Program 2022

September 26-27, 2022; San Diego, CA

7:30 AM - 8:25 AM

Registration & Refreshments

8:25 AM - 8:35 AM

Chair’s Opening Remarks

8:35 AM - 9:05 AM - Keynote

Technology & Innovation

Current and Future Perspectives for Drug Delivery and Formulation

Donna French, Vice President Pharma Development  , AstraZeneca

  • Delivery to Special Patient Populations: Geriatrics and Paediatrics
  • Next-Generation Cell and Gene Therapies
  • Optimizing Cancer Care in the Out-Patient Setting
  • Personalized Medicine and the Role of Digital Health
  • Non-invasive Delivery of Biologics (Pulmonary & Nasal)
  • Lipid Nanoparticles for drug and vaccine delivery
  • Expanding Opportunities for Nanomedicine
  • Progress of Oral Biologics Delivery

9:10 AM - 9:40 AM - Keynote

Technology & Innovation

Continuous Manufacturing Platform for Complex Parenterals

Diane J. Burgess, Ph.D., Board of Trustees Distinguished Professor of Pharmaceutics Pfizer Distinguished Chair of Pharmaceutical Technology , University of Connecticut

  • Development of a continuous manufacturing platform for liposomal products
  • Incorporation of PAT for critical quality attributes and process controls
  • Precise control over particle size and insurance of monodisperse particles
  • Adaptation to other nanoparticulates
This presentation will focus on the development of a continuous manufacturing platform for complex parenterals. Liposomes as well as polymeric micelles, and lipid nanoparticles will be discussed. Key aspects in the development of these novel therapeutics will be addressed together with insights into critical issues in the manufacturing process. Our laboratory has developed a novel continuous manufacturing platform for complex parenteral dosage forms which allows precise control over particle size and can also ensure monodisperse particles. This platform is equipped with process analytical technology to ensure all aspects of product quality. An overview of this manufacturing platform will be presented. The platform is based on co-flow technology and employs the formation of a turbulent jet at the site where the two flows mix, promoting vesicle formation. Case studies on different therapeutics prepared using this technology will be discussed.

9:40 AM - 10:15 AM - Case Studies

Small Molecules

Engineering Prodrug Therapies For Infectious Disease and Cancer Therapy

Professor Patrick Stayton, Distinguished Career Professor, Director, Molecular Engineering & Sciences Institute, University of Washington

  • Therapeutic platform targets antibiotic and antiviral drugs to cellular compartments such as the lung macrophage to extend PK profiles and potentiate drug activity against bacterial and viral pulmonary pathogens
  • Platform can be engineered to extend the PK profile of small molecule drug regulators of mRNA gene circuits or cell therapeutic regulatory circuits
  • Liver-targeting of drugs has also been shown to hepatocytes to increase therapeutic index via IV or subcutaneous routes of administration
  • Tumor-associated macrophages and antigen-presenting cells can be targeted with adjuvanting immune-modulators for use in immune-therapies and vaccines

Biologics

Formulation Strategies and Stability Characterization of siRNA Drug Products

Sathya Venkataramani, Director Pre-Pivotal Drug Product Technologies - Biologics, Amgen

Oligonucleotides in general and small interfering RNAs (siRNAs) in particular are becoming one of the fastest growing therapeutic modalities in the current age. With four FDA approved siRNA-based drugs (patisiran, givosiran, lumasiran and inclisiran) and several lined up in late stage clinical trials, this modality is becoming an essential and reliable tool for gene silencing. The progress and success of approval of siRNA therapeutics heavily depend on overcoming some of the challenges such as limited stability, off-target binding, unfavorable physicochemical properties etc. This talk is designed to highlight formulation strategies and stability studies for siRNA drug products to support manufacturability and shelf-life.

Device Development

Large Volume Patch Pumps, Challenges and Opportunities

Charles Rampersaud, VP, Head of Devices and Packaging, Genentech

The subcutaneous self-administration of biologics using a single large-volume bolus dose requires novel large-volume patch injectors. However, the usability and wearability of such on-body devices has rarely been investigated thus far. Therefore, this formative simulated use experiment studies the overall handling and acceptability in terms of the size and weight of a large-volume patch injector device platform.

10:15 AM - 10:45 AM - Solution Spotlights

Small Molecules

New Insights in the Endothelial Transport of Orally Administered PEGylated Mixed Micelles

Show more

Biologics

Inhaled Delivery of Biologics: Why it’s a Good Solution

Device Development

Improving Care Quality Through Connected Drug Delivery Devices

Show more

10:45 AM - 11:35 AM

Networking & 1-2-1 Meetings

11:35 AM - 12:10 PM - Case Studies

Small Molecules

Amorphous Solid Dispersions – A Development Overview

Raman Iyer, Associate Director and Senior Fellow, Novartis

  • ASD as a concept for early phase development of poorly soluble drugs
  • Development of ASD as a market product
  • The Future - Novel materials, Data Science and Modeling
Amorphous Solid Dispersions (ASDs) are enabling delivery systems that primarily improve the oral bioavailability of poorly soluble, crystalline drugs. The development of ASDs is challenging as it involves conversion of drug from a thermodynamically stable crystalline state to a kinetically stabilized amorphous state and retention of the amorphous state from the time of manufacturing to the time of in-vivo drug release upon dosing, a period of several months to years. The technologies used to manufacture, package and characterize ASDs as a market product play an important role in the kinetic stabilization process and determination of drug release metrics. While several ASD products have been successfully developed and marketed, the advent of new stabilizing materials and data science and modelling approaches can further enhance our knowledge of ASDs as a delivery system, reduce cycle time of development and provide highly differentiated and value-added medicines to patients.

Biologics

Predictive high-throughput screening of oligonucleotide lipid nanoparticle for gene silencing

Chun-Wan Yen, Principal Scientist, Genentech

  • Automated high-throughput preparation and characterization of oligonucleotide-loaded lipid nanoparticles
  • Translatable performance between high-throughput prepared LNPs and scaled-up LNPs
  • A systematic PEG-lipids screening for LNP performance
  • LNP structural analysis by cryo-TEM and small-angle x-ray scattering

Device Development

The evolving paradigm of post-market safety reporting (PMSR) for combination products

Khaudeja Bano, Vice President Combination Product and Device Safety, Executive Medical Director, Amgen

  • Discuss the global regulatory changing environments for PMSR
  • Key challenges faced by organizations to meet the global PMSR requirements
  • Industry best practices for PMSR readiness

12:15 PM - 12:50 PM - Solution Spotlights

Small Molecules

Scratching the Surface – Surface Characterization of Pharmaceutical Powders for Oral Solid Dosage Forms

  • Introduction to different surface characterization methods for pharmaceutical powders
  • Comprehensive drug-excipient characterization
  • How do surface properties of powders influence mechanical tablet properties?

Biologics

Surfactants in Bioformulation: Are We at the End or the Beginning of a Journey?

  • Excipient impact on biologics formulations
  • Stability studies related to chemical and enzymatic degradation
  • Reduction of mAb and protein aggregates
  • Excipient safety

Technology & Innovation

Rapid Development of Amorphous Solid Dispersions (ASDs) for Improved Bioavailability

David Lyon, Sr. Fellow, Global Research, Lonza, Small Molecules

  • Learn how oncology pipelines are dominated by poorly water-soluble compounds
  • Understand how ASD drug products can enhance bioavailability and overcome pH effects of poorly soluble weak base drugs
  • Learn how knowledge of key drug, polymer, and gastrointestinal properties can be combined with in vitro and in silico tools to develop ASD drug products without the need for reformulation or multiple studies
  • Describe key considerations driving effective selection of ASD formulations

Pharmaceutical pipelines are dominated by oncology indications. However, many oncology drugs are poorly soluble in gastrointestinal fluids, often resulting in drug-drug or food-drug interactions that limit oral bioavailability. Amorphous solid dispersion (ASD) is a leading technology for overcoming oral bioavailability issues. This talk will provide a background to the advantages in ASDs for delivering oncology drugs, and a background to using spray drying to develop ASDs. The talk further describes a case study of an ASD tablet of a weak base drug, acalabrutinib, that removed the pH effect observed with commercially marketed Calquence® at the human dose in dogs. ASD tablets outperformed Calquence 2.4-fold at high gastric pH with a 60% smaller dosage form size.

12:50 PM - 1:50 PM

Networking Lunch

1:50 PM - 2:25 PM - Case Studies

Small Molecules

Enabling Bioperformance Prediction Through Data Analytics

Pierre Daublain, Principal Scientist, Merck

  • The ability to capture and easily access structured experimental data is a prerequisite to robust data analytics. Measured compound attributes such as biorelevant solubility and formulation characteristics are key components of predictive models for oral absorption. Leveraging these models in discovery can guide molecule selection and formulation development in preclinical space prior to preclinical in vivo studies and help assess clinical bioperformance risk for compound prioritization purposes.
  • A platform was built within electronic laboratory notebooks for the structured data capture of properties relevant to preclinical and clinical bioperformance, and the generation of large, contextualized datasets.
  • The platform eases access to the data and merging with pharmacokinetics results, thereby enabling data analysis and visualization.
  • Importantly, bioperformance predictive tools were built and implemented. These include relatively simple predictors of fraction absorbed based on a small number of compound attributes, as well as more complex models - built using our experimental datasets - that related formulation selection and predicted PK.

Device Development

The Port Delivery System With Ranibizumab: A New Paradigm for Long-Acting Retinal Drug Delivery

Shrirang Ranade, Sr. Technical Development (CMC) Team Leader, Genentech

  • The Port Delivery System with ranibizumab (PDS) consists of an intraocular drug delivery implant and ancillary devices to enable initial fill, refill and explantation of the implant.
  • The implant is a permanent, indwelling drug delivery device that can be refilled in situ through a self-sealing septum and is designed to continuously release a customized formulation of ranibizumab into the vitreous by passive diffusion through a porous titanium release control element.
  • Sustained, continuous, and reproducible release from the PDS characterized in the in-vitro studies was also observed in Ladder (phase 2) and Archway (phase 3) trials.
  • PDS is the first long-acting ocular biologic drug delivery system, demonstrated to be clinically effective in providing visual and anatomic outcomes comparable to monthly injections in nAMD with refill-exchange intervals of at least 6 months.

The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system designed for the continuous delivery of ranibizumab into the vitreous for 6 months and beyond. Development of the PDS included in vitro studies performed to characterize ranibizumab release from the implant and the efficiency of refill-exchange. Ranibizumab release rate from the PDS implant was measured in vitro with different starting concentrations of ranibizumab and active release rate determined both after the initial fill and after refill-exchanges. Measurements after initial fill, first, second, and third refills, respectively, demonstrated reproducibility between implants and between multiple refill-exchanges of the same implant. A refill-exchange performed with a single stroke (100 µL) using the refill needle replaced over 95% of the implant contents with fresh drug. In vitro data support the use of the PDS with fixed refill-exchange intervals of at least 6 months in clinical trials.

Technology & Innovation

The dynamic, motile and deformative properties of RNA nanoparticles lead to efficient tumor vasculature targeting , fast renal excretion and rapid body clearance

Professor Peixuan Guo, Sylvan Frank Endowed Chair in Pharmaceutics and Drug Delivery, The Ohio State University

  • RNA nanoparticles are motile, dynamic and deformative materials that enable them to squeeze themselves through capillary to reach cancer vasculature & through the kidney glomerulus to quickly enter the urine
  • RNA nanoparticles can reach tumors fast facilitate by both the passive (amoeba property) and active (ligand-assisted) cancer-targeting effect. The fast and high efficient tumor targeting leads to high efficiency
  • The fast renal excretion and rapid body clearance resulted in low or no toxicity. The negative charge of RNA nanoparticles makes them not bind to the normal cell and not enter the organs
  • The 20-30 nm in size ensure that they are not grasped by macrophages, thus reaching the tumor efficiently
  • RNA nanoparticles can make Insoluble natural or chemical drugs soluble

2:30 PM - 3:00 PM - Case Studies

Small Molecules

Discovery and Translation of Cellular Nanoparticle Technology

Professor Liangfang Zhang, PhD, Joan and Irwin Jacobs Chancellor’s Endowed Chair, Professor, Department of Nanoengineering, University of California San Diego

  • Development of cell membrane-coated nanoparticle formulations
  • Physicochemical and biological characteristics of cellular nanoparticles
  • Organ-specific targeted delivery
  • Intracellular delivery of biological drugs

Dr. Zhang will share the research discovery and entrepreneurial translation of his Cellular Nanoparticle (CNP) platform technology. Cellular Nanoparticles are nanoparticles clocked with wild-type or engineered cell membranes. By leveraging different cell membranes and functional proteins that can be expressed on the cell membranes, the CNP technology can achieve different therapeutic or vaccination results and drug delivery goals.

Biologics

Cell Penetrating Peptide Enhancing the Intracellular Delivery of Proteins

(Invited)

Protein-based therapeutics have the potential to treat a variety of diseases, however, safe and effective methods for delivering them into cells need to be developed before their clinical potential can be realized. Peptide fusions have great potential for improving intracellular delivery of proteins. However, very few peptides have been identified that can increase the intracellular delivery of proteins, and new peptides that can enhance intracellular protein delivery are greatly needed. In this report, the authors demonstrate that the coiled-coil forming peptide (KVSALKE)5 (termed K5) can function as a cell penetrating peptide (CPP), and can also complex other proteins that contain its partner peptide E5. It is shown here that GFP and Cas9 fused to the K5 peptide has dramatically enhanced cell uptake in a variety of cell lines, and is able to edit neurons and astrocytes in the striatum and hippocampus of mice after a direct intracranial injection. Collectively, these studies demonstrate that the coiled-coil forming peptide (KVSALKE)5 is a new class of multifunctional CPPs that has great potential for improving the delivery of proteins into cells and in vivo.

Device Development

Current Challenges and Opportunities in Developing Combination Products Biologics Delivery and Medical Devices

James Leamon, Director, Biologics Device Development , Jazz Pharmaceuticals

  • Viscosity insights for effective drug delivery
  • Advances in digital health for patient adherence
  • Biologics delivery challenges and opportunities
  • Combination products development pathway to successful commercial products

3:05 PM - 3:55 PM

Networking & 1-2-1 Meetings

3:55 PM - 4:25 PM - Solution Spotlights

Small Molecules

Enabling Efficient Oral and Injectable Solubility Enhancement with Apinovex™ and Apisolex™ Polymers

Nick DiFranco, Global Market Segment Manager, Oral Treatments, Lubrizol Life Science Health

Joey Glassco, Global Market Segment Manager, Parenteral Drug Delivery, Lubrizol Life Science Health

  • Review of solubility-enhancement techniques
  • Introduction to Lubrizol’s patented solubility enhancing excipients: oral-grade Apinovex™ polymers and injectable-grade Apisolex™ polymers
  • Formulation and processing benefits of Apinovex and Apisolex
  • Case study data demonstrating solubility enhancement and high drug loading for several APIs
  • Competitive advantages compared to established excipients and techniques

Biologics

Essential components of Platform Biopharma Formulations and Covid 19 Applications

  • Commercial Biotherapeutics Stabilized with Trehalose and Sucrose
  • Key Issues in Biopharma Formulation Development
  • Essential components of a “Platform Biopharma Formulation”
  • Examples for utilizations and functionalities of Sucrose and Trehalose in Covid 19 related formulations/vaccines and techniques (m-RNA, Viral vectors, mAbs etc.)
  • Understanding important physicochemical properties of Trehalose and Sucrose

Device Development

Combination Products Biologics Delivery

  • Challenges with biologics subcutaneous delivery
  • Can devices move biologics delivery to the patient home
  • Challenges and opportunities

4:30 PM - 5:00 PM - Case Studies

Small Molecules

Overcoming Bioavailability Challenges of Very Weak Acid for Oral Delivery – A Case Study of HCV Drug Dasabuvir

Shuang Chen, Ph.D., Sr. Principal Research Scientist Solid State Chemistry, Process R&D, AbbVie

  • Dasabuvir is a BCS II compound posing a significant barrier to achieving sufficient human bioavailability. Its substantially weak acidity (pKa > 8) made salt approach challenging and risky due to disproportionation.
  • Identification of effective crystallization inhibitors captured the dissolution advantage of dasabuvir sodium salt and provided a path forward for formulation development.
  • The comprehensive evaluation of solid-state properties, biopharmaceutical properties, in-vivo pharmacokinetics, and manufacturability of dasabuvir monosodium monohydrate ensured the selection of this solid form for successful formulation development and clinical studies.
  • Oral delivery of dasabuvir via salt approach ultimately helped enable the triple combination direct acting antiviral HCV regimen Viekira Pak.

Biologics

Long acting biologics: A steep climb

Puneet Tyagi, Associate Director, Dosage Form Design & Development, Biopharmaceuticals Development, R&D , AstraZeneca

Burden of chronic diseases is soaring. A general trend is seen towards the long-term drug treatment for chronic diseases. Therefore, any drug delivery technology that can at a minimum reduce the total number of injections is welcome news for the patients. In addition to improving patient comfort, less frequent injections smoothes out the plasma concentration-time profile by eliminating the hills and valleys. However, working towards long acting formulations for biologics have diverse impediments. In this presentation, we will discuss the promises and the challenges of long acting formulations for large molecules, especially antibodies.

Technology & Innovation

mRNA delivery with acid degradable lipid nanoparticles

Professor Niren Murthy, Professor of Bioengineering, University of California at Berkeley

  • New acid degradable linkages
  • Endosomal disruption with acid degradable lipids
  • mRNA delivery to non-liver organs with acid degradable lipids
  • mRNA delivery in the brain with acid degradable lipid nanoparticles
In this presentation I will describe a new acid degradable linkage developed in the laboratory, which has a unique combination of rapid hydrolysis at pH 5.0 and stability at pH 7.4. Acid degradable linkages (ADLs) have great potential for developing endosomal disruptive agents, due to their ability to degrade in the acidic environment of endosomes. However, ADLs need to hydrolyze on the timescale of minutes at pH 5.0 to be successful, and are consequently unstable and difficult to synthesize. In this presentation, a new acid degradable linkage will be described, composed of an azide acetal, which has a t1/2 < 5 minutes at pH 5.0 and a t ½ of > 1000 minutes at pH 7.4. The azide acetal is composed of a benzaldehyde acetal that has an azide in its para position, and has a low kH, due to the low electron donating character of its azide. However, the azide acetal can be reduced to an amine, via DTT, prior to administration, and this accelerates its hydrolysis rate 1,000 fold. We demonstrate here that the azide acetal can generate lipid nanoparticles that rapidly de-PEGylate in endosomes, which are exceptionally efficient at delivering mRNA to cells in culture and in vivo. We anticipate numerous applications of the azide acetal given its unique combination of stability at pH 7.4 and rapid hydrolysis at pH 5.0.

5:00 PM - 5:30 PM - Case Studies

Small Molecules

Spray-Dry Process Application in the Pre-Clinical Stage of Drug Development

Marika Nespi, Senior Principal Scientific Researcher , Genentech

  • Amorphous Solid Dispersions (ASD)
    • Background Concepts and Approaches
    • Feasibility in early Stage of Drug Development
  • Spray Dry Dispersion (SDD)
    • Optimization of Formulation and Process Parameters for Pre-clinical Formulation Support
In oral drug delivery, Amorphous Solid Dispersion (ASD) have become an established approach to enhance aqueous dissolution, improve in-vivo absorption and bioavailability of poorly soluble molecules. Among various methods to produce ASD formulations, spray drying represents one of the most well established manufacturing techniques. However, this technology in early stage of drug development often faces different challenges, from limited API availability to numerous formulation and process variables, which can affect the range of possible screenings, increasing the development timeline and the resources requirements.

This research presentation introduces the development of a reproducible and efficient spray-drying platform to address the aforementioned challenges. The implemented strategy consisted in identifying optimized pre-set spray dry parameters to enable ASDs early screening and feasibility, excluding the need of individual optimization. Using a BUCHI mini spray-dryer B-290, the impact of two key  variables of spray drying (solid load and atomization pressure) was evaluated on the critical quality attributes (CQAs) of the ASDs, including yields, particle sizes, and in vitro release profile.  Additional variables, such as polymers, drugs type and drug loadings were also taken into consideration to confirm the pre-defined parameters. Furthermore, the strategy was applied from small to large-scale batches to support various toxicology studies.

Biologics

Liquid pre-formulation assessment for monoclonal antibodies and new modalities

Shwetha Iyer, Principal Scientist, Novartis

Liquid pre-formulation assessment for monoclonal antibodies and new modalities showed a significant impact in determining the success rate of developing a stable liquid formulation for biological entities. The portfolio now changing towards non-mabs like Fc silencing formats, bispecific mabs, therapeutics proteins and newer modalities such as gene therapies and AAV’s, designing stable liquid formulation is more challenging. Co-development of the clinical service formulation enables an in- depth understanding of the degradation pathways and the possibility of a stable liquid formulation. With the use of forced degradation studies and high throughput biophysical predictive tools, key developability questions can be addressed.

Device Development

Opportunity and Challenges with Large Volume Subcutaneous Drug Delivery

Ning Yu, Director & Head of Device Development, Biogen

  • Trend with Biologics Drug Delivery
  • Opportunities with Lage Volume Subcutaneous Drug Delivery
  • Technology/Product Landscape
  • Existing Challenges and some potential solutions
  • Conclusion

5:30 PM - 6:15 PM - Keynote

Small Molecules

Understanding Polymer Properties to Ensure Product Quality in Developing Extended-Release and Amorphous Solid Dispersion Formulations

Yihong Qiu, Ph.D., Senior Research Fellow Formulation Sciences, AbbVie

  • Enabling Drug Delivery Technologies (ER and ASD systems)
  • Commonly used functional polymers
  • Impact of polymer properties on formulation/process design
  • Impact of polymer variability on drug release, stability & processing

Polymers are integral and essential components of extended-release (ER) and amorphous solid dispersion (ASD) formulations. Hence, understanding polymer functionality, properties and variations is not only a core part of rational product and process design, but also crucial for ensuring consistent product quality and building robustness into manufacturing process. In this presentation, an overview of the basic principles and functional polymers commonly used in ER and ASD product/process design will be provided. Case studies will be used to discuss

(1) key considerations of polymer characteristics in product/process development;
(2) importance of polymer evaluation based on an integrated knowledge of API, formulation and process
(3) impact of critical properties and “natural” variations of polymers on product quality and performance, such as dissolution, stability and in vivo absorption.

6:15 PM - 6:45 PM - Keynote

Device Development

How Safe Are My Combination Products? Regulatory Strategy Lifecycle Management Considerations

James Wabby, Global Head, Regulatory Affairs (CoE), Emerging Technologies, Combination Products and Devices, AbbVie

  • Regulatory Landscape Understanding
  • Product and Usability Development Key Concepts
  • Lifecycle Management QMS Infrastructure Highlights
  • Regulatory Submission Aspects for Complex Products
  • Case Studies – Clinical Trial and Complaint Handing Concepts

6:45 PM - 6:50 PM

Chair’s Closing Remarks

6:50 PM - 7:40 PM

Evening Drinks Reception

8:00 AM - 8:30 AM

Registration & Refreshments

8:30 AM - 8:35 AM

Chair’s Opening Remarks

8:35 AM - 9:05 AM - Keynote

Small Molecules

Molecular Modelling to Support Drug Formulation for Small Molecule and Biologic Drugs

  • Molecular modelling provides a basic understanding of the structure and behaviour of drugs as formulated that compliment experimental data and informs decision making in drug formulation
  • API and excipient physical and chemical property prediction for small molecule drug formulations
  • Characterization of drug-drug and drug-excipient association including drug-polymer interactions in small molecule and biologics formulations
  • Provide structural insights into concentrated protein solutions and predict viscosity, aggregation, and the effect of excipients

9:10 AM - 9:40 AM - Keynote

Technology & Innovation

Future Opportunities for New Modalities

  • Innovation through new modalities
  • Antibody drug conjugates, Nucleic acid delivery, AAV, Cell therapy, Immune targeting Nanomedicine
  • mRNA therapeutics and delivery hurdles
  • Future outlooks

9:40 AM - 10:15 AM - Case Studies

Small Molecules

Targeted delivery of pharmacological agents in the vascular system

Vladimir Muzykantov, MD, PhD, Professor of Pharmacology and Medicine Vice-Chair, Department of Pharmacology Director, Center for Targeted Therapeutics & Translational Nanomedicine, University of Pennsylvania The Perelman School of Medicine

  • DDS targeting to endothelium lining vasculature evolving as an efficient, specific and multifaceted drug delivery paradigm
  • Coupling drugs to blood cells, in particular RBC and WBC, cardinally alters pharmacokinetics and effect of drugs
  • Blood cells can transport drugs to endothelial cells in selected areas of the vascular system
  • These approaches enable unprecedented degree of precision and efficacy of delivery and action of drugs in lungs, brain and other organs, targets of therapeutic interventions

Biologics

A single injection of a recombinant fusion loaded with rapamycin delivers effective zero-order absorption for one month

Professor Andrew Mackay, Gavin Herbert Associate Professor of Pharmaceutical Sciences, University of Southern California School of Pharmacy

  • Elastin-like polypeptides are humanized, repetitive peptides that undergo temperature-dependent phase separation
  • ELP fusion proteins can be designed to phase separate upon heating to physiological temperatures
  • When fused with the FKBP protein, ELPs can specifically bind and carry rapamycin
  • This formulation can be injected through a narrow-gauge needle and provide, while providing zero-order release for at least one month
  • Through pharmacokinetic and efficacy studies, this approach has been evaluated in multiple mouse models of disease

Device Development

Formulation and Device Considerations for Subcutaneous Delivery

Steven Persak, Director, Device Development, Merck

William Forrest, Principal Scientist I Sterile Formulation Sciences, Merck

  • Overview of subcutaneous delivery in the current market
  • Considerations when developing a target product profile for subcutaneous delivery
  • Identifying early challenges and opportunities in formulation and device development
  • Technology down selection and moving forward towards the target image

10:15 AM - 10:45 AM - Solution Spotlights

Small Molecules

Impact of Bile Salts on Solubilization and Membrane Transport of Supersaturated Drug Formulations

  • Supersaturating formulations have been developed to address the issues of inadequate aqueous solubility of new chemical entities and improve oral absorption
  • Bile salts, naturally present in the gastrointestinal tract, have been shown to impact the crystallization kinetics of supersaturated formulations
  • The effect of bile salt on thermodynamic properties of supersaturated drug solutions was evaluated. The interplay between solubilization and membrane transport was studied
  • The findings indicate that the impact of bile salts on solution thermodynamics is of relevance for improved understanding of in vivo performance of supersaturating dosage forms

Biologics

Thermokinetic Modelling of Biologics as a Tool for Accelerating Development

Thermokinetics can be used to model stability in time-consuming temperature excursion experiments, deliver estimates for hold-times during manufacturing or compare degradation in different packaging containers. Thermokinetic modelling is a versatile and reliable tool for early knowledge of stability outcomes, boosts the probability of project success and is therefore routinely used in development.

Technology & Innovation

Particle Size Control Through Micronization: Challenges and Solutions

  • Micronization is an important technique in drug formulation, but not all substances are simple to process.
  • This presentation will give an insight into how micronization processes can be developed for challenging inhalation materials.
  • What technical issues need to be addressed if an API is to be successfully micronized?
  • A robust process development strategy will be presented that ensures all attributes critical for quality are maintained, even for the most challenging.
  • A case study on the micronization of a highly potent inhalation API with a tendency to undergo surface amorphization will also be presented.
  • Key findings, including solid-state characterization and post-micronization conditioning, will be disclosed

10:45 AM - 11:35 AM

Networking Break & 1-2-1 Meetings

11:40 AM - 12:15 PM - Case Studies

Small Molecules

Pediatric Drug Development (PDD)- Challenges, Formulation & CMC considerations

Raman Iyer, Associate Director and Senior Fellow, Novartis

  • The Pediatric Drug Development Process
  • Challenges in PDD – Developmental physiology & PK
  • Formulation and CMC Factors to consider in PDD

Pediatric patients are among the most vulnerable and the most challenging patient population for treatment due to age related changes in developmental physiology and ADME characteristics. Safety, product design, dispensation and palatability of dosage forms are critical CMC considerations in developing age-appropriate dosage forms for pediatric populations.
  • Choice of excipients and additives in formulation is guided by safety and intake limits, duration of treatment and regulatory acceptance
  • Drug substance stability, compatibility and ADME profile from adult program can be reasonably adapted for pediatric drug development
  • Product design and user experience are key to developing a target product profile (TPP) that ensures safety, quality and patient compliance

Device Development

Alternative routes of administration for ADCs

Stefan  Yohe, Director, Delivery & Device , Seagen Inc.

Session Abstract (TBC)

Technology & Innovation

Advanced Biomaterials Technologies for Improving Biopharmaceutical Formulation and Delivery

Professor Eric Appel, Assistant Professor Department of Materials Science & Engineering, Stanford University

  • Discussion of the design criteria for injectable hydrogels for use as sustained release depot technologies
  • Defining “injectability” in shear-thinning hydrogels
  • Sustained co-delivery of subunit vaccine components improves the potency, durability and breadth of vaccine responses
  • Sustained co-delivery of cytokines and CAR-T cells enhances in vivo expansion and activation of the adoptive cells and improves therapeutic efficacy
Supramolecular (bio)materials exhibit highly useful properties that are impossible with traditional materials but crucial for a wide variety of emerging applications in industry or biomedicine. These materials typically employ enthalpy-dominated crosslinking interactions that become more dynamic at elevated temperatures, leading to significant softening. Herein, we will discuss the development of a supramolecular hydrogel platform exploiting dynamic and multivalent interactions between biopolymers and nanoparticles that are strongly entropically driven, providing alternative temperature dependencies than typical for materials of this type. We will discuss how tuning the thermodynamics and kinetics of these crosslinking interactions enable broad modulation of the mechanical properties of these materials, including their cargo encapsulation and controlled release. In particular, these materials exhibit viscous flow under shear stress (shear-thinning) and rapid recovery of mechanical properties when the applied stress is relaxed (self-healing), affording facile processing though direct injection or spraying approaches, making then well served for applications in biomedicine. Moreover, the hierarchical construction of these biphasic hydrogels enables innovative approaches to drug formulation and delivery as a diverse array of compounds to be entrapped and delivered over user-defined timeframes ranging from days to months. We demonstrate that these unique characteristics can be leveraged to generate vaccines exhibiting greatly enhanced magnitude, quality, and durability of humoral immune responses. Overall, this talk will illustrate our recent efforts exploiting dynamic and multivalent interactions between polymers and nanoparticles to generate hydrogel materials exhibiting properties not previously observed in biomaterials and affording unique opportunities in biomedicine.

12:15 PM - 12:50 PM - Solution Spotlights

Small Molecules

Preparation and evaluation of charge reversal solid lipid nanoparticles

  • Design and investigate solid lipid nanoparticles (SLN) providing an intestinal alkaline phosphatase (IAP) triggered charge reversion.
  • The combination of a PEG-corona and P-PEG-surfactants seem to be an effective tool, to prepare nanoparticles exhibiting a charge reversal effect comparable to nanoemulsions, which represent the most promising charge reversal lipid-based drug delivery systems so far
  • Observed results indicated that a high amount of incorporated monophosphate ester was enzymatically cleaved resulting in the most effective IAP induced charge reversion by nanoparticles.
  • Charge reversal SLN might be a promising tool for nanoparticulate drug delivery across alkaline phosphatase bearing membranes that are covered by a mucus gel layer such as the intestine.

Technology & Innovation

A Novel Approach to Justify Dissolution Differences in an Extended-Release Drug Product using Physiologically Based Biopharmaceutics Modeling and Simulation

In this work, a novel approach to establish in vivo similarity between higher and lower strength formulations without doing a BE study is presented. Physiologically Based Biopharmaceutics Model (PBBM) based approaches are also being encouraged by regulators with an effort to reduce unnecessary use of healthy human subjects for generic BE studies.

Device Development

Combination products under MDR (article 117)

  • The meaning of Article 117
  • The role and task of the Notified Body
  • Manufacturer responsibilities
  • Evidence and fulfilment of the GSPRs
  • Notified Body opinion

12:50 PM - 1:50 PM

Networking Lunch

1:50 PM - 2:25 PM - Case Studies

Technology & Innovation

Long-Acting Injectables – Biopharmaceutics and Drug Product Design

Pratik Saha, Global Head Biopharmaceutics , GSK

  • Cross-functional approach for LAI product design and development.
  • Mechanistic understanding of LAI performance
  • Integrated biopharmaceutics concepts and opportunities
  • Enterprise vision for LAI drug product development
This presentation will cover Long-Acting Injectables (LAIs) as a novel way to design and deliver patient-centric medicines. Mechanistic understanding around LAI product performance is required to ensure efficient design and development of patient-centric and stable drug product with robust control strategy. Integrated biopharmaceutics concepts will be discussed to build mechanistic understanding and drive differentiated product design.

Biologics

High-throughput, fluorescence-based esterase activity assay for assessing polysorbate degradation risk during biopharmaceutical development

Adithi Bhargava, Technical Development Scientist, Genentech

  • Hydrolytic degradation of polysorbate during 2–8°C storage of monoclonal antibody drug products has been attributed to residual enzymes
  • A fluorescence, plate-based esterase activity assay was developed as a monitoring and characterization tool for polysorbate degradation
  • High-throughput method allows for rapid characterization of monoclonal antibody samples
  • Esterase assay correlates directly with polysorbate degradation

Device Development

Role of Devices and MedTech in pharmacological treatment of chronic conditions

Karthik Lavakumar, Head, Device and MedTech Development, Takeda

  • How are chronic conditions unique?
  • Current limitations of a pharmacological only approach
  • How can devices and medical technologies improve the end-user experience and health outcomes
  • Future trends

Patients with chronic conditions that require regular ongoing pharmacological intervention have unique needs and drivers that impact their adherence, convenience which could ultimately impact their health outcomes. In such situations, devices and medical technologies when properly implemented can significantly impact the access, administration, adherence and care management. While implementing such technologies, al the stakeholders needs should be considered – prescribers, payers, care specialists, care givers and the patients. Once these are evaluated, an integrated ecosystem of pharmacological, devices and digital health solutions can be implemented to attain the desired healthcare outcomes. Technology is ubiquitous in our daily lives, and we are becoming more dependent on them. What are the future trends in improving the outcomes of chronic disease management and in personalized medicine?

2:25 PM - 3:00 PM - Case Studies

Small Molecules

Developing high drug load re-dispersible amorphous formulations

Mengqi Yu, Ph. D., Sr. Scientist I, Formulation Sciences, AbbVie

  • Formation of nanoparticles during ASD dissolution enhances oral absorption of poorly soluble drugs. The goal is to obtain amorphous nanoparticle formulation that can achieve same performance without a large amount of excipients compared to ASD.
  • Nanoparticles fabricated by solvent/anti-solvent precipitation can be stabilized by removal of organic solvent and drying. Understanding of API and formulation properties aids in design to obtain the solid form that redisperses into primary nanoparticles.
Amorphous solid dispersions can generate nanoparticles < 500nm during dissolution, which was reported to enhance oral absorption of poorly soluble drugs. However, the controlled dissolution and formation of nanoparticles require a large amount of excipients, presenting challenges for some drug product formulations. Directly engineered nanoparticles made by solvent/anti-solvent precipitation can be stabilized and dried into a solid form. This approach harnesses the effect of the drug-rich nanoparticles on oral absorption, while reducing use of the amount of excipients to obtain a high drug loading. In vivo study on animal model demonstrates this amorphous nanoparticle formulation can achieve comparable performance to commercial ASD product.

Biologics

Stress Factors in Primary Packaging, Transportation and Handling of Protein Drug Products and Their Impact on Product Quality

The impact of primary packaging-related stress on DP quality not only depends on the materials involved but also on the specific biotherapeutic molecule selected as the drug candidate, and the DP formulation, and therefore should be tested during (accelerated) storage, transportation and use for each specific product

Technology & Innovation

Transforming rectal therapies for ulcerative colitis using novel hydrogel formulation

Ravi Pamnani, Co-Founder/CEO, Intact Therapeutics Inc.

  • Rectal therapy is the most effective way to manage acute flares of ulcerative colitis, but current options either do not have adequate coverage of the colon (suppositories, foams) or are intolerable for patients (enemas)
  • Intact has developed a thermally responsive gel formulation which is self-administered as a liquid but transitions to a viscous gel inside the colon
  • Gel enables better retention of the formulation and potential for improved efficacy
  • Gel platform has been tested with mesalamine in clinical trials
  • Platform can be used to deliver range of therapies to the distal colon

3:00 PM - 3:30 PM - Case Studies

Small Molecules

Platform Strategy to Rapidly Bring Poorly Soluble Small Molecules to the Clinic

Helen Hou, Principal Scientist, Small Molecule Pharmaceutical Sciences, Genentech

  • In the past decades, a significant percentage of drugs and new chemical entities under development are poorly water soluble
  • Amorphous solid dispersions (ASDs) have become the strategy of choice for poorly soluble compounds, as they can increase the apparent solubility and dissolution rate of the drug when compared to the crystalline form, while also sustaining supersaturation for a biorelevant timeframe, thereby leading to enhanced oral bioavailability
  • A platform ASD approach enables rapid transition of drug candidates into First-in-Human clinical trials and expedites the development and manufacturing of the drug product to supply proof-of-concept (POC) studies and beyond with a scalable formulation

Biologics

Biopharmaceutics of mAbs: Challenges in Subcutaneous Bioavailability Prediction

This presentation will review the biopharmaceutics of mAbs with special emphasis on the subcutaneous absorption process and hypotheses behind incomplete systemic absorption. These are related to formulation-related events (e.g. precipitation at the site of injection or strong non-ionic interaction of mAbs with SC tissue) and physiological events (e.g. nonspecific metabolic degradation at the site of injection or during transit in the lymphatic system). A deeper understanding of these processes may facilitate developing better predictive tools, streamlined development, and cost savings.

Technology & Innovation

Vaccine Delivery via Microneedles

Yasmine Gomaa, Senior Research Scientist and Associate Director of the Laboratory of Drug Delivery, Georgia Institute of Technology

  • An overview of the microneedles: mechanism of delivery, shapes, advantages, applications, etc
  • Specific examples on drug delivery
  • Specific examples on vaccine delivery with some highlights on previous and future clinical trials we are planning
  • Future perspectives 

3:30 PM - 4:00 PM - Keynote

Device Development

Formulation & Device Lifecycle Management for Biotherapeutics - The Value of Platform Technologies

Andrew Ratz, Vice President, Drug Delivery and Device Development, Eli Lilly

This presentation will discuss advantages and disadvantages inherent to using formulation and device platform technologies to improve the drug delivery profile of medicinal products, highlight development and commercialization aspects that can be leveraged across different molecules and indications, as well as aspects that need to be assessed for each molecule individually.

4:00 PM - 4:35 PM - Panel Discussion

Technology & Innovation

How Will AI and Machine-Learning Technologies Change our Industry?

  • Digitalization starts in the labs where the data is produced – better invest in tablets for technicians than invest in the next big AI promise on the horizon?
  • The carrot: Try-out and implement advanced data analytics in very limited but easily overseeable use cases first
  • The stick: Proper data management is key to any digitalization effort!
  • Making the data FAIR creates already a first business value for data-driven drug product development
  • Big application use case for AI in drug product development?
  • Data wrangling: the 80-20 data science dilemma