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Translational Medicine FDASIA's Impact on Novel IVDs Though Not Revolutionary, New Act Could Offer Significant Benefits to In Vitro Diagnostic Firms Jeffrey N. Gibbs On July 9, President Obama signed into law the Food and Drug Administration Safety and Innovation Act (FDASIA). FDASIA signifi- cantly affects both pharmaceutical and device manufacturers. It has a direct impact on all in vitro diagnostic (IVD) manufacturers, and for IVD companies developing companion diag- nostics, an indirect effect as well through FDA- SIA's numerous provisions relating to drugs. FDASIA is long and complex with over 130 different sections. Some of the legislative language is confusing, and debates about how to apply it are inevitable. This article will focus on the provisions most important to IVD companies. Historically, IVD companies have sub- mitted relatively few investigational device exemptions (IDEs). With the rise in com- panion diagnostics, though, the number has increased. FDASIA limits the grounds for de- nying an IDE. Specifically, FDA could not deny an IDE based on its determination that: 1) the study may not support a substantial equivalence, de novo, or approval decision; 2) the investiga- tion may not meet a requirement for approval or clearance of a device; or 3) the sponsor may need to conduct an additional or different in- vestigation to support clearance or approval of the device. In other words, an IDE cannot be denied simply because FDA doesn't believe the ensuing study will be adequate. The long-term utility of this change for IVD companies is debatable. Though it could lead to the approval of more IDEs, gaining IDE approval may not be helpful if it generates data that will not ultimately sup- port clearance or approval. Still, it should fa- cilitate the initiation of research, which could be beneficial in various ways. Appeals FDASIA requires the Center for Devices and Radiological Health (CDRH) to make available to an applicant a "substantive sum- mary of the scientific and regulatory ratio- nale for any significant decision" regarding 510(k) submissions or premarket approval (PMA) or IDE applications. The summary must include "documentation of significant controversies or differences of opinion and the resolution of such controversies or differ- ences of opinion." FDA must provide the substantive sum- Jeffrey N. Gibbs (jgibbs@hpm.com) is a director at Hyman, Phelps & McNamara. mary to the party "seeking to submit, or who has submitted" a 510(k) notification or PMA or IDE application. (This language does not permit a party to request a substantive sum- mary of a decision relating to a third party.) While the section doesn't define what constitutes a "significant decision," it pre- sumably would be decisions to deny 510(k)s, PMAs, or IDEs, or adverse statements by FDA regarding a company's prospects for success or the pathway it must follow. After receiving the documentation, the applicant may appeal an adverse "signifi- cant decision." The appeal must be submit- ted within 30 days. CDRH then has 30 days to schedule the appeal in-person meeting or telephone call. CDRH then has 30 days to issue its decision after the appeal is heard. If a company submits a written appeal in lieu of a meeting or telephone call—an option which should rarely if ever be used—CDRH must issue its decision within 45 days. The appeals process has not been one of CDRH's strong suits. A major problem has been timing: the meetings take too long to schedule, and CDRH is slow in issuing deci- sions. This provision will speed up the ap- peals process. The access to documentation should give companies new insight into FDA decisions, thereby helping frame the appeal. The long delays in having appeals heard and decided have deterred appeals. FDASIA makes the appeals process a more attractive option. Unfortunately, the legislation neither addresses CDRH's strong inclination to deny appeals nor improves the fairness of the appeals process, which is pro- cedurally stacked against the manufacturer. Modifications Requiring Premarket Notification FDA has cleared thousands of IVD 510(k)s. One challenge for 510(k) holders has been de- ciding when a product change requires a new 510(k). This has long been a vexing issue. By January 9, 2014, FDA must submit a report to Congress on the criteria for when a device modification requires a new 510(k) submission. The regulation controlling when a new 510(k) must be submitted contains piv- otal but ambiguous phrases: "could signifi- cantly affect the safety or effectiveness of the device," "a significant change or modification in design, material, chemical composition, energy source, or manufacturing process," and "major change or modification in the in- genengnews.com | October 1, 2012 | 59 See FDASIA on page 61 SuperScript® Reverse Transcriptases (RTs) are engineered for top performance! 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