Rule2026-11740
Medical Devices; Immunology and Microbiology Devices; Classification of the Spinal Muscular Atrophy Newborn Screening 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
June 11, 2026
Effective
June 11, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA) is classifying the Spinal Muscular Atrophy newborn screening 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 classification of the Spinal Muscular Atrophy newborn screening test system. 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
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<title>Federal Register, Volume 91 Issue 112 (Thursday, June 11, 2026)</title>
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[Federal Register Volume 91, Number 112 (Thursday, June 11, 2026)]
[Rules and Regulations]
[Pages 35384-35387]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-11740]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2026-N-5828]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Spinal Muscular Atrophy Newborn Screening Test
System
AGENCY: Food and Drug Administration, HHS.
ACTION: Final amendment; final order.
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SUMMARY: The Food and Drug Administration (FDA) is classifying the
Spinal Muscular Atrophy newborn screening 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 classification of the Spinal Muscular Atrophy newborn screening
test system. 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 11, 2026. The classification was
applicable on November 9, 2022.
FOR FURTHER INFORMATION CONTACT: Allen Williams, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 3248, Silver Spring, MD 20993-0002, 301-796-4806,
<a href="/cdn-cgi/l/email-protection#aeefc2c2cbc080f9c7c2c2c7cfc3ddeec8cacf80c6c6dd80c9c1d8"><span class="__cf_email__" data-cfemail="85c4e9e9e0ebabd2ece9e9ece4e8f6c5e3e1e4abededf6abe2eaf3">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA (the Agency or we) has classified the Spinal
Muscular Atrophy (SMA) newborn screening test system 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
[[Page 35385]]
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.
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 July 8, 2020, FDA received PerkinElmer Inc.'s request for De
Novo classification of the Eonis SCID-SMA Kit. 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 November 9, 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
866.5980.\1\ We have named the generic type of device ``Spinal Muscular
Atrophy newborn screening test system,'' and it is identified as a
prescription device intended to detect homozygous deletion of exon 7 or
other similar mutations in the SMN1 (Survival Motor Neuron 1) gene of
DNA obtained from dried blood spot specimens on filter paper using a
polymerase chain reaction-based test as an aid in screening newborns
for SMA. Presumptive positive results are intended to be followed up by
diagnostic confirmatory testing.
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\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.
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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 Spinal Muscular
Atrophy Newborn Screening Test Systems
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Identified risks to health Mitigation measures
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Risk of false negative results............... Certain design
verification and
validation identified in
special control (1),
including certain device
description information
and documentation of
certain analytical
studies and clinical
studies.
Certain labeling
information identified
in special control (2),
including limitations,
device descriptions,
explanation of
procedures, and
performance information.
Risk of false positive results............... Certain design
verification and
validation identified in
special control (1),
including certain device
description information
and documentation of
certain analytical
studies and clinical
studies.
Certain labeling
information identified
in special control (2),
including limitations,
device descriptions,
explanation of
procedures, and
performance information.
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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, Spinal Muscular Atrophy newborn
screening test systems are for prescription use only. Therefore, these
devices are subject to the prescription labeling requirements for in
vitro diagnostic
[[Page 35386]]
(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 device
type should be exempt under section 510(m) of the FD&C Act. At this
time FDA has not made this determination for Spinal Muscular Atrophy
newborn screening test systems. 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 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 part 866 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 866.5980 to subpart F to read as follows:
Sec. 866.5980 Spinal Muscular Atrophy newborn screening test system.
(a) Identification. A Spinal Muscular Atrophy (SMA) newborn
screening test system is a prescription device intended to detect
homozygous deletion of exon 7 or other similar mutations in the SMN1
(Survival Motor Neuron 1) gene of DNA obtained from dried blood spot
specimens on filter paper using a polymerase chain reaction-based test
as an aid in screening newborns for SMA. Presumptive positive results
are intended to be followed up by diagnostic confirmatory testing.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Design verification and validation must include the following:
(i) A detailed device description, including all device parts
(e.g., instruments and associated user manuals, device software,
reagents, calibrators, controls, and consumables) and their use within
the testing procedure.
(ii) A detailed explanation of the technology, method(s) of data
processing from signal acquisition to result assignment, and pre-
specified cut-offs used to interpret the data and generate results and
sample reports.
(iii) A description of appropriate internal and external controls
that are recommended or provided. The description must identify those
control elements that are incorporated into the testing procedure.
(iv) Detailed specifications for the filter paper to be used as
part of the device, which must be appropriately labeled for in vitro
diagnostic use. Specifications must include punch size and address any
properties of the filter paper that may interfere with obtaining test
results.
(v) Detailed documentation of the following analytical and clinical
studies, including the study protocols containing descriptions of the
test methods, prescribed methods of data analysis and acceptance
criteria, final study reports, and data line listings:
(A) A study demonstrating the clinical performance of the device
using well characterized prospectively or retrospectively obtained
clinical specimens from the intended use population and include
homozygous and heterozygous specimens of sufficient number to be
determined to be acceptable to FDA. Confirmed positive specimens must
have a diagnosis based on confirmatory diagnostic methods. The
confirmed positives must include samples from SMA types 1-4.
Additionally, samples with SMN2 (Survival Motor Neuron 2) copy number
ranging to 4 must be evaluated to determine the risk of false negative
(unaffected) results due to assay cross reactivity with the SMN2 gene.
A description of the sample collection strategy and accountability must
be included. Specimens used in the study must be from patients other
than those used to design the test, and validation testing must be
based on a pre-specified clinical decision point (i.e., cutoff to
distinguish positive and negative results). Results must be summarized
in a tabular format comparing interpretation of results to the
reference method. Point estimates together with two-sided 95 percent
confidence intervals must be provided for the positive percent
agreement (sensitivity) and negative percent agreement (specificity).
Data must include the retest rate, false positive rate before retest,
final false positive rate, and false negative rate. Positive predictive
value and negative predictive value must be provided based on published
reference to prevalence in the target population.
(B) A study demonstrating device accuracy in comparison to the
results obtained by a reference or comparator method determined to be
acceptable by FDA.
(C) A study demonstrating device reproducibility generated using a
minimum of three sites, of which at least two must be external sites,
with at least two operators at each site using the specified extraction
method(s) and protocol. The evaluation must include multiple runs,
days, different instruments, and different reagent lots. The study must
include heterozygous deleted, homozygous deleted, and unaffected
specimens. Identical specimens from the same sample panel must be
tested at each site. Results must be summarized in a tabular format and
reported as standard deviation and 95 percent confidence intervals for
the quantitative result and agreement for qualitative results for
between-site, between-operator, between-day/run, and within-run
(repeatability) for each specimen.
(D) A lot-to-lot reproducibility study of each filter paper
intended to be used with the test. The lot-to-lot study must
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include a minimum of three lots of each blood spot card that will be
validated with the test and be conducted over five nonconsecutive days.
The sample panel must consist of at least one positive and one negative
specimen. Multiple punches must be obtained from each card for
demonstration of homogeneity of the analyte across the dried blood
spot. Comparability of the test performance for each filter paper must
be demonstrated. Stability and storage of SMN1 DNA on each blood spot
card must be demonstrated. Results of the lot-to-lot study must be
summarized by providing the agreement within replicates on the assay
final result for positive and negative specimens with pre-specified
acceptance criteria and 95 percent confidence intervals for all data.
Data must be calculated for within-lot and between-lot reproducibility.
Data demonstrating the concordance between results across different
filter papers must be provided. Study acceptance criteria must be
provided and followed.
(E) A study demonstrating device specificity, including
interference, carryover/cross-contamination, and analysis of potential
off-target genomic sequences, including evaluation of SMN2
amplification, to evaluate the risk of clinically false negative or
false positive results.
(F) Studies performed to support the stability of samples using the
indicated specimen collection method(s) under various storage times,
temperatures, and freeze-thaw conditions, as applicable.
(G) Studies performed to demonstrate on-board and in-use reagent
stability, including the test method(s), data analysis plans,
acceptance criteria, final study reports, and data line listings. Such
documentation must include studies to demonstrate reagent shelf-life
for the assay kit, including study protocols containing descriptions of
the test method(s), data analysis plans, and acceptance criteria.
(H) Studies performed to evaluate the risk of false positive and
false negative results (e.g., validation of the cycle thresholds or
other metric, as applicable, used to define the assay reportable range
when assessing a range of DNA input, equivalency of different filter
paper, and the limit of blank, when determined appropriate by FDA).
(I) A shipping stability study, separate from the study described
in paragraph (b)(1)(v)(G) of this section, must be performed that
demonstrates acceptable stability of the parts that comprise the kit.
(vi) A detailed description of the impacts of any software,
including software applications and hardware-based devices that
incorporate software, on the device's functions.
(vii) Identification of all risk mitigation elements used by the
device, including a detailed description of all additional procedures,
methods, and practices incorporated into the instructions for use that
mitigate risks associated with using the device.
(2) The labeling required under Sec. 809.10(b) of this chapter
must include:
(i) An intended use statement that includes:
(A) A detailed description of the target(s) the device detects; and
(B) The clinical indications appropriate for test use.
(ii) Prominent and conspicuous limiting statements clearly
explaining:
(A) This test is not intended to screen for SMA subtypes other than
those specifically stated in the intended use, nor is it intended for
carrier screening, as a stand-alone diagnostic test, or for determining
eligibility for therapeutic products.
(B) Test results are intended to be used in conjunction with other
clinical and diagnostic findings, consistent with professional
standards of practice, including confirmation of presumptive positive
results by diagnostic confirmatory testing and clinical evaluation, as
appropriate.
(iii) Description of the device information required under
paragraphs (b)(1)(i) through (iv) of this section.
(iv) A summary of the results of the studies required under
paragraphs (b)(1)(v)(A) through (G) of this section.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-11740 Filed 6-10-26; 8:45 am]
BILLING CODE 4164-01-P
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