Bringing Molecular Diagnostics to Market
There are many steps involved in bringing a product through the approval process, including different requirements for ASR, RUO, and IVD products. Walter Koch, Ph.D., vp and head of research at Roche Molecular Diagnostics (www.roche.com), will explain some of the guidelines.
ASRs, or analyte-specific reagents, are components of CLIA-certified lab’s homebrew, laboratory-developed assays. These are developed and manufactured under the Quality Systems Regulation and are listed, rather than approved, by the FDA. They do not contain instructions for use as part of the test and cannot be promoted for specific diagnostic applications.
RUO, or research use only, is a separate designation for kits sold for research only. These contain no performance data in labeling and no “intended use” diagnostic statement.
IVD, in vitro diagnostic, is a medical device, by FDA definition, that analyzes human body fluids to provide information for the diagnosis, prevention, or treatment of disease. The test kit may be a complete system commercialized for a specific intended use and require FDA clearance or approval, depending on the regulatory application made.
Dr. Koch says that, typically, a company like Roche Molecular Diagnostics follows five phases of development. These include: analysis, feasibility, development, implementation, and manufacturing/sales. In his presentation, he will explain some of the difficulties in bringing a project to market.
Further requirements may include establishing clinical utility, educating labs on new technologies, interacting with payers on reimbursement issues, consulting with regulatory agencies for guidance on correct regulatory paths for individual products, and educating clinicians who ultimately order the tests.
Promega (www.promega.com) has developed real-time quantitative PCR systems that are multiplex-capable using base-pair chemistry.
The Plexor™ Systems measure each target directly using the amplification process and not via a secondary reaction. It uses only two primers per target, which makes the design of multiplex assays simpler. “The advantages of multiplexing are huge, including more accurate data, increased productivity, and even increased efficiency of PCR,” explains Ilgar Abbaszade, Ph.D., strategic marketing manager, functional genomics.
The system works by measuring reduction in fluorescence signal during amplification. One of the two primers contains a modified base with a fluorescent reporter at the five prime end.
As amplification proceeds, fluorescence is reduced by site-specific incorporation of a fluorescent quencher, which is attached to the modified nucleotide. “As soon as the quencher is in close proximity to the fluorescent dye, it results in reduction of fluorescent signal,” explains Dr. Abbaszade. “This is the opposite of TaqMan, where the curve increases from low to high.”
After PCR, a melt analysis can be done to provide an internal control for the final assay design or to expedite troubleshooting during development. The system also provides free web-based primer-design software to design primer sets that will work together with maximum efficiency. “The probability of the software not working is low, we get about 92% of the reactions working,” adds Dr. Abbaszade. Plexor technology works on most currently available real-time instruments.