Implementation of new molecular tests in my laboratory: Where to start?

As molecular diagnostics expands in the clinical setting, diagnostic laboratories face the challenge of achieving dependable, convenient, and affordable quality control. AcroMetrix offers an effective solution through independent, external quality control materials.

With the increasing awareness of HAIs and pandemics such as the recent 2009 H1N1, diagnostic laboratories are continually increasing their investment in molecular diagnostic technologies for the benefits of increased sensitivity, specificity, and automation. However, such an investment requires an appropriate level of quality control. Proper quality control practices are vital in guaranteeing accurate and consistent test results, which are necessary in order to deliver quality patient care.

Major challenges that a diagnostic laboratory faces are 1) implementing a reliable and accurate assay and 2) obtaining dependable and affordable standards to monitor the quality of their assays. Proper validation or verification of the test prior to implementation minimizes error and maximizes patient safety. Furthermore, in order to ensure accurate and meaningful test results daily, laboratories use external controls that are independent of the assay manufacturer. Use of independent controls is critical because they are not directly linked to the assay itself, whereas the controls provided by the manufacturer are specific to the assay reagent lot and may not monitor the entire testing procedure. The difficulty for laboratories lies in obtaining independent external control material that is reliable and cost-efficient.

Verification and Validation

The implementation of new tests requires following procedures that usually rely on guidelines established by governmental agencies or international institutions that have one main goal in mind - delivering dependable results to physicians and their patients. The interpretation of those guidelines, especially in regards to new testing techniques such as Molecular Diagnostic methods, can be challenging. Access to standardized protocols that meet or exceed regulations, coupled with the appropriate control materials and software solution to aid in data analysis is what laboratory managers look for. Web-based Verification and Validation tools provided by AcroMetrix simplify the process, enhance confidence, and enable the laboratory to implement new tests quickly, reducing downtime of the test while increasing revenue generation.

Independent External Controls: Build or Buy?

One common practice for a laboratory is to develop its own controls, also known as "homebrewing." This process requires extensive hands-on time, storage space, stability testing, sourcing of reliable control material, compliance with regulations, extensive documentation, and extra testing reagents. Additionally, many laboratories lack the budget, manpower, or expertise to support the development of their own controls. Lost time and opportunity often leads the laboratory to enlist AcroMetrix to assist them with their quality control needs.

AcroMetrix provides a range of molecular and serological diagnostic quality control products that aid laboratories in meeting quality and regulatory requirements. AcroMetrix maintains its leadership in molecular quality control by developing innovative standards, external run controls, and validation and verification solutions for clinical diagnostic and blood screening laboratories. Additionally, AcroMetrix supports the goal of standardization in molecular diagnostics by establishing traceability of results and by providing commutable material that ensures consistent, accurate, and meaningful test results.

Standardization in Molecular Diagnostics

"A fundamental goal of laboratory medicine is that results for patients' samples will be comparable independent of the medical laboratory that produced the results."¹ In order to accomplish this goal of standardization, laboratories need calibration and quality control materials that are both traceable and commutable.

In order to provide traceability, AcroMetrix manufactures all of its products in compliance with ISO 17511:2003. ISO 17511:2003 is an international standard for in vitro diagnostic medical devices that defines how to achieve metrological traceability of values assigned to calibrators and controls that are used to verify the accuracy of measurement of quantities in biological samples. In other words, the calibrators and controls must yield measured values that can be traced back to a higher order standard or primary reference measurement through a chain of comparisons and uncertainties.² Traceability ensures accurate quantification of calibration and quality control materials that are used to standardize and monitor the performance of molecular assays, respectively.

An essential characteristic of any reference material is commutability, which is defined as the equivalence of the mathematical relationships between the results of different measurement procedures for a reference material and for patient samples.³ Commutable calibration and quality control materials behave like patient samples on different diagnostic analyzers. AcroMetrix pioneered the concept of commutability in molecular diagnostics with the development of the OptiQuant CMVtc Calibration Panel. In a study, different molecular testing methods that were calibrated with this traceable and commutable material demonstrated a much higher comparability of patient results than when a non-commutable calibrator was used.⁴

AcroMetrix is dedicated to providing materials that closely mimic authentic patient samples, that have minimal matrix effects, and that monitor the full testing process from extraction through amplification and detection. AcroMetrix also provides standardized quality control materials for testing hospital-acquired infections and influenza.

Hospital-Acquired Infections

Over the past several years, the clinical diagnostic industry has seen a significant shift toward molecular testing methods for hospital-acquired infections such as MRSA, MSSA, and C. difficile. Although molecular testing methods can be expensive, the cost of treating a patient who tested false negative is exponentially higher than the cost of testing. Thus, clinical laboratories may prefer to purchase standardized, independent external control materials to ensure quality of result. AcroMetrix's OptiQual MRSA and MSSA Positive Controls are currently available and AcroMetrix will introduce a control for C. difficile later in the year.

2009 H1N1

In January, AcroMetrix made significant progress in safe, reliable flu testing with the launch of the only inactivated, full-process 2009 H1N1 control material: The OptiQuant® 2009 H1N1 Panel and the OptiQual® 2009 H1N1 Positive Control⁵. The inactivation process significantly reduces the possibility of viral transmission to laboratory personnel who would otherwise have to rely on active positive patient samples.

Later this year, AcroMetrix plans to complement the 2009 H1N1 panel and controls by adding other major influenza subtypes and other respiratory viruses to its expanding product menu of quality control products.

AcroMetrix: Innovation Across Quality Control for Molecular Diagnostics

AcroMetrix, headquartered in Benicia, California and with a facility in Alkmaar, the Netherlands, upholds a strong reputation as a leader in molecular diagnostics. In February 2010, AcroMetrix was acquired by Life Technologies, expanding its capabilities to innovate and expand its product menu.

Last year, AcroMetrix developed the OptiQuant-S HCV Quantification Panel⁶, which uses Syntura™ technology. Syntura utilizes a recombinant form of bovine viral diarrhea virus (BVDV) with additional sequence elements inserted into its genome to mimic naturally occurring HCV virus. Exceptional linearity and high titers can be achieved using this technology.

More recently, AcroMetrix has broadened its focus to include full process control materials for oncology. Formalin-fixed paraffin-embedded (FFPE) synthetic tissue controls and panels will be available for KRAS testing. Planned for development are FFPE controls for additional molecular oncology targets such as BRAF, EGFR and PI3K.

AcroMetrix offers products that help expedite the implementation of molecular tests in the areas of infectious disease, oncology, serology, and blood screening. Please visit the AcroMetrix website at www.acrometrix.com for more information about our range of applications and for access to publications.

References

1. ISO 17511:2003, In vitro diagnostic medical devices-Measurement of quantities in samples of biological origin-Requirements for certified reference materials and the content of supporting documentation

2. Miller WG, Myers GL, Rej R. Why Commutability Matters. Clin Chem 2006; 52:553-4.

3. Vesper HW, Miller WG, Myers GL. Reference Materials and Commutability. Clin Biochem Rev 2007; 28:135-143.

4. Caliendo et. al. A commutable cytomegalovirus calibrator is required to improve the agreement of viral load values between laboratories. Clin Chem 2009; 55:1701-10.

5. OptiQuant 2009 H1N1 Panel and OptiQual 2009 H1N1 Control are "For research use only. Not for use in diagnostic procedures."

6. OptiQuant-S HCV Quantification Panel is for "For research use only. Not for use in diagnostic procedures."