Although nucleic acid-based medicines (NABMs) hold immense potential to treat neurological diseases, the blood-brain barrier (BBB) remains a significant obstacle that severely restricts drug delivery to the brain. Lipid nanoparticles (LNPs) offer a promising solution to this challenge; however, their composition critically influences biodistribution, cellular uptake, and efficacy. Identifying the optimal LNP formulation is an incredibly complex task, akin to finding a needle in a haystack. To overcome this challenge, we developed a high-throughput platform that combines transferrin receptor (TfR)-targeting LNPs with DNA barcoding to rapidly identify formulations capable of crossing the BBB. We designed unique LNP formulations by systematically varying lipid composition and antibody fragment (Fab) densities. Using DNA barcodes (BCs) as proxies for therapeutic payloads, we evaluated the biodistribution of these LNPs after intravenous injection into transgenic mice expressing human TfR1. Our findings revealed that specific ionizable lipids and higher Fab densities facilitated delivery to the brain, while others failed to penetrate the BBB. This novel approach not only expedites the discovery of brain-targeting LNPs but also provides critical insights into the key factors influencing BBB transcytosis, such as ligand density, lipid composition, and particle properties. Although further studies are needed to validate these findings with functional NABMs, this research represents a significant step toward systemic, non-invasive delivery of therapeutics to the brain. By addressing a long-standing challenge in central nervous system drug delivery, this approach holds the potential to trans-form the treatment landscape for neurological disorders, offering hope for more effective and accessible therapies for patients.

Here, we present a fully automated multiplexed mass spectrometry assay that enables simultaneous quantitation of multiple antibodies in vivo, which has significantly reduced the number of animals required for in-life studies and accelerated antibody candidate selection. This automated platform is now being applied to biomarker quantitation, in vivo ADC conjugation site screening, and in vitro pharmacology studies of biotherapeutics.

Chemical labeling of proteins is a key tool supporting biotherapeutic drug discovery, from initial discovery through development, enabling the capture, detection, and characterization of labeled proteins and their interacting partners. As therapeutics and their targets become increasingly complex, innovative conjugation strategies are needed. This presentation highlights tailored labeling approaches for generating and analyzing complex protein conjugates to support advances in drug discovery across multiple therapeutic areas.

Mass photometry (MP) has emerged as a powerful tool for rapid, label-free viral vector characterization on a single-molecule level, and has potential for future GMP adoption. However, significant work is needed to overcome current limitations and ensure robustness in regulated environments. This talk will focus on method development and discuss broader challenges and opportunities that could shape MP’s future as a reliable tool in gene therapy analytics and beyond.

CAR T cells are engineered T cells expressing a chimeric antigen receptor (CAR) on the cellular surface. CARs allow the T cell to engage an antigen on tumor cells and activate downstream signaling that leads to destruction of the tumor cell. Surface expression of the CAR is critical for therapeutic efficacy, but often differences in efficacy are observed between constructs that show similar surface expression. We developed a workflow using immunoprecipitation of the CAR from the cell surface to characterize the CAR itself and cellular surface proteins that could be affecting CAR activity by using  LC-MS (IP-MS) to gain insights.

Isotopically-labeled carriers offer an approach to improve the quantification and recovery of siRNA therapeutics. This presentation explores how labeled molecules offer the potential to enhance assay sensitivity, increase recovery yields, and lower limits of detection across complex biological matrices. Case studies will demonstrate applications across various in vitro and in vivo matrices as applied to pharmacokinetic and toxicokinetic studies, highlighting how these tools accelerate development of next-generation RNA-based therapeutics.

Ultra-rapid, non-activated CAR T manufacturing offers a paradigm shift, generating potent cell products within a single day. I will present principles underlying this streamlined workflow, approaches for product characterization, and its implications for decentralized or point-of-care deployment. This emerging platform provides a path toward same-day engineering while maintaining product quality and translational feasibility.

This presentation highlights key industry trends for co-formulated fixed-dose combination biologic products. We address analytical and characterization challenges, focusing on how the number, identity, and ratio of combined molecules impact control strategies. Practical insights will be illustrated with case studies sourced from recent clinical trials and literature, emphasizing key questions and considerations for bringing these innovative products to patients.

• What are the most notable CMC challenges and opportunities?
• What emerging technologies/instrumentation are making the biggest impact, and what gaps remain?
• Formulation and device strategies
• Key regulatory considerations and questions​

• Standardization and best practices: Building a community consensus
• From discovery to QC: How to release clinical material with MP data?
• Beyond AAV capsid species quantitation: Expanding MP applications in AAV characterization
• The future of single particle analysis: What does it look like for MP?​

The emergence of multispecifics and complex formats in the biologics space has led to unique challenges for characterization pipelines, especially high-throughput, small scale platforms that have been tailored to IgG discovery. This presentation will discuss limitations of high-throughput platforms in the context of multispecifics along with strategic and technical approaches to navigate these challenges. Additionally, we will discuss how carefully-selected lower throughput experiments can facilitate high-throughput outcomes.

The development of complex molecular formats is expanding our ability to engineer biological systems and enabling new mechanisms of action. However, advancing these complex biologics may presents significant challenges, making it essential to identify and engineer critical molecular features early in the research stage. This presentation highlights strategies for the biophysical characterization of novel molecular entities, with a focus on integrating experimental and predictive data to accelerate lead identification and molecule optimization.

High-concentration formulations for emerging modalities such as antibody–drug conjugates (ADCs) and bispecific antibodies (bsAbs) frequently encounter viscosity and aggregation challenges that limit manufacturability and subcutaneous delivery. We present an integrated multiscale modeling framework to predict developability at elevated concentrations. This approach supports early risk assessment, reveals sequence- and domain-level determinants of undesired behavior, and guides the rational engineering and screening of next-generation ADCs and bsAbs.

Aligning with the FDA’s New Approach Methodologies (NAMs) initiative to replace animal studies, we optimized and validated a high-precision FcRn-dependent transcytosis assay. Demonstrating exceptional correlation with human nonspecific clearance, statistical analysis established reliable PK liability cut-off thresholds. Head-to-head comparisons reveal this human-relevant in vitro assay has superior predictive power compared to SCID mouse PK studies, illustrating how NAMs can replace animal models to accelerate critical biotherapeutic development decisions.

Developing a bioanalytical strategy for T cell engaging (TCE) therapeutics requires coordinated evaluation of pharmacokinetics, immunogenicity, and engagement of target and effector cells. An integrated approach enables robust pharmacodynamic inputs to support PK/PD modeling and decision-making. This presentation outlines critical considerations and practical frameworks for designing comprehensive, fit-for-purpose bioanalytical strategies for TCE programs.

This presentation provides an overview of multispecific therapeutic development from early molecular design through clinical evaluation to commercial approval. It highlights unique quality attributes including homodimer formation and heavy/light chain mispairing, and the criticality assessment. The control strategies to mitigate these product-related impurities will be discussed. Key topics include molecule design, manufacturing process control, specification setting, analytical method development, and characterization tools. Additionally, regulatory feedback will be discussed.

Messenger RNA–lipid nanoparticle (mRNA–LNP) therapeutics have transformed modern medicine, yet achieving consistent formulation quality and rapid characterization remains a major challenge. Here, we present a microfluidic-assisted platform for precise, scalable, and reproducible mRNA–LNP formulation. This system enables real-time monitoring of particle size, encapsulation efficiency, and stability under controlled flow conditions, bridging formulation science with advanced analytics. Our approach minimizes batch variability, accelerates process optimization, and supports regulatory-compliant manufacturing of next-generation mRNA therapeutics.