The stability of high-concentration drugs can change under storage conditions, but until now, thermal testing in the lab using traditional calorimetry methods has been time-consuming and challenging. The new TA Instruments RS-DSC fills a critical antibody formulation development gap by allowing for high-throughput short-term thermal stability testing at formulation strength concentrations. In this blog, we explore why that’s essential.

Subcutaneous injection has revolutionized how billions of patients receive the crucial treatments that keep them alive. From a regular dose of insulin to treat diabetes to the monoclonal antibody adalimumab that regulates rheumatoid arthritis, the ability to self-administer these life-saving therapies provides enormous benefits for both patients and healthcare providers, saving time, money, and resources.

To be effective, though, these treatments require a higher drug concentration within each dose. Researchers already use various testing methods to evaluate drug product stability, from differential scanning calorimetry (DSC) to dynamic light scattering (DLS). While both these methods provide accuracy in the lab using diluted samples, they can’t quickly or effectively measure the stability of real-world concentration levels. Even slight adjustments to the solution environment, including increasing concentration, can introduce unknown and unpredictable changes in high-concentration biologics. Until now, though, analyzing the thermal stability of drugs under high concentration conditions has been time-consuming and challenging.

TA Instruments’ newest innovation, the RS-DSC (Rapid Screening-Differential Scanning Calorimeter), fills a critical testing gap, allowing labs to quickly understand thermal stability of their formulation strength drug products. In this blog, we explore the importance of thermal stability testing and how the RS-DSC drastically improves the process.

Until recently, most biologics have been administered through intravenous injection. For patients, that meant a trip to the doctor’s office and oversight from a professional to receive their life-saving therapies. A simple shot into the skin via needle and syringe is far cheaper and more convenient, which explains the wide adoption of subcutaneous (the innermost layer of skin tissue) injections. From 2017 to 2021, roughly half of all FDA-approved treatments were developed to be administered subcutaneously.

While the method has lowered costs and expanded global access to essential drugs, it makes research and development more complex. Unlike the steady drip of an IV, a shot through the skin requires far less volume, meaning the concentration of the biologic must be significantly higher. That ratio can change the biopharmaceutical stability — and effects the entire development pipeline.

Understanding how a biopharmaceutical responds to thermal stress is an important predictor of shelf-life and efficacy. Short-term thermal stability lends insight into biopharmaceutical structure and understanding how functional variations arise. It is a key metric employed in candidate selection and provides critical information in selecting buffer composition in the development of clinical formulations. Lower thermal stability can be an indicator of aggregation, poor shelf-life, and ultimately drug efficacy. Thermal stability testing ensures researchers know the way a drug will change under stress, letting them predict how that drug will behave in a patient’s home or on a pharmacy shelf.

Aggregation and structural stability are commonly evaluated using light scattering and calorimetry:

Dynamic Light Scattering (DLS): In this method, a laser is passed through a liquid sample, causing light to scatter between individual particles. This lets researchers determine the size distribution and aggregation of drug particles over time. Understanding these changes can help determine if a drug remains safe and effective in varying concentrations and while stored in differing temperatures.

Differential Scanning Calorimetry (DSC): This method uses the controlled application of heat to examine how and when the substance transforms. Researchers can then precisely understand the formula’s stability at different concentrations and under different conditions. Evaluating the thermal stability of a given solution gives insight into the folding and function of the protein and informs understanding of the impact of the solution environment on the protein structure as a whole.

In biologics development, DSC is the gold standard for short-term stability testing. But the process has one major flaw: high-concentration samples must be diluted. That’s because DSC requires a fixed sample cell that must be cleaned between samples. High-concentration solutions can clog the cell when heated, either making it useless or forcing researchers to employ harsh, lengthy cleaning protocols between trials. For intravenous treatments, this isn’t an issue. The low concentration means most tests never reach the instrument’s upper limit. Not so with subcutaneous injections. As the treatment delivery option becomes increasingly popular, the industry needs a scalable, cost-effective, and fast solution that outputs reproducible and accurate results.

The RS-DSC is revolutionary because it can rapidly test a high number of samples at high concentrations and low volume– while still employing calorimetry to provide the most accurate thermodynamic data possible. The key innovation comes from disposable microfluidic chips rather than relying on a fixed measurement cell as seen in traditional DSC instruments. This offers three key benefits:

1. The instrument can test 24 samples simultaneously, significantly increasing throughput while reducing sample consumption.
2. The low volume microfluidic cells only require 11 µL of sample, maximizing material use and minimizing cost.
3. Disposable chips eliminate cleaning and remove the need for dilution. Thus, the effects of formulation strength antibody treatments can be predicted far more quickly and accurately.

All this means the RS-DSC doesn’t only test higher-concentration samples with greater accuracy. It saves time and material, and therefore money. That means breakthrough therapies can reach more patients–faster and cheaper.

Advances in therapeutic biologics mean more and more people will receive life-saving treatment via a shot through their skin. But this convenient, cheap, and easily administered treatment option is only possible if pharmaceutical researchers are completely confident their high-concentration drugs can tolerate real-world conditions. That’s why, in a drug’s journey from lab development to blockbuster adoption, the RS-DSC is now a critical link to better treatments and healthier patients.