Design Space of Robust Analytical Methods in the Pharmaceutical Environment
In the pharmaceutical industry, significant paradigm shifts are transforming the quality environment to support modern and innovative manufacturing. Regulators, industry leaders, and standards-setting organizations are increasingly emphasizing risk-based and Quality by Design (QbD) approaches over traditional compliance-driven and quality-by-testing methods[1].
This shift requires a deep understanding of products and processes, leading to changes in traditional validation practices. In this article, we will review the QbD principles applied to analytical methods, their advantages, especially for developing robust and optimized methods. Finally, to illustrate the benefits, a case study will be presented.
Authors:
Thomas LESUFFLEUR, R&D Analytical Development Project Leader at Seqens' Lab.
Pirjo LUOMA-TOKOI, R&D Analytical Development Manager at Seqens' Lab.
Juliette MARTIN, Scientific Communication Manager.
Email Address: [email protected]
Website: https://pharmaceuticals.seqens.com
https://www.seqens.com/knowledge-center/design-space-of-robust-analytical-methods-in-the-pharmaceutical-environment/
INTRODUCTION:
The concept of analytical procedure validation is evolving towards a life cycle risk-based approach [2]. Current validation practices often prioritize meeting regulatory requirements over understanding and controlling variability sources.
The quality risk management (QRM) process is what drives the design of optimum conditions, allowing the identification of conditions that optimize performance and minimize/avoid bias (reducing variability) to establish an operating range called “method operable design region” (MODR). The MODR is a multidimensional region where all study factors in combination provide suitable mean performance and robustness, ensuring procedure fitness for use. The MODR is equivalent to the term “Design Space” cited in the International Conference on Harmonisation (ICH) Q8 guidelines.
Within the quality environment, analytical methods are crucial throughout a drug’s lifecycle, requiring precision, accuracy, and reliability. Liquid chromatography (LC) techniques, like HPLC and UHPLC, are commonly used to separate analytes in samples. These methods are essential for analyzing active pharmaceutical ingredients (APIs) and their related substances.
In respect with ICH guidelines, especially ICH Q2(R2) and ICH Q14, the robustness of analytical procedure should be considered during method development phase and is defined as “a measure of its capacity to meet the expected performance requirements during normal use. Robustness is tested by deliberate variations of analytical procedure parameters.”[3]
Traditional method development often uses a trial-and-error approach, called OFAT (one-factor-at-the-time), which can be time-consuming and less effective. Inconsistent method performance during routine use can lead to out-of-specification results, failure of the System Suitability Testing (SST) requiring redevelopment and regulatory approval, impacting cost and time.
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