[Federal Register Volume 81, Number 29 (Friday, February 12, 2016)]
[Rules and Regulations]
[Pages 7446-7452]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-02876]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 868 and 870

[Docket No. FDA-2012-N-1174]


Anesthesiology Devices; Reclassification of Membrane Lung for 
Long-Term Pulmonary Support; Redesignation as Extracorporeal Circuit 
and Accessories for Long-Term Respiratory/Cardiopulmonary Failure

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA) is issuing a final 
order to redesignate membrane lung devices for long-term pulmonary 
support, a preamendments class III device, as extracorporeal circuit 
and accessories for long-term respiratory/cardiopulmonary failure, and 
to reclassify the device to class II (special controls) in patients 
with acute respiratory failure or acute cardiopulmonary failure where 
other available treatment options have failed, and continued clinical 
deterioration is expected or the risk of death is imminent. A membrane 
lung device for long-term pulmonary support (>6 hours) refers to the 
oxygenator in an extracorporeal circuit used during long-term 
procedures, commonly referred to

[[Page 7447]]

as extracorporeal membrane oxygenation (ECMO). Because a number of 
other devices and accessories are used with the oxygenator in the 
circuit, the title and identification of the regulation are revised to 
include extracorporeal circuit and accessories for long-term 
respiratory/cardiopulmonary failure. Although an individual device or 
accessory used in an ECMO circuit may already have its own 
classification regulation when the device or accessory is intended for 
short-term use (<=6 hours), such device or accessory will be subject to 
the same regulatory controls applied to the oxygenator (i.e., class II, 
special controls) when evaluated as part of the ECMO circuit for long-
term use (>6 hours). On its own initiative, based on new information, 
FDA is revising the classification of the membrane lung device for 
long-term pulmonary support.

DATES: This order is effective February 12, 2016.

FOR FURTHER INFORMATION CONTACT: Fernando Aguel, Center for Devices and 
Radiological Health, 10903 New Hampshire Ave., Bldg. 66, Rm. 1234, 
Silver Spring, MD 20993, 301-796-6326, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended 
by the Medical Device Amendments of 1976 (the 1976 amendments) (Pub. L. 
94-295), the Safe Medical Devices Act of 1990 (Pub. L. 101-629), the 
Food and Drug Administration Modernization Act of 1997 (FDAMA) (Pub. L. 
105-115), the Medical Device User Fee and Modernization Act of 2002 
(Pub. L. 107-250), the Medical Devices Technical Corrections Act (Pub. 
L. 108-214), the Food and Drug Administration Amendments Act of 2007 
(Pub. L. 110-85), and the Food and Drug Administration Safety and 
Innovation Act (FDASIA) (Pub. L. 112-144), among other amendments, 
established a comprehensive system for the regulation of medical 
devices intended for human use. Section 513 of the FD&C Act (21 U.S.C. 
360c) established three categories (classes) of devices, reflecting the 
regulatory controls needed to provide reasonable assurance of their 
safety and effectiveness. The three categories of devices are class I 
(general controls), class II (special controls), and class III 
(premarket approval).
    Under section 513(d) of the FD&C Act, devices that were in 
commercial distribution before the enactment of the 1976 amendments, 
May 28, 1976 (generally referred to as preamendments devices), are 
classified after FDA has: (1) Received a recommendation from a device 
classification panel (an FDA advisory committee); (2) published the 
panel's recommendation for comment, along with a proposed regulation 
classifying the device; and (3) published a final regulation 
classifying the device. FDA has classified most preamendments devices 
under these procedures.
    Devices that were not in commercial distribution prior to May 28, 
1976 (generally referred to as postamendments devices) are 
automatically classified by section 513(f) of the FD&C Act into class 
III without any FDA rulemaking process. Those devices remain in class 
III and require premarket approval unless, and until, the device is 
reclassified into class I or II or FDA issues an order finding the 
device to be substantially equivalent, in accordance with section 
513(i) of the FD&C Act, to a predicate device that does not require 
premarket approval. The Agency determines whether new devices are 
substantially equivalent to predicate devices by means of premarket 
notification procedures in section 510(k) of the FD&C Act (21 U.S.C. 
360(k)) and part 807 (21 CFR part 807).
    A preamendments device that has been classified into class III and 
devices found substantially equivalent by means of premarket 
notification procedures (510(k)) to such a preamendments device or to a 
device within that type (both the preamendments and substantially 
equivalent devices are referred to as preamendments class III devices) 
may be marketed without submission of a premarket approval application 
(PMA) until FDA issues a final order under section 515(b) of the FD&C 
Act (21 U.S.C. 360e(b)) requiring premarket approval or until the 
device is subsequently reclassified into class I or class II.
    On July 9, 2012, FDASIA was enacted. Section 608(a) of FDASIA (126 
Stat. 1056) amended section 513(e) of the FD&C Act, changing the 
mechanism for reclassifying a device from rulemaking to an 
administrative order.
    Section 513(e) of the FD&C Act provides that FDA may, by 
administrative order, reclassify a device based upon ``new 
information.'' FDA can initiate a reclassification under section 513(e) 
of the FD&C Act or an interested person may petition FDA to reclassify 
a preamendments device. The term ``new information,'' as used in 
section 513(e) of the FD&C Act, includes information developed as a 
result of a reevaluation of the data before the Agency when the device 
was originally classified, as well as information not presented, not 
available, or not developed at that time. (See, e.g., Holland-Rantos 
Co. v. United States Department of Health, Education, and Welfare, 587 
F.2d 1173, 1174 n.1 (D.C. Cir. 1978); Upjohn v. Finch, 422 F.2d 944 
(6th Cir. 1970); Bell v. Goddard, 366 F.2d 177 (7th Cir. 1966).)
    Reevaluation of the data previously before the Agency is an 
appropriate basis for subsequent action where the reevaluation is made 
in light of newly available authority (see Bell, 366 F.2d at 181; 
Ethicon, Inc. v. FDA, 762 F.Supp. 382, 388-391 (D.D.C. 1991)), or in 
light of changes in ``medical science'' (Upjohn, 422 F.2d at 951). 
Whether data before the Agency are old or new data, the ``new 
information'' to support reclassification under section 513(e) of the 
FD&C Act must be ``valid scientific evidence,'' as defined in section 
513(a)(3) of the FD&C Act and 21 CFR 860.7(c)(2). (See, e.g., General 
Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens 
Manufacturers Assoc. v. FDA, 766 F.2d 592 (D.C. Cir. 1985), cert. 
denied, 474 U.S. 1062 (1986).)
    FDA relies upon ``valid scientific evidence'' in the classification 
process to determine the level of regulation for devices. To be 
considered in the reclassification process, the ``valid scientific 
evidence'' upon which the Agency relies must be publicly available. 
Publicly available information excludes trade secret and/or 
confidential commercial information, e.g., the contents of a pending 
PMA (see section 520(c) of the FD&C Act (21 U.S.C. 360j(c)).)
    Section 513(e)(1) of the FD&C Act sets forth the process for 
issuing a final reclassification order. Specifically, prior to the 
issuance of a final order reclassifying a device, the following must 
occur: (1) Publication of a proposed order in the Federal Register; (2) 
a meeting of a device classification panel described in section 513(b) 
of the FD&C Act; and (3) consideration of comments to a public docket.

II. Regulatory History of the Device

    FDA published a proposed order to reclassify this device in the 
Federal Register of January 8, 2013 (78 FR 1158) (the ``proposed 
order''). As noted in the proposed order, on July 16, 1982, the Agency 
issued a final rule classifying all membrane lungs for long-term 
pulmonary support into class III (47 FR 31130). On May 11, 1987, FDA 
published a final rule amending the codified language for this device 
to clarify that no effective date had been

[[Page 7448]]

established for the requirement for premarket approval for membrane 
lungs for long-term pulmonary support devices (52 FR 17732 at 17735). 
This device is currently under product code BYS.
    As discussed in the proposed order, FDA considered the available 
information on these devices and concluded that these devices could be 
reclassified to class II, subject to the identified special controls. 
As required by section 513(e)(1) of the FD&C Act, FDA convened a 
meeting of a device classification panel described in section 513(b) of 
the FD&C Act with respect to the membrane lung devices for long-term 
pulmonary support on September 12, 2013, followed by a meeting on May 
7, 2014. The deliberations of the device classification panels are 
discussed in section IV of this order. FDA received and has considered 
two comments on the January 8, 2013, proposed order, as discussed in 
section III. Therefore, FDA has met the requirements for issuing a 
final order under section 513(e)(1) of the FD&C Act.

III. Public Comments in Response to the Proposed Order

    FDA received two comments in response to the January 8, 2013, 
proposed order to reclassify membrane lung devices for long-term 
pulmonary support for conditions where imminent death is threatened by 
cardiopulmonary failure in neonates and infants or where 
cardiopulmonary failure results in the inability to separate from 
cardiopulmonary bypass following cardiac surgery.
    One comment supported FDA's reclassification proposal but requested 
that the Agency clarify the population covered and the conditions 
included in the reclassification. According to the commenter, it seemed 
that the membrane lung device could be used for long-term support in 
neonates and infants only when imminent death is threatened by 
cardiopulmonary failure, but for the remaining population (e.g., 
pediatric and adult patients), the membrane lung could be used for 
long-term support only when cardiopulmonary failure results in the 
inability to separate from cardiopulmonary bypass following cardiac 
surgery. With respect to the conditions covered, the commenter sought 
clarification as to whether the reclassification was limited only to 
cardiopulmonary conditions or to cardiac failure as well. FDA is 
clarifying the intended uses covered by the reclassification in this 
final order. Specifically, after considering the input from the 
September 12, 2013, and May 7, 2014, classification panel meetings, 
comments on the proposed order and all other available information, FDA 
has determined that the reclassification applies to ECMO as a system of 
devices and accessories that provide extracorporeal circulation and 
physiologic gas exchange of blood in patients with acute respiratory 
failure or acute cardiopulmonary failure where other available 
treatment options have failed, and continued clinical deterioration is 
expected or the risk of death is imminent. This revised scope better 
reflects use of ECMO as a tool that provides extracorporeal circulation 
and physiologic gas exchange of blood and more accurately reflects the 
function of the device. FDA has not cleared any ECMO devices that are 
indicated for specific patient populations or conditions. As such, FDA 
believes that the intended uses included in this final order should 
remain broad, rather than specify patient populations or conditions to 
be treated, to reflect use of ECMO as a tool.
    Another comment disagreed with FDA's intent to reclassify membrane 
lung devices for long-term pulmonary support, stating that ``ECMO 
devices must remain categorized as class III devices for all 
indications because they are life-sustaining devices for which clinical 
trials are necessary to provide reasonable assurance of safety and 
effectiveness.'' FDA disagrees with this comment. According to section 
513(a)(1)(C) of the FD&C Act, a class III device is defined as a device 
which: (1) Cannot be classified as a class I device because 
insufficient information exists to determine that the application of 
general controls are sufficient to provide reasonable assurance of the 
safety and effectiveness of the device; and (2) cannot be classified as 
a class II device because insufficient information exists to determine 
that the special controls would provide reasonable assurance of its 
safety and effectiveness; and (3) is purported or represented to be for 
a use in supporting or sustaining human life or for a use which is of 
substantial importance in preventing impairment of human health; or (4) 
presents a potential unreasonable risk of illness or injury.
    Although FDA considers membrane lung devices for long-term 
pulmonary support to be life-supporting, a viewpoint that was supported 
by the panel members at the September 12, 2013 (2013 Panel), and May 7, 
2014 (2014 Panel), device classification panel meetings, FDA believes 
that the available information supports FDA's determination that 
special controls, in addition to general controls, would be sufficient 
to provide a reasonable assurance of safety and effectiveness. Further, 
the 2013 and 2014 Panels largely supported reclassification of ECMO for 
use in patients with acute respiratory failure or acute cardiopulmonary 
failure as noted in section IV of this order. As mentioned previously 
and discussed further in section IV, ECMO is a tool which provides 
extracorporeal circulation and physiologic gas exchange of blood. The 
special controls identified in this final order, including clinical 
performance data, ensure that the device can function as intended to 
provide extracorporeal circulation and physiologic gas exchange of 
blood for the intended duration of device use. The Agency believes that 
the risks of ECMO devices are sufficiently understood based on valid 
scientific evidence and that the risks of ECMO devices can be mitigated 
with the special controls identified in this final order. The special 
controls mitigate the risks to health identified for the device as 
outlined in section IV, table 1. Therefore, FDA does not agree that 
membrane lung devices for long-term pulmonary support for use in 
patients with acute respiratory failure or acute cardiopulmonary 
failure should remain a class III device.
    The commenter also expressed concern that the reclassification of 
these devices would mean that companies manufacturing new versions of 
the device would not be required to show that their products are safe 
and effective. The commenter suggests that classification to class II 
(special controls) precludes FDA from requesting clinical data for 
these devices. FDA disagrees with this comment. FDA believes that the 
identified special controls provide a reasonable assurance of safety 
and effectiveness for membrane lung devices for long-term pulmonary 
support for use in patients with acute respiratory failure or acute 
cardiopulmonary failure, where other available treatment options have 
failed, and continued clinical deterioration is expected or the risk of 
death is imminent. FDA has determined that by complying with the 
identified special controls, the currently legally marketed devices 
within this classification regulation will be reasonably safe and 
effective when used for acute respiratory failure or acute 
cardiopulmonary failure. Future devices claiming substantial 
equivalence to an available predicate(s) must demonstrate that they are 
substantially equivalent, as defined under section 513(i) of the FD&C 
Act, to the predicate device and comply with all applicable FDA 
regulations and with the special

[[Page 7449]]

controls in order to be classified into class II. Classification to 
class II (special controls) does not preclude FDA from requesting 
clinical data for these devices. In some cases, clinical data may be 
needed to comply with the special controls and demonstrate substantial 
equivalence to an available predicate. For example, special control 
Sec.  870.4100(b)(v) regarding in vivo evaluation of the device could 
include clinical trial data, clinical information from the literature, 
and/or animal study data.
    The commenter further expressed concern that reclassification for 
some indications will reduce the incentive to undertake future studies 
for untested indications due to the availability of the devices for 
``off-label'' use. FDA notes in response to this comment that, 
generally, FDA regulates the use of a device as indicated by the party 
offering the device for interstate commerce.
    The commenter also sought assurance from FDA that membrane lung 
devices for long-term pulmonary support for indications not identified 
in the proposed order would remain in class III and therefore require 
the submission of a PMA. FDA notes that by identifying the intended 
uses covered by the revised classification regulation, uses that fall 
outside the definition would not be subject to the order but rather 
would be classified under section 513 of the FD&C Act.

IV. Deliberations of the Panels and FDA Consideration of Panel Input

    As required by section 513(e)(1) of the FD&C Act, FDA convened a 
meeting of the Circulatory System Devices Panel to consider the 
existing valid scientific evidence to support reclassification to class 
II of membrane lung devices for long-term pulmonary support. One 
meeting was held on September 12, 2013 (2013 Panel), regarding 
pediatric uses for ECMO and another meeting was held on May 7, 2014 
(2014 Panel), regarding adult uses for ECMO (Refs. 1 and 2).
    On September 12, 2013, FDA presented the risks associated with use 
of the membrane lung device for long-term pulmonary support. The 2013 
Panel mostly agreed that the risks to health were adequately captured 
as presented by FDA. Several 2013 Panel members discussed whether the 
list of risks to health should also include information on renal 
dysfunction, neurologic injury, disseminated intravascular coagulation, 
transfusion issues, and inflammatory responses. FDA explained that such 
effects are more appropriately characterized not as risks to health but 
rather as adverse events that may result from the risks to health. The 
2013 Panel understood this distinction but requested that FDA consider 
expanding the definition of adverse tissue reaction to include 
inflammatory response. FDA considered the 2013 Panel's input when 
updating the risks to health for the 2014 Panel and this final order.
    The 2013 Panel agreed that the available scientific evidence 
supported the safety and effectiveness for ECMO and its accessories for 
conditions where the subject is at threat of imminent death caused by 
acute reversible respiratory failure (e.g., meconium aspiration, 
congenital diaphragmatic hernia, pulmonary hypertension) in neonates 
and infants, or where acute cardiopulmonary failure results in the 
inability to separate from cardiopulmonary bypass following cardiac 
surgery in all pediatric patients.
    The 2013 Panel also agreed that the probable benefits to health 
from use of the extracorporeal circuit and its accessories for long-
term pulmonary and cardiopulmonary support for these uses outweigh the 
probable risks. As noted previously, FDA has further considered all 
available information and has determined that the risks to health 
identified for ECMO are the same across neonatal, infant, pediatric, 
and adult populations. This is consistent with input from the 2013 and 
2014 Panels, which found that the risks to health for the pediatric and 
adult populations do not differ. Further, FDA believes that the 
available safety and effectiveness information supports use of ECMO as 
a tool to provide extracorporeal circulation and physiologic gas 
exchange of blood in patients with acute respiratory failure or acute 
cardiopulmonary failure, where other available treatment options have 
failed, and continued clinical deterioration is expected or the risk of 
death is imminent. FDA is providing greater clarity in this final order 
by simplifying the identification of ECMO devices in the classification 
regulation to better reflect what an ECMO circuit performs, not specify 
patient populations or conditions to be treated. Specific indications 
for use for ECMO, including specific patient populations and/or 
conditions, are further discussed in this document.
    In general, the 2013 Panel believed the special controls in the 
proposed order would mitigate the identified risks to health and 
provide reasonable assurance of safety and effectiveness of the 
extracorporeal circuit and its accessories. However, some 2013 Panel 
members recommended that compatibility of the various circuit 
accessories be evaluated to ensure that the circuit accessories can 
function together as intended. FDA believes that the special controls 
will be able to address the issue of circuit accessories' 
compatibility. Specifically, the following special controls from the 
classification regulation address this concern: (1) The design 
characteristics of the device must ensure that the geometry and design 
parameters are consistent with the intended use; (2) non-clinical 
performance evaluation of the device must demonstrate substantial 
equivalence for performance characteristics on the bench, mechanical 
integrity, electromagnetic compatibility(where applicable), software, 
durability, and reliability; and (3) labeling must include a detailed 
summary of the non-clinical and clinical evaluations pertinent to use 
of the device and adequate instructions with respect to 
anticoagulation, circuit setup, performance characteristics with 
respect to compatibility with other circuit accessories, and 
maintenance during a procedure.
    The 2013 Panel unanimously agreed that the membrane lung device for 
long-term pulmonary support is life-supporting. The 2013 Panel further 
stated that the available scientific evidence and the proposed special 
controls, in conjunction with general controls, supported the 
reclassification to class II of membrane lung devices for long-term 
pulmonary/cardiopulmonary support in pediatric patients. The 2013 Panel 
expressed concern about not having had the opportunity to review data 
regarding use of the device in adults, given that use of ECMO in adults 
had increased significantly over the years. The 2013 Panel recommended 
that FDA convene another meeting to review the available literature 
regarding use of the membrane lung device for long-term pulmonary 
support in adults before finalizing the proposed reclassification.
    On May 7, 2014, FDA convened the 2014 Panel to discuss the 
classification of the membrane lung for long-term support, specifically 
for adult pulmonary and cardiopulmonary indications. For both pulmonary 
and cardiopulmonary intended uses, the 2014 Panel believed that the 
list of risks to health presented by FDA were comprehensive and 
adequately captured. Of note, in response to the 2013 Panel's 
recommendation regarding risks to health, FDA expanded the definition 
of adverse tissue reaction to include inflammatory response.
    The majority of the 2014 Panel believed that the available 
scientific evidence is adequate to support a

[[Page 7450]]

reasonable assurance of safety and effectiveness of the extracorporeal 
circuit and its accessories for long-term pulmonary support in adults, 
but recommended that FDA modify the intended use from ``pulmonary 
support'' to ``acute, hypoxic, reversible respiratory failure.'' FDA 
agrees with the 2014 Panel that ``respiratory failure'' is a more 
accurate reflection of the use of ECMO as a tool to provide 
extracorporeal circulation and physiologic gas exchange of blood in 
patients rather than ``pulmonary support.'' FDA has considered this 
input from the panel and has determined that acute respiratory failure 
is the appropriate intended use from a clinical and regulatory 
perspective to reflect such use. This change is reflected in the 
classification regulation. The Panel also agreed that the available 
scientific evidence is adequate to support a reasonable assurance of 
safety and effectiveness of the device for long-term cardiopulmonary 
support in adults suffering from ``cardiopulmonary failure due to acute 
catastrophic cardiogenic shock.'' FDA agrees with the 2014 Panel that 
``acute cardiopulmonary failure'' is a more accurate reflection of the 
use of ECMO as a tool to provide extracorporeal circulation and 
physiologic gas exchange of blood in patients rather than 
``cardiopulmonary support.'' FDA has considered this input from the 
panel and has determined that acute cardiopulmonary failure is the 
appropriate intended use from a clinical and regulatory perspective to 
reflect such use. This change is reflected in the classification 
regulation. For both pulmonary and cardiopulmonary support in adults, 
the 2014 Panel agreed that the probable benefits to health from use of 
the device outweigh the probable risks to health where other available 
treatment options have failed, and continued clinical deterioration is 
expected or the risk of death is imminent.
    The 2014 Panel agreed that FDA's list of special controls were 
appropriate and comprehensive. The 2014 Panel further agreed that the 
special controls would mitigate the identified risks to health and 
provide reasonable assurance of safety and effectiveness for the device 
when used to provide long-term support in adults with acute respiratory 
failure or cardiopulmonary failure.
    For both acute respiratory and acute cardiopulmonary indications in 
adults, the 2014 Panel unanimously agreed that the membrane lung device 
for long-term support is life-supporting. The 2014 Panel further 
believes that the available scientific evidence and the proposed 
special controls support the reclassification to class II of membrane 
lung devices for long-term support in adults with acute respiratory 
failure or acute cardiopulmonary failure.
    After considering input from both the 2013 and 2014 Panels, FDA 
believes that the risks to health identified can be mitigated by the 
special controls as outlined in Table 1.

     Table 1--Health Risks and Mitigation Measures for ECMO Devices
------------------------------------------------------------------------
            Identified risk                    Mitigation measures
------------------------------------------------------------------------
Thrombocytopenia.......................  Technological characteristics;
                                          Non-clinical performance
                                          evaluation; In vivo
                                          evaluation; Labeling.
Hemolysis..............................  Technological characteristics;
                                          Biocompatibility testing; Non-
                                          clinical performance
                                          evaluation; Labeling.
Adverse tissue reaction (including       Biocompatibility testing;
 inflammatory response).                  Labeling.
Inadequate gas exchange................  Non-clinical performance
                                          evaluation; In vivo
                                          evaluation; Labeling.
Gas embolism...........................  Non-clinical performance
                                          evaluation; In vivo
                                          evaluation; Labeling.
Mechanical failure.....................  Technological characteristics;
                                          Non-clinical performance
                                          evaluation; Labeling.
Hemorrhage.............................  In vivo evaluation; Labeling.
Hemodilution...........................  Non-clinical performance
                                          evaluation; In vivo
                                          evaluation; Labeling.
Thrombosis/thromboembolism.............  Non-clinical performance
                                          evaluation; In vivo
                                          evaluation; Labeling.
Infection..............................  Sterility; Shelf life testing.
Mechanical injury to access vessels....  Non-clinical performance
                                          evaluation; In vivo
                                          evaluation; Labeling.
------------------------------------------------------------------------

    At both the 2013 Panel and 2014 Panel meetings, FDA provided a 
summary of information from the clinical literature regarding specific 
patient populations and conditions to be treated using ECMO (Refs.1 and 
2). Of note, FDA has not cleared any ECMO devices that are indicated 
for specific patient populations or conditions. As such, FDA believes 
that the intended uses included in this final order should remain broad 
to reflect use of ECMO as a tool to provide extracorporeal circulation 
and physiologic gas exchange of blood in patients with acute 
respiratory failure or acute cardiopulmonary failure, where other 
available treatment options have failed, and continued clinical 
deterioration is expected or the risk of death is imminent. However, 
FDA believes that there are specific indications (patient populations 
and/or conditions) that would fall within this broader intended use and 
therefore be within the scope of this regulation as outlined in this 
document.
    Specifically, FDA has reviewed the clinical literature and has 
determined that there are sufficient data available to support labeling 
ECMO devices for the following specific indications (patient 
populations and/or conditions) at this time: Meconium aspiration in 
neonates and infants; congenital diaphragmatic hernia in neonates and 
infants; pulmonary hypertension in neonates and infants; failure to 
wean from cardiopulmonary bypass following cardiac surgery in pediatric 
and adult patients; and ECMO-assisted cardiopulmonary resuscitation in 
adults.
    FDA has further evaluated data from the clinical literature and 
determined that the data available do not support labeling ECMO devices 
for certain specific indications (patient populations and/or 
conditions) at this time without additional clinical data from sponsors 
to support such uses, consistent with the identified special controls, 
including but not limited to: High risk percutaneous coronary 
intervention; trauma resuscitation; failed heart or lung transplant; 
acute respiratory distress syndrome; and/or acute decompensation of 
chronic obstructive pulmonary disease.
    For ECMO devices that have not been legally marketed prior to the 
effective date of the final order, or models (if any) that have been 
legally marketed but are required to submit a new 510(k) under Sec.  
807.81(a)(3) because the device is

[[Page 7451]]

about to be significantly changed or modified, manufacturers must 
obtain 510(k) clearance, among other relevant requirements, and 
demonstrate compliance with the special controls included in the final 
order, before marketing the new or changed device.

V. The Final Order

    Under section 513(e) of the FD&C Act, FDA is adopting its findings 
as published in the preamble to the proposed order (78 FR 1158) with 
modifications as discussed in section IV of this final order. FDA is 
issuing this final order to reclassify the membrane lung devices for 
long-term pulmonary support from class III to class II for use in 
patients with acute respiratory failure or acute cardiopulmonary 
failure, where other available treatment options have failed and 
continued clinical deterioration is expected or the risk of death is 
imminent, and to establish special controls. FDA is removing the 
regulation from 21 CFR part 868 (Anesthesiology Devices) and adding it 
to 21 CFR part 870 (Cardiovascular Devices) to better align this device 
type (and the review thereof) with other similar types of 
cardiovascular devices. The title and identification of Sec.  870.4100 
(21 CFR 870.4100) reflects the Agency's intent to regulate ECMO and the 
accessories used in ECMO under the same set of regulatory controls. 
However, an individual device or accessory in an ECMO circuit may 
already have its own classification regulation when intended for short-
term use (<=6 hours) and, in those instances, such device or accessory 
is subject to the preexisting regulation(s).
    Following the effective date of this final order, firms marketing 
membrane lung devices for long-term pulmonary support for use in 
patients with acute respiratory failure or acute cardiopulmonary 
failure, where other available treatment options have failed and 
continued clinical deterioration is expected or the risk of death is 
imminent, must comply with the particular mitigation measures set forth 
in the special controls.
    Section 510(m) of the FD&C Act provides that FDA may exempt a class 
II device from the premarket notification requirements under section 
510(k) of the FD&C Act if FDA determines that premarket notification is 
not necessary to provide reasonable assurance of the safety and 
effectiveness of the devices. FDA has determined that premarket 
notification is necessary to provide reasonable assurance of safety and 
effectiveness of membrane lung devices for long-term pulmonary support 
for use in patients with acute respiratory failure or acute 
cardiopulmonary failure, where other available treatment options have 
failed, and continued clinical deterioration is expected or the risk of 
death is imminent, and, therefore, this device type is not exempt from 
premarket notification requirements.

VI. 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.

VII. Paperwork Reduction Act of 1995

    This final order refers to previously approved collections of 
information found in 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 21 CFR part 812 have been approved under 
OMB control number 0910-0078; the collections of information in 21 CFR 
part 807, subpart E, have been approved under OMB control number 0910-
0120; the collections of information in 21 CFR part 814, subpart B, 
have been approved under OMB control number 0910-0231; and the 
collections of information under 21 CFR part 801 have been approved 
under OMB control number 0910-0485.

VIII. Codification of Orders

    Prior to the amendments by FDASIA, section 513(e) of the FD&C Act 
provided for FDA to issue regulations to reclassify devices. Although 
section 513(e) of the FD&C Act as amended requires FDA to issue final 
orders rather than regulations, FDASIA also provides for FDA to revoke 
previously issued regulations by order. FDA will continue to codify 
classifications and reclassifications in the Code of Federal 
Regulations (CFR). Changes resulting from final orders will appear in 
the CFR as changes to codified classification determinations or as 
newly codified orders. Therefore, under section 513(e)(1)(A)(i) of the 
FD&C Act, as amended by FDASIA, in this final order, we are revoking 
the requirements in 21 CFR 868.5610 related to the classification of 
membrane lung for long-term pulmonary support as class III devices and 
codifying under Sec.  870.4100 the reclassification of membrane lung 
for long-term pulmonary support for use in patients with acute 
respiratory failure or acute cardiopulmonary failure, where other 
available treatment options have failed, and continued clinical 
deterioration is expected or the risk of death is imminent into class 
II (special controls).

IX. References

    The following references are on display in the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, and are available for viewing by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday; 
they are also available electronically at http://www.regulations.gov. 
FDA has verified the Web site addresses, as of the date this document 
publishes in the Federal Register, but Web sites are subject to change 
over time.

1. The panel transcript and other meeting materials for the 
September 12, 2013, Circulatory System Devices Panel are available 
on FDA's Web site at http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm342357.htm.
2. The panel transcript and other meeting materials for the May 7, 
2014, Circulatory System Devices Panel are available on FDA's Web 
site at. http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm395638.htm

List of Subjects in 21 CFR Parts 868 and 870

    Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR parts 
868 and 870 are amended as follows:

PART 868--ANESTHESIOLOGY DEVICES

0
1. The authority citation for 21 CFR part 868 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.


Sec.  868.5610  [Removed]

0
2. Remove Sec.  868.5610.

PART 870--CARDIOVASCULAR DEVICES

0
1. The authority citation for 21 CFR part 870 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.


0
2. Add Sec.  870.4100 to subpart E to read as follows:

[[Page 7452]]

Sec.  870.4100  Extracorporeal circuit and accessories for long-term 
respiratory/cardiopulmonary failure.

    (a) Identification. An extracorporeal circuit and accessories for 
long-term respiratory/cardiopulmonary support (>6 hours) is a system of 
devices and accessories that provides assisted extracorporeal 
circulation and physiologic gas exchange of the patient's blood in 
patients with acute respiratory failure or acute cardiopulmonary 
failure, where other available treatment options have failed, and 
continued clinical deterioration is expected or the risk of death is 
imminent. The main devices and accessories of the system include, but 
are not limited to, the console (hardware), software, and disposables, 
including, but not limited to, an oxygenator, blood pump, heat 
exchanger, cannulae, tubing, filters, and other accessories (e.g., 
monitors, detectors, sensors, connectors).
    (b) Classification--Class II (special controls). The special 
controls for this device are:
    (1) The technological characteristics of the device must ensure 
that the geometry and design parameters are consistent with the 
intended use, and that the devices and accessories in the circuit are 
compatible;
    (2) The devices and accessories in the circuit must be demonstrated 
to be biocompatible;
    (3) Sterility and shelf-life testing must demonstrate the sterility 
of any patient-contacting devices and accessories in the circuit and 
the shelf life of these devices and accessories;
    (4) Non-clinical performance evaluation of the devices and 
accessories in the circuit must demonstrate substantial equivalence of 
the performance characteristics on the bench, mechanical integrity, 
electromagnetic compatibility (where applicable), software, durability, 
and reliability;
    (5) In vivo evaluation of the devices and accessories in the 
circuit must demonstrate their performance over the intended duration 
of use, including a detailed summary of the clinical evaluation 
pertinent to the use of the devices and accessories to demonstrate 
their effectiveness if a specific indication (patient population and/or 
condition) is identified; and
    (6) Labeling must include a detailed summary of the non-clinical 
and in vivo evaluations pertinent to use of the devices and accessories 
in the circuit and adequate instructions with respect to 
anticoagulation, circuit setup, performance characteristics with 
respect to compatibility among different devices and accessories in the 
circuit, and maintenance during a procedure.

    Dated: February 8, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-02876 Filed 2-11-16; 8:45 am]
 BILLING CODE 4164-01-P