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– 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
Ryan Nolan, Ph.D., Halozyme