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Integrating a Risk-Based Approach for Informed Decision-Making and Quality Pharmaceutical Products

Quality risk management is a systematic, risk-based approach to quality management and is particularly important in the pharmaceutical industry

Waters Corporation

Quality risk management is a crucial element for addressing risks as applied to analytical procedures, especially in the pharmaceutical industry. Failing to address quality risks in the design, development, and manufacture of drug substances and products has potent implications including market withdrawal, recall, rejections, and endangering patient safety. 

Over the years, discussions around the implementation of quality risk management have been refined to facilitate sound regulatory communication between industries and regulators for an efficient, risk-based approach toward analytical procedures. Complementary efforts by the United States Pharmacopoeia (USP), via a new chapter 1220, and the International Council for Harmonisation (ICH), via its Q14 guidelines, propose a holistic, science-based approach to the design, development, validation, transfer, and routine use of analytical procedures. 

Set as a three-stage concept of procedure design, procedure performance qualification, and ongoing performance verification, the ICH and USP advise a lifecycle approach to managing analytical methods. The aim is to understand how procedural parameters affect performance through risk assessment and minimization of variability, in order to assure the performance of the procedure, and to provide an opportunity for more efficient regulatory approaches to post-approval changes. 

Risk mitigation with Waters Corporation 

Risk mitigation is an important consideration for modern pharmaceutical companies. Waters Corporation specializes in compliance and regulatory requirements, designing their products and services in line with the quality regulations and with risk mitigation in mind, while helping customers to adopt new approaches and technologies through their Analytical Professional Services organization. In partnership with third-party software companies, Waters also promotes the use of method development software based on quality-by-design principles, which works seamlessly with their state-of-the-art chromatography and mass detection systems to support the development of robust, well understood analytical methods and reduces the risk of failures once the methods are in routine use. 

Closeup of Waters Corp.'s Arc HPLC instrument
Rugged and dependable for routine testing labs, the Arc HPLC System from Waters Corporation delivers the ideal balance of performance and value for right-the-first-time analysis and trusted test results.
Credit: Waters Corporation

For decades, Waters Corporation has led the way in the development of high-value analytical technologies and consumables, backed by world-class scientific expertise. High quality instrument design, rigorous testing routines, high precision consumables manufacturing and quality training and support services result in consistency in sample preparation and accurate and repeatable analytical results. Empower, Waters renowned chromatography data software (CDS) supports compliant workflows and control charts for monitoring the consistency of performances over time. Combined with the adoption of risk-based approaches to analytical procedure development, these tools and technologies support the reduction of variability with respect to analytical measurements.

Waters strongly advocates the use of enhanced approaches to analytical procedure development and has taken a leadership position in the industry, focusing on risk management and risk mitigation, demonstrating the benefits of quality-by-design and lifecycle management approaches to analytical methods to the more conservative pharmaceutical companies. These efforts are strengthened by collaborations with third-party method development software providers, including S-Matrix and the Molnar Institute, with integrated hardware and software products bringing streamlined workflows to the customer. Waters promotes the benefits and cost savings of these enhanced approaches via diverse educational events and media including webinars, seminars, blogs, and podcasts and has acquired a reputation as the go-to vendor for information on the lifecycle management of analytical methods.

An enhanced approach to analytical method development

Among the multiple approaches available for analytical method development, analytical quality by design (AQbD) is the most comprehensive. This approach defines a region of chromatographic space where the presence of inadvertent changes does not affect results. This space is defined by performing design of experiments (DoE) which evaluates and samples the space efficiently. Knowledge about method performance characteristics and study factor limitations can be well understood in this manner. The promise of the AQbD approach stems from its regulatory flexibility to validated methods where it facilitates full understanding and control of the analytical procedures. This is enabled through thorough upfront and ongoing assessments to identify and classify elements of an analytical procedure that may introduce variability to the reportable result. This knowledge is subsequently used to develop and implement control strategies to mitigate the risks thus identified. 

The integration of Waters ACQUITY QDa mass detector with Empower CDS and S-Matrix and Molnar Institute’s method development software provide significant benefits to the enhanced method development workflow. The mass spectrometry peak tracking functionality enables rapid identification of resolved peaks, including those non-chromophoric compounds that are not visible with a TUV or PDA detector, helping with peak tracking in the analysis of spectral purity. This helps to make sure that peaks and coelutions are correctly identified and is of great significance for the separation of critical peaks especially since retention times may change and peaks can co-elute during the automated method development process. This peak tracking functionality using the ACQUITY QDa mass detector alongside the third-party method development software represents a powerful risk mitigation tool during the development of the separation. 

Through the development of fit-for-purpose products and services in support of industry and regulatory trends in compliance and quality risk management, and through many thought-leadership articles, interviews and peer-reviewed publications, Waters and Waters’ customers have led the way in the application of enhanced approaches to analytical methods, which in turn will result in more reliable, robust validated test methods, fewer failures and reduced costs in the longer term. Waters has published numerous application examples, including the analysis of aspirin and related substances, analysis of dexamethasone phosphate and related compounds, and the cross lab method transfer of a USP organic impurities method, which demonstrate very effectively the benefits of applying a risk-based approach and to investing in quality hardware and consumables in order to enhance the success rate of method validation and transfer, improve data quality and reduce regulatory submission inquiries. 

A risk-based approach to analytical procedures 

Quality risk management is a process through which a business can minimize risk while ensuring product quality is maintained or improved. Harnessing a risk-based approach enforced by AQbD principles provides a proactive means to address and resolve risks pre-emptively when making decisions on analytical procedures and delivering quality products. 

Risk-based approaches, as promoted by Waters, can involve additional investment in time and planning upfront, but provide a pathway to regulatory flexibility around methods while avoiding unnecessary financial losses and quality control failures. This allows laboratories to identify and control potential risks effectively, resulting in greater efficiencies and helping ensure profitability and uphold reputation. Waters’ commitment to service, support, excellence, quality, and innovative products and services, as well as regulatory and compliance expertise contribute to its success in creating an environment where benchmarks for product quality and testing are met while minimizing statistically significant variations in product performance and reliability. 

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