Supporting Marketing Applications
IVD applications for new types of assays will almost always need supporting clinical data. The regulatory framework for these studies, however, is different than for pharmaceuticals. Occasionally, the sponsor will need to submit an investigational device exemption (IDE), the device counterpart of an IND. This primarily occurs when the investigational IVD’s results will be the basis for a therapeutic decision. FDA receives only a handful of IVD IDEs each year.
Many IVD studies are not even subject to IDE regulations. If a study meets a four-part test, then the IDE regulations are entirely inapplicable (21 CFR 812.2(c)(3); FDA. Draft Guidance for Industry, Clinical Laboratories, and FDA Staff—In Vitro Diagnostic Multivariate Index Assays, July 2007). A majority of IVD studies fall into this category.
Also very often, an IVD study will be deemed a nonsignificant risk study and will be covered by the abbreviated IDE process (21 CFR 812.2(b)). These studies must comply with only a few elements of the IDE regulation, including having an investigator agreement as well as reporting and maintaining certain records. More important, the study can commence without prior FDA approval. The company can itself deem the study to be a nonsignificant risk study, but each institutional review board (IRB) must agree. These studies must comply with FDA’s informed consent regulations (21 CFR Part 50) and IRB regulations (21 CFR Part 56). IVD studies often use banked specimens, in which case informed consent may not be required (21 CFR Part 56).
Thus, because IVD studies rarely need FDA approval, many investigations are initiated and completed without any interaction between the manufacturer and FDA. It is usually better, though, to obtain the agency’s feedback before beginning the study.
The company can obtain this feedback via the pre-IDE process. This mechanism allows the IVD firm to submit its protocol and meet with FDA to discuss study design, intended use, preclinical testing, regulatory pathway, and other issues. FDA’s comments on a pre-IDE are not binding, and its views can change. Pre-IDE reviews are not subject to statutory time frames.
Just as is the case for pharmaceuticals, IVD companies need to define the clinical endpoints carefully. The terms safe and effective in the IVD context have different meanings than in the drug industry. Since IVDs are not administered to patients, there is no direct impact on patient health. FDA may assess among other parameters, positive predictive value, negative predictive value, clinical specificity, clinical sensitivity, linearity, reproducibility, and limit of detection.
In sum, the route to the market for the diagnostic industry differs in innumerable ways from the pharmaceutical industry. The next article, which will appear in the August issue of GEN, will discuss these pathways in detail.