Federal Register / Vol. 89, No. 179 / Monday, September 16, 2024 / Rules and Regulations 75491 

TABLE 1—CLOZAPINE TEST SYSTEM RISKS AND MITIGATION MEASURES—Continued 

Identified risks to health Mitigation measures 

Incorrect interpretation of test results ................................ Certain design verification and validation activities and Certain labeling information. 

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 

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 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 

■ 1. The authority citation for part 862 

continues to read as follows: 

Authority: 21 U.S.C. 351, 360, 360c, 360e, 

360j, 360l, 371. 

■ 2. Add § 862.3245 to subpart D to read 

as follows: 

§ 862.3245 Clozapine test system. 

(a) Identification. A clozapine test 

system is a device intended to measure 

clozapine in human specimens. 

Measurements obtained by this device 

are used in monitoring levels of 

clozapine to ensure appropriate therapy 

in patients with treatment-resistant 

schizophrenia. 

(b) Classification. Class II (special 

controls). The special controls for this 

device are: 

(1) Design verification and validation 

must include the following: 

(i) Precision study data that 

demonstrates precision that is clinically 

appropriate, as determined by FDA, for 

the clozapine test system. Precision 

studies must include a minimum of 

three samples containing different 

concentrations of clozapine including 

near medical decision points and 

throughout the expected therapeutic 

range of clozapine. Samples near the 

medical decision points must be clinical 

specimens collected from patients 

taking clozapine; 

(ii) Method comparison data that 

demonstrates accuracy that is clinically 

acceptable, as determined by FDA, for 

the clozapine test system; 

(iii) Data from studies that 

demonstrate that the device is free from 

clinically significant interference, as 

determined by FDA, from commonly coadministered medications that are used 

in patients with treatment-resistant 

schizophrenia; and 

(iv) Data from studies that 

demonstrate that the device is free from 

clinically significant cross-reactivity, as 

determined by FDA, from major 

circulating metabolites found in the 

intended use population. 

(2) The labeling required under 

§ 809.10 of this chapter must include a 

limiting statement conveying that the 

assay should only be used in 

conjunction with information available 

from clinical evaluations and other 

diagnostic procedures and that results 

from the assay alone should not be used 

in making treatment decisions. 

Dated: September 10, 2024. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2024–20895 Filed 9–13–24; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 866 

[Docket No. FDA–2024–N–4061] 

Medical Devices; Immunology and 

Microbiology Devices; Classification of 

the Device To Detect or Measure 

Nucleic Acid From Viruses Associated 

With Head and Neck Cancers 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final amendment; final order. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 

classifying the device to detect or 

measure nucleic acid from viruses 

associated with head and neck cancers 

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 

device to detect or measure nucleic acid 

from viruses associated with head and 

neck cancers’ 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. 

DATES: This order is effective September 

16, 2024. The classification was 

applicable on May 11, 2020. 

FOR FURTHER INFORMATION CONTACT: Kim 

Davis, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 3220, Silver Spring, 

MD 20993–0002, 301–796–1049, 

Kim.Davis@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 


lotter on DSK11XQN23PROD with RULES1
75492 Federal Register / Vol. 89, No. 179 / Monday, September 16, 2024 / Rules and Regulations 

1FDA 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. 

I. Background 

Upon request, FDA has classified the 

device to detect or measure nucleic acid 

from viruses associated with head and 

neck cancers as class II (special 

controls), which we have determined 

will provide a reasonable assurance of 

safety and effectiveness. 

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 

classification is considered to be the 

initial classification of the device. 

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 510(k) process, when necessary, to 

market their device. 

II. De Novo Classification 

On June 24, 2019, FDA received 

Advance Sentry Corp.’s request for De 

Novo classification of the NP Screen. 

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 May 11, 2020, 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 866.3236.1 We have named the 

generic type of device as device to 

detect or measure nucleic acid from 

viruses associated with head and neck 

cancers, and it is identified as an in 

vitro diagnostic test for prescription use 

in the detection of viral nucleic acid in 

nasopharyngeal or oropharyngeal 

cellular specimens from patients with 

signs and symptoms of head and neck 

cancer. The test result is intended to be 

used in conjunction with other clinical 

information to aid in assessing the 

clinical status of virus-associated head 

and neck cancers and/or the likelihood 

that head and neck cancer is present. 

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—DEVICE TO DETECT OR MEASURE NUCLEIC ACID FROM VIRUSES ASSOCIATED WITH HEAD AND NECK CANCERS

RISKS AND MITIGATION MEASURES

Identified risks to health Mitigation measures 

False test results ................................................................ Use of certain specimen collection and transport devices; Certain labeling information; and Certain design verification and validation. 

Failure to correctly interpret the test results ...................... Certain labeling information. 

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 


lotter on DSK11XQN23PROD with RULES1
Federal Register / Vol. 89, No. 179 / Monday, September 16, 2024 / Rules and Regulations 75493 

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 

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 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 

■ 1. The authority citation for part 866 

continues to read as follows: 

Authority: 21 U.S.C. 351, 360, 360c, 360e, 

360j, 360l, 371. 

■ 2. Add § 866.3236 to subpart D to read 

as follows: 

§ 866.3236 Device to detect or measure 

nucleic acid from viruses associated with 

head and neck cancers. 

(a) Identification. A device to detect 

or measure nucleic acid from viruses 

associated with head and neck cancers 

is an in vitro diagnostic test for 

prescription use in the detection of viral 

nucleic acid in nasopharyngeal or 

oropharyngeal cellular specimens from 

patients with signs and symptoms of 

head and neck cancer. The test result is 

intended to be used in conjunction with 

other clinical information to aid in 

assessing the clinical status of virusassociated head and neck cancers and/ 

or the likelihood that head and neck 

cancer is present. 

(b) Classification. Class II (special 

controls). The special controls for this 

device are: 

(1) Any device used for specimen 

collection and transport must be FDAcleared, -approved, or -classified as 

510(k) exempt (standalone or as part of 

a test system) for the collection of 

human specimens; alternatively, the 

sample collection device must be 

cleared in a premarket submission as a 

part of this device. 

(2) The labeling required under 

§ 809.10(b) of this chapter must include, 

as determined to be appropriate by FDA: 

(i) An intended use statement that 

includes the following: 

(A) The analyte(s) detected by the 

device; 

(B) Data output of the device 

(qualitative, semiquantitative, or 

quantitative); 

(C) The specimen types with which 

the device is intended for use; 

(D) The clinical indications 

appropriate for test use (e.g., in 

conjunction with endoscopy); 

(E) The intended use populations 

(e.g., signs and symptoms, ethnicity); 

and 

(F) The intended use location(s) (e.g., 

specific name and location of testing 

facility or facilities). 

(ii) A detailed device description, 

including reagents, instruments, 

ancillary materials, specimen collection 

and transport devices, controls, and a 

detailed explanation of the 

methodology, including all preanalytical methods for processing of 

specimens. 

(iii) A detailed explanation of the 

interpretation of results. 

(iv) Limiting statements indicating: 

(A) The device is not intended for use 

in screening for head and neck cancer 

in asymptomatic populations. 

(B) Results of the device are not 

predictive of a patient’s future risk of 

head and neck cancer. 

(C) Patients who test negative for the 

virus should be managed in accordance 

with the standard of care, based on the 

assessment of endoscopy and/or other 

clinical information by a licensed 

healthcare professional. 

(D) Results of the device are not 

intended to be used as the sole basis for 

determining the need for biopsy or for 

any other patient management decision. 

(3) Design verification and validation 

must include the following: 

(i) A detailed device description 

including pre-analytical specimen 

processing, assay technology, target 

region, primer/probe sequences, 

reagents, controls, instrument 

requirements, and the computational 

path from collected raw data to reported 

result. 

(ii) Detailed documentation and 

results from analytical performance 

studies, including characterization of 

the cutoff(s), limit of detection, limit of 

quantitation, precision (including 

multisite reproducibility, if applicable), 

inclusivity, cross-reactivity, 

interference, carryover/crosscontamination, reagent stability, and 

specimen/sample stability, as 

determined to be appropriate by FDA. 

(iii) Detailed documentation of a 

clinical performance study that includes 

patients from the intended use 

population, including the clinical study 

protocol, with a predefined statistical 

analysis plan, and a clinical study 

report with testing results and results of 

all statistical analyses. 

(iv) A detailed description of the 

impact of any software, including 

software applications and software 

incorporated in hardware-based devices, 

on the device’s functions. 

Dated: September 10, 2024. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2024–20896 Filed 9–13–24; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 876 

[Docket No. FDA–2024–N–4082] 

Medical Devices; Therapeutic Devices; 

Classification of the Pediatric 

Continuous Renal Replacement 

Therapy System 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final amendment; final order. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 


lotter on DSK11XQN23PROD with RULES1