By Douglas B. Farquhar –
In a rare request for a court to review FDA’s failure to clear a medical device for market distribution, arguments have been finalized, briefs have been filed, and oral argument has been scheduled for September 21, 2012.
The case, filed in the U.S. Court of Appeals for the D.C. Circuit (appeal no. 11-1268), relates to two medical devices for which Cytori Therapeutics, Inc., of San Diego, California, sought clearance. The first device is called the Celution 700/LAB device, which Cytori’s brief describes as, in layman’s terms, “a liposuction device which allows a physician to access a patient’s stem cells from the body fat in which the cells are stored, and then to study those cells in a clinical laboratory.” Cytori argues in its brief and in its reply brief that it first became aware of the reason FDA refused to clear the device when FDA filed in court the administrative record on FDA’s decision, and that FDA is apparently concerned that the device will be used to process stromal (or stem) cells to be transfused back into the donor’s body. In other words, while the indications for the device’s use listed in the labeling are for analytical use, FDA voiced a concern that the device would be put to therapeutic use. Cytori argues that it is wrong for FDA to refuse to clear a device because of potential off-label uses.
The second device is called the StemSource 900/MB. Cytori says in its opening brief that “the two devices have similar physical attributes,” but that Cytori “submitted them separately to the FDA to be approved for different intended uses and indications.” Cytori further states that, while “the 700/LAB device was submitted to be approved for laboratory use, the 900/MB Processor System was submitted for use in banking/cryopreservation.” Cytori admits in its brief that the StemSource 900/MB was intended to be used to remove and process stem cells at the point of care (in other words, the patient’s bedside) for potential reinsertion in the donor’s body. But Cytori argues that FDA inaccurately declined clearance because Cytori requested a Class 1 classification for the device, that FDA believed that the Class 1 classification was inappropriate for bedside use, and, as Cytori puts it, “whether a device is used in the operating room has nothing to do with whether it may be classified as Class I.”
Cytori claims that FDA’s refusal to clear the devices for distribution in the United States is thus arbitrary and capricious.
The parties agree that the standard for market clearance (under what is commonly referred to as the “510(k) process” after the relevant statutory section of the Federal Food, Drug, and Cosmetic Act) is whether the devices are “substantially equivalent” to “a legally marketed predicate device” (generally, a previously approved or cleared device). A detailed discussion of the arguments advanced by Cytori and FDA is beyond the scope of this blogpost (and, to the uninitiated, would likely be soporific).
But FDA counters in its brief that the StemSource/900 MB device is not “substantially equivalent” to the predicate devices, because the Cytori proposed device is intended to process cells from adipose (or fatty) tissue, whereas the predicate devices are intended to process cells from “cord blood” (that is, blood from an umbilical cord or placenta). One of the FDA brief’s sentences encapsulates its arguments thusly: “Fat is not blood.”
Likewise, FDA argues that the devices cited by Cytori as predicates for the Celution 700/Lab System are not predicates, because they were not cleared for processing stem cells derived from adipose tissue. FDA also argues that an enzyme Cytori proposed to process the cells is a "new technology that raises new questions of safety.”
FDA earlier asked the court to dismiss Cytori’s petition seeking review of FDA’s decisions by the appellate court, but a panel of the court denied the motion late last year and required the parties to address, in their main briefs, whether the court has jurisdiction to review the matter. FDA argues that the appellate court has primary jurisdiction to review only a decision to clear a device (not a refusal to clear a device); Cytori, of course, disagrees.
The decision issued in this case (generally, in cases of this complexity, two to ten months after the argument) could well determine two important issues: first, whether the Court of Appeals has primary jurisdiction to review an FDA decision not to clear a device for distribution (or whether the issue must first be presented to a U.S. District Court); and, second, if the court decides to issue a decision on the substance of the case, how thoroughly an appellate court will scrutinize the manner in which FDA applies the substantial equivalence criteria to a proposed medical device.