Emerging biologics, such as multispecific antibodies, mRNA vaccines, and viral vector-based gene therapies, present unique challenges in terms of product stability. These complex biologics require advanced technologies to ensure their stability and prevent adverse reactions in patients. To address this need, various product stability technologies are being developed.

Experts are collecting data earlier in the development process and utilizing new instrumentation to monitor the stability of adeno-associated virus (AAV) capsids, which are commonly used in gene therapies. Additionally, new formulations are being created to maintain stability even at high drug concentrations. The goal is to improve our understanding of product stability and develop technologies that can ensure the efficacy and safety of emerging biologics. These advancements will contribute to the successful development and utilization of these complex therapies in the field of biomedicine

Figure.1 New Stability Solutions Are Inspired By Emerging Therapeutics

Early Stability Assessment

Figure 1 shows Roberta Bucci, a fellow scientist at Catalent Biologics, emphasizes the importance of conducting preliminary stability studies early in the development of new therapeutic products. Insufficient knowledge about these emerging products can lead to stability testing problems that may not be resolved within project timelines.

Bucci recommends running early stability studies, including small-scale batches, to gain a comprehensive understanding of product stability under specific storage conditions. Implementing a structured training program in the laboratory is also crucial to ensure personnel use appropriate techniques for handling the product.

As a contract development and manufacturing organization, Catalent collaborates with new customers to assess whether additional work is required before advancing products further into development. By conducting comprehensive stability studies and providing necessary support, manufacturers can avoid potential issues and improve the overall success of their product development process.

Using New Technology

A key trend in the biopharmaceutical industry is the identification of stability parameters for product development, such as subvisible particle characteristics. These parameters are important as they can indicate the potential for product aggregation, which can trigger immune reactions and render the drug ineffective. Early assessment of product stability using nondestructive techniques, like those offered by Beckman Coulter instruments, allows for the identification and characterization of aggregation issues without destroying valuable samples. This enables manufacturers to take proactive measures to ensure product stability and patient safety.

Using Membranes And Microscopes

Halo Labs is developing Aura GT, an instrument designed for subvisible particle detection in gene therapies. The instrument utilizes an automated microscope and a membrane plate to count, size, and identify subvisible particles. By filtering the sample through the membrane, large particles are retained, allowing for imaging and analysis to determine their nature, whether they are viral capsids, contaminants, or excipient aggregates.

Aura GT offers the advantage of nondestructive analysis of small sample volumes as low as 5 μL, which is particularly crucial for viral vectors with lower yields and increased complexity compared to established biologics. The instrument addresses the need for assessing particles in gene therapies and enables researchers to gain valuable insights into the nature and composition of subvisible particles, facilitating the development of more stable and safe biologic products.

Examining The AAV Breakdown

Unchained Labs has entered the gene therapy stability testing market with its Uncle screening platform. The Uncle platform offers rapid stability assessment using three methods: full-spectrum fluorescence, static light scattering, and dynamic light scattering. It enables the evaluation of long-term storage stability by rapidly increasing the temperature of a product sample, providing stability information within two hours.

The industry trend is moving towards longer storage at more desirable temperatures, eliminating restrictions imposed by early AAV vectors. The Uncle AAV application allows monitoring of AAV breakdown, including protein unfolding and aggregation. It can also assess instability pathways that lead to DNA escaping the intact capsid before aggregation occurs. By evaluating stability behavior early in the process, potential aggregation and capsid breakdown issues can be identified. The Uncle platform contributes to ensuring the stability and effectiveness of gene therapy products.

Managing Heightened Concentrations

High-concentration biologics pose formulation and stability testing challenges. Dilution of samples for testing may distort findings and affect behaviors such as aggregation. To address this, the CTech SoloVPE system from Repligen is recommended as it allows testing without the need for sample dilution, providing a more accurate view of product attributes.

Another challenge is maintaining stability for subcutaneous injection of high-concentration formulations. Lindy Biosciences, a spinoff from Duke University, has developed Microglassification, a dehydration technology that creates solid protein particles. The Microglassified dry powder has a two-year shelf life and can be suspended in an oily substance for subcutaneous injection using a standard autoinjector syringe. Lindy Biosciences expects to reach the clinical stage with this technology by 2025, collaborating with undisclosed partners.[1]

References:

1. https://www.genengnews.com/topics/bioprocessing/emerging-therapeutics-inspire-new-stability-solutions/

Cite this article:

Janani R (2023), New Stability Solutions Are Inspired By Emerging Therapeutics , Anatechmaz, pp.457