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 Department of Health and Human Services Food and Drug Administration 21 CFR Part 876
[Docket No. FDA-2024-N-4082]
 AGENCY: Food and Drug Administration, HHS.
 ACTION: Final amendment; final order.
 SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
                        ( print page 75494)
                        classifying the pediatric continuous renal replacement therapy 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 pediatric continuous renal replacement therapy 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.
 DATES: This order is effective September 16, 2024. The classification was applicable on April 29, 2020.
 FOR FURTHER INFORMATION CONTACT: Gema Gonzalez, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 2530, Silver Spring, MD 20993-0002, 301-796-6519, 
                        *Gema.Gonzalez@fda.hhs.gov.*


SUPPLEMENTARY INFORMATION: I. Background Upon request, FDA has classified the pediatric continuous renal replacement therapy system 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 October 9, 2018, FDA received Medtronic, Inc.'s request for De Novo classification of the CARPEDIEM 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 April 29, 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 876.5861.[1]
                    
                     We have named the generic type of device pediatric continuous renal replacement therapy system, and it is identified as a device intended for use as an artificial kidney system for the management of pediatric patients with acute kidney injury and/or fluid overload by performing such therapies as hemodialysis, hemofiltration, hemodiafiltration, and isolated ultrafiltration. Using a hemodialyzer with a semipermeable membrane, the hemodialysis system removes toxins or excess fluid from the patient's blood using the principles of convection (via ultrafiltration) and/or diffusion (via a concentration gradient in dialysate). The hemodialysis delivery machine, with an automated ultrafiltration controller, controls and monitors the parameters related to this processing, including the rate at which blood and dialysate are pumped through the system, and the rate at which fluid is removed from the patient. During treatment, a patient's blood is circulated through the blood tubing set connected to the hemodialyzer's blood compartment. Blood access devices and accessories for hemodialysis required for the prescribed treatment are regulated under 21 CFR 876.5540. FDA has identified the following risks to health associated specifically with this type of device and the measures 
                    ( print page 75495)
                    required to mitigate these risks in table 1. Table 1—Pediatric Continuous Renal Replacement Therapy System Risks and Mitigation Measures
Identified risks to health
Mitigation measuresAdverse tissue reaction
Biocompatibility evaluation,
                             Pyrogenicity testing, and 
                             Non-clinical performance testing.Death
Labeling,
                             Clinical performance testing, and 
                             Usability testing.Infection
Labeling,
                             Reprocessing validation, 
                             Pyrogenicity testing, 
                             Shelf life testing, and 
                             Usability testing.Inadequate or incomplete treatment
Non-clinical performance testing;
                             Clinical performance testing; 
                             Labeling; 
                             Shelf-life testing; 
                             Usability testing; and 
                             Software verification, validation, and hazard analysis.Clearance of essential blood substances or medications
Non-clinical performance testing;
                             Clinical performance testing; 
                             Labeling; 
                             Shelf-life testing; 
                             Usability testing; and 
                             Software verification, validation, and hazard analysis.Blood loss or blood cell destruction
Non-clinical performance testing;
                             Clinical performance testing; 
                             Labeling; 
                             Shelf-life testing; and 
                             Software verification, validation, and hazard analysis.Thermal injury
Non-clinical performance testing;
                             Clinical performance testing; 
                             Labeling; 
                             Shelf-life testing; 
                             Usability testing; and 
                             Software verification, validation, and hazard analysis.Blood leak into the dialysis fluid
Non-clinical performance testing;
                             Clinical performance testing; 
                             Labeling; 
                             Shelf-life testing; and 
                             Software verification, validation, and hazard analysis.Fluid imbalance
Non-clinical performance testing;
                             Clinical performance testing; 
                             Labeling; 
                             Shelf-life testing; and 
                             Software verification, validation, and hazard analysis.Air embolism
Non-clinical performance testing;
                             Clinical performance testing; 
                             Labeling; 
                             Shelf-life testing; 
                             Usability testing; and 
                             Software verification, validation, and hazard analysis.Fluid pump(s) reversal resulting in air infusion via the arterial bloodline
Non-clinical performance testing;
                             Clinical performance testing; 
                             Labeling; 
                             Shelf-life testing; 
                             Usability testing; and 
                             Software, verification, validation, and hazard analysis.Electrical shock
Electrical safety testing.Electromagnetic interference with other devices/equipment
Electromagnetic compatibility (EMC) testing.
 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, 
                    ( print page 75496)
                    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 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 part 801, regarding labeling, have been approved under OMB control number 0910-0485. List of Subjects in 21 CFR Part 876 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 876 is amended as follows: PART 876—GASTROENTEROLOGY-UROLOGY DEVICES
 1.The authority citation for part 876 continues to read as follows: Authority:
                        21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371. 2.Add § 876.5861 to subpart F to read as follows: § 876.5861
  (a) 
                            *Identification.*
                             A pediatric continuous renal replacement therapy hemodialysis system is a device intended for use as an artificial kidney system for the management of pediatric patients with acute kidney injury and/or fluid overload by performing such therapies as hemodialysis, hemofiltration, hemodiafiltration, and isolated ultrafiltration. Using a hemodialyzer with a semipermeable membrane, the hemodialysis system removes toxins or excess fluid from the patient's blood using the principles of convection (via ultrafiltration) and/or diffusion (via a concentration gradient in dialysate). The hemodialysis delivery machine, with an automated ultrafiltration controller, controls and monitors the parameters related to this processing, including the rate at which blood and dialysate are pumped through the system, and the rate at which fluid is removed from the patient. During treatment, a patient's blood is circulated through the blood tubing set connected to the hemodialyzer's blood compartment. Blood access devices and accessories for hemodialysis required for the prescribed treatment are regulated under § 876.5540. (b) 
                            *Classification.*
                             Class II (special controls). The special controls for this device are: (1) Clinical performance testing must confirm the safety and the accuracy, precision, and reproducibility of the non-clinical performance data under anticipated conditions of use. (2) Usability testing must demonstrate that a user can correctly use the hemodialysis delivery device based solely on reading the instructions for use. (3) Non-clinical performance testing data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested: (i) Hemodialysis delivery system performance testing must include: (A) Fluid flow accuracy testing; and (B) Functional testing of system components including sensors, pumps, and scales to acceptance criteria. (ii) Hemodialyzer performance testing must include: (A) Ultrafiltration; (B) Blood and dialysate pressure drop; (C) Clearance rates; (D) Sieving coefficients; (E) Mechanical hemolysis; (F) Structural integrity; (G) Blood compartment integrity; (H) Volume of the blood compartment; and (I) Chemical analysis of the dialyzer membrane. (iii) Blood tubing set performance testing must include: (A) Pressure leak testing; (B) Worst-case endurance testing; (C) Priming volume assessment; (D) Tensile testing of joints and materials of all tubing segments; (E) Pressure transducer leak testing; (F) Clamp occlusion; (G) Mechanical hemolysis; and (H) Kink testing. (4) Software verification, validation, and hazard analysis must be performed. (5) Performance data must demonstrate the electromagnetic compatibility (EMC), electrical safety, and wireless compatibility of the device. (6) The tissue-contacting components of the device must be demonstrated to be biocompatible. (7) Performance data must demonstrate the sterility of the patient-contacting components of the device. (8) Performance data must validate the reprocessing instructions for the reusable components of the device. (9) The patient-contacting components of the device must be demonstrated to be non-pyrogenic. (10) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the identified shelf life. (11) Device labeling must include: (i) Hemodialysis delivery system labeling must provide detailed information regarding the safe use of the dialysis machine, including: (A) Overall description of the device and individual components or accessories labeled for use with the delivery system; (B) Description of the safety-related components included in the system; (C) Identification of operational parameters; (D) Alarms and troubleshooting information; (E) Cleaning, disinfection, and preventative maintenance procedures; and (F) A statement that the device is intended for use by operators trained in the administration of continuous renal replacement therapy and in the management of its complications. (ii) Hemodialyzer labeling must include: (A) Description of compatibility; (B) Shelf life; (C) Storage conditions; (D) Instructions for the preparation of the hemodialyzer, initiation of dialysis, troubleshooting, and discontinuance of dialysis; (E) Membrane surface area, priming (blood) volume, maximum transmembrane pressure, maximum blood flow and maximum dialysate rate for each model; (F) Summary of the in vitro performance data; and (G) A non-pyrogenic statement. (iii) Blood tubing set labeling must provide detailed information regarding the safe use of the device, including: (A) Description of compatibility; (B) Shelf life; (C) Storage conditions; (D) Identification of the components in the package;
                            ( print page 75497) (E) Total length of the arterial and venous tubing sets; (F) Outer diameter (OD) of the pump segment; (G) Priming volume; (H) Identification of the hemodialysis delivery systems which are compatible with the blood tubing set; (I) Identification of the largest gauge needle that can be used with the injection port, if applicable; and (J) Identification of the maximum operating pressures for the transducer protectors.
 Dated: September 11, 2024. Lauren K. Roth, Associate Commissioner for Policy.


# Footnotes

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. Back to Citation


[FR Doc. 2024-20999 Filed 9-13-24; 8:45 am] BILLING CODE 4164-01-P