By Brian R. Moyer and Lindsay King
To continue our conversation about the hot areas of biotechnology at this year’s AAPS National Biotechnology Conference, today we will discuss biomarkers and drug delivery. Check out yesterday’s post to learn about CMC and immunogenicity.
Theme 3: Biomarkers
The NBCPC saw the opportunity to cover a variety of unmet needs under the biomarker theme, from analytical technologies, faster FACs data analysis, and bioanalytical validation to application of biomarker data in precision medicine. A fundamental starting point for LBA- and LC/MS-based biomarker measurement is the availability of reliable and well characterized reference materials. This is a particular challenge for the measurement of endogenous proteins and large complex therapeutic proteins. But PK and PD biomarker assays often differ substantially with regard to the reference materials available and their similarity to the endogenous analyte.
The 2013 FDA draft bioanalytical guidance (PDF) included biomarkers for the first time, and industry and regulators continue to discuss and explore whether we can or should apply the same validation approach developed and refined for PK assays to biomarker assays defined most recently at the September 2015 Crystal City VI meeting on biomarker analytical validation. Will a one-size-fits-all acceptance criteria work for all biomarkers? How can better characterization of biomarker calibrator’s help? The NBCPC wanted biomarker sessions to address clinical chemistry biomarker experience, introduce the idea of commutability, and open the floor to discuss potential best practices identified by the protein calibrator and the biomarker stability AAPS biomarker sub-teams from within the Ligand Binding Assay Bioanalytical focus group.
Biomarker analyte stability is another foundational issue, one that is often both overlooked and difficult to address. While pre-analytical and within-run control of sample stability is a well-recognized concern for PK samples, optimal conditions can generally be defined through spike recovery off nominal concentration. However, this is not the case for endogenous biomarker samples, where levels can only be determined by measurement. If a sample is below the limit of quantification (BLQ), it’s difficult to determine whether this is a true finding or whether the analyte was degraded during sample collection, storage, or handling.
We hope that session participants will find this to be a great opportunity to discuss questions like these, share your examples, ask questions, and influence future best practices.
Theme 4: Drug Delivery
Biologics delivery is always a favorite topic of debate. How to deliver biologics? Was the protein (antibody or other structure) delivered intact? What was the timing, and was time and extent of exposure important? The NBCPC saw a dramatic need in programs that will elucidate this highly charged topic.
Vaccines and their fate are for the most part unknown except by titer expressions. Is the presentation of a biologic what triggers the ADA or a NAb? How is the biotechnology community doing so far in answering these questions? Coverage of the topic in freeze dried or frozen biologics for FIH studies is a technique that may hold promise and will be discussed. Brain delivery is one of the most challenging topics due to the blood brain barrier, which blocks large molecules like biologics and immunotherapeutics. The new advances in the Huntington arena, as described in one of our conference plenary topics, as well as the dementias, Parkinson, and brain injury (the trauma/CTE question), including stroke, are quite active research areas important clinical targets in the Boston biotech community as well as other major centers where such studies can be conducted. We selected this theme in particular as it relates to immunotherapies, imaging distributions (positron emission tomography [PET] nuclear medicine imaging), and measuring neuro-efficacies in targeted brain tissues, plus novel technologies to deliver biologics to the brain was a potential “dream theme” for Boston. Drug delivery assessment for biologics in solid tumor biology has multiple questions regarding the tumor microenvironment barriers. The wide interest in the mechanics of the subcutaneous mechanisms for absorption and translation were enticing ideas to bring to NBC. The NBCPC was well aware of the extensive approaches in publications, and the need is ever-growing for methods to deliver biologics to brain pathologies.
Please comment on these themes and share your ideas below on what you want to see from the programming. We want the 2016 NBC to be the best of experiences!