Rule2025-16031
Medical Devices; Immunology and Microbiology Devices; Classification of the Anti-Phospholipase A2 Receptor Immunological Test System
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
August 21, 2025
Effective
August 21, 2025
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, the Agency, or we) is classifying the anti-phospholipase A2 receptor immunological test system 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 the anti-phospholipase A2 receptor immunological test system's classification. 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 90 Issue 160 (Thursday, August 21, 2025)</title>
</head>
<body><pre>
[Federal Register Volume 90, Number 160 (Thursday, August 21, 2025)]
[Rules and Regulations]
[Pages 40724-40726]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-16031]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2025-N-2108]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Anti-Phospholipase A2 Receptor Immunological Test
System
AGENCY: Food and Drug Administration, HHS.
ACTION: Final amendment; final order.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
classifying the anti-phospholipase A2 receptor immunological test
system 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 the anti-phospholipase A2 receptor
immunological test system's classification. 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 August 21, 2025. The classification was
applicable on May 29, 2014.
FOR FURTHER INFORMATION CONTACT: Scott McFarland, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 3572, Silver Spring, MD 20993-0002, 301-
796-6217, <a href="/cdn-cgi/l/email-protection#174474786363395a745176657b76797357717376397f7f6439707861"><span class="__cf_email__" data-cfemail="83d0e0ecf7f7adcee0c5e2f1efe2ede7c3e5e7e2adebebf0ade4ecf5">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the anti-phospholipase A2 receptor
immunological test system as class II (special controls), which we have
determined will provide a reasonable assurance of safety and
effectiveness. 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 as, and remains
within, class III and requires premarket approval unless and until FDA
takes an action to classify or reclassify the device (see 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 application
process by adding a second procedure. A device sponsor may utilize
either procedure for De Novo classification.
Under the first procedure, the person submits a 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 (PMA) 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
For this device, FDA issued an order on March 10, 2014, finding the
EUROIMMUN Anti-PLA2R IFA not substantially equivalent to a predicate
not subject to PMA. Thus, the device remained in class III in
accordance with section 513(f)(1) of the FD&C Act when we issued the
order.
On March 28, 2014, FDA received EUROIMMUN US Inc.'s, request for De
Novo classification of the EUROIMMUN Anti-PLA2R IFA. 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, 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 general controls, will provide reasonable assurance of the
safety and effectiveness of the device.
Therefore, on May 29, 2014, FDA issued an order to the requestor
classifying the device into class II. In this final order, FDA is
codifying the
[[Page 40725]]
classification of the device by adding 21 CFR 866.5780.\1\ We have
named the generic type of device anti-phospholipase A2 receptor
immunological test system, and it is identified as a device that
consists of the reagents used to measure by immunochemical techniques
the autoantibodies in human blood samples that react with phospholipase
A2 receptor. The measurements aid in the diagnosis of primary
membranous glomerulonephritis (pMGN), in conjunction with other
laboratory and clinical 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 following risks to health associated
specifically with this type of device and the measures required to
mitigate these risks in table 1.
Table 1--Anti-Phospholipase A2 Receptor Immunological Test System Risks
and Mitigation Measures
------------------------------------------------------------------------
Identified risks to health Mitigation measures
------------------------------------------------------------------------
Inaccurate test results that provide false Special controls (1), (2),
positive or false negative results. and (3).
Failure to correctly interpret test results Special controls (1)(iii),
can lead to false positive and false (2), and (3).
negative results.
------------------------------------------------------------------------
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. 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. This device is 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 individually or cumulatively 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. 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 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 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 866
Biologics, Laboratories, Medical devices.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
866 is amended as follows:
PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES
0
1. The authority citation for 21 CFR part 866 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 866.5780 to subpart F to read as follows:
Sec. 866.5780 Anti-phospholipase A2 receptor immunological test
system.
(a) Identification. An anti-phospholipase A2 receptor immunological
test system is a device that consists of the reagents used to measure
by immunochemical techniques the autoantibodies in human blood samples
that react with phospholipase A2 receptor. The measurements aid in the
diagnosis of primary membranous glomerulonephritis (pMGN), in
conjunction with other laboratory and clinical findings.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Design verification and validation must include:
(i) A detailed description of the device that includes:
(A) A detailed description of all parts of the test system,
including a description of the assay parts in the kit and all required
ancillary reagents;
(B) A detailed description of instrumentation and equipment, and
illustrations or photographs of non-standard equipment or methods if
applicable;
(C) Detailed documentation of the device software, including
standalone software applications and hardware-based devices that
incorporate software where applicable;
(D) A detailed description of appropriate internal and external
quality controls that are recommended or provided. The description must
identify those control elements that are incorporated into the
recommended testing procedures;
(E) Detailed specifications for sample collection, processing, and
storage;
(F) A detailed description of methodology and assay procedure; and
(G) Detailed specification of the criteria for test results
interpretation and reporting.
(ii) Information that demonstrates the performance characteristics
of the device, including:
(A) Device precision/reproducibility data generated from within-
run, between-run, between-day, between-lot, between-operator, between-
instruments, between-site, and total precision for multiple
nonconsecutive days as applicable. A well-characterized panel of
patient samples or pools from the intended use population that covers
the device measuring range must be used;
(B) Device linearity data generated from patient samples covering
the assay measuring range if applicable;
(C) Information on traceability to a reference material and
description of value assignment of calibrators and controls if
applicable;
[[Page 40726]]
(D) Device analytical sensitivity data, including limit of blank,
limit of detection, and limit of quantitation if applicable;
(E) Device analytical specificity data, including interference by
endogenous and exogenous substances, as well as cross-reactivity with
samples derived from patients with other autoimmune diseases or
conditions;
(F) Device instrument carryover data when applicable;
(G) Device stability data including real-time stability under
various storage times and temperatures;
(H) Specimen stability data including stability under various
storage times, temperatures, freeze-thaw, and transport conditions
where appropriate;
(I) Method comparison data generated by comparison of the results
obtained with the device to those obtained with a legally marketed
predicate device with similar indication of use. Patient samples from
the intended use population covering the device measuring range must be
used;
(J) Specimen matrix comparison data if more than one specimen type
or anticoagulant can be tested with the device. Samples used for
comparison must be from patient samples covering the device measuring
range;
(K) A description of how the assay cut-off (the medical decision
point between positive and negative) was established and validated as
well as supporting data;
(L) A clinical performance assessment established by comparing data
generated by testing samples from the intended use population and
differential diagnosis groups with the device to the clinical
diagnostic standard. Diagnosis of pMGN must be based primarily on
clinical history, physical examination, laboratory tests (including
urinalysis), and renal biopsy. Membranous glomerulonephritis is
considered to be idiopathic/primary when no secondary cause can be
elucidated on the basis of clinical and laboratory criteria. The
differential diagnosis groups must include secondary membranous
glomerulonephritis, membranoproliferative glomerulonephritis, lupus
nephritis, focal segmental glomerulosclerosis, IgA nephritis, diabetic
nephropathy, systemic lupus erythematosus, systemic sclerosis, and
Goodpasture syndrome. Diagnosis of autoimmune and immune-mediated
diseases that are associated with membranous glomerulonephritis must be
based on established diagnostic criteria and clinical evaluation. For
all samples, clinical criteria, including demographic information, must
be considered in the differentiation between pMGN and secondary
membranous glomerulonephritis. The clinical validation results must
demonstrate correlation clinical sensitivity and clinical specificity
between the test values and the presence or absence of pMGN. The data
must be summarized in tabular format comparing the interpretation of
results to the disease status; and
(M) Expected/reference values generated by testing an adequate
number of samples from apparently healthy normal individuals.
(iii) Identification of risk mitigation elements used by the
device, including a description of all additional procedures, methods,
and practices incorporated into the directions for use that mitigate
risks associated with testing.
(2) The label required under Sec. 809.10(a) and labeling required
under Sec. 809.10(b) of this chapter must include warnings relevant to
the assay including:
(i) A warning statement that explains: The device is for use by
laboratory professionals in a clinical laboratory setting;
(ii) A warning statement that explains: The test is not a
standalone test but an adjunct to other clinical information. A
diagnosis of pMGN or secondary MGN should not be made based on a single
test result. The clinical symptoms, results on physical examination,
and laboratory tests (e.g., serological tests), when appropriate,
should always be taken into account when considering the diagnosis of
primary versus secondary MGN;
(iii) A warning statement that explains: Absence of circulating
PLA2R autoantibody does not rule out a diagnosis of pMGN; and
(iv) A warning statement that explains: The assay has not been
demonstrated to be effective for monitoring the stage of disease or its
response to treatment.
(3) The labeling required under Sec. 809.10(b) of this chapter
must include a description of the protocol and performance studies
performed in accordance with paragraph (b)(1)(ii) of this section and a
summary of the results.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-16031 Filed 8-20-25; 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 August 21, 2025.
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.