardization of the method. In short, the limitations of ELISA—reliance on polyclonal antibodies with variable coverage, its inability to differentiate individual HCPs, and the lack of standardized reagents—can lead to inaccurate HCP levels and hinder data-driven risk assessments, potentially causing costly project delays. To overcome these challenges, the USP General Chapter <1132.1> will outline best practices for mass spectrometry (MS)-based HCP analysis, offering an orthogonal analysis for more precise identification and quantification of individual HCPs. To learn more about the new chapter on HCP measurement by MS, watch our latest webinar with the US Pharmacopeia: https://lnkd.in/dxZRjemm References: [1] USP Proposed Chapter <1132.1> Residual Host Cell Protein Measurement in Biopharmaceuticals by Mass Spectrometry https://lnkd.in/dxTuTsJ

🧪 Are you confident in selecting the right host cell protein quantitation method for your project? Don’t miss this chance to get up to speed on the key elements of the new US Pharmacopeia General Chapter <1132.1>. The principles in this chapter are relevant across all biopharmaceuticals: 👉 Recombinant proteins 👉 Vaccines 👉 Gene therapies 👉 Cellular- and tissue-based products 👉 Biocatalysis products We already see regulatory agencies referencing this chapter in scientific reviews and conferences. Aligning with the new USP guidelines could be critical to avoiding delays if you’re planning IND or BLA submissions after 1 December, 2024. ******** Join us live TODAY for insights directly from a USP expert and get your questions answered in the Q&A session. 📅 Date: 18 September 2024 🕒 Time: 16.30 CEST | 10.30am EDT | 7.30am PDT 📧 Registration: alphalyse.com/usp-webinar

🌎 September 17 is WHO’s World Patient Safety Day. 🌍 Today, we highlight the need for advanced analytical methods to ensure the safety and efficacy of biologic drugs – and to expedite their licensing, making them accessible to patients in need. 🦠 Biologics represent a groundbreaking advancement over traditional small-molecule drugs. Many diseases, such as cancer, autoimmune disorders, and genetic conditions, involve complex biological mechanisms that small-molecule drugs struggle to address. Biologics offer new therapeutic options to patients suffering from chronic or previously untreatable conditions. However, the purity and safety of biologic drugs remain a key concern. Host cell proteins (HCPs) are present in all biologic drugs. Most are harmless – but certain problematic HCPs can endanger patients and shut down clinical trials. Unfortunately, there have been cases of HCPs causing adverse patient reactions – and examples of life-saving drugs that never made it to market due to protein impurities. Join Ejvind Mørtz in this play-on-demand webinar to learn more about harmful HCPs and how to identify them in your biologic ➡️ https://lnkd.in/d5eeufAw #WorldPatientSafetyDay

“We didn't want to risk impurity surprises in Phase 2 or 3, so we chose to supplement the ELISA data with an orthogonal method.” ****** Our client suspected their commercial ELISA kit could not detect all host cell proteins (HCPs) in their sample. A mass spectrometry (MS) assay using a quantification digestion protocol did not detect HCPs in the final drug sample either. ❗However, when Alphalyse applied a native digest method to lower the limit of detection (LLOD) to 0.1 ppm, we found 4 HCPs of concern in the client’s final drug sample – some of which could have caused adverse reactions in patients even at trace levels.  Learn more about the identification of sub-ppm impurities here: https://lnkd.in/dK5Gm_9Y