Industry-Wide Collaboration toward an Efficient and Systematic Approach to Quantitative Solvent Analysis in Drug Substances

Liters of organic solvents are stored in analytical laboratories across the pharmaceutical industry for the sole purpose of preparing process solvent standards that contain only microliters of solvent. The accumulation of a 10(6)-fold excess volume of unnecessary solvent is a dubious practice from both an environmental and a safety perspective. The Enabling Technologies Consortium (ETC), comprised of international pharmaceutical companies, has explored the use of pre-made solvent standards in 1 mL ampules to circumvent the environmental and safety concerns created by this common practice. In the reported work, two ampules of pre-made standards containing 29 of the most commonly used solvents in pharmaceutical development and manufacturing were evaluated. Creating mixtures of chemically compatible standards as opposed to individual standards for each solvent further minimizes the need to maintain a large inventory of multiple different ampules. Pre-made standard mixtures in conjunction with generic gas chromatography-flame ionization (GC-FID) methods, were evaluated against in-house standards of each solvent prepared according to the different GMP protocols at each company. Comparability was excellent for all solvents tested, as indicated by an overall recovery of 100.1 +/- 2.8%. These pre-made standard ampules also provide numerous advantages from both speed and greenness standpoints, including a much faster turnaround time of analytical results, with significantly less labor and greater reliability. In addition, this ETC effort demonstrates it is possible to maintain superior quality control of residual solvents in drug substances while improving safety and efficiency across the industry, as well as reducing the environmental footprint to perform the necessary experiments to ensure patients safety.