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

Small Molecules

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

Microstructure Bioequivalence of Polymer-based Long-acting Drugs

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

The study will determine the relationship between the drug microstructure (including microporosity) and in vitro release characteristics. The effect of manufacturing conditions on the release properties and physicochemical characteristics will also be examined. The project seeks to establish quantitative microstructure imaging analysis as a supplemental modeling tool to current in vitro approaches. Establishing their correlation and use of microstructure imaging may ultimately be a significant asset in developing alternative novel approaches for assessing bioequivalence.

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

Novel Nanosystems for Oral Delivery of Biologics

Oral administration is the most convenient and preferred way of taking drugs. However, apart from a few exceptions, oral administration is currently not an option for biologics. The use of absorption enhancers has limitations, including safety issues and its applicability to a narrow range of biologics. Different delivery strategies are therefore urgently needed. Nanomedicine-based approaches have promising potential for oral biologics, though one must apply a deep understanding of the gastrointestinal tract physiology and barriers in the design of nanosystems for oral delivery of biologics. In this talk, I will summarise the latest findings from my lab on nanomedicine-based approaches, including bovine milk exosomes, and their potential for oral delivery of biologics.

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

Strategic Selection for Development Candidate Targeting Oropharyngeal Administration

  • Research candidate properties to master for maximizing probability of success
  • Design of the formulation for intended clinical studies
  • Device selection for fit-4-purpose oral application in clinical studies

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

Parenteral Drug-Device Combination Products – Data Package, Integrated Control Strategy, and Platform Approach for Successful Submissions

Health Authority expectations in USA, Europe, China and around the world have risen strongly. Extensive data requirements and statistics on product robustness and user capability even under worst-case conditions require a change in mindset from the very start of product design, applying thorough scientific and engineering principles, true cross-functional collaboration, an integrated drug-device control strategy, and smart platforming, to enable successful market registrations, competitive products, and reasonable use of resources. Examples will be provided mainly for prefilled syringes with needle-safety systems and autoinjectors, the principles apply across all combination products.

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

Session Abstract (TBC)

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

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

Biologics

Understanding Biopharmaceutical Detergents

Shwetha Iyer, Principal Scientist, Novartis

  • The role of detergents in biopharmaceutical formulations
  • Discussing the stability of detergents in biopharmaceutical formulations
  • Exploring formulation effects on detergents

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

Contemporary Opportunities and Challenges in Characterizing Crystallinity in Amorphous Solid Dispersions

The first half of this presentation highlights the unique challenges of analytical methodologies to monitor crystalline drug substance in ASDs and their associated drug products. Challenges around use of limit tests, analyte spiking experiments, and method robustness are also underscored. The latter half describes the merits and limitations of the diverse analytical "toolbox" (such as XRPD, NIR and DSC), which can be readily applied during development and, in some cases, considered for potential application and validation in the commercial QC setting when necessary.

Biologics

High-Precision Ambrx ADC Conjugation Process, & Analytical Characterisation to Ensure High Homogeneity & Purity

  • Understanding the Ambrx expanded genetic code, protein expression and site-specific ADC conjugation platform
  • Investigate the development of platform analytical methods and extended characterisation to demonstrate homogeneity and high product quality
  • Assess the validation of technology with 3 ADCs

Technology & Innovation

Advanced Biomaterials Technologies for Improving Biopharmaceutical Formulation and Delivery

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

In this talk, we will discuss the investigation of a hydrogel platform exploiting dynamic multivalent interactions between biopolymers and nanoparticles. These materials exhibit viscous flow under shear stress (shear-thinning) and rapid recovery of mechanical properties when the applied stress is relaxed (self-healing), afford minimally invasive implantation in vivo though direct injection. The hierarchical construction of these biphasic hydrogels allows for multiple therapeutic compounds to be entrapped simultaneously and delivered with identical release profiles, regardless of their chemical make-up, over user-defined timeframes ranging from days to months. These materials enable novel approaches to immunomodulatory therapies such as vaccines and cancer immunotherapies that rely on precise and sustained release of complex mixtures of compounds. We demonstrate that these unique characteristics enable the development of vaccines that greatly enhance the magnitude, quality, and durability of the humoral immune response.

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

Small Molecules

A Transition from Batch to Continuous Mixing

The current presentations examine the links and the differences between a batch and a continuous blending process. The content uniformity from blends produced with batch and continuous mixing are compared. It is shown that continuous mixing could be beneficial for achieving good content uniformity and that less process optimization is required to ensure homogeneous mixtures. Additionally, the effect of over-lubrication during compression is compared for the two processes.

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

Considerations in device development for Plasma Derived Therapies

Karthik Lavakumar, Head of Device Development, Plasma Derived Therapies, Takeda

  • What are Plasma Derived Therapies?
  • Why are Plasma Derived Therapies different from other modalities?
  • What strategies do we have to tackle high drug volumes and comprehensive administration systems?
  • Challenges of higher protein concentration
  • Strategies to maintain protein stability
  • Conclusions

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

Small Molecules

Development of Prodrugs for Treatment of Parkinson‘s Disease: New Inorganic Scaffolds for Blood–Brain Barrier Permeation

This review aims to summarize the main formulations currently in use for PD treatment, explaining advantages and disadvantages for each class. The attention will be focused on the promising prodrug concept, aimed at finding a suitable L-DOPA substitute with improved pharmacokinetic behavior. In this respect, new potential candidates which show interesting properties for the intended scope, the so-called dicarba-closo-dodecaboranes(12) (carboranes), will be discussed. Carboranes are inorganic molecular icosahedral boron-carbon clusters with 12 vertices and 20 deltahedral faces. They have been extensively studied for applications in medicine as potential pharmacophores, reagents in boron neutron capture therapy (BNCT) and radiotherapy. Here, we discuss them as inorganic scaffolds for dopamine delivery at the central nervous system (CNS) level.

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

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

  • Pharmaceutical development pathway integrating patient needs, development considerations and physico-chemical/biopharmaceutical compound profile
  • Integrated CMC platform from developability assessment, formulation design and process optimization leading to a robust commercial dosage form
  • Case studies showcasing how an integrated CMC platform can accelerate timelines

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

Continuous Manufacturing: Rheological Powder Characterisation of Excipients to Understand Their Behaving During the Feeding Step

  • Powder rheology analysis of excipients with FT4
  • Influence of moisture on excipients flow behaviour
  • Correlation with feeding trials
  • L-HPC a multi-functional excipient: case study (twin screw wet granulation)

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