Cytori Therapeutics, Inc. v. Food & Drug Administration

Citations: 404 U.S. App. D.C. 447; 715 F.3d 922; 2013 U.S. App. LEXIS 5709; 2013 WL 1164775Docket: 11-1268, 11-1279

Court: Court of Appeals for the D.C. Circuit; March 22, 2013; Federal Appellate Court

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Cytori Therapeutics, Inc. petitioned the United States Court of Appeals for the District of Columbia Circuit for review of the Food and Drug Administration's (FDA) determination regarding two new medical devices, the Celution 700 and StemSource 900, which utilize adipose tissue as a source of stem cells. The FDA concluded that these devices were not "substantially equivalent" to existing devices that extract stem cells from blood or bone marrow, thus requiring Cytori to undergo the more rigorous premarket approval process instead of the streamlined premarket notification process.

Cytori challenged the FDA's decision, claiming it was arbitrary and capricious under the Administrative Procedure Act (APA), arguing that the FDA failed to provide a reasonable explanation for its rejection of their substantial equivalence application. The FDA countered that its determination was reasonable and adequately explained, and also raised a jurisdictional objection, suggesting that the district court was the appropriate venue for the petition.

The Court found that it had jurisdiction to review the FDA's substantial equivalence determination. Ultimately, the Court upheld the FDA's conclusion, affirming that the agency's decision was reasonable and well-explained, and denied Cytori's petitions for review.

Cytori is poised to enhance regenerative medicine by utilizing adipose tissue as a source of stem cells through its Celution system, which includes the Celution and StemSource devices. Before marketing these devices in the U.S., Cytori must obtain FDA approval, typically via a premarket notification process that requires a finding of "substantial equivalence" to existing devices. Cytori submitted notifications for the Celution 700, designed for clinical laboratory analysis, and the StemSource 900, intended for cell storage. However, neither device is currently labeled for specific cell therapy treatments. 

Federal law mandates that a new device must have the same intended use and basic technology as a predicate device or demonstrate equal safety and effectiveness despite technological differences. The FDA determined that Cytori's devices are not substantially equivalent because harvesting cells from fat differs fundamentally from harvesting from blood, and also highlighted different safety concerns, particularly related to an enzyme used in the devices. Additionally, FDA criticized the limited testing data from a study involving only 12 donors as inadequate to support substantial equivalence. Consequently, Cytori's devices are required to undergo the more rigorous premarket approval process.

Cytori contests the FDA's determination, arguing that its devices share intended uses and technological characteristics with predicate devices. The FDA, however, asserts that the Court lacks jurisdiction over Cytori’s petitions while defending its decision on substantive grounds.

FDA claims that this Court lacks jurisdiction to review Cytori’s petitions, arguing that initial review should occur in the district court as per relevant statutes. Initial appellate review is only permissible under a direct-review statute that explicitly grants jurisdiction. The Food, Drug, and Cosmetic Act includes such a provision, allowing “any person adversely affected” by certain FDA determinations to petition the U.S. Court of Appeals for the D.C. Circuit. Specifically, the provision covers orders determining if a new device is substantially equivalent to an existing one.

The Court must ascertain whether a "not substantially equivalent" determination qualifies as an “order” for direct review and whether it is made “pursuant to” Section 360c(i) of the Act. A "not substantially equivalent" determination is considered an “order” as it constitutes a final disposition under the Administrative Procedure Act (APA), which defines an order as any final disposition, whether affirmative or negative. FDA’s determination that Cytori's devices were not substantially equivalent was a definitive final decision, not a preliminary one.

Furthermore, the Court concludes that a "not substantially equivalent" order is indeed made pursuant to Section 360c(i), which sets criteria for substantial equivalence. FDA argues that only findings of equivalence are made under this section, as it only explicitly references affirmative orders. However, the Court interprets the statute to mean that both affirmative and negative determinations arise from the criteria in Section 360c(i). Thus, a non-equivalence determination is an order made pursuant to this section, granting the Court jurisdiction to directly review Cytori’s petitions.

The FDA's non-equivalence decision regarding the Celution and StemSource devices was evaluated under the arbitrary and capricious standard of the Administrative Procedure Act. According to Section 360c(i), a device must be substantially equivalent to a predicate device by having the same intended use and technological characteristics. The FDA determined that both the Celution and StemSource did not meet these criteria. Specifically, the intended uses differ: the Celution and StemSource derive stem cells from fat tissue, while the predicate devices derive cells from blood and bone marrow, which the FDA classified as fundamentally different uses based on the types of tissue involved. 

The FDA's guidance indicated that devices designed for processing different tissues cannot be considered equivalent. The FDA's assessment was deemed reasonable and well-explained, as the agency's scientific judgment is not subject to court second-guessing under the APA.

Additionally, the devices failed the technological characteristics test. The Celution and StemSource utilize different technology for processing fat compared to blood processing devices, requiring new methods to extract useful cells. Even if they did not share technological characteristics, they could still qualify if they were equally safe and effective as legally marketed devices. However, the FDA found that the Celution's safety study was insufficient, and concerns were raised regarding the safety of the enzyme Celase used in the StemSource, which was only approved for a different use. 

Ultimately, the FDA reasonably concluded that both devices did not satisfy the intended use or technological characteristics requirements, leading to the denial of Cytori’s petitions for review.