Rule2025-11781
Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of the Lysosomal Storage Disorder 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 26, 2025
Effective
June 26, 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 lysosomal storage disorder 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 the lysosomal storage disorder newborn screening test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) 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 121 (Thursday, June 26, 2025)</title>
</head>
<body><pre>
[Federal Register Volume 90, Number 121 (Thursday, June 26, 2025)]
[Rules and Regulations]
[Pages 27229-27231]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-11781]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 862
[Docket No. FDA-2025-N-1447]
Medical Devices; Clinical Chemistry and Clinical Toxicology
Devices; Classification of the Lysosomal Storage Disorder Newborn
Screening 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 lysosomal storage disorder 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 the lysosomal storage disorder newborn
screening test system's classification. We are taking this action
because we have determined that classifying the device into class II
(special controls) 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 26, 2025. The classification was
applicable on February 3, 2017.
FOR FURTHER INFORMATION CONTACT: Ryan Lubert, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 3574, Silver Spring, MD 20993-0002, 240-402-6357,
<a href="/cdn-cgi/l/email-protection#c391baa2aded8fb6a1a6b1b783a5a7a2edababb0eda4acb5"><span class="__cf_email__" data-cfemail="8ddff4ece3a3c1f8efe8fff9cdebe9eca3e5e5fea3eae2fb">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the lysosomal storage disorder
newborn screening 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 (see 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
[[Page 27230]]
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 August 7, 2015, FDA received Baebies, Inc.'s request for De Novo
classification of the SEEKER System. 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 21 U.S.C. 360c(a)(1)(B)). 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 February 3, 2017, FDA issued an order to the
requestor classifying the device into class II. In this final order,
FDA is codifying the classification of the device by adding 21 CFR
862.1488.\1\ We have named the generic type of device lysosomal storage
disorder newborn screening test system, and it is identified as a
device intended to measure lysosomal enzyme levels obtained from dried
blood spot specimens on filter paper from newborns as an aid in
screening newborns for a lysosomal storage disorder.
---------------------------------------------------------------------------
\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--Lysosomal Storage Disorder Newborn Screening Test System Risks
and Mitigation Measures
------------------------------------------------------------------------
Identified risks to health Mitigation measures
------------------------------------------------------------------------
Inaccurate test results that provide Special controls (1) (21 CFR
false negative test results could lead 862.1488(b)(1) and (2) 21 CFR
a newborn to not be detected as a 862.1488(b)(2)).
possible lysosomal storage disorder
case and to be delayed from timely
therapy.
Inaccurate test results that provide Special controls (1) (21 CFR
false positive test results could lead 862.1488(b)(1) and (2) 21 CFR
a newborn to have unnecessary 862.1488(b)(2)).
additional confirmatory testing and to
add emotional burden to the family of
the newborn.
------------------------------------------------------------------------
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 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 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 862
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
862 is amended as follows:
PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES
0
1. The authority citation for 21 CFR part 862 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 862.1488 to subpart B to read as follows:
Sec. 862.1488 Lysosomal storage disorder newborn screening test
system.
(a) Identification. A lysosomal storage disorder newborn screening
test system is intended to measure lysosomal enzyme levels obtained
from dried blood spot specimens on filter paper from newborns as an aid
in screening
[[Page 27231]]
newborns for a lysosomal storage disorder.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Design verification and validation must include information
that demonstrates the performance characteristics of the device,
including:
(i) Study results that adequately demonstrate the clinical validity
of the device, which must include information supporting the link
between the analyte being measured and the condition being screened.
The clinical validity of the device must be demonstrated in a clinical
validation study using either well-characterized prospectively or
retrospectively obtained clinical specimens from the intended use
population. Testing in the clinical validation study must be performed
by operators representative of the types of operators intended to use
the test. The study design of the clinical validation study must assess
the effects of sample collection and processing steps on test
performance. Confirmed positive specimens must have a diagnosis based
on confirmatory diagnostic methods or clinically meaningful information
regarding the status of the subject must be obtained.
(ii) The reference interval in the normal newborn population for
the analyte or analytes measured by the device.
(iii) Study results demonstrating the level of carryover or drift
affecting the device performance.
(vi) Study results demonstrating the concentrations of the limit of
blank, limit of detection, and limit of quantitation of the device.
Sample concentrations below the limit of quantitation must not be
reported by the device.
(v) Study results, which must be collected using sample panels from
at least three reagent lots and at least three instruments over more
than 20 testing days, demonstrating the imprecision of the device. The
sample panels must consist of blood spot specimens with a range of
analyte concentrations that span the reportable range of the device and
must include samples with concentrations in the screen positive range,
samples with concentrations at each cutoff, and samples with
concentration in the normal range.
(2) The labeling required under Sec. 809.10(b) of this chapter
must include:
(i) A warning that indicates that the test is not intended to
diagnose lysosomal storage disorders.
(ii) A warning that indicates that test results are intended to be
used in conjunction with other clinical and diagnostic findings,
consistent with professional standards of practice, including
confirmation by alternative methods, and clinical evaluation as
appropriate.
(iii) Detailed information on device performance, including the
false positive rate and the false negative rate observed in the
clinical study.
(iv) Information on device performance in any relevant subgroup
(e.g., age of newborn at time of sample collection, birth weight, sex,
gestational age, race, ethnicity) observed in the clinical study.
Dated: June 23, 2025.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-11781 Filed 6-25-25; 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 June 26, 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.