Why is it so important to be able to measure water or moisture inside a lyophilized vial? What data does this provide and how can that data be used to improve processes and/or products?
Avecia manufactures custom-synthesized oligonucleotide drug substances of which the majority are lyophilized to facilitate packing and shipping. These compounds are naturally hygroscopic and, unlike many small molecule product formulations, typically contain high percent levels of water. The water content must be accurately determined in order to perform mass balance analysis for assay. The assay content is critical for the drug product formulation calculations.
What are the ways moisture inside a lyophilized vial is determined? What are the challenges with having so many different approaches? What is the industry recommended way to analyze moisture in lyophilized vials?
The United States Pharmacopeia provides guidance on titrimetric, azeotropic, and gravimetric approaches for water determination (USP). The most common technique for moisture analysis in lyophilized products is Karl Fischer (KF) water titration. Avecia prefers to use Method 1c for KF coulometric titration which provides specificity for water, provided there are no matrix interferences. The challenge in using KF titration is that often a method must be tailored to the compound where the specificity and method ranges must be established and confirmed.
How does using a Karl Fischer oven simplify the process? What do pharma companies need to do to implement this analyzation procedure?
Avecia prefers to use the Karl Fischer oven technique with coulometric analysis for its ease of use and automation. The Metrohm instrumentation we use is computer-controlled with full 21CFR Part11 compliance, which provides assurance of data integrity for all of our GMP testing needs.
Our KF development strategy begins with using our platform titration parameters and screening for the appropriate oven temperature for the oligonucleotide. This process is automated using the control software and typically an optimal method is obtained in less than a day. We next evaluate method accuracy in the matrix using spike and recovery testing at different levels in the range of interest. The remaining method performance elements (such as specificity, precision, linearity and range) are evaluated during development and confirmed under validation.
Is the data collected required by regulatory agencies? How does the data collected assist companies with regulatory submissions and process validation?
All data collected for GMP product testing is required to support our clients’ regulatory submissions. We’ve found that our clients prefer KF methods to be fully validated, product-specific procedures to confirm both specificity in the matrix and suitability for intended use.
Metrohm offers a complete line of analytical laboratory and process systems for titration, ion chromatography, electrochemistry and spectroscopy. From routine moisture analysis to sophisticated anion and cation quantification, we are ready to help you develop your method and configure the optimum system. Move your analysis from the lab to the production line with our dedicated process analyzers. At Metrohm we provide systems that find solutions. Learn more on www.metrohm.com