Halo Labs’ Post

Oct 10th! Ready to accelerate and optimize your #bispecifics #formulations? Learn from experts in the field harnessing NanoTemper Technologies #Prometheus to rapidly assess multi-parameter protein analytics... #Register --> https://lnkd.in/edneWb2c Learn how Dr Jordan William Bye at Immunocore and his team focus on the formulation development of ImmTAX, (Immune Mobilizing Monoclonal TCRs Against X disease), potent novel #bispecific molecules, so they remain stable throughout #development, #manufacturing, and #storage until #delivery. #protein #mAb #CDMO #CRO #ADC #therapeutic #biologics

Our first outcome from a US FDA funded collaboration with University of Minnesota and University of Iowa. It is known that excipients in the formulation may interfere with characterization using typical analytical and functional techniques during this biosimilarity exercise. Consequently, the producers of biosimilar products resort to buffer exchange to isolate the biotherapeutic protein from the drug product formulation. In this study, we explore the impact of this isolation on product stability. Repeated extraction cycles do result in significant changes in higher-order structure (red-shift of 5.0 nm in fluorescence maxima of buffer exchanged samples) of the mAb and also an increase in formation of basic variants from 19.1 to 26.7% and from 32.3 to 36.9% in extracted innovator and biosimilar Transtuzumab samples, respectively. Based on the observations reported in this paper, we recommend that biosimilar manufacturers take into consideration these effects of excipients on protein stability when performing biosimilarity assessments. #biosimilars #mabs #usfda #universityofminnesota #formulationdevelopment #stabilizer https://lnkd.in/dd5WzaEu

Struggling to identify the enzymes responsible for polysorbate degradation in your biopharmaceutical formulations, even after using advanced LC-MS proteomics workflows? I’m excited to share our latest preprint on the systematic optimization of activity-based protein profiling (ABPP), enabling the identification of polysorbate-degrading enzymes in biotherapeutics down to 10 ppb, or even lower! This outstanding work was led by a talented postdoc Taku Tsukidate in the Analytical R&D Mass Spectrometry team at Merck. Check it out for insights into improving your formulation stability! #massspec #LCMS #ABPP #formulation #polysorbate

As the fastest growing sectors of the pharmaceutical industry, most therapeutic proteins have complex post-translational modifications for efficient secretion and drug efficacy and stability maintenance. PTMs can affect the activity, stability, and function of a protein. Misfolding, aggregation, variable glycosylation, oxidation of methionine, deamination of asparagine and glutamine, and proteolysis are common types of protein modifications. Incorrect modifications of protein therapeutic may result in immune response, or even serious side effects. These modifications pose a great challenge for accurate and consistent bioprocessing and a comprehensive analysis of protein modifications is a necessary. #protein #proteinmodification #drugdevelopment #posttranslationalmodifications #pharmaceuticalindustry #drugsidcovery Image from creative proteomics

An interesting article which discusses the effects trace metals can have on cell culture performance. #tracemetals #cellculturemedia #mammaliancellculture #bioprocessing #biotherapeutics #biopharmaceuticals https://lnkd.in/eduEpdCt

Here Starovoit et al describes a methodology to overcome in high temperature in column artifacts for LCMS peptide analysis 🛎Overview: High-temperature liquid chromatography (HTLC) has an important drawback. In that peptides can go unwanted modifications due to the exposure to high temperature and an acidic mobile phase while on the column 🎯Summary: Starovoit et al method employs a trapping column which is maintained at a lower temperature to keep peptides safe for a considerable amount of time before they finally elute from the separation colum. Starovoit et al observed increased peak capacity by 1.4-fold within a 110 min peptide mapping of trastuzumab and provided 10% more peptide identifications in exploratory LC–MS analyses compared with analyses conducted at 30 °C Futhermore Starovoit et al observed method reduced temperature-related artifacts by 66% for N-terminal pyroGlu and 63% for oxidized Met compared to direct injection at 60 °C. #massspectrometry #massspectrometry #biotherapeutics #biotech #chemistry #pharmacy #pharma #peptide https://lnkd.in/eGsuyQMd

In this excellent paper, Sarin et. al. describes studies on impact of excipient extraction and buffer exchange on recominant antibody stability. Quoting from the abstract: "The foundation of a biosimilar manufacturer’s regulatory filing is the demonstration of analytical and functional similarity between the biosimilar product and the pertinent originator product. The excipients in the formulation may interfere with characterization using typical analytical and functional techniques during this biosimilarity exercise. Consequently, the producers of biosimilar products resort to buffer exchange to isolate the biotherapeutic protein from the drug product formulation. However, the impact that this isolation has on the product stability is not completely known. This study aims to elucidate the extent to which mAb isolation via ultrafiltration-diafiltration-based buffer exchange impacts mAb stability. It has been demonstrated that repeated extraction cycles do result in significant changes in higher-order structure (red-shift of 5.0 nm in fluorescence maxima of buffer exchanged samples) of the mAb and also an increase in formation of basic variants from 19.1 to 26.7% and from 32.3 to 36.9% in extracted innovator and biosimilar Tmab samples, respectively. It was also observed that under certain conditions of tertiary structure disruptions, Tmab could be restabilized depending on formulation composition. Thus, mAb isolation through extraction with buffer exchange impacts the product stability. Based on the observations reported in this paper, we recommend that biosimilar manufacturers take into consideration these effects of excipients on protein stability when performing biosimilarity assessments."

BOOK YOUR SEAT FOR THIS FREE LIVE WEBINAR ON MARCH 27TH Validation of Test Result Equivalence for Alternative BET assays, Including Recombinant Methods Both the FDA’s 2012 Guidance for Industry and USP <1223> specifically use the term “equivalence” as a requirement for validating an alternative test. Traditional methods, such as the Limulus amebocyte lysate (LAL) assay, are widely accepted and have a proven record of assuring parenteral drug and device safety, but they have limitations, including reagent variability and sustainability concerns. As a result, new methods using a number of innovative platforms, including recombinant technology such as Recombinant Factor C and Recombinant Cascade Reagents (rFC and rCR), have emerged. The concept of test result equivalence bridges the gap between old and new technologies, offering cost-effective, environmentally friendly, and reproducible means of endotoxin detection, advancing the industry’s ability to ensure continued product quality and patient safety. This webinar will explore the concepts of equivalence, comparability, and the statistical methods used to evaluate them. Karen Zink McCullough, Owner, Principal Consultant at MMI Associates, John Duguid, Executive Director, Research & Development at Vericel® Corporation , Steven Walfish, Principal Consultant at Statistical Outsourcing Services, Allen Burgenson, Global Subject Matter Expert, Testing Solutions at Lonza and Alan Hoffmeister, Senior Global Technology and Market Development Manager at Charles River Laboratories #endotoxins #EndotoxinTesting #BacterialEndotoxinTest #Equivalence #LAL #rFC #rCR #StatisticalEquivalence #statisticalanalysis #Biopharmaceuticals #pharmaceuticals #biologics #biomanufacturing #BiopharmarWebinars #validation

If you are looking to design and discover new peptides to hit any drug target to cure disease, please contact us. We use our machine learning programme to design the therapeutic peptide and a physics-based rule to validate their interaction profile. #machinelearning #drugdiscovery #biologics #peptides #moleculardynamics #drugdesign #proteinengineering #computationalbiology #bioinformatics

LAST CHANCE TO BOOK YOUR SEAT FOR TODAY'S FREE LIVE WEBINAR VALIDATION OF TEST RESULTS EQUIVALENCE FOR ALTERNATIVE BET ASSAYS, INCLUDING RECOMBINANT METHODS Both the FDA’s 2012 Guidance for Industry and USP <1223> specifically use the term “equivalence” as a requirement for validating an alternative test. Traditional methods, such as the Limulus amebocyte lysate (LAL) assay, are widely accepted and have a proven record of assuring parenteral drug and device safety, but they have limitations, including reagent variability and sustainability concerns. As a result, new methods using a number of innovative platforms, including recombinant technology such as Recombinant Factor C and Recombinant Cascade Reagents (rFC and rCR), have emerged. The concept of test result equivalence bridges the gap between old and new technologies, offering cost-effective, environmentally friendly, and reproducible means of endotoxin detection, advancing the industry’s ability to ensure continued product quality and patient safety. This webinar will explore the concepts of equivalence, comparability, and the statistical methods used to evaluate them. Presented by Karen Zink McCullough, Owner, Principal Consultant at MMI Associates,John Duguid, Executive Director, Research & Development at Vericel® Corporation, Steven Walfish, Principal Consultant at Statistical Outsourcing Services, Allen Burgenson, Global Subject Matter Expert, Testing Solutions at Lonza and Alan Hoffmeister, Senior Global Technology and Market Development Manager at Charles River Laboratories: #endotoxins #EndotoxinTesting #BacterialEndotoxinTest #Equivalence #LAL #rFC #rCR #StatisticalEquivalence #statisticalanalysis #Biopharmaceuticals #pharmaceuticals #biologics #biomanufacturing #BiopharmarWebinars #validation #Microbiology