CDER Scientists Partner with Industry to Develop Critical Reference Materials for Antibody-Drug Conjugates Evaluation ++++ ++++

One of the most rapidly growing class of therapeutics, antibody-drug conjugates (ADCs), combine antibody targeting specificity with potent cytotoxic payloads. Under a new Research Collaboration Agreement, scientists at CDER's Office of Pharmaceutical Quality (OPQ) and Sutro Biopharma, Inc., will seek to develop improved analytical standards for ADCs. The research will encompass target antigen selection, payload-linker optimization, and drug conjugation sites that reflect both currently marketed products and those in clinical development pipelines. In this collaboration, CDER scientists will: Co-lead study design and target selection to ensure regulatory relevance in developing reference materials that meet current and future analytical needs for ADC evaluation Apply cutting-edge analytical capabilities to comprehensively characterize ADC reference materials using advanced instrumentation, including mass spectrometry, nuclear magnetic resonance, and functional bioassays Generate research outcomes that contribute to broader scientific understanding of ADC characterization methodologies and regulatory best practices This collaboration enhances OPQ's efforts to strengthen FDA's analytical characterization capabilities for ADCs, directly supporting the FDA's mission to ensure safety, efficacy, and quality of complex biopharmaceuticals. Research results will be made publicly available upon completion. Fc gamma receptor polymorphisms in antibody therapy: implications for bioassay development to enhance product quality https://academic.oup.com/abt/article/8/2/87/7965767?utm_medium=email&utm_source=govdelivery CDER scientists summarize current knowledge of mechanisms through which therapeutic antibodies mediate cell death and how polymorphisms in the receptors on immune cells that recognize the antibody’s Fc domain influence these mechanisms. The authors propose approaches through which the drug development community can devise bioassays to assess critical quality attributes of antibody therapeutics while taking the genetic heterogeneity of patients into account. Development and validation of a high-throughput LC-MS/MS bioanalytical method for the simultaneous quantification of cannabidiol and metabolites in human plasma https://www.sciencedirect.com/science/article/pii/S157002322500248X?utm_medium=email&utm_source=govdelivery This report describes the development and validation by CDER researchers of a rapid, high-throughput bioanalytical method based on liquid chromatography and tandem mass spectrometry for the quantification of cannabidiol and its primary metabolites in human plasma to support an FDA-sponsored clinical study. Human induced pluripotent stem cell-derived cardiomyocytes in a cardiac organ-on-a-chip NAM for electrophysiology, calcium, and contractility testing https://www.nature.com/articles/s41596-025-01166-4?utm_medium=email&utm_source=govdelivery Cardiac organs-on-chips that are made using human induced pluripotent stem cells have the potential to predict cardiac effects of new drug candidates. To promote broad adoption of these tools in drug development and ensure reproducibility, CDER researchers and collaborators have developed a protocol describing how to prepare and use these tools. Collaborative science in action: A 20-year perspective from the Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee. https://pmc.ncbi.nlm.nih.gov/articles/PMC11318526/?utm_medium=email&utm_source=govdelivery By examining past successes and prospects of the Cardiac Safety Technical Committee of the Health and Environmental Sciences Institute, CDER authors and collaborators shed light on how a multifaceted approach has 1) addressed current challenges in detecting potential cardiac failure modes and 2) paved the way for enhanced drug development and study design methodologies. These methodologies include a focus on improving the translational predictability of nonclinical evaluations and reducing reliance on animal research in cardiovascular safety assessments. A Tipping Point Method to Evaluate Sensitivity to Potential Violations in Missing Data Assumptions https://onlinelibrary.wiley.com/doi/epdf/10.1002/pst.70002?utm_medium=email&utm_source=govdelivery CDER-led research highlights the role of tipping point analyses in the evaluation of the impact of missing data in key analysis results. The authors present a tipping point analysis method that is novel in that it requires no missing data imputation and makes minimal distributional assumptions. The authors showcase the method’s use in two real CDER drug reviews. Public feedback to FDA on regulatory considerations for AI in drug manufacturing https://aapsopen.springeropen.com/articles/10.1186/s41120-025-00110-w?utm_medium=email&utm_source=govdelivery The authors summarize public feedback at a recent workshop where participants were asked to comment on the Agency’s recent discussion paper Artificial Intelligence in Drug Manufacturing. The input of participants in areas such as data management, governance, model development and validation requirements, and AI in the pharmaceutical quality system are summarized, along with other major concerns of the attendees. Impact of polymer source variations on hydrogel structure and product performance in dexamethasone-loaded ophthalmic inserts https://www.sciencedirect.com/science/article/abs/pii/S0378517325007963?dgcid=author&utm_medium=email&utm_source=govdelivery This study established a comprehensive framework of measurement methods to characterize polyethylene glycol-based ophthalmic inserts, using raw materials from multiple vendors as proof of concept. In addition, a preliminary in vitro release testing method was developed to explore how material attributes affect performance of these products. Quantitative Solid-State NMR Spectroscopy (qSSNMR) in Pharmaceutical Analysis https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/mrc.5536?utm_medium=email&utm_source=govdelivery This mini-review highlights the evolution of quantitative solid-state NMR (qSSNMR), focusing on improvements in detection limits, resolution, and high-throughput capabilities. Technical advancements and applications for analyzing complex pharmaceutical mixtures, and challenges to, and strategies for, widespread adoption are also explored.