(W0930-06-32) Applying Quality by Design Principles to the Migration of a Compendial Method between Multiple HPLC Systems

Purpose: Within the pharmaceutical industry, compendial LC methods are used to assess whether the regulatory specifications for raw materials or finished products are met. Analytical laboratories are often required to migrate these methods to different laboratories or different models of LC instrumentation. The methods may be migrated without revalidation, however equivalent performance must be demonstrated.

Method migration can be challenging. Differences across HPLC systems can impact method performance. A plan designed to identify and control how method performance is affected by differences in instrumentation is a valuable tool in obtaining a successful outcome.

Methods: Quality by Design (QbD) Principles were incorporated in the development of a plan to migrate the USP Ibuprofen Tablets Organic Impurities method from a legacy HPLC system (originator system) to two modern HPLC systems (receiver systems) from different instrument vendors. (Refer to Table 1 for system descriptions.) Development of the plan was a three-step process. The first step involved a review of each of the systems to understand their similarities and differences. In the second step, any identified system differences were examined to assess the risk posed to successful method migration. This assessment assigned a risk level to each identified parameter. In step 3 of the process, a control strategy was devised for the parameters assigned a high level of risk. This control strategy was implemented on both receiver systems, and the analysis performed.

Results: The three-step process identified the following parameters as having the highest risk to the migration of the Ibuprofen Tablets Organic Impurities method: injector carryover, detector noise, and tubing dimensions. The control strategy included defining the needle wash composition and number of washes to control carryover, ensuring an adequate lamp warm up time, defining the sampling rate and degassing the mobile phase to reduce noise, and adhering to the vendor recommended tubing dimensions for each system. (Refer to Table 2.)

With the control strategy in place, the method was run on both receiver systems. Each of the systems met the pre-defined acceptance criteria for successful method migration, specifically the USP system suitability requirements for relative standard deviation, resolution, and signal to noise ratio. In addition to meeting the acceptance criteria, the two receiver systems showed improved peak area precision (%RSD) and increased sensitivity (higher signal to noise value) compared with the legacy HPLC system. (Refer to Table 3.)

Conclusion: Quality by Design principles were utilized for the development and implementation of a plan for the migration of the USP Ibuprofen Tablets Organic Impurities method between a legacy HPLC system and two modern HPLC systems from different instrument vendors. The approach identified each system’s performance capabilities and provided an understanding of how different instrument parameters could affect method performance. Using this information, potential risks to a smooth method migration were identified, and a control strategy devised and implemented. The results obtained met acceptance criteria.

Overall, the risk-based approach provided a proactive and successful strategy for method migration and the exercise demonstrated the performance benefits of keeping instrumentation assets up to date.

References: 1. P. McGregor et al., Mitigating Risk of Validated Analytical Procedure Failures When Upgrading or Replacing LC Assets: Harnessing the Power of Quality by Design (QbD) Principles (Waters Corp., 2021).
2. A. Dlugasch et al., Successful Global Cross Lab Method Transfer of a USP Organic Impurities Method to an Arc HPLC Using a Risk-based Approach (Waters Corp., 2021).
3. United States Pharmacopeia (2022). USP Monographs, Ibuprofen Tablets. USP-NF. Rockville, MD:USP. DOI: https://doi.org/10.31003/USPNF_M39890_01_01