​Viscosity reduction is essential for enabling the manufacturability, syringeability, and accurate dosing of high-concentration biologics. Excipients play a key role in modulating protein–protein and protein–solvent interactions to reduce viscosity while maintaining stability. This talk will provide an overview of commonly used viscosity-lowering excipients, highlighting their mechanisms and limitations especially when traditional excipients are ineffective, underscoring the importance of studying properties of biologics earlier in development to guide formulation development. In this presentation, an overview of device innovations to tackle viscosity challenges will also be covered.

Development of patient-centric medicines is a current trend in pharmaceuticals. These novel presentations are based on concentrated liquid formulations of antibodies integrated with a device. High viscosity can cause manufacturing and device compatibility issues. A design of experiments approach was used to screen combinations of four excipients targeting different viscosity mechanisms. This method successfully reduced viscosity of antibody formulations (=150 mg/mL) to optimal levels and identified dominant viscosity mechanisms.

Ensuring the stability of therapeutic antibody drugs is a critical aspect of formulation development, often necessitating evaluation under real-time conditions. Arrhenius kinetics-based modeling, which leverages accelerated stability data, offers an alternative methodology when real-time data are limited. This presentation will show the development of a predictive stability model, augmented with statistical approach (e.g. Monte Carlo) to enhance accuracy and robustness, using a diverse range of antibody drug products.

Process-related impurities can severely impact product quality and patient safety. A wide range of different problematic HCPs are known which need to be tightly controlled to ensure the quality, efficacy and safety of the pharmaceutical product. HCP specific guidelines should be followed when developing appropriate methods and techniques for HCP characterization, specification setting and life cycle control. Overcoming regulatory challenges while using possible flexibilities will be discussed based on relevant case studies.

Effective removal and characterization of problematic host cell proteins (HCPs) are critical in biotherapeutic manufacturing. Using site-specific immobilization of polyclonal antibodies as a versatile platform, we selectively captured CHO-derived phospholipase B-like 2 (PLBL2), a challenging HCP. Coupled with advanced mass spectrometry, this approach unveiled previously unknown proteoforms, including multiple charge and size variants. Our method provides a powerful framework broadly applicable for enhancing purification strategies across diverse biotherapeutics.

The potential impurities of biological therapeutics originated from cell bank, raw material, upstream culture, downstream bioprocess, fill finish, container closure, and product degradation. This presentation will exemplify the product and process impurities from manufacturing process and share the phase-appropriate control strategies to ensure the process is under control and the product is safe and efficacious.

GV20-0251, a first-in-class human monoclonal antibody against IGSF8, was discovered through GV20 proprietary AI platform that predicted both target and antibody sequences. The antibody exhibits excellent performance in antibody platform process with over 36-month stability. We will also present the identification and resolution of a particulate matter challenge during drug product manufacturing. In this presentation GV20-0251 showcases how AI-driven discovery can accelerate bioprocessing development.

The development of therapeutic proteins, including monoclonal antibodies, has been accelerated through advanced formulation platforms and protein stability assessments. This presentation will focus on the use of a low-volume Extensional Flow Device (EFD), which subjects proteins to an extensional flow field commonly encountered in manufacturing processes. The EFD provides an alternative method for probing protein aggregation, supporting the screening of formulation additives and the development of more robust formulations.

Polysorbates are widely used in biopharmaceutical formulations to prevent aggregation due to interfacial stress. These excipients are susceptible to degradation via oxidation and enzymatic hydrolysis during storage, potentially leading to the formation of subvisible particles and loss of protection from surface induced aggregation. Advances in analytics help us to both quantify and understand the root cause of this degradation in our products. This presentation is focused on strategies for mitigating degradation, confirming what levels of intact polysorbate are required to protect the product, and justifying acceptance criteria to regulators.

PEGylation has been a standard for enhancing the stability and circulation of therapeutics. However, the rise of anti-PEG antibodies in up to 60% of the population has led to hypersensitivity reactions, accelerated clearance, and reduced efficacy, prompting the withdrawal of several PEGylated drugs. The widespread use of PEGylated COVID vaccines may further prime the global population to develop high anti-PEG antibody titers. POEGMA, a next-generation polymer, replaces PEGylation, eliminating antigenicity and immunogenicity while maintaining PEG’s beneficial properties. Early preclinical results suggest POEGMA’s promise for advancing biopharmaceutical development. Join us to explore how POEGMA can unlock new potential in therapeutic innovation.

Enhancing protein production processes and manufacture through stability modeling and quality by design (QbD): Recent advancements in stability modeling and quality by design have significantly improved protein production processes. These developments encompass a range of techniques including predictive stability modeling, Quality by Design (QbD), and pertinent analytical testing, and regulatory guidance and expectations.

• Explore the practical opportunities and challenges of applying predictive modeling based on the Arrhenius equation, utilizing short-term data for long-term stability prediction. Share insights on the application of stability predictive models at different clinical phases and their role in accelerating drug product development.
• Discuss the recent revisions to the ICH Q1E/Q5C guidelines that encompass the alternative modeling tools for shelf-life determination and discuss their impact on stability assessments.
• Identify and explore the challenges associated with implementing predictive modeling in drug development, with a particular focus on phase-appropriate application criteria and regulatory acceptance.
• Discuss the application of QbD approaches in formulation, analytical and process development, with a focus on practical challenges and solutions. 
• Identify and discuss the challenges faced in applying QbD in drug product development and manufacturing, including integration with existing processes and regulatory compliance.​

• High and low concentration formulation development – how to cover the clinical dose range?
• In-use stability – temperature and hold time expectations
• Forced degradation study design 
• Device selection – interplay between formulation and device functionality, especially for viscous products
  

• Data bottlenecks and model generalizability
• Hybrid models: merging structure-based simulations with ML
• Collaboration between formulation scientists and data scientists
• Validation strategies and industrial deployment​​

Currently, ADCs are among the most rapidly advancing cancer treatments due to their precision in delivering powerful cytotoxic agents directly to tumor cells, minimizing unwanted side effects. Despite their recent achievements, ADCs present various technical and manufacturing hurdles. This presentation will delve into the challenges faced by CMC in the development and production of ADC drug products, as well as potential solutions.

Nitrosamines is an industry hot topic for past 6 years due to their potential genotoxicity and carcinogenicity risks in humans. This work will present the life cycle management of two new nitrosamines for a commercial rare disease drug.

AAV-based therapies encounter interfacial stress during manufacturing, storage and administration, often resulting in adsorption loss, aggregation, and vector leakage compromising therapeutic safety and efficacy. Quartz crystal microbalance with dissipation monitoring (QCM-D) was employed to characterize AAV adsorption behavior at critical interfaces and evaluate material compatibility between different serotypes. The results can help guide formulation development and material selection for manufacturing and dose administration during drug product development.

This talk will present CLiC (Convex Lens-induced Confinement), a unique single-particle imaging platform for measuring the size, mRNA-payload, and dynamics of nanoparticles in controlled, cell-like conditions (Kamanzi et al., ACS Nano 2024, 2021). This platform enables imaging of particles in solution and during reagent-exchange to emulate manufacturing and cellular dynamics, with and without fluorescent labels. We aim to correlate multi-scale data with clinical results, advancing our understanding of vaccine effectiveness and enabling rational design and optimization.

This presentation will discuss key considerations and risk mitigation strategies for the development of AAV gene therapy products. Challenges around formulation and process development of deep-frozen AAV products, along with ultra-cold supply-chain considerations will be covered. Case studies will be shared with the goal to engage with the broader gene-therapy R&D community and facilitate information exchange.