Mass Spectrometry in the Clinical Lab: The Importance of Choosing a Medical Device

A versatile analytical tool used in fields ranging from clinical diagnostics to forensics, mass spectrometry is increasingly finding its way into the biochemistry clinic. Its original roles in drug testing and newborn screening have evolved over the years to include an ever-wider range of applications, such as therapeutic drug monitoring, microbial identification and cancer diagnosis.

In this interview, SCIEX’s Francis Fung highlights the benefits that mass spectrometry can bring to clinical laboratories, and discusses why when selecting a mass spectrometer, it is important to consider choosing a medical device.

Anna MacDonald (AM): What are some of the main challenges facing clinical labs today?

Francis Fung (FF): Large biochemistry labs in a pathology department can receive up to 5000 samples per day, a large portion of that may be samples for the mass spectrometer, therefore standard work for processing and workflow handling is a key part of daily management.  Various sections of the lab require different skill sets, and the manual section where mass spectrometry (MS) resides needs end users with MS experience to fully engage and confidently operate both the software and hardware.  Sample preparation, analysis, results generation and review, reporting out, are all part of daily routine that require strict quality assurance in the face of time pressure.

AM: Can you tell us about some of the benefits that using mass spectrometry can bring to these labs?

FF: The ability to specifically identify and quantify the molecule of interest amongst structurally similar compounds is a huge advantage, and MS with its associated technologies provide ultimate specificity when isolating the compound of interest from its associated matrix. However, that might not be enough with multi-factorial matrices, so selectivity plays a major role alongside specificity. 

Whole blood, serum, plasma, cerebral spinal fluid (CSF), these biological fluids are complex as they contain metabolites that may interfere with analyses.  MS provides the level of selectivity needed to isolate and quantify the compound of interest, without interference from its surrounding environment.  Advanced secondary fragmentation such as QTRAP® Technology further enhances selectivity for challenging matrices such as hair, while maintaining low background. 

Sensitivity is arguably the biggest advantage when it comes to mass spectrometry.  Low level detection and quantification, in the parts-per-trillion range, are often needed for biochemical assays such as aldosterone when levels are as low as the single digit pg/mL range.  The ability to detect trace level compounds in a variety of challenging matrices is one of the hallmarks of mass spectrometry technology.

AM: How does mass spectrometry compare to other technologies such as immunoassays?

FF: While immunoassays are still popular for most biochemical tests, concerns arise over their lack of specificity with structurally-similar molecules such as steroids, where cross-reactivity may play a role in false negatives and positives.  Assays requiring low levels of detection in the pg/mL range are also not suitable with an antibody-based approach, as the same cross-reactivity issue can result in over-estimation of the compound in question.  These shortcomings, combined with the advantages of mass spectrometry, are quickly increasing the adoption of the latter to further improve diagnostic accuracy of routine laboratory tests.

AM: How easy is it for a clinical lab to make the transition from other existing technologies to mass spectrometry?

FF: Choosing the correct vendor is of paramount importance, as appropriate levels of support can enhance the end-user experience dramatically. The infrastructure at SCIEX ensures the customer receives the appropriate training from Day 1.  As adopters of new technology, in a high-pressure environment such as clinical biochemistry, switching from familiar technologies to adapting new ones can be daunting.  However, with the correct tools, support, and after-sales training, a good MS provider can develop a structured transition program for the adaptation of mass spectrometry for the end user.

AM: When selecting a mass spectrometer, why is it advantageous to choose a medical device system?

FF: 4 main reasons

1. Patient-safety first: Not only are Medical Device systems from SCIEX designed and built to ISO 13485 and FDA 21 CFR 820 standards, MD-level software packages ensure the entire system is compliant and auditing capabilities are accessible for risk assessment and mitigation.

2. Designed for clinical users: Tailored service and support packages, online and troubleshooting support, as well as dedicated clinical application experts ensure the end user is in good hands.

3. Minimize risk: MD instruments only use brand new replacement parts.  Along with stringent verification processes, operational quality is maintained at the highest level.

4. Trusted Partner: SCIEX Now telephone support provides quick response for any lab-related questions.  Coupled with extensive online courses available in SCIEX University for self-paced learning, SCIEX is the leading provider and trusted partner of medical solutions for mass spectrometry.

AM: Can you tell us about the European Union In Vitro Devices Regulation which will come into full force in 2022? What impact will this have on clinical labs? How can they best prepare?

FF: Technology and instrumentation used for diagnostic purposes are required to adhere to government regulations and its guidelines, to ensure patient safety as well as compliance within the laboratory.  Strict operational procedures and requirements are in place to protect the operators from malpractice, as well as maintaining a high level of quality assurance to produce accurate diagnostic results, which directly impacts medical decisions and patient well-being. 

In North America, laboratory equipment classifications  are split into three categories.  Class I poses the lowest risk (control materials and laboratory instruments), Class II has moderate risks (disease monitoring devices or tests that help diagnose a condition), while Class III presents the highest risk (for example cancer screening devices).  Unless they have been exempted by FDA, most of the Class II devices are cleared through the 510(k) pathway and is based on demonstrating performance of a new device is substantially equivalent to an FDA-cleared or preamendment device.  It is becoming more apparent that mass spectrometers used in a clinical diagnostic setting should be a medical device to protect both the end user and the process that includes patient results generation.  This helps ensure customer confidence and compliance through use of diagnostic instruments that meet the stringent FDA Good Manufacturing Practices (GMPs) and Design Control Requirements.

On May 26, 2017, an official paper of the European Commission published a new set of guidelines on newly released European IVD Regulation (IVDR 2017/746).  There will be more attention to risk in relation to patient safety in classification of the IVDs, and the Clinical Effectiveness element will bring specific demands in relation to the quality system from manufacturers, especially in relation to Risk Management.  Regarding Lab Developed Tests, laboratories will either need to use commercially available IVDs - if available, or to develop, manufacture, and monitor their own laboratory-developed tests in compliance with the requirements of the IVDR.  Laboratories which develop these tests must have a quality management system for this specific test, after evaluation and validation. The demands formulated under this Regulation state that laboratories and manufacturers must comply with the regulations by May 2022.  This gives laboratories enough time to reevaluate their current setup, and plan what instrumentation and technology they wish to implement in the next few years.  To ensure compliance for the future, mass spectrometrists must consider the importance of purchasing and validating laboratory equipment with these guidelines in mind.

AM: After the MS implementation, what kind of support is available from the vendor to ensure smooth operation of the system?

FF: Software updates and fixes

To ensure that our customers in the clinical lab have access to all the latest software fixes, anyone that purchases IVD mass spectrometers are eligible to receive every software update and Hot Fix completely free of charge. This means that your laboratory can take advantage of every new software feature, as soon as it becomes available.

Security features

There are several standard security features that differentiate SCIEX’s IVD product offerings from other vendors. In contrast with our Research Use Only portfolio, all our IVD LC-MS/MS solutions include standard security features and audit trail functionality – no paid upgrade required. These included safety features help to ensure the integrity of your valuable data, using e-signatures and role-based access privileges to safeguard against unintentional changes.

Software built for the clinical lab

To address the unique needs of the clinical laboratory environment, SCIEX has developed the user-friendly Cliquid MD software for instrument control and data processing. This software is also available as an optional paid upgrade for RUO mass spectrometers, but comes standard with all of our IVD mass spec solutions.

AM: If a Medical Device needs repair or maintenance, what does the service organization provide over non-MD setups?

FF: Any unscheduled instrument downtime in the clinical lab can lead to delays in reporting out critical results, and potential costs associated with sample send-outs. To get you back up and running as quickly as possible, our Clinical Service plans offer dedicated telephone call back from a qualified Service Engineer, and guaranteed 2 business day onsite response for remedial repairs of the LC-MS/MS system. Repairs to IVD mass spectrometers use only brand new SCIEX parts, to maintain the highest level of system performance. Our trained Service Engineers run through a comprehensive checklist of system performance tests after every service call, to ensure that you are getting the most out of your instrument.

There are a plethora of advantages and benefits when an IVD mass spectrometer is chosen for clinical diagnostic purposes, safeguarding the end-user from all aspects of operational demands to maintain confidence in the entire sample-to-results journey.

Francis Fung was speaking to Anna MacDonald, Science Writer for Technology Networks.