Developing a formulation buffer is one of the biggest challenges. There is usually a trade-off between best stability, full functionality, lowest chemical change, aggregation, fragmentation, etc. We put the target protein into buffers of different pH, salts, and excipients and then stress it, e.g., at elevated temperatures. Biochemical and functional analyses follow, and the most promising buffer is refined in its compounds. As a supporting high-throughput screen we monitor changes in fluorescence upon increasing denaturation. Once an optimal buffer is encircled within 1-2 month, a long-term study at the intended and at slightly enhanced temperatures is performed.