2021 AAPS PharmSci 360 Program Preview

The AAPS Scientific Programming Committee presents this PharmSci 360 overview.

The Six Tracks

DISCOVERY & BASIC RESEARCH	VIEW ALL
PRECLINICAL DEVELOPMENT	BIOMOLECULAR	CHEMICAL
BIOANALYTICS	BIOMOLECULAR	CHEMICAL
CLINICAL PHARMACOLOGY	BIOMOLECULAR	CHEMICAL
MANUFACTURING & ANALYTICAL CHARACTERIZATION	BIOMOLECULAR	CHEMICAL
FORMULATION & DELIVERY	BIOMOLECULAR	CHEMICAL
CAREER DEVELOPMENT	VIEW ALL

View the full program and add sessions to your schedule today!

---

IN-PERSON sessions are held October 17 through October 21, see all the sessions here!

ON DEMAND

BIG DATA AND NEUROPHARMACOLOGY: WHERE ARE WE NOW?

Hot Topic: From Big Omics Data to Drug Discovery in Alzheimer’s Disease by Intelligent Silico

With the advent of high-throughput whole-genome sequencing data, accumulating studies indicated that many fatal diseases, e.g., cancer and neurodegenerative diseases, are complex disorders driven by interactions among multi-lay- er biological pathways within a cell, multi-cell communications and systemic pathology of multiple organs and tissues. Thereafter, an effective treatment for complex disorders requires a systematic understanding of the molecule mechanism and precision therapeutics targeting multiple key compartments of disease pathology.

ENGINEERING MICOBIAL LIVING THERAPEUTICS

Hot Topic: From Metagenomes to Therapeutics: The Human Microbiome

Metagenomic analyses of the human skin demonstrate that contrasting forces of the skin’s biogeography and individuality shape the skin microbiome and its temporal dynamics. Striking changes in the skin’s microbiome are observed in skin disease and other host factors like age or immunodeficiency. Understanding the function, structure, and dynamics of the microbiome is important to design therapeutics that precisely target the pathogen of interest, yet spare the surrounding beneficial microbiota.

Hot Topic: Delivery of Genetically Engineered Microbes

Genetically engineered live biotherapeutic products (LBPs), or therapeutic microbes, are used to treat a variety of diseases through secretion or presentation of therapeutic proteins or small molecules. Here, we will discuss the oral delivery of genetically engineered microbes and approaches to evaluate the delivery of both the microbe and the proteins they secrete. We will also provide an overview of emergent strategies to control the gastrointestinal delivery of LBPs.

 

SYSTEMIC DRUG AND GENE DELIVERY - TACKLING THE CHANLLENGES HEAD-ON

Prologue: Achieving Dichotomous Goals for Drug Delivery—Challenges with Scalability and Target Specificity

Drug delivery technologies face a unique challenge of desirability to accomplish dichotomous goals, i.e., they need to be target-specific to achieve precise efficacy, and also have to be scalable to warrant commercial manufacturing. In this lecture, we will discuss these challenges and unique strategies researchers have come across to accomplish both goals simultaneously.

Symposium: Noncationic Polyphenol Nanocapsule Enables Systemic siRNA Delivery to Solid Tumors

Non-cationic soft nanocapsules encapsulating siRNA, called Nanosac, was developed for systemic delivery of siRNA to solid tumors. Circulating Nanosac recruits serum albumin and co-opts caveolae-mediated endocytosis to enter tumor cells and silence target genes. Moreover, the softness of Nanosac improves extravasation and penetration into tumors compared to its hard counterpart. These results support the utility of Nanosac in the systemic delivery of siRNA for solid tumor therapy.

Symposium: Controlled Loading of Albumin-Prodrug Conjugates for Antitumor Efficacy

We demonstrate a facile strategy to develop ex vivo, stoichiometrically controlled albumin-pro- drug conjugates that achieve stable, highly tumor-selective drug delivery for excellent antitumor efficacy in different mouse models of pancreatic cancer.

Symposium: Nanoparticle Engineering to Tackle Complex Immunological Diseases

Aberrant immune activation is prominent in human diseases and can contribute to the development of inflammatory, autoimmune, and allergic conditions for which there are limited therapeutic options available that address the underlying immune dysfunction. Within this presentation, I will highlight the advancements in nanoparticle-based strategies used by our group and the immunological basis for their abilities to modulate non-specific and antigen-specific immune responses to treat inflammation-associated diseases.

Symposium: Peptide–Nanoparticle Conjugates: A Next Generation of Diagnostic and Therapeutic Platforms?

Peptide-functionalized surfaces have been engineered for effective nano-immunotherapy and its companion diagnostic by detecting blood-circulating biomarkers, such as circulating tumor cells and tumor-derived exosomes. Our results using engineered PD-L1-binding peptides indicate their potential to be used for both therapeutic and diagnostic applications, particularly when combined with dendritic nanoparticles that maximize the binding avidities through multivalent binding effect.

Symposium: Design of Experiment (DoE)-Driven Exosomes Delivery for Pancreatic Cancer

Exosomes as a novel bio-originated drug delivery system have drawn significant attention. Thanks to multi-modal imaging which informed the design of nano carriers and facilitated better understanding of pharmacokinetic/ pharmacokinetic correlations. It is not common for academia to adopt the industrial-standard Design-of-Experiment (DoE) approach for systematic investigation of such delivery systems. This work aims to show how combining multi-modal imaging and DoE offers a rationale nanocarrier design used to validate new targets for pancreatic cancer treatment.

Keynote: Understanding of Bionanoscale Interactions as the Route to Systemic Targeted Therapeutics: Time for (Cautious) Optimism

NOVEL APPROACHES TO MANAGE IMMUNOGENICTY OF BIOTHERAPEUTICS

Prologue: Novel Approaches to Manage Immunogenicity of Biotherapeutics

This will be a prologue to introduce the topic to general audiences regarding approaches to man- aging the immunogenicity of biotherapeutics.

Keynote: Engineering Better Biologics: Does Nature Know Best?

What if tolerance is also naturally calibrated, depending on the need to drive immune response, or to reduce immunogenicity? Natural regulatory T cell epitopes (Tregitopes) have been discovered in both biologic drugs and vaccines. Our group has developed a suite of tools that can be used to engineer proteins discover and modify Tregitopes. This talk will define knowledge deficits related to regulatory T cell epitope impacts on biologics and vaccines.

Keynote: Creating Living Drugs With Synthetic Compounds

This presentation will outline the clinical need for the rational design of injectable nanodrugs that genetically program therapeutic immune cells in situ, as well as present two emerging platforms our lab has developed.

Symposium: Engineering Immunologically Stealthy Botulinum Neurotoxin Therapies via Library Design and High Throughput Screening

Botulinum neurotoxin (BoNT, aka Botox(R)) has cornered a blockbuster cosmetic market, but its potent paralytic activity has diverse and import- ant therapeutic applications beyond reducing wrinkles. Unfortunately, antidrug antibodies in patients can limit many of these therapeutic uses. We have therefore engineered BoNT light-chain variants designed to evade immune surveillance in humans. We describe here engineering of deimmunized BoNT light-chains, immunological analysis in humanized mice, and functional analysis in a murine flaccid paralysis model.

Symposium: Immunogenicity Barriers of Protein-Based Therapeutics in Clinical Developments

Symposium: Novel Oral Reverse Vaccination Strategy (NOVA) to Prevent Immunogenicity of Therapeutic Proteins

The safety and efficacy of several life-saving therapeutic proteins are compromised due to the development of unwanted immune response such as anti-drug antibody. Prevention of immunogenicity of therapeutic proteins prior to their initial use is an effective clinical option as it is a challenging task to reverse an established response. The talk will be focused on rational design and testing of a phosphatidylserine-containing nanoparticle platform for novel oral prophylactic reverse vaccination approach to prevent immunogenicity.

 

BIO MATERIAL-FOCUSED APPROACHES FOR IMMUNOMODULATION

Prologue: Biomaterials—An Immunometabolism Modulating Tool

Degradable biomaterials can release immunoactive components that can then actively modulate the function of immune cells and eventually affect disease outcomes. In this presentation I will introduce this concept and give an example of utilization of biomaterials to generate cancer immunotherapy by utilizing biomaterials.

Symposium: Next Generation miRNA Inhibition Using Short Anti-Seed-PNAs Encapsulated in PLGA-Nanoparticles

Symposium: Modular Biomaterial Systems to Target Inflammation After Spinal Cord Injury

Symposium: Immunomodulatory Biomaterials in Regenerative Medicine

Through their dynamic phenotypic changes, macrophages function as major regulators of healing. In this talk, we will focus on our work to investigate the role of macrophage phenotype in angiogenesis and wound healing, with applications in novel biomaterials design and biomarker development.

 

DEGRADER TECHNOLOGY

Symposium: Regulation of Histone Methylation with Methyl-Lysine Reader Targeted Degraders

We are currently exploring the regulation of histone 3 methylation through perturbation of the repressive and activating marks, H3K27me3 and H3K26me2, respectively. These modifications are mutually exclusive, and deregulation of the interplay between H3K27 and H3K36 methylation leads to pathological transcriptional activation or repression, in turn promoting oncogenic reprogramming. We have developed traditional small molecule chemical probes and protein degradation reagents, or PROTACs, targeting the reader domains that recognize and regulate these modifications.

Symposium: PROTAC Technology to Overcome On-Target Drug Toxicity

On-target drug toxicity is a major barrier to develop therapeutics for cancer. New technologies that can be used to overcome on-target drug toxicity are urgently needed because they can be used to rescue the therapeutic potential of previously undruggable targets. I will use Bcl-xl as an example to illustrate how the proteolysis targeting chimera technology can be used to address this challenge.

Symposium: Understanding Cellular Mechanisms of PROTACs and Molecular Glues

Targeted protein degradation is a promising new therapeutic strategy consisting of small molecules, most commonly molecular glues or Proteolysis Targeting Chimeras (PROTACs), which elicit degradation of a target protein. Significant challenges persist to characterize the cellular mechanism of action and the highly dynamic degradation responses induced by these compounds. This talk will highlight new approaches that have been utilized to advance discoveries and mechanistic understand of many key therapeutic targets and their respective degraders.

Symposium: Mapping the Degradable Kinome: A Resource for Expedited Degrader Development

Small molecules that induce protein degradation through ligase-mediated ubiquitination have shown considerable promise as a new pharmacological modality. We and others have demonstrated that efficacious degradation of kinases and other targets can be achieved in vitro and in vivo, however, many targets remain recalcitrant to degradation. In this presentation, I will discuss the use of large-scale chemical-proteomics approaches to map kinase degradability and accelerate the development of degraders as novel chemical probes for kinases.

Keynote: Building Targeted Protein Degradation Community

Targeted Protein Degradation (TPD) is a rapidly growing field within Chemical Biology, Medicinal Chemistry and Drug Discovery and Development. TPD aims to address clinically relevant target proteins by removing them from the proteome, which is fundamentally different from how most drugs directed towards inhibiting enzyme function work. Their distinct mechanism of action have made degraders of exceptional interest as new pharmacological modalities, and opens opportunities to expand the “druggable” proteome space.

 

CANCER IMMUNOTHERAPY - WHAT'S NEXT?

Prologue: Novel Biomaterials in Cancer Immunotherapy

Despite tremendous progress in cancer immunotherapy, significant obstacles still exist, and therapeutic efficacy is often unpredictable and highly variable between patients. This presentation will cover the latest biomaterial developments in facilitating cancer immunotherapy.

Symposium: Biomaterial for Immunotherapy

Symposium: Lipid Nanoparticles for Overcoming Biological Barriers to Drug Delivery

Symposium: Immortalization and Screening of Native T Cell Receptors for Anti-Cancer Function

We will discuss the development of personalized anti-cancer TCR screening platforms.

Symposium: Microbiome and Cancer Risk

Within the body, microbial cells—bacteria, viruses, fungi, etc.—outnumber human cells and are known to play both pathogenic and commensal roles. Nevertheless, the mechanistic contributions of the human microbiome to cancer risk and prognosis remain poorly characterized. In this presentation, Dr. Vogtmann will describe the current knowledge related to the association between the human microbiome and gastrointestinal cancers and will also describe methods for collecting and handling samples for future microbiome studies.

Keynote: TRAIL-Coated Leukocytes that Target Circulating Tumor Cells in Concert with Fluid Forces

Metastasis contributes to over 90% of cancer-related deaths. Many types of cancer metastasize via the bloodstream, where circulating tumor cells (CTCs) originating from the primary tumor can travel through the circulation and engraft in distant organs. In an effort to neutralize CTCs with the potential to form new tumors, a new therapeutic approach has been developed in which circulating blood cells are functionalized with TRAIL protein that will induce cancer cell death upon contact.


INNOVATIONS IN HIGH THROUGHPUT SCREENING OF THERAPEUTIC CARRIERS

Prologue: Innovations in High Throughput Screening of Therapeutic Carriers

In the prologue presentation, the frontier research in high-throughput screening technology for developing therapeutic carriers will be reviewed. The revolutionary role of utilizing high-throughput screening to illuminate the next-generation drug and drug carriers contributed from invited speakers will then be highlighted. Transforming impact of high-throughput screening technology on the pharmaceutic industry will also be discussed.

Symposium: Nanotherapeutics to Improve Precision Drug Therapeutic Index
Using high throughput methods and advanced data analytics, we developed new methods to improve drug delivery options for a large number of precision drugs.

Symposium: Gastrointestinal Biomedical Device Development for Drug Delivery and More

Dr. Traverso will review recent developments from his group in the area of biomedical device development for drug delivery via the gastrointestinal tract including the controlled release of therapeutics as well as transport of macromolecular therapeutics.

Symposium: Drug Repurposing for COVID-19 and Future Pandemics

Symposium: Developing Counter- measure by Exploring Therapeutic Options Using AI for COVID-19

Keynote: Testing Thousands of Chemically Distinct Nanoparticles In vivo Using DNA Barcodes

Here we describe DNA barcoding platforms to quantify how thousands of nanoparticles deliver nucleic acids in vivo. In addition, we describe an open-source bioinformatics pipeline to iteratively ‘evolve’ nanoparticles that target cells in vivo. Using this high throughput, iterative, in vivo approach, we have identified nanoparticles with tropism to novel cell types, in many different tissues.

Back to top

IN PERSON programming is available October 17 through October 21. Find the track sessions here or browse by biomolecular  or chemical sessions only.

ON DEMAND
BIOMOLECULAR

POTENTIAL AND PROMISE OF CYTOKINE BASED CANCER IMMUNOTHERAPY: DESIGN, DEVELOPMENT

Hot Topic: mRNA Therapeutics for Pulmonary Disease

There remains unmet need in multiple pulmonary diseases, and delivering mRNA to the lungs has potential to address a number of them. Translate Bio is discovering and developing vehicles that can be nebulized and inhaled to directly deliver mRNA to the lungs. The advancements in this work, demonstrating delivery and expression from multiple mRNAs, will be presented and discussed.

Hot Topic: Design and Preclinical Development Aspects of Cytokine- Based Therapeutics

Xencor has pioneered the creation of potency- reduced cytokine-Fc fusions to promote increased in vivo persistence and superior tolerability. Examples include potency-reduced IL15/Ra-Fc, IL2-Fc, and IL12-Fc.

Hot Topic: Clinical Development of Cytokine-Based Therapeutics

This presentation will describe the mechanism of action for bempegaldesleukin (BEMPEG), a CD122-preferential IL-2 pathway agonist as a novel therapeutic in the cancer immunity cycle.

 

MODEL-INFORMED PRECLINICAL AND TRANSLATIONAL DRUG DEVELOPMENT

Prologue: Preparing for Success: Risk Assessment and Mitigation of Immunogenicity During Developability of Biologics

Symposium: Developability Risk Assessments for Gene Therapy— Key Mitigation Strategies

The clinical implications against adeno-associated-virus (AAV)-gene therapy may lead to life-threatening adverse reactions and/or loss of efficacy. Thus, predicting factors affecting the immunogenicity of gene therapy such as pre-existing immune status of patients, immune response to capsid serotypes, transgene product, and host/process-related factors are important for managing risk associated with the safety of AAV-mediated gene therapy. Employing a predictive toolbox and/or models for assessing risk factors for better understanding of the immune responses will be discussed.

Symposium: Implementing Preclinical Predictive Assay Outputs During Candidate Optimization and Developability

The clinical development of adeno-associated-virus (AAV)-mediated gene therapies largely excludes AAV seropositive patients to avoid the impacts of pre-existing antibodies on safety and efficacy. Here we review how antibody characteristics and functions may impact the efficacy of gene therapy administration. We review literature on strategies that may enable AAV gene therapy dosing in the presence of anti-AAV antibodies and provide non-clinical data on temporary mechanical removal of


APPLICATIONS FOR PREDICTIVE AND CLINICALLY RELEVANT IN VITRO, EX-VIVO AND IN VIVO MODELS

Prologue: Subcutaneous Delivery of Protein Therapeutics

Subcutaneous (SC) delivery of protein therapeutics is an effective route of administration that is gaining increased importance because of patient and payer demands. This trend from intravenous to SC has been accelerated by COVID-19 demands for more home drug administration. This presentation will cover market trends and the scientific gaps requiring industry academia collaboration.

Symposium: Development of T cell Dependent Therapies with SC Delivery

This presentation will describe clinical pharmacology perspectives of teclistamab (BCMA and CD3 bispecific antibody) in patients with relapsed or refractory multiple myeloma.

Symposium: Different SC Devices Parameters and Designs for PK Comparability Studies

This presentation will discuss the findings from a systematic review of device parameters and design of studies bridging biologic-device combination products using prefilled syringes and autoinjectors.

Symposium: Preclinical Development of Large Molecules for SC Delivery

Non-clinical development of SC administered proteins requires an understanding of the processes during SC absorption. In the presentation an overview on the SC absorption process will be provided, including presystemic catabolism, transport in the SC extracellular matrix and lymphatic absorption. Challenges during development include the incomplete SC bioavailability and limitations in administration volumes. Optimization strategies for candidate molecules will be presented to overcome both challenges. Animal models for SC absorption will be discussed.

Keynote: Human Organs-on-Chips: From Experimental Models to Clinical Mimicry

This presentation will describe human organ- on-a-chip microfluidic cultured devices lined by living human tissues that form tissue-tissue interfaces, integrate immune cells, contain a living microbiome, and recapitulate organ-level functions for replacement of animal testing for drug development, mechanistic discovery, and personalized medicine. Organ chip models also have been used to model multiple human diseases, repurpose drugs as potential COVID-19 therapies, discover new therapeutic targets, and predict human drug pharmacokinetic parameters.

 

ANTIBODIES BY IA-PLASMAPHERESIS AND TRANSIENT ENZYMATIC DEGRADATION

Symposium: Modeling of SC Delivery
Mechanisms underlying subcutaneous absorption of protein therapeutics are not completely understood, and accurate prediction of ab- sorption of biotherapeutics in humans remains challenging. This presentation will summarize a variety of mathematical models that have been developed for describing the pharmacokinetics of therapeutic proteins administered by subcutaneous injection, including single- and dual-pathway absorption models, mechanistic models of lymphatic uptake and redistribution, and absorption of monoclonal antibodies and smaller protein drugs.

Symposium: Integrating Preclinical Immunogenicity Risk Assessments Using Predictive Models During Developability

Symposium: Model Informed Immunogenicity Risk Assessments for Combination Therapies

Keynote: Computational Systems Biology Approach for Enhancing Preclinical-to-Clinical Translation

 

DESIGN AND PRECLINICAL DEVELOPMENT OF NOVEL THERAPEUTIC MODALITIES, MOLECULES, AND DELIVERY APPROACHES

Prologue: Preclinical Development— Biomolecular

Symposium: Developing a Preclinical Bioanalytical Package for Translation of Gene Therapies to First-in-Human Clinical Studies

Symposium: Presentation Title To-Be-Determined

This presentation will discuss role of pharmacometrics in translational mRNA drug development with specific focuses on quantifying pharmacokinetics/pharmacodynamics (PK/ PD) relationships in animals and predicting responses in humans to inform selection of starting dose and dose range for first-in-human trials; predicting exposure and response in dose escalation; and understanding early PK/PD relationships in humans.

Symposium: The DMPK Perspective on Gene Therapy: What We Have Learned and What We Can Contribute

Gene therapy is a therapeutic strategy that transfers genetic materials to a patient’s cells to correct a defective gene or gene product to treat diseases. This session will focus on the adeno-associated virus (AAV)-based gene therapy and summarize the challenges and opportunities drug metabolism and pharmaco- kinetic (DMPK) scientists have encountered in gene drug discovery.

Symposium: A Quantitative Systems Pharmacology (QSP) Approach for Modeling and Prediction of Biodistribution, Transduction, and Disposition of AAV-Based Gene Therapy

Constructs in Preclinical Animal Models This presentation will describe a data-driven modeling framework that can serve as a potential platform for projecting biodistribution/ transduction, optimizing preclinical study designs, and predicting adeno-associated virus gene therapy dose-translation between species.

Keynote: Innovations in Biological Modalities—Meeting Challenges in Translation and Development to Unlock Opportunity for Patients

Back to top

CHEMICAL

MODEL-INFORMED PRECLUNICAL AND TRANSLATIONAL DRUG DEVELOPMENT

Prologue: MIDD in Preclinical Drug Development

Symposium: Challenges and Strategies to Inform Canine- Human Translational PBPK Models

This seminar will highlight factors affecting drug pharmacokinetic (PK) translation between dogs and humans. Such information is necessary for canine-human PK extrapolations and for developing predictive tools such as in silico physiologically based PK models. Our goal is to provide insights into the quality and quantity of cross species physiology information required to inform robust PK translational models, demonstrate the potential pitfalls of adopting scaling factors when generating interspecies extrapolations, and underscore remaining gaps.

Symposium: Improving Absorption Modeling for Biopharmaceutics, Pharmacometric, and Translational Pharmacokinetic Applications

Symposium: Modeling In-Vitro Assays to Improve the Robustness of Transporters’ Ki

There is a general underprediction of trans- porter Ki values, which undermines their use in physiologically based pharmacokinetic modeling to predict transporter-mediated drug-drug interactions in vivo. The session will focus on the impact of modeling in vitro assays to improve Ki estimation by better understanding the mechanisms leading to the observed in vitro results.

Symposium: Modeling Toxicology Outcomes

Keynote: How to Fulfil Requirements of FDA Guidance on Diversity of Clinical Trial Population? Perhaps by Translational Modeling

Pressure is mounting on the pharmaceutical industry from regulators, professional associations, and patient advocacy groups to introduce more diversity in clinical drug trials (e.g., FDA guidance in November 2020 on enrollment criteria for clinical trials). Practical steps on achieving this objective are under debate considering the management of risk for patient subgroups and failure to establish efficacy due to higher variability. The presentation high- lights the value of translational modeling and simulation in this respect.

 

DESIGN AND PRECLINICAL DEVELOPMENT OF NOVEL THERAPEUTIC MODALITIES, MOLECULES, AND DELIVERY APPROACHES

Prologue: New Perspectives on Proteolysis-Targeting Chimeras in Preclinical Development

Symposium: Delivering Extended Pharmacodynamic Responses with RIPK2 PROTACs

This talk will highlight our RIPK2 PROTAC program where we demonstrate in vivo degradation of RIPK2 proteins in rats at low doses and where we observe extended pharmaco- dynamics (PD) that persists in the absence of detectable PROTAC. Our findings that RIPK2 is not required to be fully degraded to completely inhibit production of inflammatory cytokines and how this works in concert with the slow synthesis rate of RIPK2 to deliver the extended PD responses will be presented.

Symposium: Discovery and Development of Bcl-xL PROTACs for Cancer Therapy

Bcl-xL plays a key role in cancer cell survival. However, development of drugs targeting Bcl-xL has been thwarted by the on-target platelet toxicity because platelets depend on Bcl-xL to maintain their viability. To circumvent this toxicity, we have applied the proteolysis targeting chimera (PROTAC) technology to design small-molecules that target Bcl-xL to E3 ligases for degradation. This presentation will discuss our effort in preclinical development of Bcl-xL PROTACs.

Symposium: Optimization of Oral PROTACs: DMPK Perspective

We will discuss some of our early observations on the pharmacokinetic properties of oral PROTACs and highlight some of the absorption, distribution, metabolism, and excretion challenges we have encountered, including the key experimental challenges we have faced and how this has defined our early screening cascade.

Symposium: Translation of Targeted Protein Degradation from In Vitro to In Vivo

The talk will review the key steps of targeted protein process from ternary complex formation to cellular degradation kinetics, and ultimately protein degradation in vivo. Case studies of translating pharmacokinetics/pharmacodynamics from preclinical to clinical will be presented.

Keynote: Nonclinical Safety Assessment for GalNAc-conjugated Antisense Oligonucleotides

The course will describe how toxicology testing strategies for antisense oligonucleotide (ASO) drugs might differ from typical small molecule development.

 

APPLICATIONS FOR PREDICTIVE AND CLINIALLY RELEVANT IN VITRO, EX-VIVO, AND IN VIVO MODELS

Prologue: Human Pharmacokinetics Prediction: Much Better, But There’s More to Do!

Symposium: Applicability of Existing Prediction Methods to Non-Oral Routes of Delivery

Physiologically based pharmacokinetics (PBPK) modeling has a great potential for predicting systemic and local drug concentrations for non-oral routes of delivery. This presentation will focus on advances made with PBPK modeling for both oral and non-oral routes for the first-in-human predictions. We will discuss the current strengths and limitations and suggested strategies for addressing these limitations.

Symposium: Effect of Plasma Protein on Clearance In-Vitro: Implications for IVIVE

Symposium: The Role of Mechanistic Pharmacokinetics in Human Dose Projection

The next frontier in absorption, distribution, metabolism, and excretion science will be predicting and validating transporter-based drug clearance and tissue drug concentrations in humans.

Keynote: Human Organs-on-Chips: From Experimental Models to Clinical Mimicry

This presentation will describe human organ-on-a-chip microfluidic cultured devices lined by living human tissues that form tissue-tissue interfaces, integrate immune cells, contain a living microbiome, and recapitulate organ-level functions for replacement of animal testing for drug development, mechanistic discovery, and personalized medicine. Organ chip models also have been used to model multiple human diseases, repurpose drugs as potential COVID-19 therapies, discover new therapeutic targets, and predict human drug pharmacokinetic parameters.

Back to top

IN-PERSON sessions are held October 17 through October 21. See all the biomolecular sessions here. And find the chemical sessions here.

ON DEMAND
BIOMOLECULAR

Hot Topic: AAPS Perspective on the New CLSI Guideline for Flow Cytometry

In 2Q2021, the first regulatory-body-endorsed guideline for flow cytometry, the CLSI guideline H62: Validation of Assays Performed by Flow Cytometry, will published. CBER and CDRH reviewed and the guideline paving the way for recognition by the Agency. It is critical that the AAPS community becomes familiar with the guideline. This hot-topic presentation will be a practicum on how to use the guideline.

Hot Topic: ddPCR Method Development and Validation for Measurement of Gene Therapy

Gene therapy has moved to the forefront of therapeutic modalities, which has led to an increase in utilizing new platforms for bioanalytical support. There is a lack of formal regulatory guidance on how to develop and validate ddPCR assays in support of gene therapy clinical trials. The presentation will cover challenges and considerations for method development and validation of ddPCR (digital droplet PCR) for measurement of gene therapy vector DNA and RNA.


BEST PRACTICES IN BIOANALYSIS

Prologue: Bioanalytical Complexities in Support of Multi-Specific Therapeutics

Symposium: ADA Characterization of Multi-Specifics

We describe the use of the PandA method that is effective in solving the interference problems caused by drug and/or target in anti-drug antibody (ADA) detection. For the first time, we adapted the PandA to perform a deeper characterization of all confirmed positive ADA samples. We outline the process using CDR-null variants of the therapeutic to determine to which domain in multi-specific therapeutics the ADAs bind. This analysis can provide evidence of ADAs with neutralizing potential.

Symposium: Bioanalytical Strategies in Support of Multi-Specific Modalities

Multi-specific therapeutics present added benefits over classical therapeutics by their ability to bind multiple targets thus offering better tissue specificity and potentially lower toxicities in addition to increasing efficacy and reducing toxicity at the same time. With all the added benefits these therapeutics offer, bioanalytical support for these development programs has become much more complicated than that of classical drugs. Case studies will be shown highlighting these bioanalytical concerns.

Symposium: Challenges of Multi-Do- mains in PK Bioanalysis

Multi-domain antibody therapeutics offer a unique strategy for disease treatment and prevention. Depending on the mechanism of action of the various domains, challenges related to target engagement, binding affinities, target expression levels, or biodistribution may influence the design of the pharmacokinetics/ pharmacodynamic (PK/PD) assay(s). The objective of this session is to understand the challenges and approaches to development, validation, and sample testing of assays for the assessment of multi-domain and bi-specific antibodies for PK analysis.

Symposium: Overcoming Interferences in ADA Assays; Even More Critical for Multi-Specific Programs

Keynote: Evolving Best Practices in Bioanalytic—A Backstreet View of the “Fit for Purpose” Picture

All good science requires that assays be fit-for-purpose. Measurement uncertainty for a reported value is a key fitness test. Data from quantitative assays are typically used to falsify a statistical hypothesis and reach a conclusion about a study. Coeffcient of variation (%) is an often used but poor metric for reporting assay precision and measurement uncertainty in bioanalytics and quality control testing. A cell therapy biomarker case study will be used to illustrate an alternative approach.

 

THE EVOLVING WORLD OF BIOANALYSIS (BM)

Prologue: Bioanalysis for Cell Based Therapies

In part due to its complexity, cell-based therapies require novel bioanalytical approaches for drug quantitation and immune response characterization. This session will highlight the unique aspects of cell therapies as compared to biologics and small molecules, and will overview the considerations for assay designs. The presenters will share their perspective and experience in immunogenicity assessment, transgene and chimeric antigen receptor (CAR) cell quantification using PCR, and flow cytometry in clinical studies

Symposium: Digital PCR Assays for Precise Quantification of CD19-CAR-T Cells

Symposium: Flow Cytometry for Cell-Based Pharmacokinetics

In this presentation, the speaker will discuss the challenges in development of flow cytometry bioanalytical methods to quantitatively measure CAR-T/NK cell levels in adoptive cell therapy; evolving best practices, including white papers and guidance documents around validation; and regulatory hurdles and perspectives.

Symposium: Immunogenicity of CAR T Cells in Cancer Therapy

Symposium: Overview of Bioanalysis Plan for Autologous and Allogenic Cell Therapies

This presentation will review key differences in autologous and allogeneic cell therapies and provide an overview of development of a product-centric biomarker strategy for autologous versus allogeneic cell therapies. It will also describe tiered approaches for bioanalytical development for both regulatory requirements and a thorough understanding of product biology. The presentation will provide an overview of various CK and immunogenicity assays and reflect upon implications of more complex CAR designs on development of appropriate bioanalytical readouts especially cellular kinetics.

Keynote: Challenges and Advances in the Modern Bioanalytical Lab: Working Across Modalities and Enabling a Quantitative Understanding of Biology

Back to top

CHEMICAL

Hot Topic: Patient Centric Sampling: Future Standard or Too Much Complexity?

Perspectives on the FDA Bioanalytical Methods Template Guidance
Guidance on bioanalytical methods templates released by FDA in 2019 provided specific instructions in form of ready-to-use tables for summaries of bioanalytical methods. Experience within the bioanalytical industry in applying this guidance is still evolving. A group of bioanalytical scientists within the AAPS bioanalytical community collected comments and experience on the use of this guidance. This hot topic will present collected experience and seek additional comments or concerns from the attendees for discussion.

 

BEST PRACTICES IN BIOANALYSIS

Prologue: Bioanalysis of Non-Liquid Matrices: Science, Technology, and Assay Quality

Non-liquid matrices (NLM), such as tissues and cells, are important in understanding pharmaco- kinetics/pharmacodynamics in drug development. There are many challenges associated with the development of robust bioanalytical methods for NLM. To address the challenges and align on the best practices in the bioanalysis of NLM, a focus team was proposed within the Bioanalytical Community in 2020. This session is planned to propose the team’s recommendations on the best practices and seek input from the audience.

Symposium: Challenges and Considerations in Bioanalysis of Cells

There are many considerations and technical challenges associated with bioanalysis of cells. This presentation will highlight the Non-Liquid Matrices team’s discussions on the best practices in the method development and method application for bioanalysis of cells. These include technical considerations for sample collection and handling, sample stability, and the application of LC-MS and ligand-binding assay approaches to quantification of therapeutic agent pharmacokinetics and biomarkers in cells in support of submission.

Symposium: Challenges and Considerations in Bioanalysis of Tissue Samples

Bioanalysis in tissue extracts presents a unique set of technical challenges. This includes the diversity of the mechanical and physiochemical properties of targeted tissues, heterogeneity of the analyte distribution, and potential contamination from blood perfusion. The goal of this presentation is to summarize the Non-Liquid Matrices team’s discussions on the best practices and recommendations on this topic. It also examines other scientific and technical considerations for sample collection and handling for different analytical platform (LC-MS, LBA).

Symposium: FDA Experiences in Bioanalysis of Non-Liquid Matrices

Symposium: Fit-For-Purpose Assays for Bioanalysis of Non-Liquid Matrices

Assessment of therapeutic exposure in Regulated Laboratory non-liquid matrices (NLMs) is an important component in understanding pharmacokinetics/ pharmacodynamics and toxicological effects at the site of action. This presentation will provide AAPS Bioanalytical Community NLM sub-team recommendations on fit-for-purpose validation/ qualification of quantitative NLM assays based on their context of use. These recommendations will include parameters to be tested, respective parameter acceptance criteria, and best practices on the conduct of the proposed assessments, with supporting case study justifications.

Keynote: Opportunities for Non-liquid Matrices in Today’s Pharma

 

BEYOND THE BENCH

Prologue: Translating Data into Knowledge

Symposium: Applying Quality Risk Management Toward the Use of Cloud Data Storage Services in a Regulated Environment

Regulatory agencies are open to the various applications of cloud computing provided the sponsor has assessed risk(s). This presentation will discuss the use of Quality Risk Management (QRM) principles in conjunction with a hazard type of risk assessment associated to cloud storage of regulated data.

Symposium: Applying Machine Learning to Predict Breast Cancer Prognosis

If you are embarking on a digital transformation journey at your organization and you find that off the shelf software does not meet your needs, but a highly configured software and performance qualification e orts sound daunting, then this session is for you. Running PQ can be fairly streamlined as well as aligned with the appropriate use cases and regulations. We will be sure to include tangible actions that you may utilize in your next project.

Symposium: Regulatory Challenges of Implementing AI in Drug Discovery and Development

Although the initial FDA guidance has been very restrictive in nature, the 2019 concept paper and the resulting 2021 action plan has sparked excitement by being more adoptive of broader artificial intelligence (AI) and machine learning (ML) solutions. In this session, we will discuss the lay of the land of AI/ML regulations, the struggles of bringing these types of new technologies into a regulated environment, and what you can expect from such solutions.

Keynote: Bioanalysis and Biomarker Sample Logistics Challenges in Global Studies

 

THE EVOLOVING WORLD OF BIOANALYSIS

Prologue: Foundations for Contemporary Bioanalytical Validations

Symposium: Case Studies: Fit for Purpose Validation (Dystrophin in Muscle Tissue) and Cross Validations (Affinity Capture LC-MS/MS Methods)

Symposium: Execution of a 4-Lab, 6-Method Cross-Validation to Support Regulated Bioanalysis

This presentation will evaluate the cross-validation of a single analysis, spanning two calibration ranges and six methods, across four international laboratories. Consideration will be given to best practices in evaluating and confirming “sameness” of methods.

Symposium: Global Immunogenicity Guidelines: What Does the NMPA Guideline Mean?

Symposium: Good Practices in Implementation of BMV Guidance for Regulatory Science Rapid Fire: Evaluation of Capitainer qDBS Microsampling Device for Anti- Epileptic Drug Quantitation

Keynote: Towards the Implementation of Patient Centric Blood Sampling and Analysis as a Routine: Working as a Community

Patient-centric blood sampling and analysis is an emerging approach for the quantitative determination of circulating concentrations of analytes of interest, viz. drugs, metabolites, bio- markers, clinical pathology, etc. The approach puts the needs of the patient at the center and as such facilitates studies in under-represented populations, including pediatrics, elderly, and remote communities. Furthermore, it enables the sampling to be performed in locations that are more convenient to the subject, i.e., at home.

Back to top

IN-PERSON programming is October 17 through October 21. See the clinical pharmacology sessions here, or browse by biomolecular or chemical sessions only.

On DEMAND

ROLE OF MODEL INFORMED DRUG DEVELOPMENT IN DEVELOPING VACCINES

Hot Topic: QSP Application to COVID- 19 Vaccine Clinical Development

The quantitative systems pharmacology (QSP) model for our COVID-19 vaccine was created based on the immunogenicity QSP model to ad- dress our questions on the clinical development of the COVID-19 vaccine. The phase 1 study de- sign for our COVID-19 vaccine was optimized by the vaccine QSP model, and immune response in special populations (ethnic difference, older adults, etc.) could also be predicted. The vaccine QSP model supports the acceleration of vaccine clinical development.

Hot Topic: Using Vaccine Immunostimulation/Immunodynamic Modeling Methods to Inform Vaccine Dose

Decision-Making Immunostimulation/Immunodynamic (IS/ID) modeling is a novel method that has the potential to change the way we develop vaccines. Created to address the lack of quantitative methods used in vaccine development, IS/ID borrows from pharmacometric modeling concepts to accelerate vaccine dose and regimen selection. We present here an example of IS/ID modeling in the context of tuberculosis vaccines.

CLINICAL PHARMACOLOGY CHALLENGES AND OPPORTUNITES IN RARE AND NEGLECTED DISEASES AND SPECIAL POPULATIONS

Prologue: Overcoming Challenges to Successful Rare Disease Drug Early Clinical Development- A Quantitative Pharmacology Perspective

Rare disease drug development is amongst the most challenging to drug developers and regulators. This presentation will focus on how to use state-of-the art quantitative methods to integrate knowledge of pharmacokinetics, pharmacodynamics, and disease biology to inform efficient drug discovery and development of breakthroughs that will change patients’ lives. It is intended for all clinical pharmacologists and other scientists interested in drug development in rare diseases.

Symposium: Clinical Pharmacology Considerations and Challenges in Pediatric Oncology

In this presentation, considerations and challenges in pediatric oncology drug development for small and large molecules pertinent to clinical pharmacology will be discussed. Case examples of how different strategies are used to inform pediatric dosing of investigational oncology drug products will also be highlighted.

Symposium: Developing a Robust QSP Model of AAV-Based Gene Therapy for Clinical Applications

To enable clinical trial design for adeno-associated virus gene therapy, we developed a quantitative systems pharmacology model that incorporates mechanistic steps linking viral vector distributions to transgene expressions. In this presentation, we will discuss our efforts in adjusting and calibrating the model for clinical applications, including hemophilia B and A gene therapy programs. We explored different mechanistic hypothesis to explain observed clinical data in these related but distinct rare diseases.

Symposium: Opportunities and Challenges for Physiologically Based Pharmacokinetic Models of mAbs in Pregnancy and Pediatrics

It can be difficult to perform clinical trials of new drugs in paediatric and pregnant patients. Physiologically based pharmacokinetic (PBPK) models have been used to aid study design and dose adjustments for small molecule drugs in paediatrics and pregnant women. However, published PBPK models for monoclonal antibodies (mAbs) in these populations are scarce. The advantages of using and challenges to developing PBPK models to predict mAb PK in paediatrics and pregnancy will be explored.

Symposium: Pharmacokinetics of Bamlanivimab/Etesevimab, Novel COVID-19 Neutralizing Antibodies, in Special Populations

Keynote: Drug Efficacy, Safety, and Dosing Information for All Patients Regardless of Personal Disease and Characteristic Frequency

Today, we often do not know with certainty that most new drugs are efficacious and safe and how they should be dosed in a large proportion of the patients who will use the drug. The FDA approval decision is based on a fraction of the market population. By systematically combining dosing model prediction along with real world patient evidence analysis, all patients should benefit from more informed drug therapy evidence and recommendations.

CLINICAL PHARMACOLOGY AND IMMUNOGENICITY CONSIDERATIONS OF NOVEL MODALITIES

Prologue: Opportunities for Application of Model Informed Approaches for Novel Modalities

The application of model-informed drug development for cell therapies is rapidly evolving with various modeling approaches used to characterize cellular kinetics, quantify the relationship of expansion/persistence of cells to clinical efficacy/safety outcomes, and impact of various covariates (tumor burden, biomarkers. lymphodepletion, product features, etc.). This webinar will highlight the complexity in cell therapy development, and how product and patient data can be integrated into model-in- formed drug development framework.

Symposium: Bench to Bedside Translation of CAR-T Cells Using Mechanistic Modeling

Symposium: Clinical Pharmacology of Tisagenlecleucel in Adult Relapsed/ Refractory DLBCL Patients

Symposium: Regulatory Perspective on Model-Informed Drug Development Approaches to Cell Therapies

Keynote: Clinical Pharmacology and Immunogenicity Considerations of Novel Modalities

 

CLINICAL PHARMACOLOGY CHALLENGES OF SPECIAL DELIVERY ROUTES

Prologue: Predictive or Non- Predictive, What Works for Special Delivery Routes?

This session will discuss predictive experimental models for pulmonary delivery evaluation of inhalation products.

Symposium: Impact of Subcutaneous Injection Sites on Clinical Pharmacokinetics of Biologics

The speaker will discuss clinical pharmaco- kinetic (PK) data (AUC, Cmax, and Tmax) of 19 immunoglobulin G (IgGs), 18 peptides (molecular weight < 16 kDa), 8 non-IgG proteins, and 1 oligonucleotide that had clinical PK data available from multiple subcutaneous injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides, and 3 (38%) non-IgG proteins, exhibited site-dependent PK (i.e., PK differed by injection sites).

Symposium: Modeling Simulation of Long Acting Injectables / IVIVC Challenges for LAI/LAP’s: Translational Lessons and Pitfalls

Long-acting parenteral (LAP) products are desirable for patients who need long-term therapies. Formulation development and regulatory approval of such dosage forms has proven to be laborious. In vitro-in vivo correlations (IVIVCs) are often sought to enable development and regulatory flexibility. However, compared to oral modified release formulations, IVIVC development for LAPs is more complicated. The presentation will explore the unique considerations both in clinical study designs as well as modeling strategies for LAPs.

Symposium: Ocular Drug Delivery

This talk will give background and overview about ocular drug delivery, including intravitreal injections, topical administration, and long-acting delivery. The talk will review areas of interest in the eye, how the use of aqueous humor biomarker can inform target engagement, and translational pharmacokinetic modeling.

Symposium: PK/PD Modeling of Antisense Oligonucleotides After Intrathecal Administration

Intrathecal administration has been shown as an effective route of administration for antisense oligonucleotides. The use of pharmacokinetic/ pharmacodynamic (PK/PD) modeling to describe the PK/PD in animal species using tissue concentrations with general principles for translation to humans will be presented. In addition, case studies will be discussed demonstrating challenges associated with the intrathecal route along with potential solutions.

Keynote: Pharmacokinetics and Pharmacodynamics of Non-Intravenous Delivery Routes for Biologics

Back to top

CHEMICAL

Hot Topic: Risk Factors Related to Relative Bioavailability Studies for Pediatric Products

This presentation will introduce a database containing the cases of pediatric products with reported bioinequivalence or disparities in pharmacokinetic (PK) profiles in bioequivalence and relative bioavailability studies conducted in pediatric populations to improve the understanding and identification of any common risk factors that may lead to PK differences observed.

Hot Topic: Development and Characterization of Pediatric Formulations: Industrial Challenges and Solutions

The presentation will introduce the current state of knowledge and highlight the unique challenges industry is facing in developing dosage forms for pediatric patients. This session will also focus on the unmet formulation needs highlighting how improved understanding of pediatric formulations in terms of dosage form design flexibility, limited excipient portfolio, taste masking and assessment, in-vitro product characterization techniques, and ever evolving regulatory requirements can have a direct bearing on the pediatric drug development programs.

Hot Topic: Bioequivalence Evaluation of Pediatric Products Using Physiologically Based Pharmacokinetic Modeling

Symposium: Recent Developments in Physiologically Based Pharmacokinetic (PBPK) Modeling of Transporter-Mediated Drug Disposition

Prologue: Achievements/Gaps: Where Are We with the Transporter in IVIVE- PBPK Modeling

This prologue will focus on the current scientific aspects of the use of mechanistic modeling such as in-vivo-in-vitro extrapolation–physiologically based pharmacokinetic (PBPK) modeling in the prediction and evaluation of transporter-mediated drug-drug interactions and organ concentrations. Transporter expression and activities may change by age, sex, race, disease status, comorbidity, and polypharmacy. Current matrix approaches, achievements, and gaps will be reviewed. The presentation will highlight impact in drug labels, but also list what is needed for further qualification of transporter PBPK models.

Symposium: Application of PBPK Modeling on Transport DDI—Clinical Pharmacology Perspective

Symposium: Past and Future of PBPK for Predicting DDI

Membrane transporters are one of the determinants for pharmacokinetic (PK) drug-drug interactions (DDIs). In past decades, significant progress has been made in developing various tools to predict transporter mediated DDIs (tDDIs). However, the predictive performance of physiologically based PK (PBPK) models for tDDI has not been well established. This presentation will provide an overview on the past and current states of tDDI predictions using PBPK models and discuss critical challenges and future strategies to improve tDDI prediction using mechanistic modeling.

Symposium: Role of Protein Mediated Uptake in In Vitro-to-In Vivo Translation of Transporters

Accurately predicting transporter-mediated hepatic clearance is crucial; however, there is often underprediction for highly protein-bound anionic transporter substrates. The idea of protein-facilitated uptake where highly bound drugs can exhibit a greater uptake with plasma than predicted from free-drug theory, has resurfaced. This talk will describe different hypotheses that have been proposed. Case examples where addition of plasma to HEK293 cells improved predictions via physiologically based pharmacokinetics will be described, and additional advances needed will be discussed.

Symposium: The Practical Use of PBPK/PD Modeling for Brain Transporters

Sufficient drug penetration across the human blood-brain barrier is the prerequisite for sustained in vivo target inhibition and efficacious treatment of central nervous system (CNS) diseases, particularly brain cancer. This presentation illustrates a framework for the development and application of mechanism-based CNS physiologically based pharmacokinetic models to guide selection of the right drug and refinement of dosing regimen for more effective treatment of brain cancer.

Keynote: An Update on the Use of Physiologically Based Pharmaco- kinetic Modeling of Transporters: Predicting DDI, Non-Linearity and Target Tissue Exposure From In Vitro to In Vivo


CLINICAL PHARMACOLOFY AND IMMUNOGENICITY CONSIDERATIONS OF NOVEL MODALITIES

Prologue: Opportunities for Application of Model Informed Approaches for Novel Modalities

The application of model-informed drug development for cell therapies is rapidly evolving with various modeling approaches used to characterize cellular kinetics, quantify the relationship of expansion/persistence of cells to clinical efficacy/safety outcomes, and impact of various covariates (tumor burden, biomarkers. lymphodepletion, product features, etc.). This webinar will highlight the complexity in cell therapy development, and how product and patient data can be integrated into model-in- formed drug development framework.

Symposium: Bench to Bedside Translation of CAR-T Cells Using Mechanistic Modeling

Symposium: Clinical Pharmacology of Tisagenlecleucel in Adult Relapsed/ Refractory DLBCL Patients

Symposium: Regulatory Perspective on Model-Informed Drug Develop- ment Approaches to Cell Therapies

Keynote: Clinical Pharmacology and Immunogenicity Considerations of Novel Modalities


CLINICAL PHARMACOLOGY CHALLENGES AND OPPORTUNITIES IN RARE AND NEGLECTED DISEASES AND SPECIAL POPULATIONS (CE) 

Prologue: Role of Clinical Pharmacology in Rare and Neglected Diseases and Special Populations

This presentation will provide an overview of the mission and activities of the IMI consortium named ConcePTION. The overall goal of ConcePTION is to build an ecosystem for better monitoring and communicating of medication safety in pregnancy and breastfeeding. the presentation will focus mainly on progress made in terms of development of a non-clinical platform—based on in-vitro, in-vivo-animal and PBPK tools—for predicting maternal and neonatal medication exposure during lactations.

Symposium: An Update from the ConcePTION Project—Reducing Uncertainty of Drugs Effects During Pregnancy and Breastfeeding

Predict the PK during pregnancy covering a wide spectrum of gestational ages. Finally, the talk will cover the ability and challenges to predict drugs exposure in the milk.

Symposium: Dosing Approaches for Pediatric Rare Diseases—Case Examples

Symposium: Opportunities for Physiologically Based Pharmacokinetic Models in Perinatal Pharmacology

This talk will describe the impact of physiological changes during pregnancy and on drug kinetics during pregnancy. It is possible to integrate experimental and physiological data and develop a workflow of physiologically based pharmacokinetic (PBPK) model building during perinatal period with applications of PBPK models to predict the PK during pregnancy covering a wide spectrum of gestational ages. Finally, the talk will cover the ability and challenges to predict drugs exposure in the milk.

Symposium: Whole Body PBPK Modeling of Remdesivir and Its Metabolites to Aid in Estimating Active Metabolite Exposure in the Lung and Liver in Patients with Organ Impairment

 

 

Back to top

IN PERSON sessions are October 17 through October 21. Browse the programming by biomolecular or chemical sessions.

On DEMAND

BIOMOLECULAR

WORKING WITH NOVEL THERAPEUTIC AND DELIVERY SYSTEMS

Symposium: Computational Tools for Modeling Quality Attributes in Biologics—Revealing Case Studies

Overview of the in silico tools developed to aid in assessing physical and chemical liabilities of biologics such as aggregation, oxidation, deamidation etc. We demonstrate the use of these tools both in Discovery and Development for developability assessment and in identification of key critical quality attributes (CQAs) during manufacturing. Case studies will be discussed to showcase the use of computational tools to aid in mechanistic understanding of degradation as well as higher order structural characterization.

Symposium: Additive Manufacturing: Functionality, Precision, and Standardization

Symposium: Advanced Imaging Tools for Pharmaceutical Applications

Presence of micro particles can preclude the approval of protein subunit vaccines. Very few methods are available to characterize particles in the size range of 50 microns and to distinguish protein aggregates from adjuvant particles. I will discuss how we have used a home-built fluorescence imaging instrument and novel fluorescent dyes to characterize the effect of excipients and processing parameters on the aggregation properties of a bivalent protein subunit vaccine.

 

CHALLENGES IN CONTROL STRATEGIES FOR DRUG DEVELOPMENT

Prologue: Understanding Biologics Product- and Process-Related Impurities Along the Product Lifecycle

Symposium: Establishing Control Strategies to Assure Integrity of Stability Studies to Support Pharmaceutical Products Expiry

An important and often overlooked component of a well-run, compliant stability program is the stability chambers. Regardless of environmental condition, size, reach-in or walk-in, all stability chambers need to be qualified, calibrated, and properly maintained. Temperature and humidity excursions will inevitably occur and will require investigation. This presentation will provide some key factors to consider on how excursions to stability sample storage should be investigated, along with what data is required to support these deviations.

 
Symposium: Understanding Structure, Dynamics and Molecular Arrangements of New-Modalities Using ssNMR

SS-NMR spectroscopy is a powerful tool that can precisely characterize the structure and dynamics of molecules. The past decade has witnessed significant technical advancements in the field of ssNMR for overcoming the challenges of low sensitivity and poor resolution. These advances have opened new avenues of ssNMR applications to emerging modalities in the pharmaceutical industry. The aim of this session is to show advanced applications of ssNMR spectroscopic methods on new molecular modalities.

 

Symposium: Establishing Control Strategies and Setting Clinically Meaningful Specifications During the Development of Biologic Drugs

 

NEW OPPORTUNITIES IN MODELING, CONTROLS, AND ANALYTICS

Prologue: The Prospect of Artificial Intelligence (AI) in Revolutionizing Drug Development

Symposium: Modern vs Classical DOE- Reduce Runs and Expand Modelling

The advantages of using designed experiments is well recognized. So, what’s new? Computational advancements have led to new classes of designs that allow: reduction in experimental runs, varying focus to factors, adequate model precision, and evaluation of more terms. This can translate to accelerated development, more accurate modelling, and less resources. Characteristics of these new designs will be described, along with examples of the advantages of these methods compared to classical designs.

Symposium: Machine-Deep Learning in Characterization of Subvisible Particles for Biological Formulations

Symposium: Recent Advance in Lyophilization of Biologics and Vaccines

Symposium: Mechanism of mRNA Vaccines: Avenues for Improving Manufacturing Development

Keynote: Advances in Manufacturing Tools and Technologies to Meet the Challenges of Tomorrows Medicines

Back to top

CHEMICAL

Hot Topic: Printability of Materials for Novel Pharmaceutical Dosage Forms

Additive manufacturing is gaining increasing interest from pharmaceutical industry. There is a high demand to integrate these now manufacturing concept in pharmaceutical production. This session focuses on latest trends for 3D printing technologies and opens up the discussion within the scientific community to further advance this rather novel manufacturing approach to a broader community.

Hot Topic: Physical and Chemical Risk Mitigation Approach for Lyophilized Drug Products

 

CHALLENGES IN CONTROL STRATEGIES FOR DRUG DEVELOPMENT

Prologue: Managing Organic Impurities to Support Drug Product Lifecycle

Organic impurities in drug product include process impurities of active pharmaceutical ingredient (API), degradation products of API, excipient impurities and reaction products between API and excipient or excipient impurities. This prologue serves as introduction for subsequent focused presentations in this section by providing a short overview of regulatory guidelines, examples, sources/origination of impurities and generating interests from audience of potential control strategies based on the nature of the organic impurities.

Symposium: Developing Control Strategies for Organic Impurities in Small Molecule Drug Development

In the development and manufacturing of drug products, changes are inevitable. Safety of the products is established during clinical phases; therefore, changes to the product can compromise the safety of the finished product if not well managed. ICH Q12 discusses the change management system through development to evaluate and monitor organic impurities to register a pharmaceutical product. Characterization of active pharmaceutical ingredient will be discussed to demonstrate the establishment of control strategies for regulatory flexibility.

Symposium: The Need to Understand Excipient Composition Profiles: Assessment and Appropriate Control Strategy Development

Excipients help transform APIs into medicines. Excipients are a very varied and may be of natural, synthetic or semi-synthetic origin. Excipient composition is important; it can affect patient safety and efficacy, and drug product manufacturability and stability. Control strategies for our excipients must go beyond simple chemical test methods.

Symposium: Mass Spectrometry-Based Characterization of Synthetic Oligonucleotides and Structurally Related Impurities

Mass spectrometry-based high resolution analytical method applied to the characterization of the intended full-length sequence and structurally similar impurities to achieve high coverage map for confident sequencing and intense fragment ion features for high analytical sensitivity.

Symposium: Enhanced Process Under- standing of Continuous Manufacturing Using Integrated Design Space

The focus of this presentation will be on understanding the potential multi-factorial interactions across integrated operations on a continuous tableting line based on continuous wet granulation. The enhanced product understanding of the integrated continuous line underpins the development of an integrated design space across the operations.

Keynote: Lessons Learned from the Commercialization of Continuous Manufacturing and Process Analytical Technology: How Can We Enable the New Modalities?

 

NEW OPPORTUNITIES IN MODELING, CONTROLS, AND ANALYTICS

Prologue: Machine and Deep Learning in Pharmaceutical Manufacturing

Recently, machine and deep learning ap- plications have grown exponentially in the pharmaceutical industry. There are many benefits of machine deep learning approaches towards drug development, manufacturing, and analytics. Multiple contemporary applications and new approaches in real-world scenarios will be discussed.

Symposium: Machine and Deep Learning in Small-Molecule Product Development

Deep learning-based approaches are showing increasing promise and usefulness for small molecule property prediction, fueled by increasing computational power, larger industrial datasets generated in a standardized manner, and adaptation of algorithmic advances to chemistry. Here, we present recent property prediction performance advances for key small molecule properties important in pharmaceutical development, and then discuss ongoing work to address challenges in evaluating, interpreting and implementing deep learning for molecular design.

Symposium: Overview of the EIOT Method to Build a PAT Solution

Symposium: Excipient and API Characterization and Control for Dry Powder Inhalers

Keynote: Advances in Process Control, Modeling and Analytics in Pharmaceutical Manufacturing—A Regulatory Perspective

 

ADVANCES IN MANUFACTURING AND ANALYTICAL CHARACTERIZATION WORKING WITH NOVEL THERAPEUTIC AND DELIVERY SYSTEMS

Prologue: Essential Performance Requirements for Combination Products

Bringing the drug and device constituent parts together into the final combination product continues to provide challenges to pharmaceutical companies looking to deliver the drug through novel and/or platform delivery devices. Attendees will learn the important considerations in the attributes and interplay between drug and device with respect to the essential performance requirements of the combination product as a whole.

Symposium: Device Considerations for Drug-Device Combination Products

The presentation will focus on safety and performance considerations of medical devices that are part of a drug-device combination product. Using on-body delivery systems as an example, the session will discuss the concept of essential performance requirements and safety considerations such as biocompatibility and maintenance of sterility.

Symposium: Human Factor Analysis of Drug-Device Combination Products

Symposium: How to Utilize the FDA’s Comparative Analysis Pathway for Generic/Biosimilar and 505(b) (2) Combination Drug Product Applications

This presentation will provide information of how to succeed in getting US FDA approval for generic/biosimilar and selected 505(b)(2) applications through the unique comparative/ URRA process.

Symposium: CMC Assessment of FDA Submissions Related to Drug-Device Combination Products

This presentation will discuss regulatory (CMC) challenges during assessment of drug-device combination products by the USFDA.

Keynote: Novel Delivery Systems, the Needs and Challenges of Leveraging Advanced Analytical Tools

The development of novel delivery systems adds additional levels of complexity in analytical characterization beyond what is found with traditional oral and sterile delivery systems. The presentation will focus of highlighting examples of needs and challenges related to a variety of delivery systems including inhaled, implantable, nasal, and lipid nano-particle systems and how advanced analytical tools are essential in building foundational developmental understanding

Back to top

IN PERSON sessions are held October 17 through October 21. Browse all the sessions by biomolecular or chemical.

ON DEMAND
BIOMOLECULAR

ROLE OF EXCIPIENTS IN FORMULATION & DRUG PRODUCT DEVELOPMENT

Prologue: Evolution in Our Under- standing of Excipients in the Formulation of Biologics

Overview of shifts in the scientific community’s approach to the formulation of biologics, with discussion of pH buffers, salts, amino acids and disaccharides in solution, but mostly in freeze- dried, dosage forms.

Symposium: Enable Solid-state Biological Products Through the Development of Approaches to Better Understand Protein-Excipient Miscibility and Spatial Homogeneity

Protein-excipient miscibility is considered a key factor impacting the stability of solid protein formulations. However, factors governing miscibility between proteins and excipients are not well understood, and analytical methodologies to probe miscibility are lacking. Herein, we discuss theoretical and experimental aspects of protein-excipient miscibility.

Symposium: Formulation Strategies to Minimize Particles Resulting from Polysorbate Degradation

Free fatty acid particles associated with enzymatic polysorbate degradation in liquid drug products is of increasing concern to the biopharmaceutical industry. There are currently several gaps in the industry’s understanding of how to mitigate this issue. The talk will focus on formulation related strategies on how to manage polysorbate degradation and reduce particle risk.

Symposium: Role of Excipient and Molecular Mobility in Stabilizing Lyophilized Protein

Formulating proteins as freeze-dried solids can provide significant stability improvement. Excipients, such as sugars, are often used as stabilizers. The composition and processing conditions of freeze-dried protein formulations impact the physical form of excipients and hence their functionality. The protein stability can be compromised if excipient exists in an undesired physical form. We evaluated the role of excipients on the stability of lyophilized protein formulations which was comprehensively characterized using several complementary techniques.

Symposium: Molecular Mechanism of Solid-State Protein Stability for Guiding Formulation Design

Molecular understanding of the stabilization mechanism of solid-state protein therapeutics is largely unknown. In this presentation, we will provide a few examples to elaborate structural mechanism in the interplay of stability, molecular interaction and formulation process, to enable the design of products based on solid state protein, by utilizing solid-state NMR (ssNMR) spectroscopy.

Keynote: Designing and Building the Next Generation of Vaccines

An update on new technologies being used to allow the development of new vaccines, including adjuvant and RNA.

Symposium: Microneedles: Tiny Structures Targeting Big Healthcare Challenges

Symposium: Peptide-penetrating Carriers towards Pulmonary Delivery for Mucosal-associated Diseases

Keynote: Nanotechnology and Biotechnology: New Hopes and Realities

 

FORMULATION DEVELOPMENTS FOR NEW THERAPEUTIC MODALITIES

Prologue: Introducing Open Innovation Challenge: Subcutaneous Drug Delivery and Development Consortium

Subcutaneous delivery of large molecules presents a significant scientific gap with regards to the ability to predict clinical bioperformance. The in-vitro, in-silico, and in-vivo models have been inadequate in terms of translatability to clinic and thus, lead to a very empirical development requiring clinical interrogation of the product for such understanding. The presentation will aim to frame the issue and put forward an open innovation challenge for the community on predicting SC bioavailability of mAbs.

Symposium: Leveraging Preclinical Data for Bridging from Intravenous to Subcutaneous Dosing Regimens for Monoclonal Antibodies

Symposium: Evaluation of Novel PEGylated Lipid Vesicles for Their Translation Potential to Treat Cancer Patients

Cancer nanomedicine has a positive impact on f patient treatments. However, sustained, and targeted delivery of intravenously injected nano- medicines hails for development of novel formulations with improved stealth characteristics. We have developed stealth nano-formulations to improve therapeutic index of drugs while minimizing the associated side effects. These formulations are composed of a polymeric lipid (DC8,9PC) and a PEGylated lipid, comprising a simple binary system. Potential clinical use will be discussed (NIH application # E-154-2018; PCT/US2019/041464).

Symposium: Process Development & Formulations to Enhance Vector Stability for Gene Therapy

Symposium: Imaging in vivo Delivery of Nanocarriers to Tumor Targets

Nanocarrier based delivery systems have attracted increasing attention especially in the oncology area. However, tumors are rather complex, and the delivery outcome may vary depending on tumor types, development stages, etc. The talk will introduce a developed nanocapsule system for imaging tumor delivery of nanocarriers in order to gain a better understanding of delivery efficiency and foster improved therapeutic outcomes in cancer nanomedicine.

Keynote: New Materials for the Delivery of Cells, RNA, and Genome

 

DELIVERY SYSTEMS FOR EFFECTIVE SHUTTLING ACCROSS BIOLOGICAL BARRIERS

Prologue: Advances in Inhaled Nanosystem Formulations: Design and Development

Symposium: Self-Assembling Filaments as Inhalable Drug Carriers

Editing Tool Rapid Fire: Delivery Systems for Effective Shuttling Across Biological Barriers

 

Back to top

CHEMICAL

Hot Topic: Solid Dispersions and Crystallinity

Does residual crystallinity impact solid dispersion performance? Key considerations to address this question will be discussed. Several examples showing different impacts of residual crystallinity on solid dispersion release performance including supersaturation extent and duration will be presented.

Symposium: Mechanistic Evaluation and T0 Image-Based Release Prediction for Long-Acting Delivery

A time and cost efficient, T0 image-based release characterization method will be presented, along with case studies highlighting drug development applications, validations, and regulatory considerations.

Symposium: Biopharmaceutics Considerations for Long Term Ocular Drug Delivery

Symposium: Amorphous Dispersions for Achieving High Oral Performance of Oncology Medications

Oncology is prevalent in pharmaceutical pipelines. However, many oncology drugs are poorly water soluble in gastrointestinal fluids, often manifesting as drug-drug or food-drug interactions that limit oral bioavailability. This talk describes an amorphous solid dispersion (ASD) tablet of the weak base drug, acalabrutinib, that removed the pH effect observed with commercially marketed Calquence® at the human dose

 

DELIVERY SYSTEMS FOR EFFECTIVE SHUTTLING ACROSS BIOLGOICAL BARRIERS

Prologue: Long-Acting-Drug-Delivery: State of the Art in Chemistry, Processing and Formulation

This talk presents an overview of bioresorbable polymeric depot strategies for long-acting drug delivery. The presentation will provide an excellent overview on the various types of depot formulations (incl. microspheres, nanoparticles, implants, and in-situ depots), production technologies as well as a detailed dive into the possibilities with polymer chemistries (lactide-glycolide copolymers) in this space. Furthermore, the talk will explore novel and emerging chemistries and formulation techniques being explored to solve new complex delivery challenges.

Symposium: Case Study on Micro- sphere Formulation Development and Overcoming Scale-Up Challenges

Back to top

IN PERSON sessions are held October 17 through October 31. Browse the sessions online. 

ON DEMAND

Connecting to Communicate: Critical Skills for Leaders Post-Pandemic

Leaders who communicate well foster connections that inspire their team and encourage peak performance. In this workshop, you will learn skills to speak with confidence, clarity, connection, and compassion. Whether speaking from the stage in high-stakes presentations or talking with a co-worker one-on -one, you will have the tools you need to make critical shifts in the way you speak so your message lands the way you intended to produce the change you desire.

Creating a Culture that Cultivates and Sustains Innovation and Entrepreneurship

The intent of this session is to discuss strategies for creating cultures of innovation and entrepreneurship. The goal will be to share successful models that foster and develop critical thinking, hypothesis generation, emotional intelligence, growth mindset, and inclusivity. Speakers from both academia and industry will discuss strategies to develop such competencies as well as on tactics to sustain environments where innovation flourishes.

Diversity and Inclusion-How Asian Pharmaceutical Scientists Adapt to the Environment?

The content will be delivered as an hour career symposium to gain an understanding of the landscape and share different inputs from AAPS Asian leaders of their experiences and

recommendation to network and advance in the pharmaceutical industry. Experts will be sought from academia, industry and government sectors to take part in the discussion.

Effective Research Presentations During Interview

Future Leaders: Join the Conversation with our Veteran Leaders

Job Switch Checklist: To Do List for Career Transition

Navigating Non-Traditional Scientific Careers: From Bench to Board Room

This session will focus on pathways of successful professionals who started as bench pharmaceutical scientists but navigated their professional development using non-traditional pathways, utilizing their skillset to build an effective career.

Pronunciation Powerhouse: Making Your Words Heard

This session will appeal to leaders who need to explain their expertise clearly when they interact with others in and outside their field. They will get an inside look at how to speak the language of the clients and partners they hope to work with. We will illustrate how to uncover the hidden curse of knowledge, utilize the power of stories, and connect to the audience by tapping into the Soul of their Science.

Three Leadership Practices that Weren’t Part of Your Ph.D.

Welcome to the Confidence Gym

Just like exercise strengthens weak muscles, so does practicing new behaviors to build up self-confidence. Stretch your confidence muscle like other muscles. Smash self-limiting beliefs like perfectionism. Keep punching after every NO. Boost your confidence by reframing your mindset. Step up to try out power poses. Uncover 5 reasons why women struggle to balance power and leadership. Participants leave with scores of practical tips they can implement immediately to be stronger inside and out.

Leadership and Management Skills for Pharmaceutical Scientists: Make Better Decisions

The average person makes an astounding 35,000 choices per day. If most people spend around seven hours per day sleeping, that makes about 2,000 decisions per hour or one decision every two seconds. How can you improve the quality of the decisions you make? What are the blocks and biases that prevent you from making logical and practical decisions at work? This workshop offers you tools and techniques to avoid decision making errors.

The Post-Pandemic Keynote

The pandemic challenged us to reconsider how we present, share and communicate ideas to audiences. What have we learned and what can we use when things get back to normal?

---

View the full program, and add sessions to your schedule today!

Back to top