Susan Haigney

Close-up view of doctor's hand in a white glove holding syringe | Image Credit: ©ra2 studio - stock.adobe.com

Eli Lilly and Company (Lilly) announced on Dec. 1, 2025 that the first patient visit for the SURMOUNT-REAL UK five-year, randomized, real-world clinical trial has taken place. The study, which is expected to include up to 3000 participants in the Greater Manchester, United Kingdom region, will evaluate the long-term effectiveness of tirzepatide on obesity outcomes when the drug is given in primary care settings. The trial will also evaluate the drug’s potential to delay the progression of type 2 diabetes.

“Obesity is a pressing health challenge both in the UK and globally,” Professor Rachel Batterham, Senior Vice President for International Medical Affairs at Lilly, said in a press release (1). “Lilly is committed to working with partners across the health system to better understand and address its complexity. With SURMOUNT-REAL UK, we aim to generate real-world evidence on the long-term health impacts of obesity management medications—evidence that can help shape future care pathways and improve health outcomes for people living with obesity.”

Lilly, the trial sponsor, is partnering with other organizations on the trial, which will also look at impacts of obesity-related complications, such as quality of life, work productivity, and hospital visits. Trial delivery, data flows, technology, and patient recruitment will be led by North West EHealth. System engagement and communications support for the trial is being provided by Health Innovation Manchester. The Chief Investigator for the trial, Martin Rutter, Professor of Cardiometabolic Medicine at the University of Manchester, is being hosted by the University of Manchester.

“In addition to endpoints assessing weight reduction and progression to type 2 diabetes, SURMOUNT-REAL UK will assess the broader health and healthcare impacts in a diverse group of individuals living across Greater Manchester,” Rutter stated in the press release. “The trial is particularly important because it will contribute to the evidence base on intervening comparatively early in the progression of obesity. It’s fantastic that Greater Manchester was selected for the trial because of the excellent research infrastructure and the availability of primary care data for research across the region.”

“As a GP, I see patients bring more than symptoms—they bring hopes, challenges, and the realities of their communities. They trust our practice as a familiar and accessible space. This is why I am proud to be involved in this trial, which extends participation opportunities to groups often under-represented in research,” Dr. Imran Ghafoor, GP Partner at Peterloo Medical Centre and Principal Investigator for the trial, noted in the release. “Research in primary care gives the potential to address health inequalities we witness firsthand. By involving our practice, we can amplify patient voices, identify barriers, and test solutions tailored to real lives. This approach ensures research is inclusive and that the evidence generated reflects the diverse population we serve.”

The study team will identify eligible participants for the trial based on predefined criteria. The results of the trial will be published in peer-reviewed journals.

What is the latest on tirzepatide in the United States?

that it is lowering the price of single-dose vials of tirzepatide in the United States, which is marketed under the name Zepbound, via the company’s digital healthcare platform, LillyDirect (2) (see Table). This action follows 

the reduction in price of Zepbound multi-dose pens 

in November, which is subject to FDA approval (3).

Table: Updated prices for 2.5mg and 5mg doses via Self Pay Journey Program via LillyDirect for Zepbound single-dose vials. Source: Eli Lilly and Company (2).

“Far too many people who need obesity treatments still face cost and coverage barriers,” said Ilya Yuffa, executive vice president and president, Lilly USA and Global Customer Capabilities, in the press release (2). “Today’s action underscores Lilly’s commitment to improving access across the obesity care landscape. We will keep working to provide more options—expanding choices for delivery devices and creating new pathways for access—so more people can get the medicines they need.”

Eli Lilly and Company. Lilly Announces First Patient Visit in SURMOUNT-REAL UK Trial. Press Release. Dec. 1, 2025.

Eli Lilly and Company. Lilly Lowers the Price of Zepbound (tirzepatide) Single-Dose Vials. Press Release. Dec. 1, 2025. 

https://investor.lilly.com/news-releases/news-release-details/lilly-lowers-price-zepboundr-tirzepatide-single-dose-vials

Eli Lilly and Company. Lilly and US Government Agree to Expand Access to Obesity Medicines to Millions of Americans. Nov. 6, 2025. 

https://lilly.mediaroom.com/2025-11-06-Lilly-and-U-S-government-agree-to-expand-access-to-obesity-medicines-to-millions-of-Americans

Articles

Eli Lilly and Company has initiated the SURMOUNT-REAL UK trial, a five-year study in Greater Manchester, UK, to assess tirzepatide's long-term effectiveness on obesity and its potential to delay type 2 diabetes progression. The trial, involving up to 3000 participants, aims to generate real-world evidence on obesity management. North West EHealth and Health Innovation Manchester are key partners in trial management. Concurrently, Lilly has reduced the price of tirzepatide in the US to improve access, reflecting its commitment to addressing obesity treatment barriers.

The first patient visit has taken place for the SURMOUNT-REAL UK clinical trial of Eli Lilly and Company’s weight-loss drug, tirzepatide. 

Lilly Launches UK Trial of Weight-Loss Drug as US Price Drops

Ask the Expert November 2025: Audits, Inspections, and CDMOs

Contract development and manufacturing organizations (CDMOs) typically have multiple clients who each have specific needs. When regulators perform audits and inspections of CDMOs, it is sometimes unclear who is responsible for any deviations the inspector might have. However, ultimately, the sponsor company is responsible for ensuring that any contract organizations are following good manufacturing practices.

But what happens when a CDMO has a client that has specification and/or requirements that infringe on that contractor’s ability to work with other clients? How should the CDMO respond to audits and their clients? In this episode of Ask the Expert, Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, a Nelson Labs company (RCA); Siegfried Schmitt, vice president Technical at Parexel, and Anita Michaels, executive pharma compliance expert and principal consultant at RCA, give advice on how contractors and clients can work together to prepare for inspections and address regulatory actions.

“A lot of CDMOs utilize their clients' inspections to prepare for inspection. But I think you could level up, level that up higher,” Michaels says. “The first thing is you want to have a robust quality system. And you also want to integrate the other five systems into your facility. Then you'll receive, if it's a regulatory authority like the FDA, they could come to inspect you for a GMP or pre-approval inspection, which will be specific to the product they're covering. And then the GMP portion, if you have been approved for a United States product, would cover the six systems. So, I think holistically, a CDMO should prepare, number one, to handle a GMP covering the six systems and have a robust quality system, such as policies in place for your CAPAs [corrective and preventative actions], investigations, deviations, your KPIs, your tracking, and trending holistically across your facility. And then also understanding the approach for a preapproval inspection for your clients.”

Click the video above to watch Sue, Siegfried, and Anita answer the following question:

“How does a CDMO organization handle multiple client input and perspective with regard to general GMP inspections without compromising or setting up different standards within their Quality Management System?

Susan J. Schniepp, Distinguished Fellow, Regulatory Compliance Associates, a Nelson Labs company

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates and a member of 

Siegfried Schmitt, PhD, Vice President, Technical at Parexel

Siegfried Schmitt, PhD, is vice president, Technical at Parexel and a member of 

Anita Michael, executive pharma compliance expert and principal consultant, Regulatory Compliance Associates, a Nelson Labs company

Anita Michael is RCA’s Executive Pharma Compliance Expert & Principal Consultant. She has 24+ years of global regulatory and quality experience, including 16 years direct FDA experience operating globally as their Pharmaceutical Expert, FDA Investigator and FDA Pre-Approval Manager. Anita has excellent interpersonal, empathetic communication and client management skills that enable her to skillfully coach and collaborate with clients at the highest levels of an organization and prepare them for successful FDA inspections (ANDA/NDA/BLA/PMA Pre-Approvals) and global regulatory and quality assurance audits across Biotech, Biologics, Sterile Operations, Drug Substances, and 503A/B. She has been Keynote Speaker for the Pharma Industry and internally to the FDA throughout her career.

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. This new video series will expand on topic areas to include development and manufacturing concerns to help those working in the industry better understand bio/pharmaceutical requirements. Have a question you would like answered? Send it to 

, and it may appear in a future episode or print column.

Videos

In this episode of the Ask the Expert video series, Susan J. Schniepp, Regulatory Compliance Associates (RCA), Siegfried Schmitt, Parexel, and Anita Michaels, RCA, explain how CDMOs can best handle regulatory inspections and client expectations. 

Audits, Inspections, and CDMOs

Cropped shot of doctor holding transparent glass medical vial in hand, focus on bottle | Image Credit:  ©MYDAYcontent - stock.adobe.com

, which is being held from Nov. 9–12 in San Antonio, outlined a streamlined approach to identifying and mitigating the presence of visible particles in biologics. Eda Fenercioglu, Scientist, Formulations at Pfizer, explains how the workflow was applied to biologic formulations (1). The process was developed to reduce time and resources and maintain quality and data generation relevance. The approach used aligns with Six Sigma methodology, Define, Measure, Analyze, Improve, Control (DMAIC). A structured path offered particulate detection through root cause resolution. For this study, particulates were observed after manufacturing steps and in drug product that had been frozen and was then thawed.

How does the workflow help with assessment of particulates in product?

Visual inspection and microscopy imaging was first used to assess particulate morphology so that reason for the particulates could be determined. After this step, the isolated particulates were re-imaged and measured. Spectroscopic analysis, such as Fourier-transform infrared (FT-IR) spectroscopy, was used to ascertain the biochemical composition of the particulates. This allowed the particulates to be classified as either inherent, intrinsic, or extrinsic for targeted follow-up studies to determine the origin particulates and prevent recurrence. While FT-IR spectroscopy was used in this study, the workflow developed allows for the primary identification tool to be adapted, as necessary.

For non-polar or symmetric molecules, Raman spectroscopy is recommended, while scanning electron microscopy with energy dispersive X-ray spectroscopy is suggested for identifying trace metals or inclusions not visible under optical microscopy (1). More detailed characterization of fiber types is achieved with polarized light microscopy. This tool also helps differentiate between protein and nylon when it is used with FT-IR spectroscopy.

During mixing and settling studies, particulate count, size distribution, and morphology were assessed by high-accuracy light obscuration (HIAC-LO) and microflow imaging (MFI) to determine particulate formulation and possible process changes that would eliminate particulate formulation in future batches.

The study showed that particulates were inherent and their morphology and spectra were consistent with the components of the drug product. HIAC-LO and MFI were then used to identify that shear stress from mixing was the cause of the particulate formulation in the product. HIAC-LO was used to conduct a settling study that showed that turning off the mixer at a certain stage of manufacturing preserved solution homogeneity, therefore preventing the particulates from generating. The settling study also found that the drug product remained homogeneous over the hold time without continuous mixing; therefore, a process change could be made.

What does this mean for product inspection?

The study showed that an integrated approach to the identification and classification of particulates can assist in timely process improvements and process control. The use of analytical tools within the DMAIC framework provides efficient root cause analysis that can enhance the quality of the product. Robust control strategies can be established by defining and measuring particulate characteristics followed by analyzation of their composition that leads to the implementation of process improvements.

Fenercioglu, E. A Streamlined Workflow for Visible Particulate Indentification and Root Cause Mitigation in Biologic Drug Products. AAPS PharmSci 360 Poster Presentation. Nov. 11, 2025. 

https://aaps2025.eventscribe.net/fsPopup.asp?PosterID=764134&mode=posterInfo

A streamlined approach for identifying and mitigating visible particles in biologics was presented, utilizing a workflow aligned with Six Sigma's DMAIC methodology. This process, applied to biologic formulations, aims to reduce time and resources while maintaining quality. Visual inspection, microscopy, and spectroscopic analysis, including FT-IR, were employed to classify particulates as inherent, intrinsic, or extrinsic. The study identified shear stress from mixing as the cause of particulate formation, leading to process changes that preserved solution homogeneity. This integrated approach enhances product quality through efficient root cause analysis and process control.

In a poster presentation at AAPS PharmSci 360, Eda Fenercioglu, a scientist at Pfizer, outlines a streamline workflow for identifying and mitigating visible particles in biologic drugs.

Using A Streamlined Workflow to Identify Particulates in Biologic Drugs

AAPS PharmSci 360 2025: Instrumentation Innovation for Bioanalysis

The field of bioanalysis in the development of bio/pharmaceutical products is quickly advancing, and a variety of techniques is available to those working in the field. To learn more about the types of instrumentation used in bioanalysis, 

® spoke with Steve Lowes, senior director of Scientific Affairs at IQVIA Laboratories, as part of our coverage of 

According to Lowes, techniques like flow cytometry and polymerase chain reaction (PCR) are commonly used in bioanalysis; however, they challenge some of the established platforms mentioned in guidance documents. “The way to employ such alternative technologies is through an a 

 SOP [standard operating procedure]-driven and defendable assay validation that clearly defines the capabilities of the assay itself,” Lowes suggests.

“New LBA [ligand binding assay] platforms are also presenting some attractive strengths in terms of their sensitivity and even multiplexing,” Lowes continues. “For example, the proximity extension assay Olink has caught a lot of attention of late associated with the selectivity, the ability to do some multiplexing, and significantly, the sensitivity capabilities derived from the DNA tag hybridization that can be subsequently amplified using PCR. So many of these types of techniques are evolving from the proteomics field, but we are now adapting them to regulated bioanalysis, and when it comes to selectivity, liquid chromatography–mass spectrometry continues to be the benchmark.”

Steve will be monitoring the Rapid Fires: AI/ML in Bioanalysis session on Monday, Nov. 10, 2025 at 3PM CT at AAPS PharmSci 360 2025, being held Nov. 9–12 in San Antonio, Texas.

Click the video above to watch the interview.

Steve Lowes is Senior Director, Scientific Affairs at IQVIA Laboratories

Steve Lowes is Senior Director, Scientific Affairs at IQVIA Laboratories. Steve has 30+ years’ experience in bioanalysis with a focus on LC-MS and regulatory aspects and has been with the legacy LC-MS regulated bioanalytical lab of IQVIA Laboratories in Ithaca, NY since 1995. He is a regular presenter and author of publications on regulated bioanalysis, is co-editor of the text “Regulated Bioanalysis: Fundamentals and Practice,” and is the primary contributor to the popular 

 bioanalysis blog from IQVIA Laboratories. His most recent interests are the application of LC-MS to regulated bioanalysis of biologics and biomarkers. He received his bachelor’s degree in Analytical Chemistry at Sheffield Hallam University in the UK (1987) and a PhD in Biochemistry from the Open University, Milton Keynes, UK (1991).

Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

Hi, I'm Steve Lowes, Senior Director of Scientific Affairs at IQVIA Laboratories. I'm delighted to talk with you today.

We've seen a plethora of techniques and platforms targeted at biological analytes that have entered our bioanalytical laboratories, flow cytometry, PCR, in particular, are commonly discussed and applied, although they do challenge the established biological guidance precedents that I've already mentioned, the way to employ such alternative technologies is through an a priori, SOP driven and defendable assay validation that clearly defines the capabilities of the assay itself.

New LBA ligand binding platforms are also presenting some attractive strengths in terms of their sensitivity and even multiplexing.

For example, the proximity extension assay olink has caught a lot of attention of late associated with the selectivity, the ability to do some multiplexing, and significantly, the sensitivity capabilities derived from the DNA tag hybridization that can be subsequently amplified using PCR. So many of these types of techniques are evolving from the proteomics field, but we are now adapting them to regulated bio analysis and when it comes to selectivity, liquid chromatography, mass spectrometry continues to be the benchmark.

Again, proteomic originating LC-MS technologies are finding their way into the bioanalytical laboratories. A good example of this is high resolution mass spectrometry that we iqvia are heavily invested in for the primary reason that it can do things that a triple quadrupole instrument cannot do.

Now, historically, HRMS has been heavily applied to the characterization of peptides and proteins we now see in these instruments being routinely applied to quantitative bio analysis. Oligonucleotides and siRNA determinations are particularly well suited to HRMS, where conventional CID fragmentation in a triple quadrupole instrument may not always deliver the sensitivity that is required

Instead, high resolution and mass accuracy can address these assay needs. The antibody drug conjugate assays that I just mentioned are another good example here where the selectivity and the multiplexing flexibility of LC-MS can be further leveraged with high resolution mass spectrometry, and then many large molecule biomarker quantitative assays are also being demonstrated with HRMS. I think this is an exciting time for mass spectroscopists with a continuing pipeline with technology advancements finding practical application in our biological labs.I will go on to point that low flow rate chromatography with microflowrates. Now there's sub milliliter per minute and true nanoflow sub microliter per minute flow rates delivers increased sensitivity, but historically, such advanced LC techniques have presented some practical challenges around run times and robustness. Some interesting developments are coming along now, and hitting the market that are truly democratizing low flow chromatography.

I see these as having practical utility, even in high throughput bioanalytical labs. There's even a technology platform now that proposes doing away with chromatography altogether, using acoustic ejection droplets from a sample to enable sub second per sample bioanalytical quantitation for the right applications, and these were primarily in the discovery stages.

While it's difficult to envisage this having universal application in bio analysis, when combined with alternative separation technologies such as ion mobility, the scene is truly set for an evolution of rapid throughput improvements in the LC-MS laboratory, simplifying and standardizing LC-MS has been a trend from manufacturers for some time now.

This year, already, we are seeing the LC-MS systems that are being launched that are targeted at clinical laboratories with full integrated sample preparation, chromatographic separations and mass spec detection.

Bringing LC-MS into the scope of a traditional clinical analyzer is a very interesting concept, and I'm sure we'll all be watching this very closely.

Pharmaceutical Technology® spoke with Steve Lowes, senior director of Scientific Affairs at IQVIA Laboratories, ahead of AAPS PharmSci 360 to discuss some of the unique instruments used to conduct bioanalysis. 

AAPS PharmSci 360: Trends in Bioanalysis

® spoke with Long Yuan, PhD, director, Department of Drug Metabolism and Pharmacokinetics, 

, to find out how new types of instrumentation are impacting 

 and what changing regulations may be helping or hurting innovations. Liquid chromatography—mass spectrometry (LC–MS)-based assays and high-resolution mass spectrometry (HRMS) provide exceptional specificity, according to Dr. Yuan.

“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 

, which is being held from November 10–12 in San Antonio.

Long Yuan, PhD, Director and Head of the Bioanalytical group in the Department of Drug Metabolism & Pharmacokinetics at Biogen

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.

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?

 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.

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.

AAPS PharmSci 360 2025: Trends in Bioanalysis

Scene from the laboratory with pipette, test tube, microscope, DNA and formulas with copy space | Image Source: ©gopixa -stock.adobe.com

Bioanalysis, which is utilized in drug development to determine pharmacology, bioavailability, and bioequivalence, includes pharmacokinetic, toxicokinetic, or biomarker concentration measurements (1) in animal safety and clinical studies. Bioanalytical methods are required by regulators to be validated to ensure their data’s reliability (1). Artificial intelligence (AI), machine learning (ML), and other complex tools are helping drug developers evaluate the complex data involved in these types of studies.

® spoke with Dr. Mark Arnold, owner and principal, Bioanalytical Solution Integration to find out how bioanalysis enhances bio/pharmaceutical drug development. Arnold will be presenting the keynote session, “Reflections on Transformations in Drug Development, Bioanalysis, and Regulations”, at AAPS PharmSci 360 on Monday, Nov. 10, 2025 at 1:30 PM.

PharmTech: How can AI and ML be used to enhance bioanalysis in bio/pharmaceutical development?

Arnold (Bioanalytical Solution Integration):

 AI, large language models [LLMs], natural language processing, and ML have been discussed for a few years in bioanalysis but are now making actual inroads with deployed validated applications and others in development.

The earliest implementations are for reports and quality control (QC) of assay validations and study sample analysis. As the capabilities of the AIs have advanced, so have the applications in bioanalysis. New applications are looking at taking GLP [good laboratory practice] or GCP [good clinical practice] protocols and bioanalytical contracts to write bioanalytical plans. Other applications perform quality control checks that integrate ELN [electronic lab notebook], instrument, and LIMS [laboratory information management system] data on a daily basis to catch errors early and identify trends that lead to failure before they happen, and data analysis as part of investigations into assay failures.

Building on design of experiment concepts, AI will utilize databases of knowledge to improve method development for immunoassays and LC–MS [liquid chromatography—mass spectrometry] methods. I’ve heard that a mass spectrometer manufacturer is looking to apply AI to chromatogram integration to go past algorithm rules to more intelligent peak detection.Ultimately, biotech and pharma companies will be using AI to write the bioanalytical sections of filings. Health authorities are also looking at AI as a tool to analyze bioanalytical data in submissions and during on-site or remote inspections of bioanalytical labs. The resulting analyses will highlight both compliance with regulations and detect problems and errors that need further review.

PharmTech: How can large language models be applied to bioanalytical workflows?

 As noted above, AI, natural language processing, and ML are being implemented in bioanalysis for report writing and bioanalytical plans. Many LLM AIs are designed as predictive tools and operate as black boxes where it cannot be determined how they do what they do. A challenge in regulated bioanalysis in the use of LLM AIs is in their training and predictive nature; they need to find data (content) in different sources and formats and place it appropriately in the report.

For regulated bioanalysis, controls must be in place for the AI or the risk of hallucination (creation of data or content not provided) can occur as has been seen in some AIs. Not knowing if the report content is correct is not something bioanalytical labs can risk and would result in utilizing the same or greater QC and QA [quality assurance] resources to make sure of the report’s accuracy. Which is contrary to what AI is supposed to do: reduce human involvement and improve accuracy.

To address this, at least one AI-based vendor for bioanalytical labs has constraints in place to prevent hallucinated data creation and is including an audit trail in its report generation steps to demonstrate the data reached the right location. Pharma companies have started using LLMs for writing some portions of eCTDs [electronic common technical documents] and the bioanalytical sections are well-structured, making them good candidates for early implementation of AI writing.

Arnold (Bioanalytical Solution Integration): 

Most of the technologies in use for pharmacokinetic, immunogenicity, and pharmacodynamic measurements have been around but are being refined for improved sensitivity, accuracy, and precision. These include the various forms of immunoassays, hyphenated chromatographic assays (e.g., LC–MS/MS [liquid chromatography—tandem mass spectrometry], LC–HRMS [liquid chromatography—high-resolution mass spectrometry]), PCR [polymerase chain reaction], flow cytometry, and cell-based technologies. The improved flow cytometry instruments, with some instruments having 30 and 40 color detection ability, are being used not only for cellular characterization, but the improved sensitivities allow them to be applied to circulating exosome biomarkers that can detect and characterize many diseases. Mass cytometry is being used in research, and once suitable applications are identified, likely in measuring biomarkers, it will move into regulated bioanalysis. 

PharmTech: How do changing regulations impact advancements in bioanalysis?

ICH [International Council for Harmonisation] M10 standardized regulations for pharmacokinetic bioanalysis using immuno- and chromatographic assays. Having a standard accepted in many major markets eliminated the need for bioanalysts to have to keep up with changes in each of the individual countries and adjust their practices, especially when there were conflicting expectations. WHO [World Health Organization] recently published M10 which may expand its acceptance beyond the ICH-adherent countries. The expansion of gene and cell therapies require technologies (e.g., PCR, FLOW cytometry) not covered in ICH M10, and so far, the scientific community has been promoting science-based approaches to these technologies. These technologies have been used in clinical laboratories and adapted for use in pharmacokinetic assays.

For immunogenicity, a few countries have developed regulations that are reasonably similar so that achieving a consistent approach is not difficult. However, with the extensive experience for monoclonal antibody drugs, bioanalysts are proposing alternative approaches to simplify the traditional tiered-immunogenicity assay designs that generate as informative data with less effort and cost. Regulators have not formally responded to these proposals.

Another area without a global regulatory perspective is the analysis of biomarkers. In the United States, measuring biomarkers for a medical decision (i.e., those used by doctors and in hospitals) must follow the Clinical Laboratory Improvement Amendments, while those used to support the safety and efficacy of a new drug are to follow a 2025 FDA guidance which is focused on immuno- and chromatographic (e.g., LC–MS/MS) assays.The European Union and Japan have totally separate and different sets of regulations. These differences create not only challenges for the bioanalyst but also add complexities when trying to run clinical trials in multiple global regions.

To be successful in delivering data accepted globally, bioanalysts must be aware of a variety of regulations and how they apply to the purpose of the analysis, type of samples they are analyzing, and the technologies. When no regulations exist, scientists must continue to collaborate on science-based best practices. Since the science is always advancing faster than the regulations, regulators must learn about the science of the technologies and evaluate practices that generate quality data, and when they have enough understanding of the science generate regulations; hopefully, based on or in collaboration with the recommendations of the scientific community.

Bioanalytical Method Validation, Guidance for Industry

Mark E. Arnold, PhD, Owner and Principal of Bioanalytical Solution Integration

Mark E. Arnold, PhD is Owner and Principal of Bioanalytical Solution Integration; consulting with biotech and pharma companies to advance their portfolios to bring new therapies to patients in need. In that role, he collaboratively develops the bioanalytical scientific and regulatory strategy to meet current and future client needs. Mark was previously Executive Director of the Bioanalytical Sciences Department at Bristol-Myers Squibb Co. and Director of Science for the Scientific Affairs Department at Labcorp supporting bioanalytical and clinical laboratories. He received a B.S. in biology from Indiana University of Pennsylvania and a PhD in pharmacology from the University of Pittsburgh. For 40 years, Dr. Arnold has been involved in the application of bioanalysis to developing new therapies, including the review and interpretation of regulations and guidance as they apply to the evolving science in bioanalytical and clinical laboratories. He was co-chair of both the AAPS-FDA Crystal City V and VI Workshops and has been a member of AAPS since 1988 holding a variety of committee positions including 2023-2024 Scientific Advisory Chair, 2022 PharmSci360 Scientific Program Committee Chair, 2018 PharmSci360 Bioanalytical Track Chair and is an AAPS Fellow (2014). Dr. Arnold has over 115 peer-reviewed publications and numerous invited podium presentations.

Artificial intelligence (AI) and machine learning (ML) are increasingly integrated into bioanalysis, enhancing drug development by improving data evaluation and method development. AI applications in bioanalysis include report writing, quality control, and bioanalytical plan creation, with constraints to prevent data inaccuracies. New instrumentation, such as advanced flow cytometry and mass cytometry, offers improved sensitivity and precision. Regulatory changes, like ICH M10, standardize bioanalytical practices globally, but challenges remain in areas like biomarker analysis. Bioanalysts must navigate diverse regulations and collaborate on science-based best practices to ensure globally accepted data.

Pharmaceutical Technology® spoke with Dr. Mark Arnold, owner and principal, Bioanalytical Solution Integration, ahead of AAPS PharmSci 360 to find out how bioanalysis enhances bio/pharmaceutical drug development.