A systematic approach to evaluating closed-system drug-transfer devices during drug product development.

Predictive models that evaluate aggregation and viscosity behaviors at high concentrations during early-stage design can facilitate drug development. This talk describes a rational feature selection framework to develop accurate models for high concentration aggregation and viscosity at 150 mg/mL for 20 preclinical and preclinical antibodies with few features. In addition, this talk will present an efficient convolutional neural network model that predicts high concentration viscosity.

Allogeneic cell therapies present a unique challenge for drug product process development by combining aspects of autologous cell therapy and conventional biologic products. In addition, production scale may increase significantly as the process evolves towards commercial manufacturing. Technical challenges in cell process development, considerations for tech transfer, and the analytical assessment of stability-indicating attributes to guide development will be discussed.  

Mosaic Flu nanoparticles were designed to present multiple arrays of antigens to induce a stronger immune response. Preliminary formulation development utilized proteins containing a histidine tag. The nanoparticle developed for clinical trials consisted of antigens without a histidine tag. Differences in stability profile were observed between the His-tagged and non-His-tagged nanoparticle mainly after freeze-thaw stress. This talk discusses the approach taken to optimize the formulation to mitigate the freeze-thaw instability.

Biotechnology companies are extensively leveraging Adeno-Associated viruses (AAVs) to deliver therapeutic DNA for genomic medicine applications. The field however is still in early stages of gaining experience with stability, analytics, drug substance (DS) and drug product (DP) manufacturing processes. Some of the notable challenges are extremely low titers, limited manufacturing lots to develop process knowledge, and complex analytical methodologies required to characterize AAV systems. Collectively, these challenges lead to higher cost of goods (COGs) while catering to the rare/orphan disease space. This talk focuses on developing and optimizing DP formulation/presentations and manufacturing strategies to support patient safety, healthcare provider convenience, and reducing COGs to enable patient accessibility.

• Structural assessment of simulated in vitro conditions of biologics using the SCISSOR
• Understanding of destabilizing mechanisms of biologics in the sub-cutaneous environment
• Deeper dive into peptide hotspots to identify potential sites for destabilization and re-iterative formulation development

A new concept of the Inflammatory Cascade of 2022: the body organ, the endothelial glycocalyx lining, the entire vascular interior, the entire inflammatory reaction damage begins. The complex coagulation and thrombotic responses, the entities that control fever, blood pressure, fluid volumes, and cellular inflammatory responses are activated. A novel modified albumin solution initially created to prevent fluid losses prevented the hallmarks of sepsis. Sepsis was first stopped here.

In LNP Design, choice of each component determines the in vivo behavior and efficacy of nucleic acid encapsulation and delivery. These parameters can be modulated to maneuver the biodistribution of LNPs depending on the organ of interest and type of nucleic acid. Hence, choice of the correct lipid systems based on the nucleic acid, manufacturing process, and intracellular trafficking tools are important to enable improved screening prior to in vivo studies.

Monoclonal antibody solutions usually exhibit high viscosity at elevated concentrations, which prevents manufacturing and injecting of products at the small volumes needed for subcutaneous administration. Here we show that caffeine effectively reduces the viscosity of infliximab and ipilimumab formulated at high concentrations and small volumes required for subcutaneous injection. Further studies show that caffeine has no impact on accelerated stability or in vitro bioactivities of the two model proteins.

Large molecule parenteral drugs often require high concentration formulations, large volume delivery systems, or a combination of both for high efficacious doses. This can lead to major challenges in quality, manufacturability, delivery, and patient convenience. Here we present comprehensive approaches to address these challenges during developability assessment, formulation development for optimal viscosity and stability, integration with delivery devices, process design and tech transfer. We also discuss novel approaches in predicting such challenges early in drug discovery and development.

The ability to deliver stable and active dried protein therapeutics from biopharmaceutical drug delivery systems is critical for solid dosage formulation development. With the ever-growing landscape for different routes of therapeutic protein delivery like lung, intranasal, oral and subcutaneous delivery, novel excipients for enhancing the benefit-to-risk ratio while maintaining protein stability during manufacture, storage, and delivery is necessary for the successful development of a drug product. Spray-dried formulations with carefully selected excipients provide a unique opportunity in amorphous phase stabilization of the therapeutic proteins. Herein, we discuss the role of novel excipients for stabilizing spray-dried protein against physical and chemical degradation factors. As a proof of concept, the utility of two compatible nature-derived solutes, ectoine and hydroxyectoine, in stabilizing a model protein labelled Fab2 has been investigated. Specifically, the performance of ectoine and hydroxyectoine in stabilizing Fab2 in spray-dried formulation at elevated temperatures and after multiple freeze-thaw cycles has been compared with the performance of a formulation containing trehalose and no excipient as control. 

A major challenge in formulating high-dose biologics for subcutaneous injection is overcoming the viscosity and stability limitations of high-concentration (>100 mg/mL) solutions. Suspensions, however, have reduced viscosity, enabling concentrations of 400 mg/mL and higher. Microglassification™ is a dehydration technology that results in stable, dense, spherical particles of amorphous, solid protein. We will present current studies on the stability and injectability of suspensions using these particles.

Biologics drug development has experienced rapid growth in recent years. To meet the need biologics formulation development has quickly acquired a set of automation tools and analytical techniques to provide robust drug products for patients. The push for more effective therapeutics and better patient-care options has demanded new types of studies. This has motivated adaptation of our tools to meet the increases in process complexity to benefit of patients globally.

Succinate acid/succinate system has an excellent buffering capacity at acidic pH values (4.5-6.0). However, its use in formulating drug products is largely limited due to risk of its components crystallizing and the consequent pH shifts. Physicochemical behavior of succinate system was characterized under pharmaceutically representative conditions. mAbs formulated in de-risked succinate buffer maintained a good stability profile during typical pharmaceutical processing and upon storage, bolstering their wider use in drug products.