Part 1: Technologies to Facilitate High-Dose SC Administration

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Description

11:00 AM – 1:00 PM (EST) Part 1: Technologies to Facilitate High-Dose SC Administration

11:00 AM – 11:05 AM
Introduction and Welcome
Ryan Nolan, Ph.D., Halozyme

11:05 AM – 11:30 AM
Subcutaneous Injection Technologies: A Non-Aqueous Approach
Steven Prestrelski, Ph.D., MBA, Xeris Pharmaceuticals

The proprietary XeriJect technology uses a novel, viscoelastic suspension formulations to enable delivery of high concentration, low volume subcutaneous injections of therapeutic antibodies. Specialized drying and particle engineering techniques are employed to create stable antibody powders. These powders are “wetted” with biocompatible diluents, creating ultra-concentrated, low-volume suspension formulations. The suspensions highly concentrated and have viscoelastic properties such that the particles do not settle, and the formulations are 'ready-to'use'. The formulations are administered subcutaneously using commercially available pre-filled syringes or auto-injectors. With the XeriJect platform, we are able to routinely produce formulations with monoclonal antibody concentrations in excess of 450 mg/ml. Stability studies support long-term storage at refrigerated temperatures with strong potential for room temperature storage. Numerous pharmacokinetic studies in large animal models show rapid absorption, high bioavailability and good local tolerability. The XeriJect formulation process uses standard pharmaceutical processes for powder production, suspension mixing and syringe filling, and has been scaled-up to produce clinical trial materials, and is currently being ported to an aseptic manufacturing environment. It is expected that clinical studies with the XeriJect platform will commence in late 2023. The XeriJect technology platform can lead to products that are easier to use for patients and caregivers while reducing costs for payors and the health care system.

11:30 AM - 12:05 PM
Viscosity Reduction and Stability Enhancement of Monoclonal
Antibody Formulations Using Derivatives of Amino Acids
Arvind Srivastava, Ph.D., Avantor Sciences

Monoclonal antibodies are complex molecules that often require high concentration formulations to meet clinical requirements and bulk drug substance storage. Stability is a common concern in both high and low concentration formulations; however, high concentration formulations are further complicated by an increase in viscosity, leading to manufacturing and administration challenges. To manage stability and viscosity, drug developers typically use salt, amino acids, sugars, polyols, and surfactant. Often, these excipients control some of the product quality attributes (CQAs) at the cost of several others. In this poster, we have evaluated several amino acid derivatives and identified bis acetyl lysine and propionyl serine to be efficient and superior to commonly used parenteral excipients for minimizing antibody solution viscosity, as well as mitigating physical and chemical degradation by controlling protein-protein interactions and deamidation. Both bis acetyl lysine and propionyl serine were able to reduce the viscosity of a monoclonal antibody at high concentration (>250mg/ml) by 80% when compared to a buffer control formulation. Accelerated temperature stability studies at 250mg/ml and 10mg/ml protein concentration formulation demonstrated that both bis acetyl lysine and propionyl serine were able to prevent change in physical and chemical stability significantly better than other commonly used parenteral excipients.

12:05 PM - 12:40 PM
High Dose Payload Delivery Using Bioerodible Subcutaneous Implants
Stephanie Reed, Ph.D., Secant Group

Secant Group’s Hydralese™ (PGSU) technology for controlled release consists of biodegradable and shelf-stable polymers that can be manufactured into diverse forms such as implants, microspheres, coatings, and combination devices. These long-acting Hydralese dosage forms sustain zero-order release kinetics lasting many months to years at very high drug payloads, while simultaneously offering mechanical flexibility and excellent biocompatibility suitable for a variety of anatomical sites and therapies.

12:40 PM – 12:55 PM
SC Design Considerations to Minimize Regulatory and Execution Burden for High-Dose SC Biologics
Gautam Shetty, Ph.D., Congruence Medical Solutions

A number of trends are driving the need for injection of high dose biotherapeutics into the subcutaneous (SC) tissue; these include shift from IV (intravenous) to SC, development of newer therapeutic agents, including immune-oncological agents. Emerging trends and therapeutics would eventually require newer drug delivery device solutions, which in turn create uncertainty in execution during drug clinical development and eventual commercialization of the drug. We will discuss product strategies one could consider to maximize likelihood of execution success, maximizing flexibility while simultaneously mitigate potential regulatory risk. Product strategies should also consider the fact that the patient populations that may be self-administering high dose SC therapeutics are different from those currently self-administering drugs for chronic treatments using legacy technologies. We will discuss technical challenges involving high dose SC delivery, that define requirements for SC delivery devices. Layered on this are requirements stemming from users who may not have any experience of self-injections (for e.g., injection of immune-oncological agents). We will present both manual injection device (Congruence Viscous Dosing Syringe) and an autoinjection device (Congruence High Dose Autoinjector) as illustrative examples for potential high dose SC delivery devices.

12:55 PM – 1:00 PM
Closing Remarks
Ryan Nolan, Ph.D., Halozyme

Contributors

Ryan Nolan, Ph.D.

Ryan is currently a Senior Director of Nonclinical Sciences and Clinical Pharmacology at Halozyme Therapeutics. Prior to joining Halozyme, Ryan held various roles across mulitple disciplines in large and small Pharma companies, all with a focus on applying quantitative modeling and simulation to inform and optimize scientific and business strategies.
Steven Prestrelski, Ph.D., MBA

Dr. Steven Prestrelski is Founder and Chief Scientiﬁc Oﬃcer of Xeris Pharmaceuticals. He is the inventor of the Xeris platform technologies. Dr. Prestrelski is an internationally recognized expert in drug formulation and delivery, with over 30 years of drug development experience. Prior to Xeris, Dr. Prestrelski was Vice President of Pharmaceutical R&D at Amylin Pharmaceuticals. Previously, he was Executive Director of the Bydureon® program at Amylin, leading this program from Phase 2 through global regulatory ﬁlings. Prior to Amylin, Dr. Prestrelski was Vice President, Biopharmaceuticals at PowderJect Technologies, Inc., where he pioneered the delivery of solid biopharmaceuticals. Dr. Prestrelski has also worked with Alza and Amgen.
Dr. Prestrelski served on the Board of Directors of BaroFold, Inc. and on the Scientiﬁc Advisory Board of iMEDD, Inc., a Bay Area drug delivery company. Dr. Prestrelski has published over 60 invited book chapters and peer-reviewed journal articles and has over 30 issued (over 100 globally) and 40 pending patent applications in the ﬁeld of drug development, formulation and delivery.
Dr. Prestrelski holds a PhD in Molecular Biophysics from City University of New York, and an MBA from the Rady School of Management at the University of California, San Diego.
Stephanie Reed, Ph.D.

Stephanie Reed, PhD, is the Director of Translational Product Development at Secant Group, a textiles and biomaterials company outside of Philadelphia. At Secant Group, Dr. Reed leads a team of scientists whose goal is to launch new biomaterial polymers for commercial use in controlled release drug products, biomedical devices, and tissue engineering applications. Dr. Reed garners 15-plus years of experience in drug delivery, biomaterials, 3D printing technologies, regulatory submission, and product commercialization. Dr. Reed earned a BS in Mechanical Engineering at Massachusetts Institute of Technology, and an MS and PhD in Biomedical Engineering at University of California Los Angeles.
Gautam Shetty, Ph.D.

Gautam is the founder and CEO of Congruence Medical Solutions, LLC with 16+ years in technical and business leadership roles in injectable drug delivery device space. He has authored a number of patents in the injectable drug delivery device space covering ocular drug delivery systems, autoinjectors, pen injectors and patch pumps. Previously, Gautam was General Manager of Novel Drug Delivery Systems business unit at Unilife Corporation. Prior to that, Gautam held a number of positions involving R&D, strategic marketing, commercialization planning and M&A with Becton Dickinson & Co. (BDX). Gautam holds a PhD in Biomedical Engineering from Case Western Reserve University.
Arvind Srivastava, Ph.D.

Dr. Arvind Srivastava is a Technical Fellow at Avantor, leading drug product formulation and delivery of biologics, antibodies, cell and gene therapy and nucleic acids modalities. Before joining Avantor, Dr. Srivastava was Research Advisor at Eli Lilly and Company, where he managed drug product development from early development stage through commercial registration. Dr. Srivastava did his postdoctoral training from the University of North Carolina at Chapel Hill, NC, USA. He got his Ph.D. degree in biochemistry from the prestigious Tata Institute of Fundamental Research (TIFR) and M.S. in chemistry from the Banaras Hindu University (BHU). Dr. Srivastava has published numerous papers in peer reviewed journals and has been frequently invited to present his research at the national and international conferences.