Rule2026-10898
Medical Devices; Hematology and Pathology Devices; Classification of the Von Willebrand Factor Assay
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
June 1, 2026
Effective
June 1, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA) is classifying the von Willebrand factor assay into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for classification of the von Willebrand factor assay. We are taking this action because we have determined that classifying the device into class II will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.
Full Text
<html>
<head>
<title>Federal Register, Volume 91 Issue 104 (Monday, June 1, 2026)</title>
</head>
<body><pre>
[Federal Register Volume 91, Number 104 (Monday, June 1, 2026)]
[Rules and Regulations]
[Pages 32336-32338]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-10898]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 864
[Docket No. FDA-2026-N-5725]
Medical Devices; Hematology and Pathology Devices; Classification
of the Von Willebrand Factor Assay
AGENCY: Food and Drug Administration, HHS.
ACTION: Final amendment; final order.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is classifying the von
Willebrand factor assay into class II (special controls). The special
controls that apply to the device type are identified in this order and
will be part of the codified language for classification of the von
Willebrand factor assay. We are taking this action because we have
determined that classifying the device into class II will provide a
reasonable assurance of safety and effectiveness of the device. We
believe this action will also enhance patients' access to beneficial
innovative devices, in part by reducing regulatory burdens.
DATES: This order is effective June 1, 2026. The classification was
applicable on September 29, 2022.
FOR FURTHER INFORMATION CONTACT: Yan Cai, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 3453, Silver Spring, MD 20993-0002, 240-402-1094,
<a href="/cdn-cgi/l/email-protection#3e675f50107d5f577e585a5f1056564d10595148"><span class="__cf_email__" data-cfemail="de87bfb0f09dbfb79eb8babff0b6b6adf0b9b1a8">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA (the Agency or we) has classified the von
Willebrand factor (VWF) assay into class II (special controls), which
we have determined will provide a reasonable assurance of safety and
effectiveness of the device. In addition, we believe this action will
enhance patients' access to beneficial innovation, in part by reducing
regulatory burdens by placing the device into a lower device class than
the automatic class III assignment.
The automatic assignment of class III occurs by operation of law
and without any action by FDA, regardless of the level of risk posed by
the new device. Any device that was not in commercial distribution
before May 28, 1976, is automatically classified into, and remains
within, class III and requires premarket approval unless and until FDA
takes an action to classify or reclassify the device (21 U.S.C.
360c(f)(1)). We refer to these devices as ``postamendments devices''
because they were not in commercial distribution prior to the date of
enactment of the Medical Device Amendments of 1976, which amended the
Federal Food, Drug, and Cosmetic Act (FD&C Act).
FDA may take a variety of actions in appropriate circumstances to
classify or reclassify a device into class I or II. We may issue an
order finding a new device to be substantially equivalent under section
513(i) of the FD&C Act (21 U.S.C. 360c(i)) to a predicate device that
does not require premarket approval. We determine whether a new device
is substantially equivalent to a predicate device by means of the
procedures for premarket notification under section 510(k) of the FD&C
Act (21 U.S.C. 360(k)) and part 807 (21 CFR part 807).
FDA may also classify a device through ``De Novo'' classification,
a common name for the process authorized under section 513(f)(2) of the
FD&C Act (see also part 860, subpart D (21 CFR part 860, subpart D)).
Section 207 of the Food and Drug Administration Modernization Act of
1997 (Pub. L. 105-115) established the first procedure for De Novo
classification. Section 607 of the Food and Drug Administration Safety
and Innovation Act (Pub. L. 112-144) modified the De Novo
classification process by adding a second procedure. A device sponsor
may utilize either procedure for De Novo classification.
[[Page 32337]]
Under the first procedure, the person submits a premarket
notification (510(k)) for a device that has not previously been
classified. After receiving an order from FDA classifying the device
into class III under section 513(f)(1) of the FD&C Act, the person then
requests a classification under section 513(f)(2).
Under the second procedure, rather than first submitting a 510(k)
and then a request for classification, if the person determines that
there is no legally marketed device upon which to base a determination
of substantial equivalence, that person requests a classification under
section 513(f)(2) of the FD&C Act.
Under either procedure for De Novo classification, FDA is required
to classify the device by written order within 120 days. The
classification will be according to the criteria under section
513(a)(1) of the FD&C Act. Although the device was automatically placed
within class III, the De Novo classification is considered to be the
initial classification of the device.
We believe this De Novo classification will enhance patients'
access to beneficial innovation, in part by reducing regulatory
burdens. When FDA classifies a device into class I or II via the De
Novo process, the device can serve as a predicate for future devices of
that type, including for 510(k)s (see section 513(f)(2)(B)(i) of the
FD&C Act). As a result, other device sponsors do not have to submit a
De Novo request or premarket approval application to market a
substantially equivalent device (see section 513(i) of the FD&C Act,
defining ``substantial equivalence''). Instead, sponsors can use the
less burdensome 510(k) process, when necessary, to market their device.
II. De Novo Classification
On October 28, 2020, FDA received Siemens Healthcare Diagnostics
Products GmbH's request for De Novo classification of the INNOVANCE VWF
Ac device. FDA reviewed the request in order to classify the device
under the criteria for classification set forth in section 513(a)(1) of
the FD&C Act.
We classify devices into class II if general controls by themselves
are insufficient to provide reasonable assurance of safety and
effectiveness of the device, but there is sufficient information to
establish special controls that, in combination with the general
controls, provide reasonable assurance of the safety and effectiveness
of the device for its intended use (see section 513(a)(1)(B) of the
FD&C Act). After review of the information submitted in the request, we
determined that the device can be classified into class II with the
establishment of special controls. FDA has determined that these
special controls, in addition to the general controls, will provide
reasonable assurance of the safety and effectiveness of the device.
Therefore, on September 29, 2022, FDA issued an order to the
requester classifying the device into class II. In this final order,
FDA is codifying the classification of the device by adding 21 CFR
864.7293.\1\ We have named the generic type of device ``von Willebrand
factor assay,'' and it is identified as a prescription device intended
for the measurement of von Willebrand factor activity or von Willebrand
factor size distribution in human plasma. This device is indicated to
aid in the diagnosis and management of patients being evaluated for von
Willebrand factor disorders in conjunction with other clinical and
laboratory findings.
---------------------------------------------------------------------------
\1\ FDA notes that the ``ACTION'' caption for this final order
is styled as ``Final amendment; final order,'' rather than ``Final
order.'' Beginning in December 2019, this editorial change was made
to indicate that the document ``amends'' the Code of Federal
Regulations. The change was made in accordance with the Office of
Federal Register's (OFR) interpretations of the Federal Register Act
(44 U.S.C. chapter 15), its implementing regulations (1 CFR 5.9 and
parts 21 and 22), and the Document Drafting Handbook.
---------------------------------------------------------------------------
FDA has identified the risks to health associated with this type of
device and the measures required to mitigate these risks in table 1.
Table 1--Risks to Health and Mitigation Measures for Von Willebrand
Factor Assays
------------------------------------------------------------------------
Identified risks to health Mitigation measures
------------------------------------------------------------------------
Falsely elevated VWF activity results Certain design verification and
may lead to delayed diagnosis and validation identified in
delayed patient management of von special control (1), including
Willebrand disease (VWD). Patients documentation of certain
with delayed diagnosis and resulting analytical studies and
delayed patient management of VWD are clinical studies.
at increased risk of bleeding due to Certain labeling information
the withholding of appropriate identified in special control
treatment. (2), including limitations and
performance information
identified in special control
(1).
Falsely depressed VWF activity results Certain design verification and
may lead the physician to suspect VWD validation identified in
in patients who do not have the special control (1), including
disease. As a result, the patients may documentation of certain
receive unnecessary follow-up testing analytical studies and
and unnecessary treatment as well as clinical studies.
delays in receiving a correct Certain labeling information
diagnosis and appropriate patient identified in special control
management. In addition, affected (2), including limitations and
patients may experience mental anxiety performance information
because of the erroneous diagnosis. identified in special control
(1).
No results may lead to delayed patient Certain design verification and
management. validation identified in
special control (1), including
documentation of certain
analytical studies and
clinical studies.
Certain labeling information
identified in special control
(2), including limitations and
performance information
identified in special control
(1).
------------------------------------------------------------------------
FDA has determined that special controls, in combination with the
general controls, address these risks to health and provide reasonable
assurance of safety and effectiveness of the device. For a device to
fall within this classification, and thus avoid automatic
classification in class III, it would have to comply with the special
controls named in this final order. The necessary special controls
appear in the regulation codified by this final order.
At the time of classification, von Willebrand factor assays are for
prescription use only. Therefore, these devices are subject to the
prescription labeling requirements for in vitro diagnostic (IVD)
products (see 21 CFR 809.10(a)(4) and (b)(5)(ii)).
Under the FD&C Act, submission of a premarket notification under
section 510(k) is required to reasonably assure the safety and
effectiveness of class II devices unless FDA determines that the
[[Page 32338]]
device type should be exempt under section 510(m) of the FD&C Act. At
this time FDA has not made this determination for von Willebrand factor
assays. This device is therefore subject to premarket notification
requirements under section 510(k) of the FD&C Act.
III. Analysis of Environmental Impact
The Agency has determined under 21 CFR 25.34(b) that this action is
of a type that does not normally have a significant effect on the human
environment. Therefore, neither an environmental assessment nor an
environmental impact statement is required.
IV. Paperwork Reduction Act of 1995
This final order establishes special controls that refer to
previously approved collections of information found in other FDA
regulations and guidance. These collections of information are subject
to review by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). The collections
of information in part 860, subpart D, regarding De Novo classification
have been approved under OMB control number 0910-0844; the collections
of information in 21 CFR part 814, subparts A through E, regarding
premarket approval have been approved under OMB control number 0910-
0231; the collections of information in part 807, subpart E, regarding
premarket notification submissions have been approved under OMB control
number 0910-0120; the collections of information in 21 CFR part 820
regarding quality management system regulation have been approved under
OMB control number 0910-0073; and the collections of information in 21
CFR parts 801 and 809 regarding labeling have been approved under OMB
control number 0910-0485.
List of Subjects in 21 CFR Part 864
Blood, Medical devices, Packaging and containers.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
864 is amended as follows:
PART 864--HEMATOLOGY AND PATHOLOGY DEVICES
0
1. The authority citation for part 864 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 864.7293 to subpart H to read as follows:
Sec. 864.7293 von Willebrand factor assay.
(a) Identification. A von Willebrand factor assay is a prescription
device intended for the measurement of von Willebrand factor activity
or von Willebrand factor size distribution in human plasma. This device
is indicated to aid in the diagnosis and management of patients being
evaluated for von Willebrand factor disorders in conjunction with other
clinical and laboratory findings.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Design verification and validation must include:
(i) Detailed documentation of studies demonstrating acceptable, as
determined by FDA, analytical performance, including, as applicable,
precision, linearity, assay interference, detection capability,
specimen and reagent stability, and hook effect, with a sufficient
number of specimens tested in order to obtain unbiased estimates of
analytical performance. For devices measuring multiple analytes, the
detailed documentation must include studies demonstrating the
analytical performance of the device in regard to each individual
analyte, including precision, linearity, assay interference, cross-
reactivity, detection capability, specimen and reagent stability, and
hook effect, as applicable.
(ii) Detailed documentation of a comparison study of clinical
samples demonstrating performance relative to clinically relevant and
appropriate, as determined by FDA, clinically validated laboratory
tests. Further, the studies must meet all of the following criteria:
(A) All eligible subjects must meet appropriate study inclusion and
exclusion criteria that define the intended use population. Specimens
must be representative of the intended use population(s) and must
representatively cover the full range of the device output and any
clinically relevant decision points, as appropriate;
(B) The study must be conducted at a minimum of three external
sites representative of the intended use setting by operators
representative of the intended user population;
(C) For all intended pediatric patient populations, clinical
outcome validation studies must study those populations in accordance
with paragraphs (b)(1)(ii)(A) and (B) of this section; and (D) Expected
(reference) values for test output must be demonstrated by testing a
statistically appropriate number of samples from apparently healthy
normal individuals in all relevant subpopulations (i.e., blood group O
and non-O, male and female, and, if applicable, pediatric and adults),
as applicable to the intended use of the device.
(2) The labeling required under Sec. 809.10(b) of this chapter
must include:
(i) Limiting statements indicating, as applicable:
(A) This device should always be used in conjunction with the
patient's medical history, clinical presentation, and other laboratory
findings.
(B) Identification of any known interferents, including all
endogenous, exogenous, technology-specific, and patient population-
specific interferents, specific to the test outputs. The information
must include the concentration(s) or level(s) of the interferent at
which clinically significant interference was found to occur, and the
concentration range or levels at which interference was not found to
occur.
(ii) A detailed summary of the performance testing results of
analytical and clinical performance testing, including results of
concordance evaluation (overall agreement, positive percentage
agreement and negative percentage agreement) as required under
paragraph (b)(1) of this section.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-10898 Filed 5-29-26; 8:45 am]
BILLING CODE 4164-01-P
</pre><script data-cfasync="false" src="/cdn-cgi/scripts/5c5dd728/cloudflare-static/email-decode.min.js"></script></body>
</html>Indexed from Federal Register on June 1, 2026.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.