The AAPS Scientific Programming Committee presents this PharmSci 360 overview.
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The Five Tracks
End-to-End Hot Topic Sessions
BIOMOLECULAR
NEXT GENERATION TECHNOLOGIES IN PRECLINICAL DEVELOPMENT
Prologue: Advancements in Antibody Engineering and Applications
Bispecificc antibodies (bsAb) are a large family of molecules designed to recognize two different epitopes or antigens. Landmark advances in the engineering and development of bsAbs are enabling unprecedented versatility in therapeutic antibody concepts. More than 20 different commercialized technology platforms are available for bsAb creation and development, two bsAbs are marketed, and more than 85 are in clinical development. bsAbs have the potential for novel functionalities; that is, activities that do not exist in mixtures of the parental or reference antibodies. This presentation will discuss the design, function, and potential of these so-called obligate bsAbs.
Monday, Nov. 4 8:30 am – 9:00 am
Maximizing Therapeutic Potential by Affinity and Avidity Engineering
Monday, Nov. 4 9:00 am – 9:30 am
A Cell-Based Assay for Predicting Non-Specific Clearance of Therapeutic Antibodies
A cell-based assay employing Madin-Darby canine kidney cells stably expressing human neonatal Fc receptor (FcRn) heavy chain and β2-microglobulin genes was developed to measure transcytosis of monoclonal antibodies (mAbs) under conditions relevant to the FcRn-mediated IgG salvage pathway. The FcRn-dependent transcytosis assay is modeled to reflect combined effects of nonspecific interactions between mAbs and cells, cellular uptake via pinocytosis, pH-dependent interactions with FcRn, and dynamics of intracellular trafficking and sorting mechanisms. This session will discuss the utility of this assay as a cost-effective and animal-sparing screening tool for evaluation of mAb-based drug candidates during lead selection, optimization, preclinical development, and process development for desired pharmacokinetic properties.
Monday, Nov. 4 9:30 am – 10:00 am
Drug Discovery Driven by Antibody Engineering Technologies
Previously, antibody engineering was mainly applied to improve the properties of a parent antibody by methods such as humanization, affinity maturation, stability engineering, and half-life extension. Recent advances in antibody engineering have enabled us to conceive and realize novel antibody drug concepts. This presentation describes how antibody engineering technologies, such as bispecific antibody, recycling antibody, and sweeping antibody, can drive the discovery of innovative antibody drugs.
Monday, Nov. 4 10:00 am – 10:30 am
Panel Discussion: T-Cell Redirectors (Cd3-Bispecifics)—Engineering Toward Success
Bispecific T-cell engagers (bs-TCE) are a promising class of immune-oncology agents in targeted cancer immunotherapy. Classical bs-TCE designs consist of a tumor antigen-binding domain combined with a binding domain against the CD3 T-cell receptor-signaling complex. CD3-based bs-TCE development is encountering challenges, in part because they activate all T-cells irrespective of lineage, which may lead to exaggerated T-cell activation and cytokine release in some patients and limited efficacy due to T suppressor cell activation in others. The optimization of bs-TCEs design and development to increase tumor selectivity and widen the therapeutic window can maximize their therapeutic potential.
Monday, Nov. 4 10:30 am – 11:00 am
EMERGING RESEARCH TOOLS FOR HIGH QUALITY CANDIDATE SELECTION
Prologue: Preclinical and Translational Science Considerations of Emerging Novel Therapies
Recent scientific breakthroughs, such as nanobodies, bispecifics, nucleic acid-based, and cell and gene therapies, will transform the current approaches of drug development. We will cover the groundwork for developing such program-specific risk-based assessments and their mitigation strategies, consider state-of-the-art tools to assess the safety and long-term risks for new modalities to ultimately design clinical studies to have minimal impact on safety of these modalities.
Tuesday, Nov. 5 8:30 am – 9:00 am
Horizon Scan of Existing CAR-T Immunotherapies from Development to Trials
Tuesday, Nov. 5 9:00 am – 9:30 am
Considerations for Immunogenicity Risk Assessment and Mitigation and Bioanalytical Strategies for the Next Generation of Biologics
Tuesday, Nov. 5 9:30 am – 10:00 am
Analysis of T-Cell Vector Integration Sites for a Murine Gamma-Retroviral Vector Encoding the Anti-CD19 Chimeric Antigen Receptor Used in the Production of Axicabtagene Ciloleucel
Tuesday, Nov. 5 10:00 am – 10:30 am
Making Sense of Deep Sequencing: FDA Perspective
Tuesday, Nov. 5 10:30 am – 11:00 am
PK AND PD MODELING IN EFFECTIVE PRECLINICAL TO CLINICAL TRANSLATION
Prologue: Critical Insights and Methods from Modeling Mechanisms to Support Discovery through Early Clinical Development
Wednesday, Nov. 6 8:30 am – 9:00 am
Discovery and Development of Emicizumab, an Antibody for Hemophilia A
Emicizumab is a humanized anti-FIXa/FX bispecific antibody, which was approved in 2017 for prophylactic treatment of patients with hemophilia A with inhibitors. This presentation will provide an overview of hemophilia A and how emicizumab was designed based on FVIII mimetic activity, pharmacokinetics, immunogenicity, etc. The preclinical characterization of emicizumab, determination of first-in-human dose, clinical development, and how the preclinical data translated to the clinical will be presented.
Wednesday, Nov. 6 9:00 am – 9:30 am
QSP Model of Agonist-Mediated T-Cell Dynamics in Mouse Tumor Micro Environment
T-cell interaction in the tumor microenvironment (TME) is a key component of immuno- oncology therapy. Glucocorticoid-induced TNFR-related (GITR) protein is expressed on immune cells including regulatory T-cells (Tregs) and effector T-cells (Teffs). Preclinical data suggest that agonism of GITR in combination with FcgR-mediated depletion of Tregs results in an increased intratumoral Teff:Treg ratio and tumor shrinkage. Using quantitative systems pharmacology (QSP) modeling, the dynamics of Tregs and activated Teffs in TME under the effect of an anti-GITR agonistic antibody was described in syngeneic mouse tumor models. The speakers’ QSP model provides a quantitative understanding of the trade-off between maximizing Treg depletion vs. Teff agonism and insights to optimize drug design, dose regimen, and patient population.
Wednesday, Nov. 6 9:30 am – 10:00 am
Virtual Population Approaches Using Prior Clinical Data for Immuno-Oncology Development
Immuno-oncology (I-O) quantitative systems pharmacology platforms provide an additional resource for investigating mechanistic interactions and synergy of I-O combinations, interpreting the role of biomarkers in therapeutic responses, and recommending dose expansion before clinical data become available. To provide population level predictions for new therapies, I-O platforms should quantitatively reproduce observed biomarker and response variations in real-world patient population, which entails developing a virtual population. The goal is to develop a suitable virtual population in an algorithmically automated and efficient fashion while considering I-O prior clinical trial data. Learn how virtual population could accurately predict second line anti-CTLA4 therapy after progression on anti-PD1 therapy, and the anti-CTLA4 and anti-PD1 therapy combination response.
Wednesday, Nov. 6 10:00 am – 10:30 am
QSP for Efficacy and Safety Decisions in Bispecific Antibody Development
Wednesday, Nov. 6 10:30 am – 11:00 am
Panel Discussion: AI Driven Alternative Methods for Drug Safety and Efficacy
Wednesday, Nov. 6 4:00 pm – 5:00 pm
CHEMICAL
NEXT GENERATION TECHNOLOGIES IN PRECLINICAL DEVELOPMENT
Prologue: Simple and Interpretable Signatures to Revolutionize Drug Development in the World of AI and Ml
Monday, Nov. 4 8:30 am – 9:00 am
Science-Driven Design of the Preclinical Package: Case by Case
Monday, Nov. 4 9:00 am – 9:30 am
Computational Toxicology Strategies for Drug Discovery: Present and Future
Monday, Nov. 4 9:30 am – 10:00 am
Choose the Right Cancer Cell Line for Your Research: A Genomics-Guide Prioritize System (CCL-GPS)
This session describes a study to develop a prioritizing system for cancer cell line selection by integrated analysis of cancer cell lines and tumor samples. A computational method prioritized 779 cell lines by accounting the number of matched patients from The Cancer Genome Atlas. Validation experiments on predicted top cell line with the closest resemblance to a certain tumor group were conducted using FDA-approved drugs on breast and thyroid carcinoma. The CCL-GPS on papillary bladder carcinoma was applied to screen the potential antitumor drugs among 1068 FDA-approved drug library for drug repurposing. A web tool was developed for on-the-fly evaluation, which offers good insight for drug screening or mechanism study.
Monday, Nov. 4 10:00 am – 10:30 am
Fair Principles and Implementations in the Pharmaceutical Industry
Monday, Nov. 4 10:30 am – 11:00 am
EMERGING RESEARCH TOOLS FOR HIGH QUALITY CANDIDATE SELECTION
Prologue: Emerging Research Tools for High Quality Candidate Selection
This prologue will discuss emerging tools for improving drug candidate selection and drug product optimization. It will cover the challenges in early stage drug development, specifically between lead optimization and drug formulation design. The increasing importance of modeling tools and biopredictive approaches will be discussed. The presentation will describe emerging trends for predicting developability and applying risk-based/model-informed decision-making in lead candidate selection. This encompasses improved understanding and characterizing of biological systems, advances in screening tools, and biorelevant characterization incorporating early stage fit-for-purpose models for formulation optimization.
Tuesday, Nov. 5 8:30 am – 9:00 am
Adoption and Impact of Microphysiological Systems in Pharmaceutical Development
Tuesday, Nov. 5 9:00 am – 9:30 am
Leveraging Scalable Organ Chips to Gauge Inflammatory Responses in Preclinical Drug Development
Tuesday, Nov. 5 9:30 am – 10:00 am
3D Intestinal Tissues for Lead Optimization, Safety, and Permeability
Availability of human primary cell-based 3D small intestinal microtissues that recapitulate structural and functional mimicry with the in vivo counterpart is critical to obtain reproducible in vitro testing tool to predict safety and bioavailability of compounds for oral administration and other xenobiotics. These 3D intestinal tissue models bridge the gap in preclinical testing to predict safety. Data from a panel of 30 benchmark drugs with known human absorption values that were evaluated on the intestinal tissue model will be presented. Study results of drug-drug interactions and drug metabolism will be shared. The functionality and limitations of these models for GI toxicity studies will be discussed.
Tuesday, Nov. 5 10:00 am – 10:30 am
Microbiome Contributions to Drug Metabolism
Oral drugs can exhibit incomplete absorption in the upper gastrointestinal tract or reach the gut after enterohepatic circulation. Thus, drugs encounter enormous densities of commensal microbes. These microbes collectively encode 150-fold more genes than the human genome, including enzymes that can potentially metabolize drugs. The microbiome’s contribution to drug and drug metabolite exposure is largely unexplored. Examples suggest that gut microbial activity can be responsible for a significant portion of systemic exposure to a toxic drug metabolite. The first systematic exploration of microbiome-encoded drug-metabolizing activity and how these studies can identify microbial genes that predict the capacity of an individual’s gut microbiome to metabolize a drug will be discussed.
Tuesday, Nov. 5 10:30 am – 11:00 am
PK AND PD MODELING IN EFFECTIVE PRECLINICAL TO CLINICAL TRANSLATION
Prologue: Quantitative Systems Pharmacology and Toxicology Modeling in Preclinical to Clinical Translation
Wednesday, Nov. 6 8:30 am – 9:00 am
QSP Can Improve Hypothesis Generation and Testing in Pharmaceutical R&D
Quantitative systems pharmacology (QSP) is an approach to mechanistic mathematical modeling of human disease pathophysiology and drug pharmacology that integrates data from both clinical and nonclinical sources to build predictive models. The cycle of hypothesis generation and testing drives pharmaceutical R&D. However, hypothesis generation needs to become more robust by integrating a broader range of nonclinical and clinical data. QSP can be the means of integrating this data in a comprehensive and mechanistic manner, and thus generate rigorous biological/pharmacological hypotheses. An example will be presented in which a QSP model of autoimmune disease is used to generate hypotheses about a therapeutic mechanism of action that is investigated in nonclinical and clinical experiments.
Wednesday, Nov. 6 9:00 am – 9:30 am
How Does QSP Modeling Support R&D Decisions? Case Examples of Modeling Impact in Central Nervous System and Inflammatory Diseases
Wednesday, Nov. 6 9:30 am – 10:00 am
Mechanistic Insights into Drug-Induced Liver Injury for Macrolide Antibiotics Using Quantitative Systems Toxicology Modeling
Drug-induced liver injury (DILI) is a primary reason for the failure of pharmaceutical agents during drug development and withdrawal of approved drugs from the market. Quantitative systems toxicology (QST) modeling is a useful tool to investigate underlying mechanisms of DILI or predict this multifactorial event. This session will provide scientific background, data inputs, and step-by-step processes of QST modeling of DILI and its applications in drug development. A case study will be presented where DILIsym, a QST modeling platform, was employed to investigate underlying mechanisms of macrolide-mediated DILI.
Wednesday, Nov. 6 10:00 am – 10:30 am
Toward Bridging Translational Gap in Cardiotoxicity Prediction: Progressive Cardiac Risk Assessment Strategy for Moxiflox
Wednesday, Nov. 6 10:30 am – 11:00 am
BIOMOLECULAR
INNOVATIVE BOANALYTICAL SOLUTIONS AND FUTURE OF BIOANALYSIS
Prologue: Introduction to Innovative Bioanalytical Solutions and Future of Bioanalysis for Biomolecules
Monday, Nov. 4 8:30 am – 9:00 am
Advanced Bioanalysis to Evaluate How Immunogenicity Impacts Drug Pharmacokinetics
Immunogenicity of biotherapeutics is a major challenge. The generation of antidrug antibodies against therapeutic proteins leads to formation of immune complexes (ICs) that can vastly influence drug activity and pharmacokinetics (PK) and provoke adverse events. Understanding IC formation, structure, and PK would help interpret clinical data and improve drug development. We lack optimal bioanalytical methods. Bioanalytical challenges will be discussed and currently available methods will be critically reviewed. A novel analytical approach will be proposed that combines various bioanalytical and biophysical methods that enabled the generation, characterization, and quantitative determination of defined ICs. These methods enabled a size-specific IC PK analysis in in-vivo studies.
Monday, Nov. 4 9:00 am – 9:30 am
CAR-T: Bioanalytical Challenges and Considerations to Support Pharmacokinetic Characterization
Monday, Nov. 4 9:30 am – 10:00 am
Multispecific Bioanalytical Assay Strategies for Pharmacokinetic Analysis
Monday, Nov. 4 10:00 am – 10:30 am
Multiplexed PK Assay in Support of Biologics Combination Clinical Studies
The presenters developed and fully validated a twoplex assay on the U-PLEX platform where two therapeutic monoclonal antibodies in Merck’s pipeline could be measured simultaneously in one sample. The results demonstrated that the multiplexed pharmacokinetic (PK) assay had performances, including accuracy, precision, and cross-reactivity, that met regulatory requirements. Results of MK-A from the multiplex assay are comparable to results from a previously validated MK-A singleplex assay. The multiplex assay was used to support a phase 1 MK-A/MK-B combination therapy clinical study and generated results consistent with historical MK-A monotherapy PK data.
Monday, Nov. 4 10:30 am – 11:00 am
ADVANCES IN PRECISION/PERSONALIZED MEDICINE and BIOMARKERS
Prologue: Introduction to Advances in Precision/Personalized Medicine and Biomarkers
Tuesday, Nov. 5 8:30am – 9:00 am
Exosome-Based Proteins: Emerging Biomarker Type from Liquid Biopsies
Exosomes may play a role in cancer progression. A recent article in Cell reported that the suppression of exosomal PD-L1 induces systemic antitumor immunity and memory. In addition, tumor- or immuno-cells–derived exosomal biomarkers have been suggested as predictive and prognostic biomarkers for monitoring the results of treatment in cancers. The regulatory bioanalytical guidelines and industry best practices mainly address the need for measuring soluble molecules. The presentation will cover exosome biology, preparation and assay methods, and examples of biomarker uses. Case studies will focus on bioanalytical considerations for both exosome preparations and analytical method development.
Tuesday, Nov. 5 9:00 am – 9:30 am
Characterization of Human Plasma Extracellular RNA Biomarkers by RNA-SEQ
Tuesday, Nov. 5 9:30 am – 10:00 am
Translating New Technologies into Precision Medicine and Diagnostic Sphere for Huntington Disease
Tuesday, Nov. 5 10:00 am – 10:30 am
Biomarker Assay Considerations from Exploratory Endpoint to Companion Diagnostic: How to Ensure Program Success
Tuesday, Nov. 5 10:30 am – 11:00 am
DIALOGUE ON EMERGING REGULATORY GUIDELINES AND EXPERIENCES
Prologue: Introduction to Dialogue on Emerging Regulatory Guidelines and Experiences
Wednesday, Nov. 6 8:30 am – 9:00 am
ADA Validation Testing and Reporting Harmonization Recommendations
Wednesday, Nov. 6 9:00 am – 9:30 am
Evolution of nAb Assays: Emerging Modalities
Wednesday, Nov. 6 9:30 am – 10:00 am
Challenges and Insights to Assess Immunogenicity Risk of I-O Therapeutics
Wednesday, Nov. 6 10:00 am – 10:30 am
Current and Future States of Bioanalysis in Biosimilar Development
Wednesday, Nov. 6 10:30 am – 11:00 am
Panel Discussion: Immunogenicity and Biomarker Regulatory Science Discussion Panel
Wednesday, Nov. 6 4:00 pm – 5:00 pm
CHEMICAL
INNOVATIVE BIOANALYTICAL SOLUTIONS AND FUTURE OF BIOANALYSIS
Prologue: Innovative Bioanalytical Solutions and the Future of Bioanalysis
Productivity gains in bioanalysis have resulted from advancements in instrumentation, data processing capabilities, and development of robust assays with minimal sample size. Improved technology and ease of logistical and operational communication support the integrity of study samples from collection to analysis. The challenge is to partner effectively with stakeholders and implement new technologies, services, and workflows. This symposium will highlight operational, logistical, and communication considerations to generate meaningful data with novel bioanalytical solutions. Case studies for tissue analysis, successfully applying Microflow Liquid chromatography–mass spectrometry methods for the bioanalysis of large molecules, and microsampling will be presented.
Monday, Nov. 4 8:30 am – 9:00 am
Quantitative Intestinal Tissue Assay of a Triphosphate Active Drug Metabolite
A quantitative method has been developed and validated to handle bioanalysis of a triphosphate active drug metabolite from human intestinal tissue. Unique sample handling and processing measures enabled reproducible recovery and quantitation accuracy of the triphosphorylated analyte from the matrix of interest within determined stability limitations. Sample state, storage conditions, container systems, homogenization bead selection, and sample processing protocols were critical to mitigate nonspecific binding of the phosphorylated analyte and to assay samples within known stability limitations. This method was used to support the analysis of biopsy tissues from human clinical trials to treat noroviruses.
Monday, Nov. 4 9:00 am – 9:30 am
Bioanalytical and Logistical Considerations in Patient-Centric Volumetric Absorptive Microsampling
Monday, Nov. 4 9:30 am – 10:00 am
Optimized Microflow LC-MS/MS Methods for the Bioanalysis of Large Molecules
Monday, Nov. 4 10:00 am – 10:30 am
Mass Spectrometry and the Battle from Bench to Bedside
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based tests are not used everywhere because of the rigor required to validate the test, the throughput requirements, and the unexpected challenges that arise in dealing with samples from a wide variety of disease states. This session will discuss the challenges in transiting a biomarker analyte into a routine hospital environment using MS. Examples will include more difficult steroid analyses such as aldosterone, estradiol, 1,25 dihydroxyvitamin D, and modern protein MS techniques such as MS immunoassay and stable isotope standards and capture by antipeptide antibodies in application to synthetic insulin analogues, immunoglobulins and therapeutic monoclonal antibodies, and thyroglobulin.
Monday, Nov. 4 10:30 am – 11:00 am
ADVANCES IN PRECISION/PERSONALIZED MEDICINE and BIOMARKERS
Prologue: Overview of Precision Medicine and Biomarkers to Better Understand Patients, Disease, and Clinical Outcome
Precision medicine uses information of individual variability in genes, environment, and lifestyle for each person to apply individualized treatment and prevention strategies. Biomarker identification and confirmation relies on high-quality bioanalytical methods. Analytical validation depends on assay context of use prior to clinical validation. Understanding regulations from the Food and Drug Administration (for applications), Center for Devices and Radiological Health (in vitro diagnostic methods), and Centers for Medicare & Medicaid Services (Clinical Laboratory Improvement Amendments assays) is critical to design a suitable assay. This presentation will review assay performance expectations and provide examples.
Tuesday, Nov. 5 8:30 am – 9:00 am
A Methylated Protein Biomarker Method to Assess Target Engagement: from Proteomic Screen to Clinical Support
Tuesday, Nov. 5 9:00 am – 9:30 am
A Reagent-Free Sensitive LC-MS/MS Assay to Quantify Myostatin as a Target Engagement and Pharmacodynamic Biomarker
Tuesday, Nov. 5 9:30 am – 10:00 am
Novel In-Sample Calibration Curves for LC-MS/MS Bioanalysis
Lack of authentic matrices for external calibration curves is one of the challenges in liquid chromatography-tandem mass spectrometry (LC-MS/MS) biomarker analysis. Without the need to use external calibration curves, a novel methodology of in-sample calibration curves (ISCC) using multiple isotopologue reaction monitoring (MIRM) of multiple naturally occurring isotopologue transitions of a stable isotope labeled (SIL)-analyte for instant LC-MS/MS bioanalysis and quantitative proteomics will be presented. The MIRM-ISCC-LC-MS/MS methodology addresses the key issues and challenges in current LC-MS/MS bioanalysis, and allows accurate bioanalysis for the first time without using external calibration curves, impacting the bioanalysis of biomarkers, biotherapeutics, and small-molecule compounds.
Tuesday, Nov. 5 10:00 am – 10:30 am
Leveraging Real-World Data in Rare Diseases: Longitudinal Data Sets as “Virtual Natural History”
Tuesday, Nov. 5 10:30 am – 11:00 am
DIALOGUE ON EMERGING REGULATORY GUIDELINES AND EXPERIENCES
Prologue: Historical and Current Perspective of the Fda Bioanalytical Method Validation Guidance
Wednesday, Nov. 6 8:30 am – 9:00 am
A Surveillance Perspective on Bioanalytical Method Validation
Wednesday, Nov. 6 9:00 am – 9:30 am
A Regulatory Science Perspective on Bioanalytical Method Validation: FDA Regulatory Research
Bioanalytics play an important role for the bioanalysis of clinical studies for bioequivalence, bioavailability, and pharmacokinetics. Bioanalytics, based on the Food and Drug Administration’s (FDA) Bioanalytical Method Validation guidance and innovation, are essential to advance regulatory understanding of the drug evaluation for preclinical and clinical studies. Understanding the nature and scope of the guidance and its on-going regulatory evolution will benefit sponsors and regulators. The speakers were involved in preparing FDA’s Bioanalytical Method Validation guidance and are involved in its revision and ongoing FDA studies that may be included in subsequent guidance revisions.
Wednesday, Nov. 6 9:30 am – 10:00 am
OGD Perspective on Bioanalytical Method Validation
Bioanalytical Method Validation guidance provides the Food and Drug Administration’s recommendations on the development, validation, and in-study use of bioanalytical methods for quantitative evaluation of drugs and their metabolites. Understanding the assessor’s perspective on bioanalytical data submitted in abbreviated new drug applications (ANDAs) will help applicants submit quality data for drug product approval. The presentation will review important aspects of Bioanalytical Method Validation guidance and what Office of Generic Drugs assessors look for when reviewing generic drug applications. Case studies on review-related issues during method validation and in-study analysis of ANDAs will be provided.
Wednesday, Nov. 6 10:00 am – 10:30 am
Panel: Science-Based Perspectives for Advancing the Application of Bioanalytical Method Validation
Bioanalytical method development and validation is critical for limiting immunologically related adverse clinical events related to therapeutic protein products. Antidrug antibodies (ADA) can develop during therapeutic protein treatment, and thus their potential formation must be assessed early in clinical trials. Detection and analysis of ADA is an important tool for understanding these potentially dangerous immune responses. The methods for addressing ADA formation and immunogenicity in trial patients, how ADA can be detected, and challenges for method development and validation will be discussed.
Wednesday, Nov. 6 10:30 am – 11:00 am
BIOMOLECULAR
ROLE OF MODELING AND SIMULATION IN DOSE AND DOSING REGIMEN SELECTION
Prologue: Model-Informed Dose Selection and Optimization of Novel Biotherapeutics
Monday, Nov. 4 8:30 am – 9:00 am
FIH Starting Dose Selection for Novel Therapeutics: Learning from IQ Mabel Survey Results
Monday, Nov. 4 9:00 am – 9:30 am
Clinical Pharmacology Considerations for Bispecifics
Bispecific antibodies bind to two different antigens or two different epitopes on the same antigen. There are more than 100 different bispecific antibody formats, and new avenues are emerging. Bispecific antibodies may link target cells with effector cells or bind two epitopes on the same cell to block more than one signaling pathway. Redirecting the cytotoxic potential of immune effector cells in the destruction of tumor cells has been an important driver in developing bispecific antibodies. This session focuses on designs of bispecific molecules and clinical pharmacology considerations of such drivers of efficacy, regulatory guidance on starting dose, bioanalytical challenges, selecting recommended phase 2 dose, and applying various modeling and simulation approaches.
Monday, Nov. 4 9:30 am – 10:00 am
Dosing Approaches for Novel Therapeutic Modalities: CAR-T Therapies
Monday, Nov. 4 10:00 am – 10:30 am
Regulatory Perspective on Dosing Approaches for Novel Therapeutic Modalities
Monday, Nov. 4 10:30 am – 11:00 am
CLINICAL PHARMACOLOGY PATHS FOR SMALL POPULATIONS
Prologue: Utilizing the Clinical Pharmacology Storehouse to Inform Drug Development in Special Populations and Rare Disease
Tuesday, Nov. 5 8:30 am – 9:00 am
Leveraging Preclinical and Historic Clinical Data to Obtain Approval of G-CSF Treatments for Acute Radiation Syndrome Under the Animal Rule
Tuesday, Nov. 5 9:00 am – 9:30 am
Clinical Perspective on Immune Tolerance and Ada Mitigation Strategies for Rare Populations
Tuesday, Nov. 5 9:30 am – 10:00 am
How Can Electronic Health Records Be More Useful as Real-World Data?
Real world data (RWD) and real world evidence (RWE) are hot topics. RWD can generate RWE that may not be obtained from typical randomized clinical trials. RWD can be especially useful for small, underrepresented populations. Electronic health records (EHRs) are a rich resource for exploring comparative effectiveness, pharmacoepidemiology, pharmacogenomics, and postmarketing pharmacokinetics and pharmacodynamics for various populations, including special populations. Accurate medication data is critical, and a wide spectrum of granularity is necessary in dosing information depending on study aim. We will discuss using EHRs and key challenges, overcoming these challenges, and achieving common goals.
Tuesday, Nov. 5 10:00 am – 10:30 am
How to Expedite Pediatric Drug Development in Inflammatory Bowel Disease
Tuesday, Nov. 5 10:30 am – 11:00 am
LESSONS LEARNED FROM REGULATORY INTERACTIONS IN CLINICAL PHARMACOLOGY FOR INNOVATIVE NEW CHEMICAL ENTITIES, COMPLEX GENERICS, AND BIOSIMILARS
Prologue: Lessons Learned in Biotherapeutics Development
Wednesday, Nov. 6 8:30 am – 9:00 am
Industry Learnings on the Impact of Prognostic Factors on Time-Dependent PK and Exposure-Response Analyses in Oncology
Prognostic factors can pose challenges to clinical pharmacology analyses. Particularly in oncology, prognostic factors can profoundly influence drug disposition and exposure-response relationships. Patients’ health status can impact the pharmacokinetics (PK) of drugs resulting in a complex time-dependent PK phenomenon. An imbalance in prognostic factors when subset by exposure may lead to false conclusions about the exposure-response relationships. This presentation will discuss mitigation strategies to overcome the confounding effects of prognostic factors in clinical pharmacology assessments.
Wednesday, Nov. 6 9:00 am – 9:30 am
Considerations for Exposure-Response Analyses in Biotherapeutics Development
Wednesday, Nov. 6 9:30 am – 10:00 am
Novel Approaches on Minimizing Residual Uncertainty in Biosimilar Product Development
Wednesday, Nov. 6 10:00 am – 10:30 am
Challenges and Opportunities in Development of Subcutaneously Administered Biotherapeutics
Subcutaneous administration is a safe and efficacious dosing alternative to intravenous administration of biotherapeutics. The presentation will detail developing subcutaneous dosing alternatives for monoclonal antibodies in oncology. Specific focus will be on generic clinical bridging principles that can be applied across different molecules, including dose finding and confirmation and noninferiority studies. Attendees will learn about changing from a body-weight-adjusted to a fixed dosing regimen and the role of modeling and simulation in dose selection based on an ongoing data assessment and adaptive trial designs. Drug delivery technologies for high volume subcutaneous injections will be introduced.
Wednesday, Nov. 6 10:30 am – 11:00 am
Panel Discussion: Clinical Pharmacology
Wednesday, Nov. 6 4:00 pm – 5:00 pm
CHEMICAL
ROLE OF MODELING AND SIMULATION IN DOSE AND DOSING REGIMEN SELECTION
Prologue: Dosing in an Era of Personalized Medicine
Monday, Nov. 4 8:30 am – 9:00 am
QSP: How to Avoid “Going Up The Down Staircase”
Monday, Nov. 4 9:00 am – 9:30 am
Different Perspectives: Informing Drug Development Decision Making through Complementary M&S Approaches
Applications of modeling and simulation (M&S) methodologies in pharmaceutical development have evolved considerably. However, opportunity remains to further improve the predictability of these approaches and consider alternative strategies for their application in addressing specific drug development challenges. Application of more than one complementary M&S methodology could be beneficial in assessing and reducing prediction uncertainty in dose determination and in improved decision making. A brief overview of model-informed dose selection methodologies will be presented. Case studies illustrating the use of two complementary M&S methods in addressing a specific clinical development program question will be discussed.
Monday, Nov. 4 9:30 am – 10:00 am
Challenges of Time-Varying Exposure in Oncology Exposure-Response Analysis and Solutions to Overcome It: A Case Study of Ceritinib in NSCLC
Exposure-response (E-R) analysis has been well recognized and frequently used to support regulatory approval. The quantitative relationship between drug exposure and response with regard to efficacy and safety is critical in justifying or confirming a dosing regimen in the context of the overall risk/benefit balance. Frequently, oncology E-R analyses were conducted using time-independent models. These models use a summary-level exposure measure such as average trough concentration without accounting for the time-varying exposure due to dose modifications. In this program, a more appropriate E-R analysis approach will be presented, one which takes into consideration the entire concentration-time profile of the drug.
Monday, Nov. 4 10:00 am – 10:30 am
Machine-Learning and Network Pharmacology Modeling of Chemotherapy-Induced Peripheral Neuropathy
Monday, Nov. 4 10:30 am – 11:00 am
CLINICAL PHARMACOLOGY PATHS FOR SMALL POPULATIONS
Prologue: Applications of Non-Linear Mixed Effect Models to Define Systems: Shifting Focus away from Single Drug
The ability to predict comes from understanding trends and patterns. The ability to discern trends and patterns relies on separation between “noise” (uncertainty) and “signal” (variation due to a covariate). While “top-down” data analysis and “bottom-up” projections have had their own camps in modeling and simulation, these two seemingly different philosophies are complementary to each other. Expect an overview of the data analysis needed for reverse translation to obtain system parameters. These often combine in vitro in vivo extrapolation with classical data analysis (e.g., nonlinear mixed effect, epidemiological).
Tuesday, Nov. 5 8:30 am – 9:00 am
Reverse Translational Assessment of CYP450- and OATP-Mediated Clearance in Chronic Kidney Disease: From Clinical Data to PBPK Modeling
Chronic kidney disease (CKD) is becoming a global health burden. Altered drug exposure, efficacy, or toxicity can result from disturbances in renal function, particularly for drugs that are primarily renally eliminated, but may also impact drugs in which hepatic clearance is dominant. The mechanistic aspects resulting in the altered hepatic clearance are not fully understood. The presentation describes using cohorts of clinical studies, focusing on CYP450s and OATPs in healthy and differing severity CKD patients, to provide general rules on the need to conduct clinical studies for nonrenally eliminated drugs.
Tuesday, Nov. 5 9:00 am – 9:30 am
Reverse Translation for UGTS: Leveraging Clinical Data to Obtain UGT-Mediated Intrinsic Clearances for IVIVE-PBPK
This presentation focuses on estimating intrinsic clearances per picomole of UGT enzyme from clinical pharmacology data. The method uses parameters such as CLpo, fraction of drug metabolized (fm), and fraction of drug escaping gut metabolism (Fg), for compounds where clearance is at least in part UGT-mediated. An RT infrastructure is proposed to enable determining intrinsic clearances per picomole of enzyme. Integration of the clinically derived parameters alongside system parameters such as liver, kidney, and gut UGT abundances; organ volumes; and their blood flows can help define UGT CLint in different populations.
Tuesday, Nov. 5 9:30 am – 10:00 am
Assessing the Impact of Birth and Maturation on Renal Function and Drug Metabolism
The use of drug clearance as the link between drug concentration and elimination rate can describe both renal excretion and drug metabolism. During gestation and for around two years after birth, both renal and organ function undergo a combined process of growth and maturation. At the time of birth, there are major changes affecting organ function that also affect drug clearance processes. Empirical functions describing maturation and postnatal changes in clearance indicate that postnatal changes are transient and relatively small in relation to the overall changes due to maturation.
Tuesday, Nov. 5 10:00 am – 10:30 am
Understanding Inflammatory Disease-Mediated Drug Interactions in Cancer Patients
Tuesday, Nov. 5 10:30 am – 11:00 am
LESSONS LEARNED FROM REGULATORY INTERACTIONS IN CLINICAL PHARMACOLOGY FOR INNOVATIVE NEW CHEMICAL ENTITIES, COMPLEX GENERICS, AND BIOSIMILARS
Prologue: The Regulatory Impact of PBPK Modelling and How We Got There
Wednesday, Nov. 6 8:30 am – 9:00 am
Practical Challenges in Conducting Quantitative DDI Analysis for Regulatory Interactions: Case Examples
Recently the Food and Drug Administration and European Medicines Agency have issued draft physiologically based pharmacokinetic (PBPK) guidances. Applications of PBPK modeling range from early compound selection for first-in-human trials to dosing recommendations in product labeling. Drug-drug interaction (DDI) represents one of the major factors to be evaluated. PBPK models provide a powerful platform to predict DDI risks as it integrates drug and system data together with extrinsic factors. The session will cover the hurdles faced in implementing and conducting PBPK modeling and simulation analyses and applications in drug development. Successful case examples include Olaparib, Osimertinib, and Naloxegol.
Wednesday, Nov. 6 9:00 am – 9:30 am
Regulatory Interactions on PPBK Modelling: A Case of PPIs Not DDIs
Wednesday, Nov. 6 9:30 am – 10:00 am
Application of PBPK Modeling in Regulatory Submission: FDA Experience
Wednesday, Nov. 6 10:00 am – 10:30 am
Application of PBPK Modeling in Regulatory Submission: EMA Experience
Learn how the European Medicines Agency is assessing physiologically based pharmacokinetic (PBPK) modeling for drug products applications and line extensions. Hear about real life examples when PBPK modelling has been successful and not.
Wednesday, Nov. 6 10:30 am – 11:00 am
BIOMOLECULAR
INNOVATION IN CONVENTIONAL MANUFACTURING TECHNOLOGIES
Prologue: Manufacturing and Bioprocessing
Monday, Nov. 4 8:30 am – 9:00 am
Biologic Manufacturing from Concept to Fill-Finish Operations
Monday, Nov. 4 9:00 am – 9:30 am
Facility of the Future: Aseptic Smart, Modular, Robotic Filling Isolator and Its Potential Applications
Monday, Nov. 4 9:30 am – 10:00 am
Data Analytics Transformation in Manufacturing
Monday, Nov. 4 10:00 am – 10:30 am
Innovation In Filter Validation and Technology Transfer
Monday, Nov. 4 10:30 am – 11:00 am
CONTINUOUS PROCESSING IN SYNTHETIC AND BIOLOGICS MANUFACTURING
Prologue: Advances in Continuous Processing for Biologics Manufacturing
Tuesday, Nov. 5 8:30 am – 9:00 am
A Continuous and Controlled Pharmaceutical Freeze-Drying Technology for Unit Doses
Driven by growing needs in the biopharmaceutical market and regulatory pressure, a continuous and controlled freeze-drying technology for unit doses to preserve biopharmaceuticals has been developed. This technology offers clear advantages over current batch production, such as cost reduction (up to 50%), track-and-trace product quality control at unit dose level, a significant reduction of processing time, reduced need for a clean room, and a substantial sustainability gain. Feasibility studies and results using continuous freeze-drying prototypes will be shown. For freeze drying, unique PAT opportunities for control will be demonstrated.
Tuesday, Nov. 5 9:00 am – 9:30 am
Perfusion-Based Continuous Manufacturing for Biologics
Tuesday, Nov. 5 9:30 am – 10:00 am
Next Generation Continuous Manufacturing at Amgen
Tuesday, Nov. 5 10:00 am – 10:30 am
Intensifying the Viral Vector Manufacturing Process: The Role of Continuous Technologies
Current manufacturing processes for gene therapies have often been developed with limited scalability in mind, and large shifts in technology have to take place to enable industrialization. Application of continuous bioprocessing is in its infancy in the field of biologics and to date has only been applied to the field of monoclonal antibodies. It has the potential to significantly improve the economics of making biologics. In this session, we will investigate the application of continuous technologies to the manufacture of viral vectors for gene therapy, particularly in the area of chromatography.
Tuesday, Nov. 5 10:30 am – 11:00 am
TRANSITION FROM CLINICAL TO COMMERCIAL MANUFACTURING: ENABLING SUCCESSFUL PPQS
Prologue: Manufacturing and Bioprocessing
Wednesday, Nov. 6 8:30 am – 9:00 am
CMC Challenges in Accelerated Development
Wednesday, Nov. 6 9:00 am – 9:30 am
Scale-Down Models and Predictive Tools for Robust Tech Transfer: Enabling Successful PPQs
Wednesday, Nov. 6 9:30 am – 10:00 am
Optimize Validation Using Innovative Statistical Modeling Across the Process Lifecycle
Wednesday, Nov. 6 10:00 am – 10:30 am
Enabling Successful PPQs in Contract Manufacturing Organizations (CMO) Under Expedited Timelines
Wednesday, Nov. 6 10:30 am – 11:00 am
CHEMICAL
INNOVATION IN CONVENTIONAL MANUFACTURING TECHNOLOGIES
Prologue: Manufacturing and Bioprocessing: Molecule to Product
This prologue session will highlight “Molecule to Product: Utilizing Interconnected Attributes for Understanding and Control” in conventional pharmaceutical processing and manufacturing technologies with an emphasis on powder processing and process analytical technologies.
Monday, Nov. 4 8:30 am – 9:00 am
A Modernized Approach to Wet Granulation Process Development: Applying Granule Porosity, Regime Maps and Crystal Form Understanding
Monday, Nov. 4 9:00 am – 9:30 am
Improving Powder Bed Wetting in Continuous Twin Screw Granulation via Foamed Systems
Monday, Nov. 4 9:30 am – 10:00 am
Terahertz: from Functional Coat Analysis to Prediction of Tablet CQAs
For more than a decade, GSK has used Terahertz Pulsed Imaging (TPI) in product development for products employing a functional coat and/or for troubleshooting. However, there are far fewer products with a functional coating compared to cosmetic coating, and issues with tablet coating can typically be solved through process development and application of first principles thermodynamic models. Interest in terahertz and TPI waned, until recently. External collaborations examining the application of transmission terahertz has renewed interest in the application as a process analytical technology tool for understanding tablet porosity and ultimately predicting dissolution.
Monday, Nov. 4 10:00 am – 10:30 am
PAT Applications for Freeze Drying System Monitoring and Health Management
Although a number of process analytical technologies (PAT) are currently available for lab scale freeze drying cycle monitoring, there are many restrictions in the implementation. Further, not many of these PAT tools can effectively monitor all the stages of a freeze drying cycle. This session will discuss two approaches to monitor pharmaceutical freeze drying: product/process characterization with the help of mass spectrometers, and process/equipment monitoring with a data analytics sensor framework.
Monday, Nov. 4 10:30 am – 11:00 am
CONTINUOUS PROCESSING IN SYNTHETIC AND BIOLOGICS MANUFACTURING
Prologue: Manufacturing and Bioprocessing: Continuous Manufacturing
Continuous manufacturing (CM) is playing an increasingly important role in pharmaceutical manufacturing. This symposium will provide an updated discussion on CM, including an overview of the state of the field highlighting where we are now and the gaps that need to be filled for broad adoption of CM in pharmaceutical manufacturing.
Tuesday, Nov. 5 8:30 am – 9:00 am
A Fearless Approach to CM
Tuesday, Nov. 5 9:00 am – 9:30 am
Excipient Engineering and Design to Enable CM
This presentation will cover the latest advances in commercially available excipients designed for continuous manufacturing (CM). Multiple case studies will be used to demonstrate the ideation, design, engineering, and testing of excipients that enable oral solid dosage form CM. Specific examples will include the design of novel excipients optimized for continuous direct compression, granulation, extrusion, and coating. Pharmaceutical formulation scientists, materials engineers, process engineers, and strategists with interest in CM will be able to use this presentation as a guide for how to select and evaluate excipients for CM.
Tuesday, Nov. 5 9:30 am – 10:00 am
Agile PAT Development for CM of DP
In early development, the benefits of agile/lean process analytical technology (PAT) approaches have improved process understanding and prepared its readiness for good manufacturing practice decision making. In late stage, the value of PAT is manifested on its critical roles in the control strategy to assure product quality. The presentation will survey the industry on what roles PAT methods played in the control strategy, discussing the comprehensive considerations and challenges from technical, regulatory, and quality aspects.
Tuesday, Nov. 5 10:00 am – 10:30 am
Strategies to Maintain Drug Stability During Twin Screw Melt Granulation
Tuesday, Nov. 5 10:30 am – 11:00 am
TRANSITION FROM CLINICAL TO COMMERCIAL MANUFACTURING: ENABLING SUCCESSFUL PPQs
Prologue: Manufacturing and Bioprocessing
Wednesday, Nov. 6 8:30 am – 9:00 am
Right-Sized Sampling and Statistics For PPQ
Wednesday, Nov. 6 9:00 am – 9:30 am
Biotech’s Innovative Approaches to PPQ In a Competitive Market with Aggressive Timelines
Wednesday, Nov. 6 9:30 am – 10:00 am
Process Validation for CM: Past, Present and Future
Wednesday, Nov. 6 10:00 am – 10:30 am
Continuous Process Verification of a Continuous Tablet Manufacturing Process
Wednesday, Nov. 6 10:30 am – 11:00 am
BIOMOLECULAR
FORMULATION DEVELOPMENT: NEW CHALLENGES, APPROACHES, AND SOLUTIONS
Prologue: Advanced Therapy Medicinal Products: How Advanced Are They Really?
This session will introduce advanced therapy medicinal products (ATMPs), or cell and gene therapy products. It will highlight differences between ATMPs and classical biopharmaceuticals, and discuss issues related to their production, formulation, characterization, immunogenicity, storage, and handling.
Monday, Nov. 4 8:30 am – 9:00 am
Industry Perspective on Gene Therapy Development
Monday, Nov. 4 9:00 am – 9:30 am
What’s Different about Potency Assays for Cell and Gene Therapy?
Monday, Nov. 4 9:30 am – 10:00 am
Formulation of Cell and Gene Therapy Products: Current Status and Challenges Ahead
The formulation of cell and gene therapy products poses major challenges due to their complexity, heterogeneity, interaction with their environment, and susceptibility to degradation. These challenges can be quality, safety, and efficacy related. This presentation will discuss the current status in formulation strategies of these complex biologicals and highlight the advantages and disadvantages. Analytical tools for the characterization and stability of cell and gene therapy product formulations and unmet needs in cell and gene product formulations will also be highlighted.
Monday, Nov. 4 10:00 am – 10:30 am
Immunogenicity Risk of ATMPs
Monday, Nov. 4 10:30 – 11:00 am
NOVEL ANALYTICAL METHODS FOR CHARACTERIZATION AND LIFECYCLE MANAGEMENT
Prologue: Analytical Methods for Characterization: Current Status
Tuesday, Nov. 5 8:30 am – 9:00 am
Molecular Determinants of Monoclonal Antibodies with Drug-Like Biophysical Properties
Tuesday, Nov. 5 9:00 am – 9:30 am
A Multi-Company Assessment of Submicron Particle Levels in Biotechnology-Derived Protein Products
One of the major product quality challenges for injectable biologics is controlling the amount of protein aggregates and particles present in the final drug product. A cross-industry collaboration was undertaken through the International Consortium for Innovation and Quality to address some of the analytical gaps in measuring submicron particles (SMP), developing best practices, and surveying the concentration of these particles present in 52 unique clinical and commercial protein therapeutics covering 62 dosage forms. Two emerging SMP characterization techniques, nanoparticle tracking analysis and resonant mass measurement, were used. The results from this study will be discussed.
Tuesday, Nov. 5 9:30 am – 10:00 am
Don’t Cook Your Protein: Rational Choice of Stress Conditions
Accelerated stability is a widely used and valuable tool in formulation/analytical/process development of protein-based drug candidates. Due to time pressure, researchers often attempt to super-accelerate the procedure by putting exaggerated stress on protein formulations. Such approaches tend to result in denatured/degraded states of protein that are seldom relevant to predicting pharmaceutical stability and degradation routes. This session will discuss best practices of accelerated stability approaches in various modules of biologics development and science-based selection approaches for accelerated conditions. Case studies will be included in discussions.
Tuesday, Nov. 5 10:00 am – 10:30 am
Panel Discussion: Forced Degradation Studies
This panel discussion will include current opinions in biopharmaceutical industry regarding purpose, design, assumptions, and caveats in forced degradation (FD) studies. Best practices in temperature, pH, and other stress conditions used in protein therapeutics will be in the scope of discussion, keeping in mind that the purpose of the FD studies (analytical method development/validation, formulation development, process development/characterization, long-term stability, etc.) will also dictate the FD study design. Recent examples from various laboratories will be cited to support the best practices.
Tuesday, Nov. 5 10:30 am – 11:00 am
ADVANCES IN DRUG DELIVERY AND DEVICE TECHNOLOGIES
Prologue: Drug Delivery Systems and Devices: How Far Have We Come?
Wednesday, Nov. 6 8:30 am – 9:00 am
Innovative Development for Oral Formulation of Biologics with Great Bioavailability
Oral dosing of biologics is one of the major challenges in biopharmaceutical development. In this presentation, the results of three preclinical studies with a new oral delivery approach that overcomes these hurdles will be demonstrated. The formulation utilizes existing manufacturing technologies and various generally recognized as safe excipients to obtain formulated monoclonal antibodies that are delivered to the gastrointestinal tract in a capsule and subsequently taken up into circulation for systemic availability.
Wednesday, Nov. 6 9:00 am – 9:30 am
Beyond ITV Bolus: Long Acting Delivery Systems for Retinal Disease
Wednesday, Nov. 6 9:30 am – 10:00 am
Smart Delivery Systems: Challenges and Opportunities
Wednesday, Nov. 6 10:00 am – 10:30 am
Biologic Drug Product Challenges with Closed System Transfer Devices
Closed system transfer devices (CSTDs), when appropriately designed and used, are meant to offer enhanced protection to health care personnel against occupational exposure of harmful drugs during clinical preparation and administration. Although there has been much focus on CSTDs in the context of drug containment and safety, there has not been much discussion on the compatibility of these devices with biological drug products. This presentation will address the complex challenges associated with using CSTDs from a drug product perspective, including biologic compatibility and hold-up volume concerns.
Wednesday, Nov. 6 10:30 am – 11:00 am
CHEMICAL
FORMULATION DEVELOPMENT: NEW CHALLENGES, APPROACHES, AND SOLUTIONS
Prologue: Beyond the Pills: A Blueprint for Designing Complex Small Molecule Formulations of the Future
This session will share perspectives and an outlook on the future of small molecule pharmaceutical development. It will focus on new and emerging modalities to deliver complex drug formulations and how advanced analytical characterization techniques complement the formulator in this endeavor.
Monday, Nov. 4 8:30 am – 9:00 am
Characterizing the Phase Behavior of Solubility Enhancing Formulations Using Orthogonal Analytical Approaches
Monday, Nov. 4 9:00 am – 9:30 am
Advanced Solid-State NMR Investigation of Molecular Miscibility, Homogeneity, and Interaction in Pharmaceutical Dispersions
The complexity of modern therapeutic modalities and amorphous solid dispersions challenges solid-state analysis and pushes the boundary for investigating physiochemical properties at a higher resolution. This presentation will provide advanced solid-state nuclear magnetic resonance (NMR) spectroscopic techniques, for the first time, to probe the intermolecular interaction of amorphous drug substances and polymeric additives at angstrom (Å) level. Specifically, we will introduce a novel technique, spin diffusion NMR, for quantifying drug-polymer miscibility and homogeneity in pharmaceutical dispersions at sub-100 nm resolution.
Monday, Nov. 4 9:30 am – 10:00 am
The Similarity Question for Non-Biological Complex Drugs; Advances in Characterization, Regulation, and Global Harmonization
What is the current state of the debate on nonbiological complex drug products? This presentation will reflect ongoing discussions around the challenges in demonstrating therapeutic equivalence of complex drug products, including nanosimilars and complex generics. Case studies will highlight the different approaches taken around the world by developers and regulatory authorities. After indicating outstanding issues, this presentation will conclude with recommendations for advancing the science-based discussions on an international level.
Monday, Nov. 4 10:00 am – 10:30 am
Nano-Templated Hydrogels as an Effective and Scalable Oral Dosage Form
Recent estimates suggest that up to 75% of new chemical entities are poorly soluble compounds. Achieving sufficient bioavailability via the preferred oral delivery route with these types of molecules places a significant burden on effective formulation design. Here, we discuss hydrogels modified with hydrophobic domains (or “nano-templated hydrogels”) as a novel oral dosage form capable of overcoming current formulations challenges facing poorly soluble compounds. Nano-templated hydrogels simultaneously transform the molecule into nanocrystals and encapsulate them in a customizable, preformed semi-solid gel.
Monday, Nov. 4 10:30 am – 11:00 am
NOVEL ANALYTICAL METHODS FOR CHARACTERIZATION AND LIFECYCLE MANAGEMENT
Prologue: Novel Analytical Methods for Characterization and Lifecycle Management
Tuesday, Nov. 5 8:30 am – 9:00 am
Development of Accelerated API Release and Polymer Degradation Methods
Tuesday, Nov. 5 9:00 am – 9:30 am
Risk Assessment of Drug Recrystallization in Transdermal Delivery System
Drug-in-adhesive transdermal delivery systems (TDS) are designed to provide a controlled rate of drug delivery across human skin to elicit a desired pharmacologic effect. The standard formulation strategy helps minimize the surface area of the TDS, but it increases the risk of drug recrystallization over the product life cycle and shelf life. This presentation will focus on understanding the effects of drug recrystallization on drug release and permeation kinetics, as well as TDS physical characteristics. The regulatory considerations for assessing and mitigating the risk of drug recrystallization in TDS will also be discussed.
Tuesday, Nov. 5 9:30 am – 10:00 am
3D Drug Micro-Imaging for Microstructure Characterization and Release Prediction
Tuesday, Nov. 5 10:00 am – 10:30 am
Technology and Software Considerations to Enable Analytical Procedure Lifecycle Management
Analytical methods developed based on the quality-by-design (QbD) concept provide better method performance and enhanced method understanding, which leads to fewer method failures and better regulatory communications. Adopting the QbD concept requires us to change the workflow on method development and characterization, and thus poses some new challenges. This presentation will use high performance liquid chromatography methods as examples to discuss the application of these tools across all stages of the analytical procedure lifecycle.
Tuesday, Nov. 5 10:30 am – 11:00 am
ADVANCES IN DRUG DELIVERY AND DEVICE TECHNOLOGIES
Prologue: Innovations that are Shaping the Future of Drug Product Science and Manufacturing
Wednesday, Nov. 6 8:30 am – 9:00 am
Oral Peptide Delivery
Wednesday, Nov. 6 9:00 am – 9:30 am
Bioresorbable Polymers: Design, Performance and Control in Drug Delivery and Medical Devices
This presentation will provide scientists and technical strategists with a detailed overview of the chemistry controls that exist within bioresorbable polymers (BRPs) and demonstrate how theoretical chemistry is coupled with advanced formulation knowledge in several different formulation formats. This presentation will also provide an overview of processing strategies and emerging techniques in materials chemistry. Lastly, this presentation will explore some medical device applications and exciting processing technologies for BRPs in the development of cardiovascular stents and regenerative scaffolds that have potential for implementation in the pharmaceutical industry.
Wednesday, Nov. 6 9:30 am – 10:00 am
Optimized Dosage Form for Personalized Medication: The Clinical Perspective
The routine manufacturing of oral dosage forms as tablets and capsules is outdated and does not provide dosage flexibility for children, swallowability for approximately 50% of the U.S. population, or taste masking. At-home reformulation of these dosage forms is a common practice, despite resultant lack of dosing accuracy and potential caregiver contact with toxins and teratogens. Newer technologies such as 3D printing and manufacture of minitablets, to allow dose optimization, exist and should be more widely applied to enable dose accuracy and patient compliance.
Wednesday, Nov. 6 10:00 am – 10:30 am
3D Printing to Engineer Personalized Medicines
Wednesday, Nov. 6 10:30 am – 11:00 am
Keynote Sessions
Keynote sessions take place at 1:30 pm.
Monday, November 4
Weida Tong, Ph.D. (U.S. Food and Drug Administration)
Bridging the Gap in Reproducibility of AI
in Predictive Medicine: Lessons from
FDA Projects
Paul Moore, Ph.D. (MacroGenics)
Applying Bispecific Antibodies to Enhance Immune Responses for Therapeutic Intervention
Tuesday, November 5
Cristel Bergstrom, Pharm.D. (Uppsala University)
Fit for Purpose Models for Formulation Optimization and Performance Evaluation
in ADME
William Slikker Jr., Ph.D. (U.S. Food and Drug Administration)
Emerging Technologies for Regulatory Science: How Can FDA Help?
Wednesday, November 6
Filippos Kesisoglou, Ph.D. (Merck)
Quantitative Biopharmaceutics: Translation from Preclinical to Clinical
Paul Fielder, Ph.D. (Genentech)
Integrating Novel Predictive Approaches
to Translation
Monday, November 4
Kevin Bateman, Ph.D. (Merck)
Shaping the Future of Bioanalysis: From Innovation to Implementation
Russell Weiner, Ph.D. (Bill & Melinda Gates Medical Research Institute)
The Challenges of Conducting Infectious Disease Clinical Trials in Low Income Countries: The Reality of Bioassays that Can Work under a Tree
Tuesday, November 5
Lara Mangravite, Ph.D. (Sage Bionetworks)
Open Science in Medicine: From Ideology to Methodology
John Wagner, M.D., Ph.D. (Takeda Pharmaceuticals)
Precision Medicine: Hype and Reality, from Biomarkers to Wearables
Wednesday, November 6
Chris Leptak, M.D., Ph.D. (U.S. Food and Drug Administration)
Regulatory Perspective on Biomarker Qualification and Impact on Drug Development
Monday, November 5
Mats Karlsson, Pharm.D. (Uppsala University)
Role of Modeling and Simulation in Dose and Dosing Regimen Selection and Optimization
Tuesday, November 5
Dan Howard, Ph.D. (Novartis)
Clinical Pharmacology Paths for Small Populations
John Davis, Ph.D. (Regeneron)
From Big to Small: Clinical Pharmacology Challenges and Opportunities, Particularly in Rare Diseases
Wednesday, November 6
Shiew-Mei Huang, Ph.D. (U.S. Food and Drug Administration)
Regulatory Perspectives on Clinical Pharmacology Strategy for Development of New Chemical Entities
Yow-Ming Wang, Ph.D. (U.S. Food and Drug Administration)
Regulatory Perspectives on Clinical Pharmacology Strategy for Development
of Biosimilars
Monday, November 4
Thomas De Beer, Ph.D. (Ghent University)
Model-Based Formulation and Process Development and Design for Innovative Drug Product Manufacturing
2:30 pm – 3:00 pm
Continued Conversation on
Model-Based Formulation and Process Development and Design for Innovative Drug Product Manufacturing
Sponsored by
Peter Marks, M.D., Ph.D. (U.S. Food and Drug Administration)
A Holistic Approach to the Advancement of Cellular and Gene Therapies
Tuesday, November 5
Thomas O’Connor, Ph.D. (U.S. Food and Drug Administration)
FDA’s Continuous Manufacturing Journey: Past, Present, and Future
Rohini Deshpande, Ph.D. (Amgen)
Next Generation Biomanufacturing: A Journey
Wednesday, November 6
Christina Capacci-Daniel, Ph.D. (U.S. Food and Drug Administration)
Process Validation Opportunities:
A Regulatory Perspective
Shishir Gadam, Ph.D. (Juno Therapeutics)
Reimagining Manufacturing Process Control and Validation for Cell and Gene Therapy; New Frontier in Personalized Medicines
Monday, November 4
Lawrence X. Yu, Ph.D. (U.S. Food and Drug Administration)
Pharmaceutical Product Development: Evolving Regulatory Landscape
Hanns-Christian Mahler, Ph.D. (Lonza)
Formulating Biologics: Quo vadis?
2:30 pm – 3:00 pm
Continued Conversation on
Formulating Biologics—Quo vadis?
Sponsored by
Tuesday, November 5
Justin Hanes, Ph.D. (Johns Hopkins Medicine)
Noninvasive Drug and Gene Delivery to the Brain
John Stults, Ph.D. (Genentech)
Knowledge-Based Strategy to Establish Clinically Relevant Initial Commercial Specifications When Few Clinical Lots
Are Available
Wednesday, November 6
Craig McKelvey, Ph.D. Ch.E. (Merck)
What Enabling a Revolution in Hepatitis C Virus Treatment Can Teach Us about Solid Solutions
Darrell J. Irvine, Ph.D. (Massachusetts Institute of Technology)
Engineering Immunity in Cancer and Infectious Disease through Formulation Design
END-TO-END HOT TOPIC SESSIONS
Monday, November 4, 2019
Mechanism of Action and Target Selection for Antisense Oligonucleotide Therapies
9:00 am – 9:30 am
Antisense oligonucleotides (AONs) are chemically modified single-stranded DNA molecules, typically 14 to 20 nucleotides in length, developed for therapeutic use. To date, five AONs have been approved for treatment, and there are currently more than 30 AONs in active clinical development around the world. AONs are designed to bind to an RNA target of interest and modulate its function. AON mechanisms of action include eliciting ribonuclease H-mediated cleavage of the RNA, interfering with splicing during processing of the RNA from primary to mature transcript, sequestering of small noncoding microRNAs, and modulation of protein translation rates by blocking regulatory sequence elements in the mRNA. Developments in AON mechanisms of action go hand-in-hand with research on how to disrupt normal RNA function, or correct RNA dysfunction, to modulate disease progression. That is, exploring how an RNA of interest is causatively linked to disease, as well as how to engineer AONs with a mechanism of action able to affect this target-to-disease link, are activities that are often considered in parallel when evaluating new RNA targets for AON drug discovery. This presentation will give current status in the field with examples from our own work, and outline possible future developments.
Nonclinical ADME and Translational PK/PD in Antisense Oligonucleotide (ASO) Drug Development
9:30 am – 10:00 am
This presentation will review the basic ADME/PK/PD profiles and properties of ASOs in nonclinical species and provide a comparison of the same across species. The session will also highlight the evolution of ASOs as a platform and some recent breakthroughs in target tissue delivery that have transformed the platform. Different methods for the nonclinical to clinical translation of ASOs such as allometry and PK/PD modeling will also be discussed. A case study briefly explaining the translational approaches from nonclinical species to first-in-human dose selection and studies will also be presented.
ADME and PK Properties of Galnac-Conjugated siRNAs in Nonclinical Species
10:00 am – 10:30 am
The presentation will highlight the unique preclinical ADME and pharmacokinetic properties of GalNAc-siRNAs. In addition, radiolabeled quantitative whole-body autoradiography and metabolite profiling data will be included to provide a quantitative illustration of in vivo disposition of GalNAc-siRNAs in preclinical animal species. Comprehensive in vitro drug-drug interaction involving drug metabolizing enzymes (CYPs) and transporters will be summarized.
QSP Model for a Messenger RNA Therapy
10:30 am – 11:00 am
Monday, November 4, 2019
Early Bioanalytical and Pk/Pd Support of Oligonucleotide Discovery Programs
3:00 pm – 3:30 pm
Bioanalytical Considerations in Support of a Gene Therapy Product From Discovery to Clinical: A Case Study
3:30 pm – 4:00 pm
Pharmacokinetic and Immunogenicity Analysis of a siRNA Nanoparticle Drug Product
4:00 pm – 4:30 pm
The presentation will focus on an intravenously administered lipid nanoparticle drug product containing a small interfering ribonucleic acid (siRNA) drug substance for the treatment of liver and pulmonary fibrosis. The presentation will describe the various pharmacokinetics (PK) assays and discuss the issues of drug intactness, stability, and relevance of measured analytes to drug exposure and immunogenicity assessments. Current concepts of antidrug antibody assay sensitivity and drug tolerance and related regulatory guidelines will be reexamined in the context of the various PK and immunogenicity assessments that are ongoing for this novel modality.
An RT-QPCR Assay to Detect Gene Integration Post Gene Editing
4:30 pm – 5:00 pm
Tuesday, November 5, 2019
Clinical Pharmacology of Small Interfering Ribonucleic Acid
9:00 am – 9:30 am
Antisense Oligonucleotide Drug Development: Some Lessons Learned and Progress from Clinical Pharmacology Perspectives
9:30 am – 10:00 am
Dosing Approaches for Novel Therapeutic Modalities: Nucleic Acid-Based Therapies
10:00 am – 10:30 am
Assessment of Clinical Stage Oligonucleotide: A Clinical Pharmacology Reviewer’s Perspective
10:30 am – 11:00 am
Tuesday, November 5, 2019
Regulatory Considerations for Cell and Gene Therapy Products
3:00 pm – 3:30 pm
Manufacturing Considerations for Gene Therapy Products: Case Studies
3:30 pm – 4:00 pm
Delivering RNA for Therapeutic Applications
4:00 pm – 4:30 pm
The presentation will focus on RNA-based therapeutics which are a less known modality, but one that holds significant promise in treating conditions not amenable to protein-based therapeutics. Various modes of RNA-based therapeutics will be introduced. The specific challenges for utilization of RNA-based therapeutics and the technical approaches to the delivery of these molecules will be addressed.
Advances in Gene Therapy Manufacturing
4:30 pm – 5:00 pm
Wednesday, November 6, 2019
Dosing RNA-Based Products
9:00 am – 9:30 am
The CMC Regulatory Aspects of Oligonucleotide Therapeutics
9:30 am – 10:00 am
Delivering Flexible Dosage Forms for In Vivo Gene Therapy Products
10:00 am – 10:30 am
Technical Considerations for Use of Oligonucleotide Liquid API
10:30 am – 11:00 am
Monday, November 4, 2019
Assessing Tissue-Specific Exposure with Microdialysis
9:00 am – 9:30 am
Establishing Preclinical Safety and Efficacy of Novel Ocular Delivery Systems
9:30 am – 10:00 am
Preclinical Models for Pulmonary Delivery
10:00 am – 10:30 am
Challenges and Applications in Quantitative Systems Pharmacology (QSP) for Heart Failure
10:30 am – 11:00 am
The fast-growing interest in its application to decision-making support along the pharmaceutical R&D pipeline has made quantitative systems pharmacology (QSP) one of the most important issues in drug development. And QSP will have a profound impact on human healthcare and the pharmaceutical industry in the future. Despite great promise, many obstacles prevent QSP from immediately transforming biomedical science and pharmacology. This talk will address the knowledge gaps in cellular, tissue, and biomechanical responses to drug actions.
Tuesday, November 5, 2019
Advancing Mass Spectrometric Techniques to Study the Disposition of Small Molecules in the Brain
9:00 am – 9:30 am
Bioanalysis of Small Molecule Drugs and Biotherapeutics in Tissues: Scientific Drivers, Technologies, and Challenges
9:30 am – 10:00 am
The Bioanalytical Challenges of Determining Released and Encapsulated Drug Exposures from Tumor-Targeting, Polymeric Nanoparticles
10:00 am – 10:30 am
RNAi Therapeutic Development on Liver Specific Targeting
10:30 am – 11:00 am
This presentation will focus on development of siRNA therapeutics targeting liver-specific diseases. By reduction of undesired gene expression and consequent lowering of the pathogenic protein, the disease-causing mechanism is interrupted/stopped. Alnylam has designed small interfering RNAs conjugated to a tri-GalNAc ligand that delivers drug specifically to the liver via the asialoglycoprotein receptor (ASGPR). Case studies designed to investigate how alterations of the tri-GalNAc ligand structure and ASGPR expression can affect the pharmacokinetics/pharmacodynamics of the siRNAs will be presented.
Tuesday, November 5, 2019
Current Status of Drug Delivery to Tumors: Determinants, Challenges, and Opportunities
3:00 pm — 3:30 pm
The basic determinants associated with drug delivery to a tumor will be discussed including drug characteristics, physiological factors, and drug pharmacokinetics. Methods to study drug delivery will be considered including imaging, tumor measurements, and microdialysis. Lastly, during the presentation, the unique challenges of a pediatric brain tumor will be briefly reviewed as well as opportunities to improve drug delivery to tumors.
PBPK Model-Based Drug Development to Support Formulation and Dose Regimen Selections for Cutaneous Topical Drugs
3:30 pm – 4:00 pm
The presentation will provide a short overview of skin physiology and a step-by-step process how to use in vitro and in vivo information from early development of a dermal formulation through physiologically based pharmacokinetic modeling to increase the formulation drug knowledge to support study designs and dose and dose regimens selections from nonclinical to clinical development.
Challenges in the Development of Pharmacotherapies for NAFID/NASH
4:00 pm – 4:30 pm
Drug Properties + CNS PBPK Model = Prediction of Drug PK Profiles in Multiple CNS Compartments
4:30 pm – 5:00 pm
Monday, November 4, 2019
Advanced Particle Surface Characterization for Formulation and Manufacturing of Pharmaceutical Solids
3:00 pm – 3:30 pm
Manufacturing of Drug Powders For Intranasal Delivery: Truly a Combination of Powder and Device
3:30 pm – 4:00 pm
The Design and Science of Handling Fine Powder Formulations for Large Scale Manufacturing
4:00 pm – 4:30 pm
Fine Powder Filling: The Science and the Art
4:30 pm – 5:00 pm
Monday, November 4, 2019
Targeted Ocular Drug Delivery: Leveraging the Fascinating Ocular Anatomy
9:00 am – 9:30 am
Tumor-Specific Radioactive Nanoparticles for Treating Peritoneal Metastases
9:30 am – 10:00 am
The talk will describe a radiotherapeutic nanoparticle system that predominantly accumulates in peritoneal metastatic tumors upon intraperitoneal delivery. The radiation delivered induces deep tumor penetration of the nanoparticles. The tumor-specific radiation therapy significantly improves the median survival and ascites free survival of mice with peritoneal metastases. The presentation will facilitate a discussion among the audience that would help close the gap in understanding how peritoneal tumors can be specifically targeted by intraperitoneal administration of nanotherapeutics, and how their penetration into deep tumor tissues is enhanced by radiation.
Microarray Patches for Transdermal and Intradermal Drug Delivery
10:00 am – 10:30 am
This talk seeks to change the mindset of researchers considering transdermal drug delivery. Microarray patches (microneedle arrays) can actually be formulated to deliver high drug doses across the skin. Instead of thinking about microarray patches as small postage-stamp sized squares coated with a vaccine, attendees will be shown how larger patches can now be manufactured, and if formulation design is optimized, doses of tens to hundreds of milligrams can be delivered into and across the skin. Thus, the range of types of drugs that can be delivered transdermally can be greatly expanded.
Drug, Device, and Formulation Considerations for Pulmonary Drug Delivery
10:30 am – 11:00 am
Inhalation aerosol systems are complex drug products requiring a balance between the advantages and limitations of each of the major components: the drug, formulation, and device. The balance sought for these components should optimize patient therapy taking into account diversity of patient factors such as disease, adherence, etc. This presentation will provide an introduction to these considerations for those interested in developing products for pulmonary drug delivery.
Preconference Workshops and Short Courses
All preconference workshops and short courses will be held on Sunday, November 3.
Full Day Short Course: Beyond Compliance: Essential Statistical Thinking for Business and Patient Benefit
The use of statistics in the pharmaceutical industry has rapidly increased in recent years, motivated partly by regulatory expectations and enabled by greater availability of easy-to-use statistical software. Companies that leverage sound statistical thinking and practical statistical analysis throughout the process or method lifecycle will have a competitive advantage. But, without a good understanding of how to use statistical thinking (as opposed to just statistical tools), the benefits will not be fully realized—and in fact, a misunderstanding of statistical techniques and their assumptions can lead to incorrect conclusions and decisions.
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Half Day Short Course: CMC Challenges with In-Licensed and Partnership Assets
There has been a rise in diversifying and growing R&D portfolios and pipelines through in-licensing and partnership of assets in the pharmaceutical industry. This course will discuss the challenges and best practices associated with these activities. The focus will be on considerations in aligning the in-license or partnered asset from a different company with already established standards and practices for chemistry, manufacturing, and controls submissions in the acquiring company. The evaluation of prospective in-licensing opportunities from nonclinical evaluations, and determination of bridging studies will be presented.
Half Day Short Course: Increasing Effectiveness and Drug Safety through Patient-Focused Drug Development
This workshop will address the emerging requirement to involve patients throughout the drug development process with the objective to provide a common understanding of its implementation for formulators. We will discuss the definition of patient-focused/patient-centric drug product development, the regulatory framework in the U.S. and E.U., the methodologies used to collect patient feedback including results from studies in special populations, and drug delivery technologies for patient-centric drug products.
Half Day Workshop: How To Administer? Design and Testing of Clinical Administration of Parenteral Drug Products
Biotech products are increasingly developed and used as commercial products for life-threatening indications. These products need to be administered parenterally, by infusion, or via implant. A lot of effort goes into developing and manufacturing such products related to the cell line, fermentation, purification, formulation, and filling into adequate primary packaging. This event will provide a better understanding of what is required to design, adequately test, and qualify the administration of parenteral preparations in clinical studies. The workshop will cover considerations related to physio-chemical and microbiological quality considerations for biologic drug products that relate to parenteral administration.
Half Day Short Course: Introduction to Mechanistic Modeling and Simulation In Physiologically Based Pharmacokinetic (PBPK) Modeling Programs: Industrial and Regulatory
This workshop will introduce the discipline “Mechanistic Absorption and PBPK” and discuss the specific standards these mechanistic models should meet to be fully reliable from a regulatory perspective. This workshop will serve as a bridge within DMPK; chemistry, manufacturing, and controls; and clinical pharmacology for scientists to acquire additional expertise and transition into a related yet new knowledge base and expertise.
Full Day Workshop: Advanced Drug Delivery Strategies for Nucleotide-Based Therapeutics: Addressing Intracellular Trafficking
This workshop will highlight recent progression in advanced drug delivery strategies that have driven the evolution and development of research within the field of nucleotide-based therapeutics. In addition, the workshop will start with an introduction to the cell biology and intracellular trafficking patterns that are so crucial for successful delivery of these therapies. Collectively, the workshop will provide an authoritative overview of the recent progress and unmet needs in the formulation and delivery of nucleotide-based drugs.
Full Day Short Course: Translational PKPD and First-In-Human (FIH) Studies for Novel Modalities
This short course will present a comprehensive overview of translational pharmacokinetic/pharmacodynamic (PKPD) aspects for first-in-human (FIH) study design of novel modalities and provide networking opportunities with experts in the field. The program will have two sections. In the morning, experts from industry and health authorities will share their experience and perspectives in preclinical safety assessment, translational PKPD, and strategies for selecting starting dose for FIH studies. In the afternoon, real-world case studies for different novel biologics modalities will be presented.
Full Day Workshop: Best Practices and Bioanalytical Strategies for Cell And Gene Therapies
Nearly 1,300 cell and gene therapies are currently in the preclinical space. This rapid growth has created an urgent need for industry scientists to gather and share lessons learned and approaches that are not currently covered under any regulatory guidance or industry white papers. This workshop will provide a better understanding of the key bioanalytical and biomarker strategies and best practices in support of cell and gene therapy drug development. The workshop will cover bioanalytical approaches for key endpoints, modalities, and technological platforms.
Full Day Workshop: Best Practices for the Development and Fit-For-Purpose Validation of Biomarker Methods
This workshop will bring together thought leaders in biomarker assays from the pharmaceutical sector and regulatory agencies to discuss best practices for biomarker assay development, with an emphasis on identifying the key statistic measures and assay parameters that need to be considered when developing an assay and the minimum validation requirements based on intended use. The outcome of the workshop will be a conference report followed by a white paper, which will propose recommendations for the industry and regulatory agencies.
For the complete preliminary program with details and locations, visit the PharmSci 360 app.