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 Department of Health and Human Services Food and Drug Administration 21 CFR Part 866
[Docket No. FDA-2017-N-5657]
 AGENCY: Food and Drug Administration, HHS.
 ACTION: Final order.
 SUMMARY: The Food and Drug Administration (FDA or we) is classifying the device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 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 and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis'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 October 24, 2017. The classification was applicable on February 20, 2016.
 FOR FURTHER INFORMATION CONTACT: Ryan Lubert, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 4545, Silver Spring, MD 20993-0002, 240-402-6357, 
                        *Ryan.Lubert@fda.hhs.gov.*


SUPPLEMENTARY INFORMATION: I. Background Upon request, FDA has classified the device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 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 (the 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 to a predicate device that does not require premarket approval (see 21 U.S.C. 360c(i)). We determine whether a new device is substantially equivalent to a predicate by means of the procedures for premarket notification under section 510(k) of the FD&C Act and part 807 (21 U.S.C. 360(k) and 21 CFR part 807, respectively). 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. Section 207 of the Food and Drug Administration Modernization Act of 1997 established the first procedure for De Novo classification (Pub. L. 105-115). Section 607 of the Food and Drug Administration Safety and Innovation Act modified the De Novo application process by adding a second procedure (Pub. L. 112-144). 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 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 21 U.S.C. 360c(f)(2)(B)(i)). As a result, other device sponsors do not have to submit a De Novo request or premarket approval application in order to market a substantially equivalent device (see 21 U.S.C. 360c(i), defining “substantial equivalence”). Instead, sponsors can use the less burdensome 510(k) process, when necessary, to market their device. II. De Novo Classification On March 4, 2015, B·R·A·H·M·S GmbH, part of Thermo Fisher Scientific, submitted a request for De Novo classification of the B·R·A·H·M·S PCT sensitive KRYPTOR. 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 general controls, will provide reasonable assurance of the safety and effectiveness of the device. Therefore, on February 20, 2016, FDA issued an order to the requestor classifying the device into class II. FDA is codifying the classification of the device by adding 21 CFR 866.3215. We have named the generic type of device, device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis, and it is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the 
                    ( print page 49099)
                    assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings. 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 and Measure Non-Microbial Analyte(s) in Human Clinical Specimens To Aid in Assessment of Patients With Suspected Sepsis Risks and Mitigation Measures
Identified risks
Mitigation measures/21 CFR sectionIncorrect determination of procalcitonin (PCT) value, including false positives and false negatives, by the device can lead to improper patient management
Special Controls (2), (3), and (7) (21 CFR 866.3215(b)(2); 21 CFR 866.3215(b)(3); and 21 CFR 866.3215(b)(7)).Incorrect interpretation of device results by end user can lead to improper patient management
Special Controls (1), (4), (5), (6), and (7) (21 CFR 866.3215(b)(1); 21 CFR 866.3215(b)(4); 21 CFR 866.3215(b)(5); 21 CFR 866.3215(b)(6); and 21 CFR 866.3215(b)(7)).Manual calculation error of final results
Special Control (7) (21 CFR 866.3215(b)(7)).
 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. In order 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. 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. 3501-3520). 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 part 820 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, 360
                            *l,*
                             371. 2.Add § 866.3215 to subpart D to read as follows: § 866.3215
  (a) 
                            *Identification.*
                             A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings. (b) 
                            *Classification.*
                             Class II (special controls). The special controls for this device are: (1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended. (2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection. (3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability. (4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information: (i) Results must demonstrate adequate device performance relative to a well-accepted comparator. (ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population. (iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses. (5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
                            *e.g.,*
                             age, racial, ethnic, and gender distribution) similar to the Intended Use population. (6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be 
                            ( print page 49100)
                            offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument. (7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
                            *e.g.,*
                             collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.
 Dated: October 18, 2017. Leslie Kux, Associate Commissioner for Policy.


[FR Doc. 2017-22994 Filed 10-23-17; 8:45 am] BILLING CODE 4164-01-P