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

Perspectives on Advancements in Formulation, Drug Delivery and Devices for Biologics

Donna French, Vice President, Dosage Form Design & Development, AstraZeneca

  • Patient centricity driving dosage form design and lifecycle improvements
  • Current and future direction of parenteral delivery devices
  • A multitude of approaches to solving the high dose delivery problem
  • Novel routes of administration and long-acting formulations
  • Formulation and drug delivery of new and novel modalities

Patient centric design of dosage forms is essential for product positioning in the marketplace and commercial success.  Aspects of biologics administration have become well-established, and the focus is on efficient and rapid development.  Key scientific challenges remain and are associated with formulation technologies and drug delivery systems that will improve the patient experience and enable delivery of an increasing diversity of biologics modalities.

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.

9:45 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
A polymeric prodrug platform has been developed for infectious disease and cancer therapeutics.  The “drugamers” can be designed to target the macrophage reservoir in organs and tumors, and with controlled and extended pharmaco-kinetic profiles. The polymeric prodrugs have been initially developed against pulmonary infections, where they have shown excellent activity against highly lethal bacterial disease models. The platform has been further broadened to include other pulmonary infectious disease therapy including antiviral therapeutics against Covid. The macrophage- and APC-targeting properties also have opened new applications for immune-therapy of cancer and vaccines, in concert with cell and biologic drug combination therapy. In addition, this platform has been extended to target drugs to the liver, using GalNAc targeting of liver hepatocytes to improve PK/PD and therapeutic index.   Finally, the polymeric prodrugs are also showing promise as a new long-acting depot product for antiviral therapies, including HIV prophylaxis. Recent advances across these applications will be covered.


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.

10:20 AM - 10:50 AM - Solution Spotlights

Small Molecules

Modified Release Development Strategies to Achieve Your Target Product Profile

Helen Baker, Director, Pharmaceutical Sciences, Quotient Sciences

  • Bridging from an Immediate Release (IR) formulation to Modified Release (MR) - What drives the need and what are the benefits?
  • Key formulation design strategies and technologies – Which approaches to deploy?
  • The relationships between formulation parameters, in-vitro data and in-vivo performance – Can we establish an IVIVC?
  • The use of Design Space concepts – How to evaluate and optimize formulation performance “real-time” using clinical data
  • Featured Case Studies on Modified Release Drug Programs and MR Best Practices
A large number of modified release (MR) technologies are available to drug developers, each designed to fulfil very specific performance requirements, such as gastro-retention or sustained-, pulsatile-, or delayed- release formats. The design and development of an effective MR formulation is however an inherently complex process, presenting many challenges for the development team. Human GI anatomy and physiology strongly influences drug release and performance of MR dosage forms. Challenges are further exacerbated by an over-reliance on in vitro and preclinical test results to inform formulation prototype selection, despite evidence that these data often correlate poorly with PK performance in humans.

In this presentation Helen will discuss the drivers for MR development and key considerations for rational formulation design and technology selection. Using case studies, she will describe the specialized formulation technologies that are available in the “toolbox” in order to achieve an optimal target product profile, and the use of innovative, adaptive clinical programs where human PK data is used to optimize MR formulation compositions in real-time.


Understanding Biopharmaceutical Detergents

Stephen Rumbelow, PhD., Life Sciences Research Fellow, Croda

  • The role of detergents in biopharmaceutical formulations
  • Discussing the stability of detergents in biopharmaceutical formulations
  • Exploring formulation effects on detergents
Polysorbates are the workhorse detergents used in biopharmaceutical formulations due to their long established ability to protect therapeutic proteins from interfacial stresses which can other wise lead to protein aggregation. However, research over the last decade has highlighted that polysorbates can undergo oxidative or enzymatically driven degradation with potential knock on impacts to the stability of the biotherapeutic formulation. In this talk key attributes of polysorbates will be reviewed regarding the complexity and consistency of polysorbate structure depending on polysorbate source and quality grade, followed by an exploration into differing impurities present in polysorbates dependant on their quality. Ultimately the effect of these polysorbate qualities will be discussed in the context of storage stability, aqueous solutions along with glass and buffer effects on specific polysorbate species stability, followed by the effect of enzymes on polysorbate derived particulates and the consequences of polysorbate quality on protein aggregation.

Device Development

Patient-Centric Device Solutions for Subcutaneous Biopharmaceutical Delivery

Dr. Ingo Waschulewski, Business Development & Sales Manager, Gerresheimer AG

  • On-body drug delivery devices
  • Cartridge-based autoinjector
  • Subcutaneous drug delivery devices for home use
  • Biologics and monoclonal antibodies injection
  • Device connectivity
  • Small volume (< 3 ml) to large volume (> 10 ml) s.c. drug delivery
Safe, reliable and easy application at home or home-like environments are the main needs when it comes to developing drug delivery devices in near future. Furthermore, better adherence monitoring and patient compliance are demanding a more complex device functionality such as connectivity features. With focus on the individual needs of patients, healthcare professionals as well as pharmaceutical companies for certain therapeutic areas such as oncology, immune system disorders or chronic diseases, Gerresheimer device solutions are specifically tailored to fulfill the requirements for biopharmaceuticals. The cartridge-based Gerresheimer autoinjector for biologics covers a broad range of injection volume from 1.5 to 3ml. The SensAIR technology is designed to address injection of larger volumes up to 20 ml with an on-body device. Both devices enable the injection of large molecule biopharmaceuticals over a desired application time.

10:50 AM - 11:40 AM

Networking & 1-2-1 Meetings

11:40 AM - 12:10 PM - Case Studies

Small Molecules

Amorphous Solid Dispersions (ASD) – Considerations in Product Development

Raman Iyer, Associate Director, Technical R&D, Novartis Pharmaceuticals Corp.

  • ASD in current market place  
  • Challenges and considerations in early and late phase ASD development
  • Technologies and Analytical Characterization
  • The Future - Novel materials, Data Science and Modelling
Amorphous Solid Dispersions (ASD) are enabling delivery systems that primarily improve the oral bioavailability of poorly soluble, crystalline drugs. The development of ASD 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 formulation composition and technologies used to manufacture, package and characterize ASD in a market product play an important role in the kinetic stabilization process and determination of drug release metrics. Considerations in early phase development include establishing solubility and supersaturation limits, determining drug polymer affinity and enabling a molecular level dispersion with high drug loading with a suitable technology. The challenges in late phase development include conversion of ASD to an acceptable market product governed by physical and mechanical properties, scale-up of technology and commercial registration, ensuring stability of ASD through shelf-life storage and acceptable performance in clinical and relative bioavailability studies. Throughout the development process, analytical characterization of ASD plays a key role in determining its quality attributes. 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 ASD as a delivery system, reduce cycle time of development and provide highly differentiated and value-added medicines to patients.


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
Lipid nanoparticles (LNPs) are gaining traction in the field of nucleic acid delivery following the success of two mRNA vaccines against COVID-19. As one of the constituent lipids on LNP surfaces, PEGylated lipids (PEG-lipids) play an important role in defining LNP physicochemical properties and biological interactions. Previous studies indicate that LNP performance is modulated by tuning PEG-lipid parameters, including PEG size and architecture, carbon tail type and length, and PEG-lipid concentration. Owing to these numerous degrees of freedom, a high-throughput approach is necessary to fully understand LNP behavioural trends over a broad range of PEG-lipid variables. We report a low-volume, high-throughput screening (HTS) workflow for the preparation, characterization, and in vitro assessment of LNPs loaded with a therapeutic antisense oligonucleotide (ASO). A library of 54 ASO-LNP formulations with distinct PEG-lipid compositions was prepared using a liquid handling robot and assessed for their gene silencing efficacy in murine neurons. Our results show anionic PEG-lipid concentration regulates LNP particle size. In contrast, PEG-lipid carbon tail length controls ASO-LNP gene silencing activity, with up to 5-fold lower mRNA expression achieved in neurons treated with ASO-LNPs as compared to naked ASO. We then scaled up the HTS hits using a well-established microfluidic formulation technique, demonstrating a smooth translation of ASO-LNP properties and in vitro efficacy across different formulation scales. Our HTS workflow can be used to screen additional LNP multivariate parameters with significant time and material savings, guiding the selection and scale-up of optimal formulations for nucleic acid delivery to various cellular targets.

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 - 12:45 PM - Solution Spotlights

Small Molecules

Melt-Extruded Dexamethasone Ophthalmic Implants: Process, Structure, and in vitro Drug Release

Dr. Feng Zhang, Associate Professor Molecular Pharmaceutics and Drug Delivery , The University of Texas at Austin College of Pharmacy

  • Dexamethasone is dispersed in PLGA matrix as crystalline particles
  • Accurate dimension control is achieved with a two-step extrusion process and two-stage feeding with a purpose-built downstream puller.
  • Critical features of implants: diameter, pore size/distribution, and surface roughness
  • Tri-phasic drug release profiles with drug release controlled by the erosion of the implant matrix
The presentation discusses the (1) structure of dexamethasone implant, (2) in vitro release characteristics of dexamethasone implant, and (3) a manufacturing process for precise dimension and structure control.

Technology & Innovation

The Early-Development Journey of a Small Molecule: An Integrated Perspective

Beth Negash, Scientist III in the Solid Oral Formulation Development, Catalent Pharma Solutions

In the era of seamless drug development, reducing time to the clinic and getting rapid regulatory approval has become the goal of nearly every early drug development sponsor. Handling drug development, manufacturing, and clinical supply efficiently can help sponsors save costs and provide maximum benefit for patients. In order to improve the efficiency of the drug development continuum, integrated solutions have become an effective option for sponsor companies to streamline the transition from early development to the clinic, in addition to providing timely clinical supplies to help keep study timelines and budgets on track.

In this session, learn about the benefits and challenges of integrated approaches, as well as insights on whether integrated solutions can be the key to achieving today’s more aggressive development milestones. Examples of real-life tactical and operational decisions involved in the integrated approach to drug development will also be presented.

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.

12:45 PM - 1:45 PM

Networking Lunch

Lunch & Learn Roundtable:

Fundamentals of RNA Lipid Nanoparticle Formulations

This lunch and learn aims to provide:
  • An understanding of the mechanisms of lipid nanoparticle mediated delivery of RNA into the cytoplasm with a molecular level view of endosomal release
  • A molecular level understanding of the mechanism of RNA-LNP self-assembly
  • Structural and mechanistic differences between liposomes and LNPs
  • An overview of process and chemistry considerations for optimizing RNA-LNP formulations
  • An overview of drug substance and drug product manufacturing
Moderated by:
Shell Ip, Phd, Client Learning & Scientific Content Manager, Precision-NanoSystems Inc. 

1:45 PM - 2:15 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.

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
A large number of noncoding RNAs have key roles in the regulation of cellular functions. The dynamic nature of RNA leads to its motion and deformation behavior. These conformational transitions, such as breathing within the complementary area, pseudoknot formation at the 2D level; induced fitting by substrate interaction, conformational capture by key and lock, and shifting in base pairing all are important for their biological functions including tissue binding, cell entry, gene regulation, and protein translation. Their dynamics, catalytic and motile features have led to the belief that RNA is the origin of life. We recently reported that the rubbery, amoeba and shape-shifting properties of RNA nanoparticles enhance their penetration through leaky blood capillary, leading to efficient accumulation in tumor vasculature. These dynamic, motile, and deformable properties of the RNA nanoparticles also enable the RNA nanoparticles to pass through the glomerulus, overcoming the filtration size limitation, resulting in rapid renal excretion and fast body clearance, therefore low or no toxicity. The performance of RNA nanoparticles can be further improved by incorporating cancer-targeting ligands. The inherent negative properties of RNA charge reduce nonspecific cell binding and organ retention due to the repulsion with the cell membrane which is also negatively charged. The multivalent nature of RNA nanoparticles allows for multi functionalities, which can be applied as an approach to overcome drug resistance. In addition to favourable biodistribution characteristics, RNA nanoparticles have other unique properties including self-assembly, programmable synthesis, advantageous size; antigenicity free, large volume distribution, CMC ease, solubilizing drugs, and high payload. All of these make them an excellent material for pharmaceutical applications. RNA drug has become the third milestone in pharmaceutical drug development!

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.

2:20 PM - 2:50 PM - Case Studies

Technology & Innovation

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.


Approach to Critical Quality Attributes (CQA) Designation of Lipid Nanoparticles Enabling Gene Therapies

Keeth Jain, Associate Director, Drug Product Tech Transfer, Generation Bio

  • Critical Quality Attributes
  • Approach to CQA and Criticality Roadmap
  • Quality Attributes Classification
  • Assessment Rubric
  • CQA Assessment Process Flow
  • Example Criticality Assessment

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
The medical device industry today is a fast paced environment filled with application of new technologies and challenging integrated corporate collaborations. Combination products have brought the complexities of drug products to the medical device industry and have required the development of many new methods of drug delivery. The future brings digital device integration to simplify user interfaces and improve patient safety. Some technologies in this area are already in approved products.

Biologic drugs create delivery challenges with high viscosities. New electro-mechanical devices have started to meet these challenges. Pre-filled syringe and cartridge systems have been developed to optimize torque and the forces required to move the drug through small diameter needles or directly through the skin. New on-body systems have addressed these user needs and have been developed into platform products that include large volumes.

SaMD is active in the combination product world and in the diagnostics area for monitoring sleep and other biorhythms. Digital-Device combinations are more common now in the consumer product area. As we meet the challenges to integrate advanced digital systems into medical devices we will improve the standard of care not only in the health care industry but also at home!

2:50 PM - 3:40 PM

Networking & 1-2-1 Meetings

3:40 PM - 4:10 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


Accelerating the Development of RNA-Based Medicines: A Case Study on Developing an mRNA-LNP-based COVID-19 Vaccine

Viet Anh Huu Nguyen, Senior Field Application Scientist, Precision NanoSystems Inc.

  • RNA-lipid nanoparticle (RNA-LNP) medicines are a proven manufacturable and scalable modality for genomic medicines, enabling silencing, expression, and editing specific genes
  • Precision NanoSystems has developed a Genomic Medicine Toolbox, comprising of lipid reagents, as well as the NanoAssemblr® microfluidic manufacturing platform, enabling end-to-end development of RNA-LNPs
RNA can be designed to silence, express, and edit specific genes providing a flexible and powerful approach to treating or preventing diseases. The recent success of RNA-lipid nanoparticle (RNA-LNP) COVID-19 vaccines has exemplified the massive potential and need to rapidly develop and scale up new genomic medicines to protect from emerging viral threats and treat a wide range of serious diseases with unmet medical needs.

Due to the RNA degradation and low cellular uptake, an essential element of genomic medicines are LNP-based delivery systems. Precision NanoSystems has developed a Genomic Medicine Toolbox for the end-to-end development of RNA-LNPs. The toolbox comprises off-the-shelf and proprietary lipid nanoparticle reagents, the NanoAssemblr® microfluidic nanoparticle manufacturing platform, and in-house expertise in formulation and process development. In this presentation, we provide examples of how these platform technologies are enabling (bio)pharma companies and research institutions to rapidly discover new RNA-LNP vaccines, gene therapies, and cell therapies and seamlessly scale them towards the clinic.

Device Development

Effect of Silicone Oil Viscosity on Observed Particle Counts in Parenteral Container Closure Systems

Jeff Smythe, Commercial Development Manager, Datwyler Pharma Packaging

In this study we looked at various grades and viscosities of silicone fluid both neat and as an emulsion to understand their effect on the subvisual particle load on the closures on which they were applied.

This information gives parenteral developers a science and risk based strategy to qualify primary parenteral packaging and enables them to make informed decisions based on quantitative data from this study.

Silicone oils provide the advantage of reducing friction, they also have drawbacks which can include transfer to filling line surfaces. Moreover, interactions with proteins and other drugs, causing haze on reconstitution of lyophilized drugs can occur as well as formation of subvisible and visible particles that frequently are counted as part of the overall particle burden in finished parenterals.

4:15 PM - 4:45 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.
Dasabuvir is a non-nucleoside polymerase inhibitor for the treatment of hepatitis C virus (HCV) infection. It is an extremely weak diacidic drug (pKa = 8.2 and 9.2) and a prolific solvate former. Due to its exceedingly low aqueous solubility (≤ 0.127 µg/mL at pH 1 ‒ 6.8, dose number of 1.31 × 104), crystalline dasabuvir free acid exhibited poor oral bioavailability in animal PK assessment. While salt formation has been widely used to enhance solubility and dissolution rate of solids, this approach has rarely been applied to develop oral solid dosage forms for acidic drugs as weak as dasabuvir due to concerns of rapid disproportionation and crystallization of free acid. In this presentation, we highlight our efforts in identifying dasabuvir monosodium monohydrate as drug substance that is stable, manufacturable, and significantly enhances dissolution and oral absorption of this poorly soluble drug. The oral delivery of dasabuvir through salt approach has enabled the commercialization of triple combination direct acting antiviral HCV regimen Viekira Pak. The methodologies and solutions identified in targeted studies to overcome technical challenges (i.e., incorporation of polymers to inhibit crystallization and disproportionation and species mapping to enable salt manufacturing process, etc.) can be applied to other insoluble compounds.


Long Acting Biologics: A Steep Climb

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

  • Long-acting formulations for biologics address critical patient needs, and industry trends suggest a growing interest.
  • We will discuss what challenges are to be overcome to capitalize on long-acting formulation opportunities.
  • Predictive and investigative tools have to be developed to achieve success and innovation.
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.

4:50 PM - 5:20 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.


Liquid Pre-Formulation Assessment for Monoclonal Antibodies and New Modalities

Shwetha Iyer, Principal Scientist, Novartis

  • The roll out of the 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.
  • With early assessment for monoclonal antibodies, this success rate was close to 90%, wherein we saw that the data provided by our preformulation team was crucial to lockdown the Clinical service formulation in development organization.
  • However, the portfolio now changing more towards non-mAbs such as Fc silencing formats, bispecific mAbs, therapeutics proteins and newer modalities such as gene therapies and AAV’s, designing a stable liquid formulation is more challenging. Moreover, platform formulations alone cannot be assessed for such modalities in the preformulation phase due to the complexity of the molecule and the narrow space for liquid formulations.  Hence, a co-development of the clinical service formulation between the research and development organizations could enable in an in- depth understanding of the degradation pathways and the possibility of a stable liquid formulation.
  • When divided into different work packages that comprises of the use of forced degradation studies and high throughput biophysical predictive tools, we could potentially answer key developability questions in the space of formulations.
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 Large Volume Subcutaneous Drug Delivery
  • Technology/Product Landscape
  • Existing Challenges and some potential solutions
  • Conclusion
Biologics drug delivery has been driven by the trends towards self-administration, accelerated momentum behind biologics, differentiation in more competitive markets and patent expiration of certain block buster drug.   Large volume subcutaneous injector offers unique value due to its capability to deliver a large volume in a patient friendly way.   This presentation will start with a review of current technology and product landscape.  Then, the focus of the discussion will be on some known challenges with large volume subcutaneous delivery and potential solutions.

5:25 PM - 5:55 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
Next generation combination products are emerging as innovative medical products due to their contribution in advancing medical care and are expected to have a major impact in the coming years.  Future technologies are most appealing to patients with ongoing medical conditions that require consistent treatment with daily injections or weekly procedures and unmet medical needs. The opportunity to work within the combination product space and to work cross functionally with medical device, software, pharmaceutical and biologic experts will be a great experience which will involve a ton of knowledge sharing across the team of experts.  While there are similarities there are also many differences in the development of various combination product therapeutic applications. Overall, the successful development of combination products will require significant collaboration within the industry to overcome regulatory, clinical, technical and lifecycle management challenges.

5:55 PM - 6:05 PM

Poster Presentation

6:05 PM - 6:10 PM

Chair’s Closing Remarks

6:10 PM - 7:10 PM

Evening Drinks Reception

8:00 AM - 8:15 AM

Registration & Refreshments

8:15 AM - 8:20 AM

Chair’s Opening Remarks

8:20 AM - 9:05 AM - 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, and (3) impact of critical properties and “natural” variations of polymers on product quality and performance, such as dissolution, stability and in vivo absorption.

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

Small Molecules

3D Printing in Development of Pharmaceutical Dosage Forms and Personalized Medicine

Fakhrul Ahsan, Ph.D., Distinguished Professor, California Northstate University

Current technology for development and fabrication of tablets is time consuming and resource intensive that involves the mixing and milling of drugs and additives, preparation and sizing of granules, coating and multiple compression and even drilling of holes into some types of tablets. In case of any change in the shape and size of a tablet, the tableting machine requires a completely new set of tools to match the new shape and altered size. Thus, currently tablets can only be fabricated in large manufacturing facilities, which are not amenable to small-scale fabrication and preparation of personalized dosages. Further, existing tableting machines are not portable because they weigh thousands of pounds and require a separate room for placement. Using the existing technology, we cannot prepare tablets based on patients’ needs, such as elderly patients who take multiple tablets a day or who may not be responsive to a given dose. The 3DP technology can be used to design and fabricate pharmaceutical products and so to reduce the number of processes, eliminate the requirement of equipment retooling, and avoid large manufacturing facilities. We believe 3DP will help personalize treatments:  pharmacists can prepare pills at patients’ bedside such as in hospital and long-term care facilities. Being portable and flexible, 3DP can be used to fabricate tablets of different doses, release profiles, sizes, and shapes, just by changing the computational design. Perhaps, one day, we can prepare and dispense tablets on an as-needed basis instead of making millions of pills in advance, many of which end up in the landfill after expiration. The 3DP technology can be deployed in makeshift hospitals, battlefields, and in areas afflicted by natural disasters. The technology would be at the disposal of health care professionals in case of national emergencies or when commercial products are in short supply.

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.

Device Development

Strategies and Approaches for Integrating Multi-Sourced Syringe Components into Combination Product CM&C Development

Pete Sargent, Advisor—Engineering , Eli Lilly and Company

  • Drivers for Second Sourcing
  • Considerations in Source Selection
  • Strategies for Performance Evaluation
  • Case Study
The efficiency of delivery and improved patient experiences have long made pre-fillable syringes preferred options for incorporation into drug/device combination products.  Pharmaceutical companies often source these constituent components, e.g. syringe barrels and elastomeric plungers, from multiple suppliers to maintain business continuity, lower manufacturing cost(s), and to ensure reliable and consistent supply of these products to patients. However, inclusion of multi-sourced components in a clinical asset, or a marketed product, can significantly increase CM&C development complexity, adding cost and timeline risk. This presentation discusses a streamlined strategy for selecting, developing, and integrating multi-sourced syringe components into CM&C development.  Bracketing and matrixing principles are leveraged to reduce development study design while still producing robust suitability, equivalency, and stability data packages required to support regulatory submissions.  Approaches to assessing and mitigating specific timeline, regulatory, and technical risks are also discussed in detail.

9:45 AM - 10:15 AM - Case Studies

Small Molecules

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

Raman Iyer, Associate Director, Technical R&D, Novartis Pharmaceuticals Corp.

  • 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.
  1. Choice of excipients and additives in formulation is guided by safety and intake limits, duration of treatment and regulatory acceptance
  2. Drug substance stability, compatibility and ADME profile from adult program can be reasonably adapted for pediatric drug development
  3. Product design and user experience are key to developing a target product profile (TPP) that ensures safety, quality and patient compliance


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

Show more

Device Development

Formulation and Device Considerations for Subcutaneous Delivery

Steven Persak, Director, Device Development, Merck

William Forrest, Principal Scientist, Sterile & Specialty Products, 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
Subcutaneous (SC) delivery of biotherapeutics is often preferred over other routes of administration, i.e. intravenous (IV). This presentation provides an overview of subcutaneous products with a focus on those that have developed IV and SC formulations. We will discuss aspects of target product profile (TPP) development critical to enabling SC delivery, both from formulation and delivery device perspectives. Once the TPP is established, the focus then moves towards identifying early challenges and opportunities. This includes deploying a strategy for formulation and delivery technology selection that identifies both innovative (best in class) and robust, risk averse options. We will include in this presentation methods and approaches to leveraging the interplay between formulation and device to down select toward the most appropriate target image.

10:20 AM - 10:50 AM - Solution Spotlights

Small Molecules

The Developability Classification System as a Guide in Drug Formulation

Dr Daniel Joseph Price, Director – Head of Excipients Solid Application , MilliporeSigma

  • Poor solubility is a critical challenge to be overcome during drug formulation
  • The root-cause of low solubility can be understood using the developability classification system
  • This system can allow a more targeted and cost-effective development of formulations for oral solid dosage forms
  • For dissolution limited compounds, incorporation of dissolution enhancers can overcome low solubility
  • For solubility limited compounds, amorphous solid dispersions can overcome low solubility
The developability classification system (DCS) was proposed as a modification of the BCS to assist in formulation of poorly soluble compounds. The DCS introduced two new compound categories: dissolution limited (DCS IIa) and solubility limited (DCS IIb). For DCS IIa molecules, particle size reduction and wetting agents can be considered. For DCS IIb compounds, solid state modification can be utilized. Tune in to our webinar on the developability classification system to learn more about this emerging field of research, which is allows more targeted and optimized formulation development of poorly soluble compounds.

Technology & Innovation

Streamlining End-to-End Amorphous Formulation Development into a Tablet Suitable for Continuous Direct Compression

Pedro Valente, R&D Director - Oral Drug Product Development , Hovione

  • Learn how bioavailability enhancement of Amorphous Solid Dispersions (ASDs) can vary from one to three orders of magnitude by optimizing both ASD and tablet formulations and processes
  • Learn how state-of-the-art tools and methodologies can shorten time to Phase I/IND by accelerating formulation and development process  
  • Learn how Dispersome(R) technology, based on natural proteins derived from milk, broaden the formulation landscape enabling high drug load and high performing formulations
  • Learn how ASD formulations manufactured by spray drying can be designed to be directly compressible by Continuous Tableting
  • Learn more how Continuous Tableting is enabling disruptive innovations in the Pharma industry with respect to quality, scalability and improving supply chain flexibility and broadening Lifecycle Management options.

Technology & Innovation

An End-to-End Pharmaceutical Development Pathway to Rapidly Bring Poorly Soluble New Chemical Entities to the Market

Santipharp Panmai, Vice President & Head of Early-phase Formulation Development, WuXi STA

  • End-to-end pharmaceutical development of poorly soluble compounds
  • Enabling formulations for clinical and market formulations
  • Integrated CMC services to expedite formulation development
  • Development and manufacture of bioavailability-enhancing formulations
  • Case studies including spray-dried dispersion and nanoformulation
This presentation outlines an end-to-end pharmaceutical development pathway to rapidly bring poorly soluble compounds to the clinic and to the market. The pathway encompasses the use of bioavailability-enhancing formulation platforms as well as integrated CMC services. Various bioavailability-enhancing formulation approaches are available to facilitate development and manufacture of clinical supplies. The development can be accelerated further by leveraging integrated CMC services that include drug product with drug substance as well as analytical and regulatory functions. Case studies covering early-stage and late-stage development of spray-dried dispersion and nanoformulation will be provided.

10:50 AM - 11:40 AM

Networking Break & 1-2-1 Meetings

11:40 AM - 12:10 PM - Case Studies

Technology & Innovation

Alternative Routes of Administration for ADCs

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

  • Rationale for alternative, non-intravenous routes of administration for ADCs
  • Unique challenges for delivery of ADCs in comparison to other modalities
  • Alternative dosage form insights that can be drawn from small biologics and biologics
  • Case studies for alternative routes of administration of ADCs
  • What does the future hold for ADC delivery?
Antibody drug conjugates (ADCs) have rapidly grown in prominence across clinical development pipelines and as commercial products over the past decade, specifically in oncology. These complex molecules offer tremendous potential to combine the advantages of two separate modalities – monoclonal antibody and cytotoxic small molecules – leveraging both the ability to have an antigen-targeted therapy with a highly potent cytotoxic payload. This talk will discuss alternative routes of administration and alternative dosage forms of ADCs to mirror their growing clinical and commercial maturity, and the unique challenges and opportunities in moving away from a purely intravenous delivery model.


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.

Device Development

Enhancing Patient-Centricity During Product Development

Casey Dean, Manager, Device Development, Tolmar

  • Defining and integrating a human-centred perspective into our innovation and product development process
  • Creating and strengthening processes for defining use cases and understanding user need
  • Eliminating knowledge gaps to make data-driven decisions by better understanding the link between insights and potential downstream impact.
  • Challenges with implementation of a patient centric approach to product development.
  • Making the best selection for each program; striking a balance between desirability, feasibility, and viability
The healthcare landscape continues to evolve. Patients are playing larger roles in their own disease management, drug technology, including formulation, device capabilities, and administration modalities, are changing drug delivery and patient experiences, and market competition is stronger than ever amidst a complex ecosystem of stakeholders (i.e., HCPs, payers, etc.). By understanding the key stakeholder’s needs, we can optimize product solutions to deliver the best “blended value” for success.

12:15 PM - 12:45 PM - Solution Spotlights

Small Molecules

Nanoparticle Engineering: The Small Ingredient Enhancing Formulations

Dr Christopher Worrall, VP US Business Development, Nanoform

  • Nanoparticle engineering technologies such as CESS® have the power to enhance the pharmacokinetic properties of crystalline or amorphous APIs, maintaining tight control of particle size distribution and polymorphism.
  • This is supported by case study examples, including for budesonide, fenofibrate and atovaquone.
  • This presentation will showcase the data demonstrating the enormous power of nanoparticle engineering, and further discuss how nanoformed particles can even enable oral formulations with delayed release.
  • The wider implications for drug development will also be explored.
This presentation will dive into the power of advanced nanoparticle engineering technology, and in particular Controlled Expansion of Supercritical Solutions (CESS®), for controlling particle size distribution, crystalline vs. amorphous form, polymorphism, and for enhancing pharmacokinetic properties. It will feature case study examples of controlled nanoparticle formation for budesonide, fenofibrate and atovaquone. The talk will showcase in-vivo and in-vitro data demonstrating how nanoparticle engineering can be applied to enhance dissolution and even enable oral formulations with delayed release. The broader implications for drug development will also be discussed.

Technology & Innovation

Innovative Gastro-Retentive Drug Delivery Technologies for Improving Therapeutic Outcomes of Oral Drugs

Pavan Handa, MBA, Senior Vice President, Specialty Portfolio Management, Amneal Pharmaceuticals

Dipen Desai, PhD., MBA, VP Formulation & Analytical, Amneal Pharmaceuticals

  • Differentiating features of next generation gastro-retentive technologies and their utility in untapping the therapeutic potential of a wide range of molecules
  • Advanced gastro-retentive drug delivery in combination with solubility enhancement techniques for challenging oral compounds to address low bioavailability, high doses, and poor tolerability
  • Case studies of drugs using these technologies to improve the drug’s efficacy, adverse events, and compliance

Device Development

Using Early Drug Development Decisions to Facilitate and Accelerate Device Development Strategies

Jerzy Wojcik, VP Regulatory and Quality Services, EdgeOne Medical Inc

Too often the development of the device constituent of a combination product continues to be reactive to the drug development deadlines.

This case study presentation will focus on how decisions early in the drug development program can be leveraged for creation of the device strategy, timely execution of selected strategy and earlier insights of risks to timelines, safety and cost.

12:45 PM - 1:45 PM

Networking Lunch

1:45 PM - 2:15 PM - Case Studies

Technology & Innovation

Melting Microneedle Patches: A Novel Approach from the Manufacturing and the Delivering Aspects

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

  • Introduction to the novelty of this microneedle based approach
  • Optimization of the microneedle manufacturing and in vitro characterization
  • Specific application examples showing solutions to existing constrains/problems and added benefits to the current status of microneedle-based delivery systems  


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
Realization of magnificent potential of biologicals requires targeted delivery to the desirable sub-cellular compartments in the cells of interest. To achieve this goal, we as hundreds of other labs devise drug delivery systems (DDS), artificial - liposomes and nanoparticles, or natural such as proteins, cells and cell fragments. The intravascular targets include endothelial cells, lining the blood vessels, blood cells and components of the reticuloendothelial system (RES), all directly accessible to blood. In order to shift the uptake of DDSs circulating in the vascular system from high-capacity capturing by RES, we and others employ ligands of the epitopes that specifically exposed to blood from endothelial cells in the vascular areas of interest. The roster of such epitopes includes cell adhesion molecules (e.g., PECAM, ICAM, VCAM) and other endothelial markers. Liposomes. LNPs, fusions and other CAM-targeted carriers and DDS offer improved localization and effect. DDS featuring dual affinity to endothelial cells and red blood cells (RBCs) bind to RBCs, circulate on the surface of RBCs and transfer to endothelial cells expressing secondary binding sites (RBC hitchhiking). RBC carriers may also change other parameters of DDS pharmacokinetics (PK) and targeting. We will discuss examples of DDSs with solo avidity to endothelium or RBCs, as well as DDS with dual avidity to the vascular target cells.  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.

Device Development

Role of Devices and MedTech in Pharmacological Treatment of Chronic Conditions

Karthik Lavakumar, Head, Device and MedTech Development - Plasma Derived Therapies, 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?

2:20 PM - 2:50 PM - Solution Spotlights

Small Molecules

Target Product Profile-Based Product Development: The Importance of Using a Holistic Approach for Your Program

Lisa Caralli, Senior Director, Scientific Advisory, Catalent

A key element of a drug product’s long-term success is its Target Product Profile (TPP), specifically in building a framework for understanding patient needs, market differentiators, and potential hurdles in the development of a new product. Traditional dosage form design and development is frequently driven by cost and timeline constraints; however, additional profiling is required to make the program commercially successful. For example, a holistic evaluation of factors including pharmacokinetics, stability, patient compliance, disease state, and IP or market protection can significantly impact the product’s ultimate market success.

In this session, learn about the importance of a holistic approach to drug development and using the TPP to identify and address key considerations that will ensure a robust drug design strategy. Case study scenarios will illustrate how a holistic assessment of an API’s biopharmaceutic properties, manufacturability, market requirements, and target patient population has helped innovators identify the most suitable development path to ensure their product’s success.

Device Development

Design and Development Challenges in Direct–to–Organ Drug Delivery Platforms

Harshal Shah, Head of Global BioPharma Commercial, Cambridge Consultants

Join Cambridge Consultants' Harshal Shah, head of global BioPharma medical technology, as we discuss what are the design and development challenges in direct-to-organ drug delivery platforms:
  • Many new therapies require administration directly to organs, tissues or even tumors.
  • Selection of the delivery method and device technology will depend on accessibility of target site, surrounding anatomy, drug volume, formulation characteristics and frequency of drug administration.
  • The options to consider are: miniature active implants, purpose built delivery systems with embedded visualization and navigation technologies or drug handling and delivery tools designed to be compatible with existing surgical robotic systems.

2:50 PM - 3:30 PM

Networking Break

3:30 PM - 4:00 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.


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
Hydrolytic degradation of polysorbate during 2–8°C storage of monoclonal antibody drug products has been attributed to residual enzymes from
bioprocessing steps. Robust detection of esterase activity using non-polysorbate surrogate substrates can provide an alternate and faster
method to assess polysorbate degradation risk, if the correlation between the esterase activity and polysorbate degradation is established. A
general esterase activity assay, utilizing 4-methylumbelliferyl caprylate (MU-C8) as the esterase substrate, was developed as a monitoring and
characterization tool during bioprocess development of monoclonal antibodies. The assay was first assessed for substrate, inhibitor and pH
specificity using both model enzymes and purified protein samples. In addition, the assay was tested to understand sample matrix effects on
activity rates. The use of this high-throughput method allows for rapid characterization of protein samples in under three hours. The esterase
activity also correlated directly with polysorbate degradation, providing valuable information on polysorbate degradation risk throughout drug

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
Current rectal therapies for ulcerative colitis are either intolerable (enemas) or provide limited proximal reach (suppositories, foams). Thermally responsive hydrogels have been widely used as pharmaceutical excipients but their thermosensitive gelation properties have not been leveraged, particularly for at-home use formulations. The first, at-home use thermosensitive rectal gel provides significant advantages over other rectal dosage forms, with respect to drug release, retention, and patient comfort. The gel platform has the potential to deliver a range of therapies to the distal colon, including both small and large molecules.

4:05 PM - 4:35 PM - Case Studies

Small Molecules

Microstructure, Properties, and Drug Release Performance of ASDs Prepared by Different Processes

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

Formulating poorly water-soluble compounds as amorphous solid dispersions (ASDs) is one of the most promising approaches to enhance solubility and/or dissolution, and membrane flux to improve bioavailability. Due to the unstable nature of amorphous materials and the underlying principle for their formation, it is clear that the manufacturing technology and process conditions would impact ASD material characteristics and properties, and in turn in vivo performance. The purpose of this work is to evaluate the interrelationship of microstructure, properties, and dissolution performance for ASDs prepared using spray drying and co-precipitation via resonant acoustic mixing. We applied both conventional characterization tools and X-Ray Microscopy (XRM) to assess the contribution of microstructure to the characteristics of ASDs and obtain additional quantification and understanding of the drug product intermediates and tablets. The results showed strong interrelationship of microstructure, particulate and bulk powder properties, and dissolution performance for ASDs. XRM image-based analysis is a powerful tool to assess the contribution of microstructure to the characteristics of ASDs and provide mechanistic understanding of the interrelationship.

Technology & Innovation

Development of tumor-targeted-combination therapies on PEGylated gold nanoparticle platform

Giulio F. Paciotti, Ph.D., Chief Science Officer , CytImmune

Session Abstract TBC

4:40 PM - 5:10 PM - Keynote

Device Development

Delivery Devices at Lilly – Evolution and Future Trends

Karthik Vaideeswaran, Associate Vice President, DDCS (Delivery, Device and Connected Solutions), Eli LIlly

Drug-Device integration and interactions
  • Container-Closure/Device interface
  • Tissue/Needle interface
Current challenges and potential pathways
  • High dose delivery
  • Large volume injections
  • Injection tolerability
  • Delivery/device preference
Concluding remarks and a look into the future

Drug delivery is a complex subject that requires the interdisciplinary engagement of various science and technology functions as well as the discipline of project management to effectively drive the development and commercialization of drug-device combination products to the market.