Residual Analysis

Residual Analysis

While generic techniques for analyzing residuals and impurities may exist, it is crucial to assess each method for potential interference from buffers, excipients, and protein loads before incorporating them into routine sample analysis. Additionally, evaluating and noting the limit of detection (LOD) and limit of quantitation (LOQ) using the client's samples and matrices is essential. Qualification and/or ICH validation of these methods are necessary steps before applying these assays to cGMP lot release programs.

Impurities Arising from the Biologics Manufacturing Process

Throughout the product manufacturing journey, various chemicals are usually introduced upstream as integral components of the bioprocess to enhance product expression and recovery. While the downstream purification process largely eliminates these chemicals, trace amounts may persist in the bulk drug substance and the final drug product. To verify that the concentrations of these agents remain within acceptable limits, it is essential to employ highly sensitive residual testing methods for the detection and quantification of such chemicals.

Impurities Associated with Biologics Products

In addition to process residuals, there exists the potential for product-related impurities to persist through the manufacturing and purification process. These impurities, encompassing host cell proteins, host cell DNA, N-terminal truncations, and other potential modifications, have the potential to induce adverse reactions in animals and humans. Therefore, impurity testing is imperative to ascertain that any contaminants present are maintained below predefined acceptable levels.