Rule2025-10788
Medical Devices; Immunology and Microbiology Devices; Classification of the Clinical Mass Spectrometry Microorganism Identification and Differentiation System
Primary source
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Published
June 13, 2025
Effective
June 13, 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 clinical mass spectrometry microorganism identification and differentiation 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 clinical mass spectrometry microorganism identification and differentiation 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
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<title>Federal Register, Volume 90 Issue 113 (Friday, June 13, 2025)</title>
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[Federal Register Volume 90, Number 113 (Friday, June 13, 2025)]
[Rules and Regulations]
[Pages 24964-24966]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-10788]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2025-N-1505]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Clinical Mass Spectrometry Microorganism
Identification and Differentiation System
AGENCY: Food and Drug Administration, HHS.
ACTION: Final amendment; final order.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
classifying the clinical mass spectrometry microorganism identification
and differentiation 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 clinical mass
spectrometry microorganism identification and differentiation 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 13, 2025. The classification was
applicable on April 20, 2018.
FOR FURTHER INFORMATION CONTACT: Dina Jerebitski, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 3574, Silver Spring, MD 20993-0002, 301-
796-2411, <a href="/cdn-cgi/l/email-protection#4f0b26212e61052a3d2a2d263b3c24260f292b2e6127273c61282039"><span class="__cf_email__" data-cfemail="32765b5c531c78574057505b4641595b725456531c5a5a411c555d44">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the clinical mass spectrometry
microorganism identification and differentiation 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 to market a
substantially equivalent device
[[Page 24965]]
(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 September 29, 2017, FDA received Bruker Daltonik GmbH's request
for De Novo classification of the MALDI Biotyper CA 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 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 April 20, 2018, FDA issued an order to the requester
classifying the device into class II (special controls). FDA issued a
correction to the order on June 22, 2018. In this final order, FDA is
codifying the classification of the device by adding 21 CFR
866.3378.\1\ We have named the generic type of device ``clinical mass
spectrometry microorganism identification and differentiation system,''
and it is identified as a qualitative in vitro diagnostic device
intended for the identification and differentiation of microorganisms
from processed human specimens. The system acquires, processes, and
analyzes spectra to generate data specific to a microorganism(s). The
device is indicated for use in conjunction with other clinical and
laboratory findings to aid in the diagnosis of bacterial and fungal
infection.
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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 following risks to health associated
specifically with this type of device and the measures required to
mitigate these risks in table 1.
Table 1--Clinical Mass Spectrometry Microorganism Identification and
Differentiation System Risks and Mitigation Measures
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Identified risks to health Mitigation measures
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Incorrect identification or lack Special controls (1) (21 CFR
of identification of a pathogenic 866.3378(b)(1)), (2) (21 CFR
microorganism. 866.3378(b)(2)), (3) (21 CFR
866.3378(b)(3)), (4) (21 CFR
866.3378(b)(4)), and (5) (21 CFR
866.3378(b)(5)).
Failure to correctly interpret Special control (3) (21 CFR
test results. 866.3378(b)(3)).
Failure to correctly operate the Special controls (3)(i) (21 CFR
instrument. 866.3378(b)(3)(i)), and (5)(iv)(H)
(21 CFR 866.3378(b)(5)(iv)(H)).
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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. 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 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 the 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 part 866 continues to read as follows:
Authority: 21 U.S.C. .351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 866.3378 to subpart D to read as follows:
Sec. 866.3378 Clinical mass spectrometry microorganism identification
and differentiation system.
(a) Identification. A clinical mass spectrometry microorganism
identification and differentiation system is a qualitative in vitro
diagnostic device intended for the identification and differentiation
of microorganisms from processed human specimens. The
[[Page 24966]]
system acquires, processes, and analyzes spectra to generate data
specific to a microorganism(s). The device is indicated for use in
conjunction with other clinical and laboratory findings to aid in the
diagnosis of bacterial and fungal infection.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) The intended use statement must include a detailed description
of what the device detects, the type of results provided to the user,
the clinical indications appropriate for test use, and the specific
population(s) for which the device is intended, when applicable.
(2) Any sample collection device used must be FDA-cleared, -
approved, or -classified as 510(k) exempt with an indication for in
vitro diagnostic use.
(3) The labeling required under Sec. 809.10(b) of this chapter
must include:
(i) A detailed device description, including all device components,
control elements incorporated into the test procedure, instrument
requirements, ancillary reagents required but not provided, and a
detailed explanation of the methodology and all pre-analytical methods
for processing of specimens, and algorithm used to generate a final
result. This must include a description of validated inactivation
procedure(s) that are confirmed through a viability testing protocol,
as applicable.
(ii) Performance characteristics for all claimed sample types from
clinical studies with clinical specimens that include prospective
samples and/or, if appropriate, characterized samples.
(iii) Performance characteristics of the device for all claimed
sample types based on analytical studies, including limit of detection,
inclusivity, reproducibility, interference, cross-reactivity,
interfering substances, carryover/cross-contamination, sample
stability, and additional studies regarding processed specimen type and
intended use claims, as applicable.
(iv) A detailed explanation of the interpretation of test results
for clinical specimens and acceptance criteria for any quality control
testing.
(4) The device's labeling must include a prominent hyperlink to the
manufacturer's website where the manufacturer must make available their
most recent version of the device's labeling required under Sec.
809.10(b) of this chapter, which must reflect any changes in the
performance characteristics of the device. FDA must have unrestricted
access to this website, or manufacturers must provide this information
to FDA through an alternative method that is considered and determined
by FDA to be acceptable and appropriate.
(5) Design verification and validation must include:
(i) Any clinical studies must be performed with samples
representative of the intended use population and compare the device
performance to results obtained from an FDA-accepted reference method
and/or FDA-accepted comparator method, as appropriate. Documentation
from the clinical studies must include the clinical study protocol
(including predefined statistical analysis plan, if applicable),
clinical study report, and results of all statistical analyses.
(ii) Performance characteristics for analytical and clinical
studies for specific identification processes for the following, as
appropriate:
(A) Bacteria,
(B) Yeasts,
(C) Molds,
(D) Mycobacteria,
(E) Nocardia,
(F) Direct sample testing (e.g., blood culture),
(G) Antibiotic resistance markers, and
(H) Select agents (e.g., pathogens of high consequence).
(iii) Documentation that the manufacturer's risk mitigation
strategy ensures that their device does not prevent any device(s) with
which it is indicated for use, including incorporated device(s), from
achieving their intended use (e.g., safety and effectiveness of the
functions of the indicated device(s) remain unaffected).
(iv) A detailed device description, including the following:
(A) Overall device design, including all device components and all
control elements incorporated into the testing procedure.
(B) Algorithm used to generate a final result from raw data (e.g.,
how raw signals are converted into a reported result).
(C) A detailed description of device software, including validation
activities and outcomes.
(D) Acquisition parameters (e.g., mass range, laser power, laser
profile and number of laser shots per profile, raster scan, signal-to-
noise threshold) used to generate data specific to a microorganism.
(E) Implementation methodology, construction parameters, and
quality assurance protocols, including the standard operating protocol
for generation of reference entries for the device.
(F) For each claimed microorganism characteristic, a minimum of
five reference entries for each organism (including the type strain for
microorganism identification), or, if there are fewer reference
entries, a clinical and/or technical justification, determined by FDA
to be acceptable and appropriate, for why five reference entries are
not needed.
(G) DNA sequence analysis characterizing all type strains and at
least 20 percent of the non-type strains of a species detected by the
device, or, if there are fewer strain sequences, then a clinical and/or
technical justification, determined by FDA to be acceptable and
appropriate, must be provided for the reduced number of strains
sequenced.
(H) As part of the risk management activities, an appropriate end
user device training program, which must be offered as an effort to
mitigate the risk of failure from user error.
Dated: June 9, 2025.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-10788 Filed 6-12-25; 8:45 am]
BILLING CODE 4164-01-P
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