2024-10-10

Q: Tell us about the key portfolio of TA Instruments that is centered around the pharmaceutical industry and what differentiates these products from its competitors?

Calliste Scholl: TA Instruments, a division of Waters Corporation, is a global leader in manufacturing cutting-edge systems for thermal analysis, rheology, microcalorimetry, and mechanical analysis. These instruments play pivotal roles in small molecule and biological drug characterization in pharmaceutical research and development across various stages, from late discovery to manufacturing. Our instrumentation is used to tackle the following industry challenges:

• Drug-Target Binding: TA Instruments™ Isothermal Titration Calorimeters (ITC) help researchers characterize binding interactions to ensure drug candidates are selected with high specificity and minimal unwanted side effects.
• API Stability and Interaction: Differential scanning calorimetry (DSC) is used to assess API stability, detect the presence of polymorphs and evaluate interactions with excipients. Isothermal microcalorimetry can also be used to guide formulation development of complex samples via the direct measurement of the formulations’ thermal activity.
• Oxidation Assessment: Thermogravimetric analysis (TGA) is used to detect oxidative degradation, for API stability studies.
• Water Sorption: Sorption analysis (SA) is used to characterize water sorption behavior, addressing hygroscopicity concerns.
• Texture Evaluation: Rheology is used to study cream texture, ensuring desirable product characteristics.
• Powder Flow: Rheology is also used to assess powder flow properties to help design and prevent hopper clogging.
• Viscosity: Rheology is used to measure drug viscosity, essential for injectability assessment.
• Biologic Stability: The TA Instruments Nano DSC helps characterize the thermodynamic details of molecular thermal unfolding and conformational stability, while the TA Instruments RS-DSC (Rapid Screening DSC) offers high throughput thermal stability measurement to accelerate biologic developability.

Our products offer exceptional sensitivity, ease-of-use, and versatility. With our TRIOS™ Software Platform and NanoAnalyze™ Software, instrument control and analysis become effortless allowing users to focus on solving problems that matter.

Q: How does the design of the TA Instruments DSC ensure high throughput and accuracy and what technological advancements have been incorporated into the TA Instruments RS-DSC?

Calliste Scholl: The unique sensor design of the TA Instruments RS-DSC decouples the sensor from the sample cell. This is a different paradigm than what is available today with the current capillary DSC designs, which use a large, non-removable, metal capillary sample cell that is hardwired to a sensor. The design of the TA Instruments RS-DSC, using a microfluidic chip for sample containment, helps eliminate the need to rigorously clean the sample cell to prevent sample carry over to the next experiment.

While automatable, a typical capillary DSC can only test a single sample per experiment. The TA Instruments RS-DSC consists of 24 twin sample and reference area sensors, enabling greater throughput and reducing test times from days to hours.

Q: Discuss the importance of microfluidic chips in the TA Instruments RS-DSC for biological drug stability testing.

Calliste Scholl: The microfluidic chips of the TA Instruments RS-DSC were designed for single-use, reducing cleaning time and potential cross-contamination. The sample volumes of the microchips are also significantly reduced – from 100s of microliters to approximately 10 microliters – helping to ensure precious biotherapeutics are conserved while also helping to eliminate the need to dilute samples. Researchers are now able to use formulation-strength drug products during thermal stability testing, to better understand aggregation, self-association, or other unexpected destabilizing forces that could possibly compromise drug effectiveness or developability.

Q: Explain the advantages of using microcalorimetry for studying drug formulation stability and how is microcalorimetry applied in the development of biopharmaceuticals?

Calliste Scholl: Microcalorimetry directly measures the heat released or absorbed during a biomolecule’s structural or phase changes as a function of temperature. By analyzing heat capacity changes, enthalpy, and entropy, microcalorimetry yields valuable thermodynamic parameters. These parameters inform stability, folding behavior, and aggregation propensity. Importantly, microcalorimetry is not affected by buffer components or excipients, providing accurate data even in complex formulations.

In our microcalorimetry product line, TA Instruments provides two differential scanning calorimeters (DSCs) with varying sensitivity levels. These instruments allow concentration studies across a wide range, from < 0.1 mg/mL to 200+ mg/mL, addressing diverse customer needs and real-world applications. An additional advantage of microcalorimetry is its modality non-specificity: many biomolecules can be studied in native forms without the need for labels or dyes.

In the context of biopharmaceutical development, microcalorimetry plays a crucial role in selecting candidates that bind specifically to their target using isothermal titration calorimetry (ITC). ITC directly measures the heat released or absorbed when two molecules interact. Ideally, a strong candidate will exhibit both strong binding affinity and specificity to avoid unwanted interactions with other molecules, minimizing potential side effects. Additionally, microcalorimetry is employed in formulation optimization using DSC. Scientists evaluate stability under various conditions, such as pH, excipients, and buffers. By conducting experiments across different conditions, they can compare stability profiles and select the formulation that provides the greatest stability. This systematic approach helps ensure robust drug formulations.

Q: How does automation in thermal analysis instruments enhance laboratory productivity and discuss the role of software in enhancing the precision of thermal analysis measurements?

Calliste Scholl: Thermal analysis plays a crucial role in pharmaceutical development and biopharmaceuticals, especially when products require lyophilization to extend shelf-life stability. Automation is essential in this industry for several reasons:

• Time Efficiency: By automating sample queues, scientists can focus on other experiments or analyses. It frees up their time and ensures efficient use of resources.
• Continuous Operation: Automated systems may allow samples to run 24/7 unattended. This significantly increases the throughput, enabling more samples to be analyzed per day compared to standard work schedules.
• High Test Volume: Drug development involves numerous tests—sometimes hundreds. Rapid data collection and analysis are critical for timely decision-making. Faster processes lead to cost savings in drug development.

Efficient software for instrument control and data analysis is crucial. Our user-friendly and intuitive software simplifies programming, method development, and can perform automated data analysis with a few simple clicks. By streamlining these tasks, it frees up valuable time for scientists. In this industry, it is also necessary to provide solutions for regulatory requirements, which is made possible by our TRIOS Guardian Software offering, ensuring data integrity. Both automation and software help streamline workflows, enhance productivity, and contribute to more efficient drug development.

Q: How are high-throughput screening technologies by TA Instruments impacting the pharmaceutical industry and what strategies does TA Instruments use to maintain its reputation for reliable and high-quality products?

Calliste Scholl: Our cutting-edge TA Instruments RS-DSC is a high-throughput system specifically designed for biologic drug development. It accelerates research and streamlines decision making by providing rapid insights into drug product stability by analyzing up to 24 samples simultaneously. Our Nano DSC, Affinity™ ITC, and thermal analytical tools offer serial automation as an option for precision and routine unattended physical characterization. High-throughput technologies enable scientists to collect extensive amounts of data efficiently. As AI-assisted drug development gains momentum, pharma companies are increasingly embracing high-throughput methodologies and technologies. Models and libraries derived from these data will likely reduce future therapy development time, ultimately lowering time-to-market and overall costs. TA Instruments remains dedicated to excellence, innovation, and customer satisfaction, maintaining its reputation for reliable, high-quality scientific instruments.

TA Instruments, TRIOS, NanoAnalyze, and Affinity are trademarks of Waters Technologies Corporation.