Krista Pratico (Presenter)
UCSD Center for Advanced Laboratory Medicine
Bio: Krista Pratico works as a clinical lab scientist in the clinical toxicology lab at the Center for Advanced Laboratory Medicine, UC San Diego Health System. Her research interests include development of IT tools to improve LC-MSMS workflows and interfacing, and LC-MSMS method development.
Authorship: Krista Pratico
UCSD Center for Advanced Laboratory Medicine
| Short Abstract With regulation of LDTs on the horizon, the need for laboratories to develop a feasible method of logging LC-MS/MS reagents and solvents is inevitable. Such a system must be able to document and track all lot changes and lend itself to retrospective troubleshooting when the components of a prepared solvent or reagent cause subpar performance. We have developed a workflow that involves the use of individual barcodes - to document lot and expiration of reagents, track where and when they were used, and document that validation was performed - all in a MS Access database. This system can be customized to track anything in the LC-MS/MS lab - from chemicals to consumables. |
Long Abstract
According to the FDA, a laboratory developed test (LDT) is a type of in vitro diagnostic test that is designed, manufactured and used within a single laboratory[1]. LDTs have been around for decades, but recent improvements in technology have caused a substantial increase in such tests, some with questionable validity, prompting the FDA to put LDTs back under their radar. The FDA has claimed that LDTs have since evolved to become more advanced, complex tests that bear higher risks to patients since they are not subject to pre-market review[1]. Currently LDTs are regulated by CMS through the Clinical Laboratory Improvement Amendments (CLIA), which governs all clinical laboratory testing in the United States. In July 2014, the FDA announced to Congress that they would be producing a draft oversight framework for LDTs that would include pre-market review for higher risk LDTs and continuing enforcement discretion for low risk and rare disease LDTs[1]. Opposition from various organizations and significant debate followed the proceedings of the FDA's framework; however, plans remain to finalize the documents in 2016[1].
Preparation for potentially more stringent regulation in a LDT laboratory drives the need for better methods of ensuring that proper documentation occurs. In a clinical LC-MS/MS lab where many of the solvents and reagents are prepared in-house, it is imperative to document not only lot numbers of the chemicals used, but also information such as expiration dates, when a reagent lot was put into production, and if its use was instrument specific. In October 2014, The Clinical and Laboratory Standards Institute (CLSI) released a document entitled C62-A: Liquid Chromatography-Mass Spectrometry Methods; Approved Guideline that recommends that all lot changes of solvents, extraction reagents, columns, filters, and other components of reagents and consumables (pipette tips, tubes, autosampler vials, etc.) should be documented[2]. Since lots for various reagents and consumables change frequently, manually record keeping is not ideal. To comply with this guideline, we developed a "homebrew solution" for tracking the solvents and reagents that we use in production for patient testing.
The system created tracks all chemicals as they are received in the lab through the application of a barcode that contains its lot number and expiration date. When the chemical is used, it is scanned into a database containing records of all the prepared solvents and reagents currently in production testing. Therefore, any given chemical can be traced back to when it was used, what it was used for, and where it was used (if it resides on an instrument, e.g. a mobile phase). With lot numbers recorded for every prepared reagent, it allows the lab to retrace its steps when there is a sudden change in chromatography or other mass spectrometry related issue. Additionally, lot data from each sheet is captured by automatic queries that compile a running list of the lots in use. The queries can be used as an easy reference to view the current lot in use in order to avoid having multiple, different lots in production. For quality assurance purposes, documentation exists for reagent validation, a "check box" that confirms that its preparation followed exactly that of the standard operating procedure (SOP), and a field for the user to add his or her initials.
Seemingly small differences in lot or grade of a chemical can translate to dramatic changes in LC-MS/MS analysis. Our laboratory recently experienced a series of batches with measurably lower internal standard peak area, leading to QC failure and inability to report patient results. Through the normal course of troubleshooting, we discovered that the mobile phase for these batches had been prepared with HPLC grade instead of LC-MS grade Methanol. Replacing these bottles with mobile phase prepared from the proper grade of Methanol resulted in acceptable batches once again. Although this event precedes the implementation of the barcode system, the system now in place would have provided an easily deciphered evidence trail for when the HPLC grade methanol was used to prepare mobile phase, the date the mobile phase came into use, and which instrument(s) were affected, decreasing the downtime and troubleshooting required in resolving the issue.
The barcode system and a database for solvents and reagents have greatly improved our labs compliance with the documentation and tracking that is expected of a LDT laboratory. A highly customizable system such as ours provides a feasible method of completing such a task and allows for future modifications with the ever-changing menu of tests available.
References & Acknowledgements:
References
1. Laboratory Developed Tests. U.S. Food and Drug Administration website. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm407296.htm Published November 17, 2015. Accessed December 5, 2015.
2. CLSI. Liquid Chromatography-Mass Spectrometry Methods; Approved Guideline. CLSI document C62-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2014.
Acknowledgments
Judy Stone | UCSD Toxicology/Mass Spectrometry Laboratory
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IP Royalty: no
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