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Technologies have a life cycle. Typically, the time line traces an idea to acceptance and decline as something new replaces it. Fax machines, floppy discs, eight-tracks, and cassette tapes are all good examples. All have endured the fad cycle. In analytical chemistry, analytical methods—for instance, USP and ASTM methods—have a life cycle, also. Both are periodically reviewed for advances in technology and need.
I attended a users’ conference on method life cycle management (MLCM) organized by Waters at the company’s customer support office in Pleasanton, CA, on June 25, 2019. Isabelle Vu Trieu, market development manager for Waters, introduced the goals of the event with an explanation of the properties of analytical methods. For example, when a method is introduced, it may represent and utilize the best available technology, but with time, unavoidable changes creep in and the technology advances. Eventually, methods become obsolete.
For example, in the 1970s, HPLC with ~6000-psi pumps was leading the state-of-the-art, but in 2004, Waters introduced the ACQUITY UPLC. This set a new standard of performance. Today, the market is in transition, with instruments capable of running at more than 10,000 psi using columns packed with particles smaller than 2 µm. Emphasis is on reducing run and response time and improving resolution, detection limit, and data quality.
Ms. Vu Trieu pointed out that even regulators recognize that locking down an analytical method does not prevent the method obsolescence problem. Plus, with 30+ years of experience, nearly all recognize that pharmaceutical manufacturing technology has changed for the better—sometimes dramatically, but incremental changes also compound to become significant.
She illustrated that MCLM should be an essential part of the enterprise operation. The plan for MCLM involves applying Good Manufacturing Practices (GMP) to the production of data, as in Good Laboratory Practices (GLP). Quality-by-design (QBD) programs using factorial design are the key to measuring robustness and overall performance of the method. The beauty of implementing MCLM with GMP tools is that regulators, including FDA, recognize and accept USP and ICH principles of GMP for change control. For support, she referred to several guidance documents including USP <1220>, ICH Q12, Q2 (R2), and ICH Q14, which is expected soon.
Vu Trieu went on to show that the analytical target profile (ATP) is the work product of considering the critical quality attributes (CQAs) of the therapeutic product. This reversibly maps to a list of analytical target profiles for the drug, drug active, impurities, and degradants. A simple matrix of variance source, frequency, and impact provided a quick risk assessment.
Following Ms. Vu Trieu’s introduction, Dr. Fadi Alkhateeb of Waters described implementation of the method development and validation using Fusion software from S-Matrix. Once the methods have been studied for robustness, etc., the run conditions can be seamlessly ported to Waters Empower software to implement the assays. Comparison of Fusion predictions and observed results from an instrument running Empower are within about 2%.
Dr. Alkhateeb discussed how Fusion will soon be able to use m/z values from a Waters QDa to aid in peak tracking. With traditional UV and diode array detectors, peak mapping between runs is often an issue, but with the QDa, the m/z values significantly reduce the ambiguity.
Another point of potential improvement is that Fusion only reports the most recent data. But there is a need to store all data, including historical archives, which is one of the strengths of Empower.
This meeting addressed issues of measuring and managing data quality in a changing world. The focus on using existing concepts and tools such as CQA, GMP, QBD, and factorial design to manage GLP is refreshing and inspires confidence. Meeting attendees were from traditional biopharma enterprises. However, the topics covered would also be of interest to other vertical segments such as forensics and natural products such as cannabis.
If you are fortunate enough to receive an invitation to this meeting when it comes to your region, I think you and your colleagues should attend.
Robert L. Stevenson, Ph.D., is Editor Emeritus, American Laboratory/Labcompare; e-mail: [email protected]