Cardiovascular Devices; Reclassification of Intra-Aortic Balloon and Control Systems (IABP) for Acute Coronary Syndrome, Cardiac and Non-Cardiac Surgery, or Complications of Heart Failure; Effective Date of Requirement for Premarket Approval for IABP for Other Specific Intended Uses
Federal Register, Volume 78 Issue 118 (Wednesday, June 19, 2013)
Federal Register Volume 78, Number 118 (Wednesday, June 19, 2013)
Proposed Rules
Pages 36702-36711
From the Federal Register Online via the Government Printing Office www.gpo.gov
FR Doc No: 2013-14553
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 870
Docket No. FDA-2013-N-0581
Cardiovascular Devices; Reclassification of Intra-Aortic Balloon and Control Systems (IABP) for Acute Coronary Syndrome, Cardiac and Non-Cardiac Surgery, or Complications of Heart Failure; Effective Date of Requirement for Premarket Approval for IABP for Other Specific Intended Uses
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed order.
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SUMMARY: The Food and Drug Administration (FDA) is issuing a proposed administrative order to reclassify intra-aortic balloon and
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control system devices when indicated for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure, a preamendments class III device, into class II (special controls) based on new information. FDA is also proposing to require the filing of a premarket approval application (PMA) or a notice of completion of a product development protocol (PDP) for intra-aortic balloon and control systems when indicated for septic shock or pulsatile flow generation. The Agency is also summarizing its proposed findings regarding the degree of risk of illness or injury designed to be eliminated or reduced by requiring the devices to meet the statute's approval requirements when indicated for septic shock or pulsatile flow generation. In addition, FDA is announcing the opportunity for interested persons to request that the Agency change the classification of any of the devices mentioned in this document based on new information. This action implements certain statutory requirements.
DATES: Submit either electronic or written comments by September 17, 2013. FDA intends that, if a final order based on this proposed order is issued, anyone who wishes to continue to market intra-aortic balloon and control system devices indicated for septic shock or pulsatile flow generation will need to file a PMA or a notice of completion of a PDP within 90 days of the effective date of the final order. See section XVII of this document for the proposed effective date of any final order based on this proposed order.
ADDRESSES: You may submit comments, identified by Docket No. FDA-2013-
N-0581, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov. Follow the instructions for submitting comments.
Written Submissions
Submit written submissions in the following ways:
Mail/Hand delivery/Courier (for paper or CD-ROM submissions): Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
Instructions: All submissions received must include the Agency name and Docket No. FDA-2013-N-0581 for this rulemaking. All comments received may be posted without change to http://www.regulations.gov, including any personal information provided. For additional information on submitting comments, see the ``Comments'' heading of the SUPPLEMENTARY INFORMATION section.
Docket: For access to the docket to read background documents or comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ``Search'' box and follow the prompts and/or go to the Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Angela Krueger, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 1666, Silver Spring, MD 20993, 301-796-6380, angela.krueger@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
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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), establish 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 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 (510(k)) procedures to such a preamendments device or to a device within that type may be marketed without submission of a 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.
Although, under the FD&C Act, the manufacturer of class III preamendments device may respond to the call for PMAs by filing a PMA or a notice of completion of a PDP, in practice, the option of filing a notice of completion of a PDP has not been used. For simplicity, although corresponding requirements for PDPs remain available to manufacturers in response to a final order under section 515(b) of the FD&C Act, this document will refer only to the requirement for the filing and receiving approval of a PMA.
On July 9, 2012, FDASIA was enacted. Section 608(a) of FDASIA amended section 513(e) of the FD&C Act, changing the process for reclassifying a device from rulemaking to an administrative order. Section 608(b) of FDASIA amended section 515(b) of the FD&C Act changing the process for requiring premarket approval for a preamendments class III device from rulemaking to an administrative order.
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Reclassification
FDA is publishing this document to propose the reclassification of intra-aortic balloon and control system devices when indicated for acute coronary syndrome, cardiac and non-
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cardiac surgery, or complications of heart failure from class III to class II.
Section 513(e) of the FD&C Act governs reclassification of classified preamendments devices. This section provides that FDA may, by administrative order, reclassify a device based upon ``new information.'' FDA can initiate a reclassification under section 513(e) 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) must be ``valid scientific evidence,'' as defined in section 513(a)(3) of the FD&C Act and Sec. 860.7(c)(2) (21 CFR 860.7(c)(2)). (See, e.g., General Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens Association v. FDA, 766 F.2d 592 (D.C. Cir.), cert. denied, 474 U.S. 1062 (1985).)
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 520(h)(4) of the FD&C Act, added by FDAMA, provides that FDA may use, for reclassification of a device, certain information in a PMA 6 years after the application has been approved. This can include information from clinical and preclinical tests or studies that demonstrate the safety or effectiveness of the device but does not include descriptions of methods of manufacture or product composition and other trade secrets.
Section 513(e)(1) of the FD&C Act sets forth the process for issuing a final 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. FDA has held a meeting of a device classification panel described in section 513(b) of the FD&C Act with respect to intra-aortic balloon and control system devices, and therefore, has met this requirement under section 515(b)(1) of the FD&C Act.
FDAMA added section 510(m) to the FD&C Act, which provides that a class II device may be exempted from the premarket notification requirements under section 510(k) of the FD&C Act, if the Agency determines that premarket notification is not necessary to assure the safety and effectiveness of the device.
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Requirement for Premarket Approval Application
FDA is proposing to require PMAs for intra-aortic balloon and control system devices when indicated for septic shock or pulsatile flow generation.
Section 515(b)(1) of the FD&C Act sets forth the process for issuing a final order. Specifically, prior to the issuance of a final order requiring premarket approval for a preamendments class III 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 from all affected stakeholders, including patients, payers, and providers. FDA has held a meeting of a device classification panel described in section 513(b) of the FD&C Act with respect to intra-
aortic balloon and control system devices, and therefore, has met this requirement under section 515(b)(1) of the FD&C Act.
Section 515(b)(2) of the FD&C Act provides that a proposed order to require premarket approval shall contain: (1) The proposed order, (2) the proposed findings with respect to the degree of risk of illness or injury designed to be eliminated or reduced by requiring the device to have an approved PMA or a declared completed PDP and the benefit to the public from the use of the device, (3) an opportunity for the submission of comments on the proposed order and the proposed findings, and (4) an opportunity to request a change in the classification of the device based on new information relevant to the classification of the device.
Section 515(b)(3) of the FD&C Act provides that FDA shall, after the close of the comment period on the proposed order, consideration of any comments received, and a meeting of a device classification panel described in section 513(b) of the FD&C Act, issue a final order to require premarket approval or publish a document terminating the proceeding together with the reasons for such termination. If FDA terminates the proceeding, FDA is required to initiate reclassification of the device under section 513(e) of the FD&C Act, unless the reason for termination is that the device is a banned device under section 516 of the FD&C Act (21 U.S.C. 360f).
A preamendments class III device may be commercially distributed without a PMA until 90 days after FDA issues a final order (a final rule issued under section 515(b) of the FD&C Act prior to the enactment of FDASIA is considered to be a final order for purposes of section 501(f) of the FD&C Act (21 U.S.C. 351(f))) requiring premarket approval for the device, or 30 months after final classification of the device under section 513 of the FD&C Act, whichever is later. For intra-aortic balloon and control system devices, the preamendments class III devices that are the subject of this proposal, the later of these two time periods is the 90-day period. Since these devices were classified in 1980, the 30-month period has expired (45 FR 7939; February 5, 1980). Therefore, if the proposal to require premarket approval for intra-
aortic balloon and control system devices indicated for septic shock or pulsatile flow generation is finalized, section 501(f)(2)(B) of the FD&C Act requires that a PMA for such device be filed within 90 days of the date of issuance of the final order. If a PMA is not filed for such device within 90 days after the issuance of a final order, the device would be deemed adulterated under section 501(f) of the FD&C Act.
Also, a preamendments device subject to the order process under section 515(b) of the FD&C Act is not required to have an approved investigational device exemption (IDE) (see part 812 (21 CFR part 812)) contemporaneous with its interstate distribution until the date identified by FDA in the final order requiring the filing of a PMA for the device. At that time, an IDE is required only if a PMA has not been filed. If the manufacturer, importer, or other sponsor of the device submits an IDE application and FDA approves it, the device may be distributed for investigational use. If a PMA is not filed by the later of the two dates, and the
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device is not distributed for investigational use under an IDE, the device is deemed to be adulterated within the meaning of section 501(f)(1)(A) of the FD&C Act, and subject to seizure and condemnation under section 304 of the FD&C Act (21 U.S.C. 334) if its distribution continues. Other enforcement actions include, but are not limited to, the following: Shipment of devices in interstate commerce will be subject to injunction under section 302 of the FD&C Act (21 U.S.C. 332), and the individuals responsible for such shipment will be subject to prosecution under section 303 of the FD&C Act (21 U.S.C. 333). In the past, FDA has requested that manufacturers take action to prevent the further use of devices for which no PMA has been filed and may determine that such a request is appropriate for the class III devices that are the subject of this proposed order, if finalized.
In accordance with section 515(b) of the FD&C Act, interested persons are being offered the opportunity to request reclassification of intra-aortic balloon and control system devices indicated for septic shock or pulsatile flow generation.
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Regulatory History of the Device
In the preamble to the proposed rule (44 FR 13369; March 9, 1979), the Cardiovascular Device Classification Panel (the 1979 Panel) recommended that intra-aortic balloon and control system devices be classified into class III because the device is life-supporting, and there was insufficient medical and scientific information to establish a standard to assure the safety and effectiveness of the device. The 1979 Panel noted that controversy exists as to whether the device is beneficial in many situations in which it is used and that it is difficult to use the device safely and effectively. The 1979 Panel further noted that accurate and precise labeling and directions for use are especially critical and voiced concern that the various components of the device would not function properly if its modular components were poorly matched. The 1979 Panel indicated that the balloon of the device is used within the main artery of the body and because this portion of the device is in contact with internal tissues and blood, the materials used with it require special controls, and because the device is electrically powered and portions of the device may be in direct contact with the heart, the electrical characteristics of the device, e.g., electrical leakage current, need to meet certain requirements. Additionally, if the design of the device is inadequate for accurate and precise blood pumping, a resulting failure could lead to death. Consequently, the 1979 Panel believed that premarket approval was necessary to assure the safety and effectiveness of the device. In 1980, FDA classified intra-aortic balloon and control system devices into class III after receiving no comments on the proposed rule (45 FR 7939; February 5, 1980).
In 1987, FDA published a clarification by inserting language in the codified language stating that no effective date had been established for the requirement for premarket approval for intra-aortic balloon and control system devices (52 FR 17736; May 11, 1987).
In 2009, FDA published an order for the submission of information on intra-aortic balloon and control system devices by August 7, 2009 (74 FR 16214; April 9, 2009). FDA received four responses to that order from device manufacturers. One manufacturer stated in their response that they were ``not aware of adequate and valid scientific information that would support reclassification of the device to Class I or II.'' The other three manufacturers recommended that intra-aortic balloon and control system devices be reclassified to class II. The manufacturers stated that safety and effectiveness of these devices may be assured based on data available in the clinical literature; preclinical and clinical testing; 40 or more years of knowledge and information regarding the clinical use of the devices; and the overall number of marketed devices.
As explained further in sections VII and XI of this document, a meeting of the Circulatory System Devices Panel (the 2012 Panel) took place December 5, 2012, to discuss whether intra-aortic balloon and control system devices should be reclassified or remain in class III. The 2012 Panel recommended that intra-aortic balloon and control system devices be reclassified to class II with special controls when indicated for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure based on available evidence that supports the safety and effectiveness of the devices for these uses and the ability of special controls to mitigate identified risks to health. The 2012 Panel also recommended that intra-aortic balloon and control system devices indicated for septic shock or pulsatile flow generation remain in class III because the devices are life-supporting and there was insufficient information to establish special controls for these uses. FDA is not aware of new information that would provide a basis for a different recommendation or findings.
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Device Description
An intra-aortic balloon and control system, also known as an intra-
aortic balloon pump (IABP), consists of a balloon, which inflates and deflates in synchronization with the cardiac cycle, and console, which provides the pneumatic flow of helium to the balloon so that it can inflate and deflate. The balloon is usually manufactured from polyurethane. It is inserted through the femoral artery and resides in the descending aorta. Conventional timing sets inflation of the balloon to occur at the onset of diastole or the aortic valve closure timepoint. During diastole, the balloon will inflate, increasing blood flow to the coronary arteries, therefore increasing myocardial oxygen supply. The balloon remains inflated throughout the diastolic phase, maintaining the increased pressure in the aorta. The deflation of the balloon takes place at the onset of systole during the isovolumetric contraction or very early in the systolic ejection phase. This deflation will cause a decrease in pressure in the aorta and this decrease in pressure assists the left ventricle by reducing the pressure that needs to be generated to achieve ejection through the aortic valve. As the balloon deflates during systole, it increases blood flow to the systemic circulation by reducing afterload and also decreases the oxygen demand of the myocardium.
The console includes software that controls the inflation and deflation of the balloon based upon the patient's electrocardiogram or arterial pressure waveform. The console also controls the amount of helium that is transferred from the internal helium cylinder to the balloon. Most balloons come in sizes of 30cc, 40cc, and 50cc with a catheter diameter of 7.5Fr or 8Fr.
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Proposed Reclassification
FDA is proposing that intra-aortic balloon and control system devices when indicated for acute coronary syndrome, cardiac and non-
cardiac surgery, or complications of heart failure be reclassified from class III to class II. In this proposed order, the Agency has identified special controls under section 513(a)(1)(B) of the FD&C Act that, together with general controls applicable to the devices, would provide reasonable assurance of their safety and effectiveness. Absent the special controls identified in this proposed order, general controls applicable to the device are insufficient to provide reasonable assurance of the safety and effectiveness of the device.
Therefore, in accordance with sections 513(e) and 515(i) of the FD&C
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Act and Sec. 860.130, based on new information with respect to the devices and taking into account the public health benefit of the use of the device and the nature and known incidence of the risk of the device, FDA, on its own initiative, is proposing to reclassify this preamendments class III device into class II when indicated for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure. FDA believes that this new information is sufficient to demonstrate that the proposed special controls can effectively mitigate the risks to health identified in the next section, and that these special controls, together with general controls, will provide a reasonable assurance of safety and effectiveness for intra-aortic balloon and control system devices when indicated for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure.
Section 510(m) of the FD&C Act authorizes the Agency to exempt class II devices from premarket notification (510(k)) submission. FDA has considered intra-aortic balloon and control system devices when indicated for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure in accordance with the reserved criteria set forth in section 513(a) of the FD&C Act and decided that the device requires premarket notification. Therefore, the Agency does not intend to exempt this proposed class II device from premarket notification (510(k)) submission.
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Risks to Health
After considering available information, including the recommendations of the advisory committees (panels) for the classification of these devices, FDA has evaluated the risks to health associated with the use of intra-aortic balloon and control system devices and determined that the following risks to health are associated with its use:
Cardiac arrhythmias or electrical shock: Excessive electrical leakage current can disturb the normal electrophysiology of the heart, leading to the onset of cardiac arrhythmias.
Ineffective cardiac assist (poor augmentation): Failure to sense or synchronize on heartbeat, failure to inflate and deflate at the proper intervals, and/or failure of the balloon to fully unwrap can lead to improper or ineffective pumping of blood.
Thromboembolism: Inadequate blood compatibility of the materials used in this device and/or inadequate surface finish and cleanliness can lead to potentially debilitating or fatal thromboemboli.
Aortic rupture or dissection: Improper sizing or over inflation of the balloon can cause a rupture in the main artery.
Limb ischemia: Improper operation of the device which restricts blood flow to the peripheral vascular tree results in tissue ischemia in the limbs.
Gas embolism: Balloon rupture or a leak in the balloon can cause potentially debilitating or fatal gas emboli to escape into the bloodstream.
Hemolysis: Poor material-blood compatibility or excessive disruption of the normal hemodynamic flow patterns can cause hemolysis.
Infection: Defects in the design or construction of the device preventing adequate sterilization can allow pathogenic organisms to be introduced and may cause an infection in a patient.
Insertion site bleeding: Improper sizing of the cannula can cause trauma to the artery during insertion of the catheter.
Thrombus/large blood clots: Leaks of the membrane (balloon surface) or catheter can result in gaseous embolic injury of organs or cause a large blood clot to form within the balloon membrane requiring surgical removal of the catheter.
Balloon entrapment: A balloon perforation can cause blood to enter the balloon forming a large hardened mass of blood within the balloon. This can cause the balloon to become ``entrapped ``in the femoral/iliac system upon removal. Balloon entrapment is characterized by undue resistance to balloon removal.
Insertion difficulty/inability to insert the catheter: Device sizing, insertion technique and/or patient anatomy, specifically tortuous and/or narrowed femoral arteries, can cause insertion difficulties. As a result, therapy can be delayed and there could be an increased risk of vascular damage and/or bleeding due to forceful insertion.
Vessel occlusion resulting in ischemia, infarction to an organ (including paraplegia) and/or compartment syndrome: Malposition of the balloon can compromise circulation due to large vessel occlusion from catheter migration, resulting in ischemia, infarction to an organ or increased compartment pressures, leading to muscle and nerve damage. Vessel occlusion can also be caused by dislodged atherosclerotic plaque and/or clots.
Thrombocytopenia: Improper inflation of the balloon can cause a drop in platelets.
Stroke: Mechanical disruption of atheroma or thrombus liberation causing embolism; disruption of the cranial circulation by the balloon, including obstruction, dissection or perforation; or complications resulting from the use of anticoagulation, can lead to stroke.
Death: Mechanical failure of the device, vascular complications or bleeding can lead to death.
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Summary of Reasons for Reclassification
If properly manufactured and used as intended, intra-aortic balloon and control system devices can provide a treatment option for patients when indicated for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure, by increasing myocardial oxygen supply, decreasing myocardial oxygen demand, and improving cardiac output. FDA believes that intra-aortic balloon and control system devices indicated for acute coronary syndrome, cardiac and non-
cardiac surgery, or complications of heart failure, should be reclassified from class III to class II because, in light of new information about the effectiveness of these devices, FDA believes that special controls, in addition to general controls, can be established to provide reasonable assurance of the safety and effectiveness of the device, and because general controls themselves are insufficient to provide reasonable assurance of its safety and effectiveness.
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Summary of Data Upon Which the Reclassification Is Based
Since the time of the original 1979 Panel recommendation, sufficient evidence has been developed to support a reclassification of intra-aortic balloon and control system devices to class II with special controls when indicated for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure. FDA has been reviewing these devices for many years and their risks are well known. FDA conducted a comprehensive review of available literature for IABP devices for acute coronary syndrome, cardiac and non-cardiac surgery, and complications of heart failure. FDA's review found 18 cohort studies (9 retrospective and 9 prospective), 6 randomized controlled trials, 3 case-control studies, 2 case series, 4 systematic reviews, and a meta-analysis, which provided consistent evidence of the safety and effectiveness of intra-aortic balloon and control system devices for acute coronary syndrome, cardiac and non-cardiac surgery, and complications of heart failure.
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Collectively these studies support that the overall complication rates for intra-aortic balloon and control systems is low. For example, in the Benchmark Registry (Ref. 1), there were low IABP complication rates, including IABP-related mortality (0.05 percent and 0.07 percent in the United States and European Union, respectively), major limb ischemia (0.09 percent, 0.8 percent) and severe bleeding (0.9 percent, 0.8 percent). This is consistent with other studies of IABP use with large sample sizes. Additionally, in the most recently published trial of IABP use, the IABP SHOCK II trial (Ref. 2), published in October 2012, 600 patients were randomized to IABP (301 patients) or no IABP (299 patients). The IABP group and the control group did not differ significantly with respect to the rates of adverse events, including major bleeding (3.3 percent and 4.4 percent, respectively; P = 0.51), peripheral ischemic complications (4.3 percent and 3.4 percent, P = 0.53), sepsis (15.7 percent and 20.5 percent, P = 0.15), and stroke (0.7 percent and 1.7 percent, P = 0.28). These rates represent recent IABP usage outcomes in a randomized trial of patients with high associated morbidity using modern aggressive interventional approaches to acute myocardial infarction (MI) and cardiogenic shock, which include the use of percutaneous coronary intervention and aggressive anticoagulation. The trial demonstrates low rates of adverse events that can be attributed directly to the IABP itself.
It is important to note that the patients in whom IABP is used have severe comorbidities and underlying illnesses. As a result, overall mortality in these patients is high. Patients recruited for studies on the IABP are of a population segment that is at an inherently greater risk of mortality because of the high-risk procedures they require, and the illnesses that necessitated the procedures. Additionally, there are trends to less balloon-related mortality over time, as balloon catheter sizes have decreased and procedural techniques have improved.
The literature data also supports the effectiveness of IABP for acute coronary syndrome, cardiac and non-cardiac surgery, and complications of heart failure. With respect to acute coronary syndrome, the Benchmark Registry (Ref. 1) demonstrated that the mortality of patients with cardiogenic shock was 30.7 percent, which was low compared to other cardiogenic shock trials, and has been cited as evidence of a benefit from IABP use. Further evaluation of this registry has shown that in U.S. patients, compared to patients outside the United States (OUS), an IABP was placed at earlier stages of the disease. After appropriate adjustment of risk factors, U.S. patients showed decreased mortality (10.8 percent (U.S.) vs. 18 percent (OUS), P 0.8 vs. 12.20.6 days, P 9.6 to 82.34.7 mmHg (P = 0.02), and ejection fraction from 14.76.4 to 21.08.6 (P = 0.014). Improvement of the cardiac index, pulmonary wedge pressure, and end-organ perfusion markers did not reach statistical significance. The authors concluded that IABP support may be successfully and safely used in acute decompensated dilated cardiomyopathy patients as an urgent measure of cardiac support to stabilize the patient and maintain organ perfusion until transplant is available, ventricular assist device is placed, or the patient is weaned from the IABP.
Rosenbaum et al. (Ref. 9) studied 43 patients with end-stage congestive heart failure in whom an IABP was used as a bridge to transplant. Twenty-seven patients had non-ischemic CMP (NICM), and 16 had ischemic CMP (ISCM). Hemodynamics improved in both groups, immediately (15 to 30 minutes) following IABP insertion, with greater improvement (p
