Live from AMP: Addressing Reference Material Challenges
The morning plenary at AMP today was an excellent one: "Issues Surrounding Lack of Laboratory Reference Materials: Impact on Assay Development and Validation,
QC and Proficiency Testing." This three-prong session looked at the challenges surrounding the distinct lack of valid reference materials for most tests for genetic disorders, presenting the U.S. perspective (Lawrence Jennings, MD, PhD, Children's Memorial Hospital, Chicago), a European perspective (David E. Barton, PhD, National Centre for Medical Genetics, Dublin) and Lisa Kalman, PhD, from the CDC, addressing the needs and explaining what's being done.
Reference materials (RMs), of course, are needed for test development and validation, internal quality control, method development and assay calibration. Jennings explained that there is a distinct lack of reliable reference materials because of challenges in finding enough ‘positive' samples, finding samples with rare mutations or with known allele burden, and finding ‘super controls' for multiplex assays that can target all of the mutations you might test for.
There are a number of options for reference materials, such as patient samples, derivatives of patient samples, cultured cells or engineered constructs, each with its own list of pros and cons. "There is no perfect reference material," Jennings reminded. "Every material has its advantages and disadvantages. The reference material should be chosen for its intended use."
Kalman explained that between certified, standard RMs and WHO standards, FDA-approved/CE-marked RMs, non-FDA-approved/CE-marked commercial RMs, and characterized genomic DNA from cell lines or clinical samples, there are reference materials (some more highly characterized than others) available for about 350 tests for genetic disorders -- but there are tests available for about 2,400 genetic disorders. "This means most tests do not have reference materials," Kalman said. "This is a problem -- labs often use uncharacterized, non-renewable clinical materials for test validation and QC, and the quality of genetic tests may be compromised."
To address this issue, the CDC established a collaborative program called GeT-RM (Genetic Testing Reference Materials), with involvement from IVD manufacturers, professional organizations, patient advocacy groups, cell repositories, government agencies and clinical genetic testing labs. The GeT-RM program acts as an information exchange and attempts to monitor RM needs while facilitating submission, development and characterization of RMs.
Labs can be encouraged by these efforts to address challenges in obtaining high quality reference materials. Stay tuned to ADVANCE for more on this topic -- and more from the AMP meeting in Long Beach.