AAPS PharmSci 360 2025: Trends in Bioanalysis
Long Yuan, PhD, director of the Department of Drug Metabolism and Pharmacokinetics at Biogen, provides a look into some of the trends impacting bioanalysis in biopharmaceutical development and manufacturing.
Pharmaceutical Technology® spoke with Long Yuan, PhD, director, Department of Drug Metabolism and Pharmacokinetics,
“Specificity, for example, for oligonucleotides, sometimes the commonly used portable mass spectrometer may not be able to differentiate the parent and metabolites,” Dr. Yuan explains. “HRMS has a unique advantage to provide additional specificity for these type of applications. Another advantage is it has the ability to obtain quantitative and qualitative information in the same run, so later, if needed, people can do data mining to dig out the needed information and avoid reassessing the samples. For chromatography technology, like microflow LC, nanoflow LC, these are very helpful tools to achieve superior sensitivity for the assay.”
Supercritical fluid chromatography (SFC), which is an instrumentation used to separate chiral compounds, is starting to be utilized for quantitative bioanalysis of chiral compounds for sample separation, according to Dr. Yuan. “There are also novel techniques, like hybridization extraction, for bioanalysis of oligonucleotides,” he continues. “This technique can achieve very clean sample extraction with high efficiency. Therefore, it can achieve highly improved sensitivity compared to the traditional sample preparation methods. It can even achieve [it] for LC–MS-based assays. It can achieve similar sensitivity as [an] enzyme-linked immunosorbent assay [ELISA] oligo binding assay. Some other techniques people are also looking into [include] microsampling, or patient-centric sampling. So, this will be very helpful to reduce the sample volumes and improve the patient convenience, and also compliance…and enable the remote home sampling for clinical studies.”
Dr. Yuan will be moderating the symposium, “Oligo Bioanalysis, Platforms and Methods” on Wednesday, Nov. 12, 2025 at 9AM in 221 AB at
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About the speaker
Long Yuan, PhD, is currently the Director and Head of the Bioanalytical group in the Department of Drug Metabolism & Pharmacokinetics at Biogen. He leads a group of scientists to provide bioanalytical support for diverse modalities including small molecule drugs, oligonucleotides, biologics and AAV gene therapies, in drug discovery and development. Long received his B.S. in Medicinal Chemistry from Fudan University (Shanghai, China), and his Ph.D. in Medicinal Chemistry from the College of Pharmacy, University of Illinois Chicago (IL, USA). Before joining Biogen, he worked in the Department of Bioanalytical Sciences at Bristol Myers Squibb (NJ, USA). His research focuses on developing bioanalytical methodologies for various molecules, with recent emphasis on oligonucleotides, including ASO, siRNA and antibody-oligonucleotide conjugates. He has published over 50 peer-reviewed papers, including 7 book chapters.
Transcript
Editor's note: This transcript is a direct, unedited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.
My name is Long Yuan. I'm currently the Director and Head of biomedical group in Biogen DNPK, so I'm needing a group of scientists to provide bionic support for different mortalities, including small molecule drugs, oligonucleotides, biologics and AV gene therapies.
PharmTech: What are some of the new instrumentations that are being used in bioanalysis? What makes these unique?
Long Yuan: There have been significant advances in new instrumentations and technologies applied in Bioanalysis, for example, for LC MS based assays, high resolution mass spectrometry, HRMS has been playing more and more important role because it has the unique advantage to provide exceptional specificity. Specificity, for example, for oligonucleotides, sometimes the commonly used portable mass spectrometer may not be able to differentiate the parent and metabolites. HRMS has a unique advantage to provide additional specificity for these type of applications. Another advantage is it has the ability to obtain quantitative, quantitative and qualitative information in the same run so later, if needed, people can do data mining to dig out the needed information and avoid reassess of the samples for chromatography technology like microflow LC, nanoflow LC, these are very helpful tools to achieve superior sensitivity for the assay. For example, for some biomarker assays, it may require ultra sensitive assay. So in this case, this type of nanoflow or microflow LC will be very helpful. Another new instrumentation for LC system is super critical fluid chromatography. SFC. Traditionally, this technique is more used for the separation of chiral compounds, but nowadays people also starting to use this SFC for the quantitative bio analysis of chiral compounds, for sample preparation. There are also novel techniques like hybridization extraction, for Bioanalysis of oligonucleotides. This technique combines can achieve very clean sample extraction with high efficiency. Therefore, it can achieve highly improved sensitivity compared to the traditional sample preparation methods. It can even achieve for LC MS based assays, it can achieve similar sensitivity as ELISA assay oligon binding assay. Some other techniques people also looking into is the micro sampling, or patient centric sampling. So this will be helpful, very helpful, to reduce the sample volumes and improve the patient convenience and also compliance. This will help to enable the remote home sampling for clinical studies.
How do changing regulations impact advancements in bioanalysis?
Changing regulations in the past few years has had a profound impact on advancement of Bioanalysis, especially for biomarker assays and the bioanalysis of new modalities like gene and cell therapies, for example, for biomarker bioanalysis. In January this year, FDA published a guidance on bioanalysis method validation for biomarkers. So in general, the standards are getting stricter for biomarker assays and the bioanalytic method validation for biomarkers, it should be addressed consistent with the principles of ich MJH guidance. But still, there's some kind of lack of clarity around the context of youth one and how we can apply the ICH guidance or biomarker essays. Another area is new modalities or new bio analytical techniques like qPCR based bilingual essays. There's still lack of clear guidance on those type of new essays or new techniques, regulatory agencies like FDA, EMA, Health Canada, those agencies are working towards harmonization of regulatory guidances. It has been a tremendous achievement with the. The publication of the ICH guidance, but still there have some regional differences, and I think still all the scientists and regulators around the world need to work more towards the harmonization of the guidance in this year's AAPS, I will moderate a session focused on bioanalysis of oligonucleotides. We will have four very interesting talks focused on different techniques has been applied for oligonucleotide Bioanalysis for both the PK assays and also the immunogenicity assay. The first three talks will be focused on the PK assays, three different speakers, they have put together a very interesting comparative study compared different platforms for bioanalysis of oligonucleotides, including LCMS based assay, ligand binding assay, and also qPCR based assays. It will be very interesting to see how these different types of binding platform, when people apply to the same oligo nucleotides, how the results will come out, how is, what's the pros and cons for these different types of methods? And the last presentation will be a speaker talk about the immunogenicity, as seen for only oligonucleotides. It will be also very interesting talk. Welcome to my session. I look forward to seeing you there. Thank you. Bye.
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