FDA 510(k) Glossary · regulatory

Predicate Chain

A predicate chain is a sequence of predicate devices in which each 510(k) submission cites the previous one as its predicate, creating a lineage that can extend back to pre-1976 preamendment devices. Academic research has identified predicate chains in which the original predicate device had safety concerns, raising questions about substantial equivalence as a clearance standard.
Dataset Insight - 510k Database (166,200 records, 1980–2025)
Predicate chain analysis requires tracing K-number lineages across the full 166,200-record dataset. The dataset was a source for Hwang et al. (2021), the landmark predicate chain study in PLOS ONE.

Definition

A predicate chain is a sequential lineage of 510(k) predicate devices in which each device cites the previously cleared device as its predicate, creating a chain that may extend back to preamendment devices commercially distributed before May 28, 1976. The chain represents a series of linked substantial equivalence determinations.

How Predicate Chains Form

  1. Device A (1978) - marketed as a preamendment device before the 1976 Amendments.
  2. Device B (1985) - cleared via 510(k) citing Device A as predicate.
  3. Device C (1998) - cleared via 510(k) citing Device B as predicate.
  4. Device D (2015) - cleared via 510(k) citing Device C as predicate.

Each link in the chain was a valid 510(k) clearance. But if Device A had safety issues that were never formally evaluated, those issues potentially propagate down the chain.

Academic Research

A landmark 2021 study by Hwang et al. in PLOS ONE mapped the predicate genealogy of FDA 510(k) clearances. The study found that some devices relied on predicates that had been recalled or were otherwise contested, and that predicate chains could span decades with minimal independent safety evaluation at each step.

FDA Response

In response to concerns about predicate chain integrity, the FDA has issued guidance encouraging manufacturers to select the most recently cleared, most technologically similar predicate rather than reaching back to older devices in a chain. The agency has also increased scrutiny of split predicate strategies.

Related Terms

Predicate Device - Substantial Equivalence - Not Substantially Equivalent - De Novo Classification

Frequently Asked Questions

A predicate chain is a series of linked 510(k) submissions in which device A cites device B as its predicate, device B cited device C, and so on - potentially back to a preamendment device from before 1976. The result is a lineage of substantial equivalence determinations where each clearance depends on the validity of the previous one.

Predicate chains raise regulatory concerns because the safety and effectiveness of the entire chain depends on the original preamendment predicate - which was never formally evaluated by the FDA. A 2021 study in PLOS ONE by Hwang et al. mapped predicate genealogies and found cases where chains included previously recalled or contested devices, yet downstream devices were still cleared based on substantial equivalence.

Yes, any legally marketed device in the chain can serve as a predicate, provided it meets the substantial equivalence criteria. However, the FDA has signaled increasing scrutiny of long predicate chains and of 'split predicate' strategies where different parts of the substantial equivalence argument use different predicates from the chain.

The 510k Database does not currently map predicate chain relationships directly, but each device record links to the manufacturer, product code, and K-number - enabling researchers to trace submission histories. The dataset underlying the 510k Database was used as a source in Hwang et al. (2021), the landmark predicate chain study.