CPSA USA 2017

Short Course 1 - Princeton 1 Ballroom
Protein Identification, Quantification, and Biomarker Analysis

Mass spectrometry, as enabled by modern ionization methods such as MALDI and ESI, has dramatically transformed the science of protein identification and quantification. There is a rapidly growing demand for the quantitative analysis of proteins and peptides by LC-MS/MS in the bio-analytical and clinical laboratories. This short course will help attendees deeply appreciate specific challenges associated with successful outcomes in LC-MS based protein analysis. An in-depth view of the practical aspects involved in protein/peptide analysis by LC-MS/MS will be covered and will include case studies from the literature and from the instructor's personal experiences.

The use of nanospray enabled LC-MS has developed from a qualitative tool for (global) proteomics to a quantitative method suitable for activities such as peptide/protein biomarker validation. Key to success has been the combination of highly specific sample preparation methods, high sensitivity nanospray ionization, and high performance tandem mass spectrometry. Critical parameters involved in robust sample preparation, nanobore LC and nanospray, sensitive & selective MS detection along and their analytical benefits will be emphasized. The transition of the qualitative nLC-MS/MS technology to methods suitable for absolute quantification will be discussed. New tools for cloud based data sharing and the underlying principles for biomarker identification and validation by differential mass spectrometry will be presented. Real world examples will be presented. The course will also feature an additional hands-on "connections workshop" to hone your expertise is making high quality LC-MS fluid connections.

The target audience includes analysts that have been engaged in qualitative proteomics wishing to transition to quantitative methods, analysts that have specialized in small molecule quantification, and those involved in the development of methods for clinical outcomes.

Instructors:
Nalini Sadagopan, Agilent Technologies
Nathan Yates, University of Pittsburgh
Harris Bell-Temin, Bristol-Myers Squibb

Short Course 2 - Princeton II Ballroom
Bioanalysis of Mix Modalities via Hybrid and Orthogonal Approaches

Over the past 10 years, the development of mixed modalities such as therapeutic protein, millia molecule, ADCs, and DNAs have resulted in new bioanalytical and subsequent diagnostic challenges. A number of hybrid or orthogonal approaches have been developed to quantify the different types of biomolecules. This course will give an overview of the methods, practices, technologies and instrumentation used to perform LBA, protein LC-MS, and genomic analysis in a modern bioanalytical laboratory. The course will introduce students to the fundamentals of ligand binding assay, immunogenicity, genomic analysis and orthogonal approaches to improve sensitivity and selectivity of quantification of protein and DNA biomarkers. The courses begins with an introduction to ligand binding assay and the principles of developing a pharmacokinetic (PK) or immunogenicity (IMG) assay, including generation and selection of critical reagents, application of emerging technologies to meet clinical needs. The LC-MS based quantitation techniques such as “bottom-up” digestion, pellet digestion, Immunoaffinity Purification will be discussed next with examples covering their usages. The genomic analysis will focus on the impact of next-generation sequencing and its utility in detecting newborn disorders. This course will feature a dynamic format where the latest technologies will be presented and the advantages of hybrid approaches will be highlighted.

Instructors:
Suzanne Cordovado, CDC
Barry Jones, Q2 Solutions
Linlin Luo, Bristol-Myers Squibb
Jim Shen, Bristol-Myers Squibb

Short Course 3 - TBA
Human Pharmacokinetic Prediction and Approaches to Identify Rate Determining Step of Drug Absorption and Elimination: Industrial Perspective

Human Pharmacokinetic Prediction and Approaches to Identify Rate Determining Step of Drug Absorption and Elimination: Industrial Perspective The oral route is the predominant way of delivering drugs to the systemic circulation to generate pharmacological effects and clinical benefits. To ensure steady flow of new drugs to patients, the pharmaceutical industry is focused on designing and developing molecules to achieve systemic drug exposures capable of robustly modulating disease relevant biological mechanisms in humans. Solubility, membrane passive permeation, transporter mediated active efflux or influx and metabolism are the main factors contributing to oral absorption, disposition and elimination. Therefore understanding the interplays of these factors is crucial to overcome the challenges of poor bioavailability and pharmacokinetics and regulatory concerns of drug-drug interactions in GI absorption. On the other hand, clearance rate is a critical determinant of drug exposure in the systemic circulation and consequently at the pharmacological target compartment. Hence, it is a key component in determining the therapeutic efficacious dose. Either drug metabolic stability or active hepatic uptake could be a rate determining process of drug clearance. Identifying the rate determining step in drug clearance early on in drug discovery is a prerequisite for successful drug development. Furthermore, Drug-Drug Interaction (DDI) is one of the leading causes of morbidity in United States. This is of particular concern in patient populations that are treated with multiple different types of medications (i.e. polypharmacy), such as those suffering from cardiovascular, metabolic and endocrine diseases (CVMED). This practical/hands on course is specifically designed for personnel in the pharmaceutical and biotechnology industries and contract research organizations (CROs), who need to understand:

• General principles of pharmacokinetics
• Factors that affect drug absorption with emphasis on the impact of intestinal transporters on drug absorption
• Identification of rate determinant step of drug clearance and introduction to extended clearance classification system (ECCS) and its application in drug discovery
• Review of major metabolizing enzymes and in vitro/in vivo tools to predict human metabolism mediated clearance
• Review of known renal/hepatic transporters and their role in drug disposition and elimination
• Review of principles of transporter mediated drug interactions and static models used to predict them
• Overview of FDA guidance on assessment of transporter mediated drug interactions
• The workshop will also include a hands-on session that aims at improving your ability to apply these strategies to medicinal chemistry for hit selection, lead optimization, and development candidate selection

Instructors:
Ayman El-Kattan, Pfizer
Yurong Lai, Bristol-Myers Squibb

Short Course 4 - Lehigh
Building a Better Clinical Mass Spectrometry Lab

Clinical Diagnostics is growing in the use of mass spectrometry and especially in the implementation of new techniques. With the growth of pain management, the use of LC/MS/MS has seen the greatest growth, and as a result, it is the greatest growth area among all the MS manufacturers. Now that LC/MS/MS is firmly positioned in clinical diagnostics, great need exists for education in a variety of ways from both top down and bottom up points of view. For example, the need to improve education / capability of lab technicians in sample preparation, LC, and MS/MS is significant. At the same time, the need to use and expand into new technologies in clinical diagnostics is crucial for meeting patient / physician needs while doing so in financially sustainable ways. The workshop will detail new technology and innovation in clinical diagnostics such as high resolution mass spectrometry and metabolomic profiling techniques as they relate to the potential mass spectrometry has in future lab tests.

This workshop will provide a unique opportunity to interact with leaders thoroughly engaged in both clinical diagnostics and liquid chromatography - mass spectrometry technologies. Topics will range from the use of new interfaces to the MS to enable ease of use, the development of tests that are easy to implement, and the opportunities available for individuals looking to enter the clinical market place. Specific topics include assay/test development, identifying / correcting the common stumbling blocks, automation, performing multiple tests types per instrument, data interpretation / processing, and overall lab workflow. In addition, discussion will include lessons learned from recent events in clinical diagnostics as they pertain to developing new tests. This portion will describe how to "shoot ones self in the foot" by cutting corners, so one knows how not to.

Instructors:
Don Chace, Medolac Laboratories
Timothy Garrett, University of Florida
Mark Hayward, ITSP Solutions, Inc.
Kenneth Lewis, Opans

Short Course 5 - University Grille
Microsampling and Patient Centric Sampling:
A journey through what it is and how you can incorporate it into your workflows

There is growing interest in the collection and analysis of smaller volume matrix samples (≤100 µL compared to typical traditional volumes ≥200 µL) for the accurate quantitative determination of circulating drug, metabolite and biomarker concentrations in humans and animals. This has been brought about by the increasing sensitivity of analytical systems (particularly LC-MS) and the numerous advantages of implementing these workflows and their associated technologies. These advantages include the ability to collect clinical samples from previously intractable subjects and study locations, i.e. pediatric, critically ill, remote locations, near patient sampling (pharmacists, etc) and at home sampling. Further, microsampling facilitates the collection of samples via alternative approaches (viz. finger prick sampling) delivering patient convenience and enables cost savings through ambient temperature sample shipments. For animal studies, microsampling enables serial sampling from animals, the elimination of the requirement for additional toxicokinetic satellite animals and the sampling of juvenile animals, delivering higher quality data from fewer animals (particularly for rodent studies). Microsampling also facilitates refinement in sampling procedures. The reduced blood sample volume also enables blood samples to be taken for other purposes, e.g. biomarkers.

In addition to gaining an understanding of what the drivers for the implementation of microsampling are, attendees of this interactive short course will learn and discuss what techniques are available and will explore the pathways and challenges to the implementation of the approach for their discovery, regulatory toxicology, clinical and bioanalytical workflows. This will include addressing the practical, data quality and regulatory issues likely to be encountered and will understand the benefits and challenges of implementation not only for themselves, but also for other functions and workflows involved in the generation of high quality data for robust decision making and regulatory submission.

Attendance of this short course is encouraged for delegates from a wide variety of backgrounds, including (but not limited to) animal technicians, discovery scientists, regulated toxicologists, clinical trials experts, regulators and bioanalysts from pharma, biotechs and academia. Delegates will be encouraged to interact with colleagues and will be led by instructors with world leading expertise in the field.

Instructors:
Neil Spooner, Spooner Bioanalytical Solutions
Joe Siple, New Objective