Method Lifecycle Management Strategies Pave the Way for Greater Procedure Understanding and Fewer Transfer Failures

Posted by Stephanie Harden, PhD on April 24, 2020

 

In recent years, the increased number of method transfer failures has led to greater transfer scrutiny by industry and regulators. And for good reason. Simple paper transfers between sending and receiving units and provision of ambiguous information are widely regarded as insufficient. These outdated practices are now being superseded by more proactive approaches to support successful method transfer, including the provision of method transfer packages and improved lab-to-lab communication1. Indeed, it was a decade ago that Nethercote, et al2 described the benefits of Quality-by-Design based method development with the goal of creating more robust analytical procedures. Despite these advances, however, there are still situations where methods that come into the receiving lab are poorly understood, or insufficient information is available. Even with the implementation of pharmacopoeial methods, or well-understood robust methods, predicting problems can be challenging, and many only show up over time.

 

A risk-based approach to analytical method transfer

So, what should you do when a new method comes into your laboratory? There will always be differences between sending and receiving labs, so the key is to make sure that the method works in its final location – in your lab, with your staff, and with your ways of working3.

 

Proposed guidelines related to the lifecycle management of analytical methods4 outline a framework based on sound science and risk management. The guidelines advocate review of the method design and performance and the analysis of any areas of potential risk based on use in your laboratory.

 

Take the time to perform a risk analysis that considers the previous experience and knowledge of your lab staff, the complexity and specifications of the product, and the analytical procedure itself, and consider adopting Failure Mode Effect Analysis (FMEA). Ermer and Nethercote5 describe this as a systematic approach that relies on method understanding, which breaks down large complex processes into manageable steps and evaluates potential method failures and their impact on the reportable result. These principles are all outlined in stage 1 of the analytical procedure lifecycle4 but are equally applicable to method transfer.

 

The level of activities required will depend largely on the nature of the product being analyzed. The more complex the product, the more complex the transfer. Combination drug products, inhaled medicines, biologics, and modern therapies can be inherently complex and the more variables you add, the greater the chance of failure.

 

Of course, this enhanced understanding of the method takes time and budget, and a mechanism is needed by which staff with the right skill set are freed to do this work. Once areas of potential risk have been assessed, control strategies need to be implemented to ensure that the method will perform as required and that quality objectives for the reportable values are met on a consistent basis.

 

Mitigating your risk with quality consumables and fit-for-purpose analytical technologies

Part of your risk assessment should, of course, focus on the quality and performance of your consumables, analytical technologies and software systems, as well as the ability of your staff to use or operate them effectively. At Waters we actively ensure that our products and services evolve with customer need.  

 

In response to customer demand, Waters released a new range of ACQUITY Ultra Performance Liquid Chromatography (UPLC) Systems, the PLUS series, developed to accommodate the needs of more challenging methods and to mitigate risks associated with robust operation7. In addition, our ACQUITY Arc, a quaternary-based, modern LC system, is uniquely designed to ease method transfer, offering the versatility and robustness required to emulate methods developed on other chromatographic systems8. All of our quaternary ACQUITY platforms are AutoBlend Plus-ready, allowing automated, on-demand mobile phase creation, eliminating the cumbersome and error-prone approach of manual solvent mixing and are compatible with eCords for automated monitoring and tracking of column usage9, designed to mitigate risk associated with column history.

 

Many years ago, Waters invested in particle synthesis technology and quickly became a primary manufacturer of chromatographic particles. The ability to synthesize our own materials delivers several significant advantages, including complete traceability from final product to raw materials, which in turn led to vastly improved reproducibility of final product – batch-to-batch and year-to-year. The quality of sample preparation products and vials should also be considered as part of a risk assessment in order to reduce recovery variabilities and avoid ghost peaks that could compromise data reliability10.

 

Of course, it takes time to fully understand your procedure – to consider all the potential areas of associated risk, and to identify additional controls needed to ensure consistent performance of the method in your laboratory once in routine use. But the investment made up front should result in lower operating costs from fewer failures and deviation investigations down the line. At Waters we are committed to working with you to help understand and mitigate risk associated with bringing new methods into your lab. Contact us for more information around the products and professional services we can offer. 

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The author gratefully acknowledges Phil Nethercote, Independent consultant in Pharmaceutical Analysis and Gérald de Fontenay, Scientific and Technical Director at Cebiphar for interesting and helpful discussions pertaining to method transfer and analytical method lifecycle management.

 

References

  1. W. Rushing, Analytical Method Transfer Best Practices, ContractPharma.com, 11.07.2017 https://www.contractpharma.com/issues/2017-11-01/view_features/analytical-method-transfer-best-practices
  2. Nethercote, P., Borman, P., Bennett, T.,Martin, G., and McGregor, P. “QbD for Better Method Validation and Transfer”,Pharmaceutical Manufacturing, 9(4), 2010 https://www.pharmamanufacturing.com/articles/2010/060/
  3. Waters MLCM Podcast series, Nr. 3: Interview with Dr Pauline McGregor
  4. G. Martin et al., 2013 Stimuli to the Revision Process. Proposed New USP General Chapter: The Analytical Procedure Lifecycle ⟨1220⟩
  5. Method Validation in Pharmaceutical Analysis: A Guide to Best Practice, 2nd Edition, Section 6.2, Joachim Ermer and Phil W. Nethercote, 2015
  6. Achievement in Service Excellence - Making Our Customers Successful. Waters Library Number:LITR1531263 https://www.waters.com/waters/library.htm?cid=511436&lid=1531263&locale=en_GB
  7. Expedient Method Transfer of a UPLC Method for Budesonide Nasal Spray Using ACQUITY UPLC H-Class PLUS Binary and ACQUITY UPLC Systems. Waters Library Number: APNT135035420
  8. Impact of Instrument Characteristics on Reversed Phase Chromatography Method Transfer Across Biocompatible UHPLC Systems. Waters Library Number: APNT135003910
  9. Column Performance and Data Management Using eCord Intelligent Chip Technology, ACQUITY UPLC System, and Empower 3 Software. Waters Library Number:LITR134918901 https://www.waters.com/webassets/cms/library/docs/720005856en.pdf
  10. Waters LCGC Certified Sample Vials Technical Whitepaper. Waters Library Number:LITR134915920 https://www.waters.com/webassets/cms/library/docs/720001303en.pdf

Topics: Sample Handling and Preparation, Method Development

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