What’s Changing Analytical Method Transfer Today?
Part 1. New Technologies, New Opportunities
There’s a new analytical testing landscape taking shape, and it’s having a big effect on how we develop, transfer, and update methods. Data quality and business efficiency are both at stake. Are you ready?
Let’s find out. This new series explores the drivers, challenges, and payoffs you face – whether your analytical method is bound for the lab down the hall, or a lab halfway around the world.
First up: Changing technologies.
Your analytical method may well have a long and useful life ahead of it – as long as the lifetime of the pharmaceutical product you may be creating the method for. After all, many pharmaceutical companies have methods dating as far back as the 1970s or 1980s.
Still, a lot has changed since then. Even tried-and-true (and validated) methods require updates, whether to boost efficiency or adapt to industry and regulatory shifts. For liquid chromatography today, the trade-offs are often worth the time and costs of method updates and even equipment upgrades. And the pressures to change are substantial.
Efficiency and data quality go hand-in-hand
A general squeeze on lab operating budgets worldwide has made efficiency gains a high priority. In parallel, analytical regulatory requirements drive a need for lower detection limits and product complexity presents the necessity to track more analytes per sample. Labs running routine analytical methods face increasing pressure to produce faster results, in greater volume, within a smaller footprint – all without compromising data quality.
There has been a growing focus on characterizing and controlling impurities in pharmaceutical processes over the last decade, as is evidenced by the release of various agency guidance documents (e.g., ICH Q3A, 3B), with requirements in the low-ppm detection limits for things such as mutagenic impurities, to ensure ongoing patient safety in products.
For chromatographic methods in particular, technical advances offer substantial gains in performance, reliability, and throughput, with corresponding reductions in labor and materials cost.
You can realize some or all of these gains with a higher-pressure, lower-dispersion LC system. In addition, adding mass data can bring greater certainty of identification to complement many existing UV/Vis methods. Even without an entirely new technology, you can still update older legacy methods for improved robustness, for example, using newer column technologies that provide greater stability, simpler protocols, and broader market availability if operating within the constraints of regulatory and guidance agency recommendations.
Competition and change
To keep up with the latest technology and remain competitive, contract labs need to support the growing influx of new LC method requirements from project sponsors or originating laboratories. Due to varying degrees of complexity and performance of these methods, a contract lab’s operations also requires flexibility in how it approaches methods, including the analytical LC equipment and the range of method types that must be accommodated while maximizing the investment of that equipment.
In testing a drug product, say, a contract lab may receive the final product from its sponsor. Additionally, it might also test an active ingredient from an alternative supplier. Each lab may have its own testing method or preferred LC platform, whether UPLC, UHPLC, or HPLC. In such a case, the ability to run a common method could be essential to understanding and controlling the final product.
Regulatory shifts follow technology changes
We’re constantly learning new things about biology and toxicity. As this knowledge increases, regulatory guidance demands greater precision and a higher number of analytes, pushing the limits of analytical methods and equipment. For example, in keeping with the ICH M7 guidance, the U.S. FDA in 2015 set new guidelines calling for more detailed profiling of mutagenic impurities in drug products (U.S. FDA 2014). Similarly, the FDA Guidance on Evaluation of Biosimilarity (U.S. FDA 2015) prompted a shift to include additional detection methods such as mass detection alongside older UV/Vis methods.
As more regulatory guidance documents such as ICH Q10 Pharmaceutical Quality System and FDA Analytical Procedures and Methods Validation for Drugs and Biologics continue to be released reflecting a risk-based and lifecycle approach to understanding and controlling pharmaceutical processes, many labs are updating their capabilities to meet the requirements. As they do so, many are adopting new methods and practices that offer longer lifetimes and greater equipment flexibility to meet these emerging and ongoing needs. Using the most current technology available can extend the useful life of an assay, reducing the need for method update and revalidation throughout the marketed lifetime of the product.
There have been many efforts over the years to harmonize towards common regulatory expectations in an effort to reduce multiple market burdens for drug producers. Changes proposed in the upcoming USP41-NF 36 2S Chapter <621> guidelines provide some clues as to how to direct resource investment when bringing newer technology into regulated and QC analytical labs.
The current USP Chapter <621>, enacted in 2014, place limits on allowable parameter adjustments before full-method revalidation is required, as part of ensuring consistency across chromatographic systems. Isocratic methods can undergo a number of adjustments to parameters with only verification of method suitability for intended purpose, rather than a full revalidation. However, gradient methods require revalidation for “any change to column configurations.” Therefore, adjustment to gradient methods involves time and resource investment to optimize and validate the method for the product being tested. We’ve written about how LC labs can work within those guidelines: Chapter and Verse: USP 621 and You.
In the proposed USP <621> chapter, anticipated to be official in December 2018, allows for adjustments to gradient methods in addition to isocratic methods.
This change will enable QC labs to realize savings in time and operating costs while ensuring reliable results are achieved without need for revalidating methods. The addition of mass detection can further help labs to streamline confident identification and quantitation workflows.
As you respond to competitive, technological, and regulatory pressures, you have the opportunity to move toward more agile, future-proof analytical strategies. But those strategies are only as robust as your method performance.
Your own organization—or the organization you partner with—could be causing method transfer issues.
Find out how in part two of our series.
Visit waters.com/methodtransfer for ideas on how to approach change.
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- U.S. Food and Drug Administration. M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk; International Conference on Harmonisation; Guidance for Industry; Availability. Federal Register 28 May 2015. Accessed online 28 Oct. 2017.
- U.S. Food and Drug Administration. Quality Considerations for Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product April 2015.
- Future-Proof Solutions for Regulated Laboratories In the Face of Changing USP <621> Guidelines. Summers M and Carlson G. Waters white paper, Feb. 2015.
- ICH Harmonized Tripartite Guideline. Impurities in New Drug Substances Q3A (R2). Current Step 4 version 25 Oct. 2006
- ICH Harmonized Tripartite Guideline. Impurities in New Drug Products Q3B (R2). Current Step 4 version 2 June 2006
- ICH Harmonized Tripartite Guideline. Pharmaceutical Quality System Q10. Current Step 4 version 4 June 2008
- USFDA Analytical Procedures and Methods Validation for Drugs and Biologics; Guidance for Industry. July 2015. Pharmaceutical Quality/CMC. CDER/CBER
- USP <621> PF43(5)