SmartFreeZ’s unique method enables protein aggregation acceleration for temperatures below 0°C, allowing to estimate in a few days the cold storage stability of years
THE PROTEIN STABILITY CHALLENGE
Preventing aggregation of therapeutic proteins during storage is a major challenge for the biopharmaceutical industry because aggregation is highly related to immunogenicity. It is important to understand the protein stability to anticipate aggregation associated to the processing and storage of biotherapeutics.
STABILITY STUDY DESIGN
Stability of various candidate formulations is generally evaluated by a combination of real-time and accelerated stability. Real-time stability testing is usually very slow to be studied thoroughly a practical time, for this reason several methods have been developed to accelerate kinetics by destabilising the proteins at elevated stress conditions (e.g. high temperatures and/or humidity).
THE COLD STABILITY ACCELERATION METHOD
This method is based on the recently developed capability of running protein isothermal stability studies below freezing temperatures while preventing ice growth below the normal freezing temperature.
The Cold Stability Acceleration (CSA) method complements the generalized method for accelerated studies, which consists in modeling degradation kinetics at high temperature and extrapolating the mechanisms to calculate rates at typical storage temperatures (much lower). The stability measurements obtained with the CSA clarifies the behavior of proteins over a wide temperature range (-25 to 0 °C), allowing for consistent models and avoiding the uncertainty associated with extrapolations.
The CSA method enables to rapidly evaluate the sensitivity of the molecule to cold stress and the impact of supposed stabilizing conditions (buffer, pH) or excipients at relevant temperatures for cryoprocessing (down to -30 °C).
SMARTFREEZ’S COLD STABILITY ACCELERATION 4-STEP SERVICE
It is necessary a minimum amount of product, from 5 to 10 ml for each isothermic curve.
2. Aggregation Acceleration
Aggregation is induced with the Cold Stability Accelerator equipment.
3. Aggregation Assessment
The samples are analyzed using 2 different methods, such as SEC-HPLC and DLS.
4. Final Reporting
SmartFreeZ will deliver a report with conclusions and guidelines to improve stability and to extend the shelf of the product.
SMARTFREEZ’S COLD STABILITY ACCELERATOR EQUIPMENT
To perform these acceleration studies SmartFreeZ developed a new automated and user-friendly equipment – the Cold Stability Accelerator. This device can be easily operated by lab-trained personnel, in case of preference to acquire the equipment.