Kimberly Huggler, PhD
Christopher Farnsworth, PhD
May 2026—Has your blood collection container been validated for the assays you have employed it for? At what point does a verification of a blood collection tube become a validation, and how is a laboratory supposed to know when this threshold has been crossed and what actions to take? These questions may often be overlooked by laboratorians but carry significant implications for test results. In many cases, the information needed to make this determination is lacking or unpublished, leaving laboratories to navigate significant uncertainty.
Blood collection containers may be perceived as simple interchangeable components of an assay. However, they are in vitro diagnostic devices cleared by the Food and Drug Administration that directly influence analytical performance. Interestingly and perhaps unbeknownst to many laboratorians, clearance for a blood collection container does not require exhaustive evaluation across all possible analytes or analytical platforms. As recommended by the Clinical and Laboratory Standards Institute guideline GP34-A, tube manufacturers should validate performance using a panel of representative analytes with at least two instrument platforms, rather than every assay that might ultimately be used with the tube.1 This approach reflects a practical compromise, since comprehensive testing across the expanding catalog of potential measurands would be impossible. However, it also means that FDA clearance and commercial availability of a tube does not imply universal compatibility with all assays or analyzers clinical laboratories use.
For manufacturers of IVD assays, tube compatibility is often addressed in general terms within instructions for use. These IFUs rarely specify tube manufacturer, coagulant or additive concentration, draw volume, or whether rapid-clot or gel tubes were evaluated. This leaves substantial ambiguity for laboratories. Likewise, IFUs for blood collection tubes often lack detailed information on the performance metrics, instrumentation used, or analytes assessed during the validation process. The net result is a transparency gap: Laboratories are expected to ensure compatibility but are rarely told precisely what has been tested and under what conditions. This gap becomes particularly problematic when relatively minor modifications are made over time, such as changes to separator gels, additives, or clot activators, which may not be communicated to end users but can still affect assay performance.
At many hospitals, blood collection container selection is often driven by availability, cost, or workflow considerations rather than a detailed understanding of FDA clearance language or assay‑specific validation. However, this opens laboratories up to potential issues when tubes are employed for an analyte/instrument that has not yet been validated. There is a risk, albeit small, that a tube and its matrix may interfere with a specific measurand or instrument platform. Further, as new instruments and methods enter the market, existing tubes are not automatically revalidated for those platforms. Perhaps of greatest consequence are novel measurands that the tube manufacturer has never assessed.
To this end, in 2025, one blood tube manufacturer issued a customer communication clarifying that one of its serum tubes was not cleared for routine clinical chemistry analysis; rather, it was intended for viral marker testing and immunohematology applications such as red cell grouping and antibody screening. This clarification surprised laboratories that had historically used serum gel and non‑gel tubes interchangeably from this manufacturer. Further, a quick perusal of the literature demonstrates dozens of studies in which the matrix or blood collection tubes had an impact on laboratory results. As an example, a 2008 study by Meng, et al., showed that lithium heparin under recovered on bromocresol green-based albumin methods in dialysis patients.2
These examples highlight two key points. First, it is critically important that both blood collection tube and clinical assay manufacturers perform appropriate validations. Second, there is a need for more transparency regarding which studies have been performed. This also exposes how easily assumptions about equivalence between manufacturers can persist for years without challenge, reinforcing a false sense of security around tube interchangeability. Thus, our big problem: Often, the laboratory does not know which tube-assay combinations have been tested and which have not.
CLSI guidance document GP34-A clearly distinguishes validation as a manufacturer responsibility and verification as an end-user responsibility. However, when is a verification study warranted? GEN.40942 in the CAP accreditation checklist requires that laboratory directors or designees review literature and evaluate information from device manufacturers to determine if a verification study is indicated. However, if a laboratory introduces a tube type that was not explicitly evaluated for a given assay-instrument combination, local verification may escalate into a de facto validation. Laboratories must therefore make deliberate decisions about when local studies are warranted and how extensively they should be designed. This is a difficult proposition when it is not fully clear what tube-assay combinations were validated by manufacturers.
In practice, many laboratories have chosen to perform targeted evaluations to ensure tube compatibility, especially for assays known to be affected by adsorption or additive interference. CLSI provides a structured framework for such evaluations, emphasizing representative analyte selection, appropriate acceptance criteria, and clinical relevance. However, local validation should be a complement to—not a substitute for—robust manufacturer transparency around tube and assay validation.
Ultimately, greater disclosure in IFUs from manufacturers of blood collection containers and IVD assay manufacturers is needed. Knowing the additive composition, draw volumes tested (full tube, half-full tube, etc.), and assay-instrument combinations used would materially improve laboratories’ ability to assess risk. As assay complexity grows and preanalytical variables continue to challenge result integrity, closer alignment between tube manufacturers, assay developers, and clinical laboratories is essential to ensure that the “match made in heaven” truly delivers reliable patient results.
- Clinical and Laboratory Standards Institute. GP34-A: Validation and Verification of Tubes for Venous and Capillary Blood Specimen Collection; Approved Guideline; 2010.
- Meng QH, Krahn J. Lithium heparinised blood-collection tubes give falsely low albumin results with an automated bromcresol green method in haemodialysis patients. Clin Chem Lab Med. 2008;46(3):396–400.
Dr. Huggler is a clinical chemistry fellow and Dr. Farnsworth is section head of clinical chemistry, Department of Pathology and Immunology, WashU Medicine, St. Louis, Mo. Dr. Farnsworth is professor of pathology and immunology and of emergency medicine, Washington University in St. Louis.