CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH)
FDA regulates as medical devices numerous in vitro diagnostic tests, including those utilizing products of modern biotechnology methods. Some of these tests, such as those involving retroviruses, are handled by CBER under the medical device requirements of the FFDCA (as described above).
CDRH has cleared a number of biotechnology-based IVDs for marketing. For instance, many of the DNA probe assays submitted to FDA have gained acceptance via the 510(k) route. Hundreds of IVD assays incorporating monoclonal antibodies have been submitted to CDRH via 510(k) notices and most have been cleared. Many of these CDRH-regulated IVD assays use biotechnology products to detect genetic mutations known to be related to specific disease conditions, such as Tm Bioscience Tag-It Cystic Fibrosis Kit and the Roche Diagnostics’ Factor V Leiden and the Factor II (prothrombin) G20210A kits.
Apart from disease screening or monitoring using biotechnology products, CDRH has cleared for marketing through the 510(k) pathway IVD assays intended to detect genetic mutations related to drug metabolism. These assays include the Amplichip test, which detects allelic variation in the CYP450 Cytochrome genes and the UGT1A1 Molecular Assay, which detects variations in the UGT1A1 gene that affects how certain drugs are broken down and cleared by the body. Doctors can use information from both tests to help determine the right drug dosage for individual patients, and to minimize harmful drug reactions and to personalize treatment decisions.
FDA also recently downclassified through the de novo downclassification process at least one IVD assay assessing a patient’s risk of cancer that is intended neither as a screening nor a monitoring tool. Agendia, through The Molecular Profiling Institute (“TMPI”) CLIA-certified reference laboratory, offers the MammaPrint assay as a gene expression profiling service that measures the presence or absence of messenger RNA in tumor specimens and provides prognostic information based on the level of RNA expression to determine the risk of progressive disease and survival in breast cancer patients (see FDA’s May 9, 2007 Class II Special Controls Guidance Document: Gene Expression Profiling Test System for Breast Cancer Prognosis). This guidance document also is applicable to other prognostic tests intended to measure gene expression profiles for other cancer types, such as colorectal cancer.
Exceptions to the usual rule that similar products using R-DNA technology will be cleared via 510(k) include Digene's ViraPap assay for human papilloma virus and GenProbe and Roche's amplified probes for Mycobacterium tuberculosis (M. tb). In the case of the ViraPap assay, FDA determined that the test was so much more sensitive than current detection methods that there was no device to which substantial equivalence could be claimed. The rationale for the M. tb decision was related to the upsurge in tuberculosis cases in the United States, making the disease of greater public health significance than in the past. The same result can be expected for other biotechnology-based products whose intended uses differ or whose performance characteristics exceed those of presently marketed products.
In the same area of IVD assays, CDRH has approved through the PMA pathway several “companion diagnostic” tests that aid in selecting patients eligible to receive specific biotechnology-derived drug products. These products include IVD assays, such as the HER-2 DNA Probe Kit, which is used as an aid in the assessment of patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered, and the EGFR pharmDx™, which is indicated as an aid in identifying colorectal cancer patients eligible for treatment with ERBITUX™ (cetuximab).
Aside from IVD assays, CDRH has been responsible for the assessment and regulation of medical devices, such as catheters and implanted bone substitutes, coated or impregnated with drug substances, silver compounds, and antibiotics, as well as more complex combination products, such as drug eluting stents and orthopedic implants containing recombinant growth factors (e.g., OP-1 and Bone Morphogenic Protein-2). While many of these devices and substances are not biotechnology-derived, the inclusion of more complex materials, recombinant proteins, and the use of devices to deliver locally-acting substances to specific anatomical locations bodes well for the development and delivery of novel device-biological products.
