The 510(k) Program: Evaluating
`Substantial Equivalence in Premarket
`Notifications [510(k)]
`Guidance for Industry and Food and Drug
`Administration Staff
`
`
`
`Document issued on: July 28, 2014
`
`The draft of this document issued on December 27, 2011.
`
`This document supersedes FDA’s Guidance on the CDRH Premarket Notification
`Review Program, 510(k) Memorandum K86-3, dated June 30, 1986.
`
`
`
`For questions for the Center for Devices and Radiological Health regarding this document, contact the
`Premarket Notification (510(k)) Section at 301-796-5640.
`
`For questions for the Center for Biologics Evaluation and Research regarding this document, contact the
`Office of Communication, Outreach and Development at 1-800-335-4709 or 240-402-7800.
`
`
`
`
`
`
`U.S. Department of Health and Human Services
`Food and Drug Administration
`Center for Devices and Radiological Health
`Center for Biologics Evaluation and Research
`
`Ex. 2040-0001
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`

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`Contains Nonbinding Recommendations
`
`
`Preface
`
`
`
`
`Public Comment
`
`
`You may submit electronic comments and suggestions at any time for Agency consideration to
`http://www.regulations.gov. Submit written comments to the Division of Dockets Management, Food and
`Drug Administration, 5630 Fishers Lane, Room. 1061, (HFA-305), Rockville, MD, 20852. Identify all
`comments with the docket number FDA-2011-D-0652. Comments may not be acted upon by the Agency
`until the document is next revised or updated.
`
`
`Additional Copies
`
`CDRH
`Additional copies are available from the Internet. You may also send an e-mail request to CDRH-
`Guidance@fda.hhs.gov to receive a copy of the guidance. Please use the document number 1766 to
`identify the guidance you are requesting.
`
`CBER
`Additional copies are available from the Center for Biologics Evaluation and Research (CBER) by written
`request to the address below, by email request to the email address below, by calling the phone number
`below, or from the Internet at the webpage below:
`
`
`
`Center for Biologics Evaluation and Research (CBER),
`Office of Communication, Outreach and Development,
`10903 New Hampshire Ave, Bldg. 71, Room 3128
`Silver Spring, MD 20993, or by calling 1-800-835-4709 or 240-402-7800, by email ocod@fda.hhs.gov, or
`from the Internet at
`http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm.
`
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`Ex. 2040-0002
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`

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`Contains Nonbinding Recommendations
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`Table of Contents
`
`
`I.
`
`Introduction _____________________________________________________________________ 1
`
`II. Background _____________________________________________________________________ 2
`A. The Medical Device Amendments and Device Classification _________________________________ 2
`B. The 510(k) Classification Process ________________________________________________________ 3
`C. Evolution of the 510(k) Program ________________________________________________________ 4
`
`III.
`
`Scope ________________________________________________________________________ 5
`
`The 510(k) Decision-Making Process ______________________________________________ 5
`IV.
`A. The 510(k) Review Standard ___________________________________________________________ 6
`B. The Flowchart ______________________________________________________________________ 10
`C. Predicate Device(s) ___________________________________________________________________ 10
`D.
`Intended Use ________________________________________________________________________ 15
`E. Technological Characteristics __________________________________________________________ 18
`F. Requests for Performance Data ________________________________________________________ 22
`G. The 510(k) Summary _________________________________________________________________ 26
`
`Appendix A. 510(k) Decision-Making Flowchart __________________________________________ 27
`
`Appendix B. The 510(k) Summary Document Requirements ________________________________ 28
`
`Appendix C. Sample of 510(k) Summary Complying with 21 CFR 807.92 ______________________ 33
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`Appendix D. Glossary of Significant Terminology _________________________________________ 39
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`Ex. 2040-0003
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`

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`Contains Nonbinding Recommendations
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`
`The 510(k) Program: Evaluating Substantial
`Equivalence in Premarket Notifications
`[510(k)]
`Guidance for Industry and Food and Drug
`Administration Staff
`
`
`
`
`
`This guidance represents the Food and Drug Administration's (FDA's) current thinking on this
`topic. It does not create or confer any rights for or on any person and does not operate to bind
`FDA or the public. You can use an alternative approach if the approach satisfies the requirements
`of the applicable statutes and regulations. If you want to discuss an alternative approach, contact
`the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate
`FDA staff, call the appropriate number listed on the title page of this guidance.
`
`
`
`I. Introduction
`
`FDA developed this document to provide guidance to industry and FDA staff about current review
`practices for premarket notification (510(k)) submissions. The intent of this guidance is to identify,
`explain, and clarify each of the critical decision points in the decision-making process FDA uses to
`determine substantial equivalence. This guidance is not intended to implement significant policy
`changes to the current 510(k) review process. Rather, the intent of this guidance is to enhance the
`predictability, consistency, and transparency of the 510(k) program by describing in greater detail the
`regulatory framework, policies, and practices underlying FDA’s 510(k) review.
`
`The draft of this guidance document contained sections addressing FDA’s Special and Abbreviated
`510(k) programs. FDA intends to finalize those sections separately. Until FDA issues new final
`recommendations on the Special and Abbreviated 510(k) programs, the recommendations for Special
`and Abbreviated 510(k)s contained in “The New 510(k) Paradigm - Alternate Approaches to
`Demonstrating Substantial Equivalence in Premarket Notifications,” dated March 20, 1998,
`(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm0801
`87.htm) remain in effect.
`
`FDA's guidance documents, including this guidance, do not establish legally enforceable
`responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be
`viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The
`use of the word should in Agency guidances means that something is suggested or recommended, but
`not required.
`
`
`
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`1
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`Ex. 2040-0004
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`Contains Nonbinding Recommendations
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`II. Background
`A. The Medical Device Amendments and Device Classification
`
`The Medical Device Amendments (MDA) (Pub. L. 94-295) to the Federal Food, Drug, and Cosmetic
`(FD&C) Act were enacted on May 28, 1976. The MDA directed FDA to issue regulations that
`classify all devices that were in commercial distribution at that time into one of three regulatory
`control categories: Class I, II, or III, depending upon the degree of regulation necessary to provide
`reasonable assurance of their safety and effectiveness. The class into which a device is placed
`determines the requirements that a medical device manufacturer must meet prior to distributing a
`device in interstate commerce. According to section 513(a)(1) of the FD&C Act (21 U.S.C.
`§ 360c(a)(1)), the three device classes are defined as follows:
`
` Class I: Devices are subject to a comprehensive set of regulatory authorities called general
`controls that are applicable to all classes of devices.1
`
` Class II: Devices for which general controls, by themselves, are insufficient to provide
`reasonable assurance of the safety and effectiveness of the device, and for which there is
`sufficient information to establish special controls to provide such assurance.2
`
` Class III: Devices for which general controls, by themselves, are insufficient and for which
`there is insufficient information to establish special controls to provide reasonable assurance
`of the safety and effectiveness of the device. Class III devices typically require premarket
`approval.3
`
`Premarket notification is the process by which a new device,4 i.e., a post-amendments device, is
`classified into one of these three device classes.5 A manufacturer who intends to market in the United
`
`1 General controls apply to all classes of medical devices and provide FDA with the means of regulating devices to assure their safety
`and effectiveness. General controls include but are not limited to provisions that relate to establishment registration and device listing;
`premarket notification, although most class I devices are exempt by regulation from this requirement; prohibitions against adulteration
`and misbranding; records and reports; and good manufacturing practices. Section 513(a)(1)(A) of the FD&C Act (21 U.S.C.
`§ 360c(a)(1)(A)).
`
` 2
`
` The original definition of a class II device in the Medical Device Amendments of 1976 (Pub. L. 94-295) identified performance
`standards rather than special controls as the mechanism by which FDA could establish reasonable assurance of safety and effectiveness.
`The Safe Medical Devices Act of 1990 (Pub. L. 101-629) added “special controls,” which can include the promulgation of performance
`standards as well as postmarket surveillance, patient registries, development and dissemination of guidelines (including guidelines for
`the submission of clinical data in premarket notification submissions), and other appropriate actions as FDA deems necessary to
`provide such assurance. Section 513(a)(1)(B) of the FD&C Act (21 U.S.C. § 360c(a)(1)(B)).
`
` 3
`
` Certain types of devices classified into class III that were in commercial distribution in the United States before May 28, 1976, and
`those determined to be substantially equivalent to such devices, may be cleared through the 510(k) process until FDA issues an
`administrative order requiring them to go through the premarket approval process. Section 515(b)(1) of the FD&C Act (21 U.S.C.
`§ 360e(b)(1)). Prior to the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA) (Pub. L. 112-144) on
`July 9, 2012, FDA had to publish regulations to require such devices to go through the premarket approval process. Section 608(b) of
`FDASIA (126 Stat. 1056) changed the process from rulemaking to administrative order.
`
`4 For the purpose of this guidance document, a “new device” means a device within the meaning of section 201(h) of the FD&C Act
`that is not legally marketed. It can be either a completely new device or a modification of a legally marketed device that would require
`a new 510(k).
`
` 5
`
` By contrast, an unclassified devices, as defined in FDA’s Guidance for Industry and Food and Drug Administration Staff, “Medical
`Device Classification Product Codes”
`(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm285317.htm), is a pre-amendments
`
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`2
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`Ex. 2040-0005
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`Contains Nonbinding Recommendations
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`States a Class I, II, or III device intended for human use, for which a Premarket Approval application
`(PMA) is not required, must submit to FDA a premarket notification submission (often referred to as
`a 510(k)), unless the device is exempt from the 510(k) requirements of the FD&C Act and does not
`exceed the limitations of exemptions for each of the device classification regulations (Section .9 of 21
`CFR Parts 862 through 892, e.g., 21 CFR 862.9, 21 CFR 864.9, etc.). Under section 510(k) of the
`FD&C Act, a manufacturer must submit a 510(k) to FDA at least 90 days before introducing, or
`delivering for introduction, a device into interstate commerce for commercial distribution so the
`Agency can determine whether or not the device meets the criteria for market clearance (Sections
`510(k) and (n) of the FD&C Act (21 U.S.C. §§ 360(k) & (n))). The Agency bases its decision on
`whether the device is substantially equivalent (SE) to a legally marketed (predicate) device (Section
`513(i) of the FD&C Act (21 U.S.C. § 360c(i))). The device cannot be commercialized until FDA
`issues an order (510(k) clearance) stating that the device has been determined to be SE (Section
`513(f)(1) of the FD&C Act (21 U.S.C. § 360c(f)(1))).
`
`B. The 510(k) Classification Process
`
`According to section 513(f) of the FD&C Act, a new (i.e., post-amendments) device is automatically
`in Class III and must undergo premarket approval or reclassification before it can be marketed, unless
`it is a type of device that was in commercial distribution prior to May 28, 1976, and is SE to another
`such device; or it is within a type of device introduced after May 28, 1976, that has been reclassified
`into Class I or II and is SE to another device within such classification. For information about how
`FDA’s classification product codes assist in accurate identification and tracking of current medical
`devices, please see FDA’s Guidance for Industry and Food and Drug Administration Staff, “Medical
`Device Classification Product Codes”
`(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm2853
`17.htm).
`
`When FDA determines under sections 510(k), 513(f)(1), and 513(i) of the FD&C Act that a new
`device is SE to a legally marketed (predicate) device, the new device is classified into the same class
`and subject to the same requirements as the predicate device. (See Section IV.C.) A determination
`that a new device is not substantially equivalent (NSE) to a predicate device results in the new device
`being classified into Class III. Thus, 510(k) review is both the mechanism by which a manufacturer
`seeks marketing authorization for a new device and by which FDA classifies devices into their
`appropriate regulatory category. Because devices are classified according to the level of regulatory
`control necessary to provide a reasonable assurance of safety and effectiveness,6 classification of a
`
`device for which a classification regulation has not been promulgated. Unclassified devices require submission of a 510(k) premarket
`notification to FDA. A not-classified device is a post-amendments device for which the Agency has not yet reviewed a marketing
`application or for which the Agency has not made a final decision on such a marketing application. A pre-amendments device is a
`device that was on the market prior to the enactment of the Medical Device Amendments to the FD&C Act on May 28, 1976.
`
` 6
`
`
`
` The three device classes are described in section 513(a) of the FD&C Act (21 U.S.C. § 360c(a)):
`(1) There are established the following classes of devices intended for human use:
`(A) CLASS I, GENERAL CONTROLS.—
`(i) A device for which the controls . . . are sufficient to provide reasonable assurance of the safety and effectiveness of the
`device.
`(ii) A device for which insufficient information exists to determine that the controls referred to in clause (i) are sufficient to
`provide reasonable assurance of the safety and effectiveness of the device or to establish special controls to provide such
`assurance, but because it—
`(I) is not 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, and
`(II) does not present a potential unreasonable risk of illness or injury,
`is to be regulated by the controls referred to in clause (i).
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`3
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`Ex. 2040-0006
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`

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`Contains Nonbinding Recommendations
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`new device through the 510(k) process requires FDA to determine the issues of safety and
`effectiveness presented by the new device, and the regulatory controls necessary to address those
`issues.7
`
`C. Evolution of the 510(k) Program
`
`Since its inception, the 510(k) program has undergone a number of statutory changes. Notably, the
`Safe Medical Devices Act of 1990 (Pub. L. 101-629) added section 513(i), which codified FDA
`review practice in applying the “substantial equivalence” review standard. In addition, FDA has
`modified its implementation of the program to adapt to changing circumstances and to accommodate
`the evolving medical device landscape. For example, the alternative options of a Special 510(k) or an
`Abbreviated 510(k) still exist today. Additional information regarding these alternative options can
`be found in FDA’s guidance, “The New 510(k) Paradigm – Alternative Approaches to Demonstrating
`Substantial Equivalence in Premarket Notifications”
`(http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocument
`s/ucm080189.pdf). The current 510(k) program reflects the current statutory framework and FDA’s
`implementation of that framework through regulation, guidance, and administrative practice. A
`history of the 510(k) program has been summarized in other documents that FDA has published.8
`
`This guidance document provides updated information to the existing guidance document entitled
`“Guidance on the CDRH Premarket Notification Review Program, 510(k) Memorandum K86-3”
`(K86-3 Guidance), issued on June 30, 1986. The K86-3 Guidance was written and issued as final
`guidance prior to the February 27, 1997 implementation of FDA’s Good Guidance Practices (GGPs),
`and has not been updated since its initial publication date. This guidance replaces the K86-3
`Guidance.
`
`
`
`(B) CLASS II, SPECIAL CONTROLS.—A device which cannot be classified as a class I device because the general controls
`by themselves are insufficient to provide reasonable assurance of the safety and effectiveness of the device, and for which
`there is sufficient information to establish special controls to provide such assurance . . .
`(C) CLASS III, PREMARKET APPROVAL.—A device which because—
`(i) it (I) 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 (II) cannot be
`classified as a class II device because insufficient information exists to determine that the special controls described in
`subparagraph (B) would provide reasonable assurance of its safety and effectiveness, and
`(ii)(I) 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
`(II) presents a potential unreasonable risk of illness or injury,
`is to be subject, in accordance with section 515, to Premarket approval to provide reasonable assurance of its safety and
`effectiveness.
`
`7 If FDA has established special controls applicable to the device type, the 510(k) would need to adequately address the issues covered
`by the special controls for the device to be classified into Class II. See Section 513(a)(1)(B) of the FD&C Act (21 U.S.C.
`§ 360c(a)(1)(B)).
`
` 8
`
` See CDRH Preliminary Internal Evaluations – Volume I: 510(k) Working Group Preliminary Report and Recommendations
`(http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDRH/CDRHReports/UCM220784.pdf). See also CDRH Preliminary
`Internal Evaluations – Volume II: Task Force on the Utilization of Science in Regulatory Decision Making Preliminary Report and
`Recommendations (http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDRH/CDRHReports/UCM220783.pdf). See also
`510(k) and Science Report Recommendations: Summary and Overview of Comments and Next Steps
`(http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDRH/CDRHReports/UCM239449.pdf).
`
`4
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`Ex. 2040-0007
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`Contains Nonbinding Recommendations
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`III. Scope
`
`This guidance provides recommendations to industry and FDA staff about the content of 510(k)
`submissions and the decision-making process for determining substantial equivalence of devices
`reviewed under the 510(k) program. The guidance has been organized to coincide with the critical
`decision points outlined in the 510(k) Decision-Making Flowchart (See Appendix A), which has
`been updated to track section 513(i) of the FD&C Act and relevant regulations more closely. This
`document provides guidance on the following issues:
`
`
`
`
`
`
`
`the appropriate use of multiple predicates (See Section IV.C);
`the processes associated with determining whether a new device with new indications for use
`has a new intended use (See Section IV.D);
`the process for determining whether different technological characteristics raise different
`questions of safety and effectiveness (See Section IV.E);
` when performance data, with special emphasis on clinical performance data, may be
`necessary to support an SE determination (See Section IV.F); and
` how to develop 510(k) Summaries to promote greater transparency in the 510(k) decision-
`making process (See Section IV.G).
`
`
`The overarching principles in this guidance are applicable to devices that are subject to 510(k) review
`by CDRH, including the Office of Device Evaluation (ODE) and the Office of In Vitro Diagnostics
`and Radiological Health (OIR), as well as devices that are subject to 510(k) review by the Center for
`Biologics Evaluation and Research (CBER). This guidance is not intended to supplant existing
`device-specific guidance, but may cover broader areas not addressed in device-specific guidance
`documents. If you have questions about how this guidance and a device-specific guidance apply to a
`particular issue, please contact FDA to discuss. In addition, this guidance does not address review
`issues unique to combination products. For information on combination products, please refer to the
`Office of Combination Products webpage
`(http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/OfficeofScien
`ceandHealthCoordination/ucm2018184.htm).
`
`
`IV. The 510(k) Decision-Making Process
`
`A 510(k) is a premarket submission made to FDA to demonstrate that the new device to be marketed
`is “substantially equivalent” to a legally marketed device9 (21 U.S.C. §§ 360(k), 360(n), 360c(f)(1) &
`360c(i); 21 CFR 807.92(a)(3)) which is not subject to PMA. Manufacturers must compare their new
`device to a similar legally marketed device to support its substantial equivalence (21 U.S.C.
`§ 360c(i); 21 CFR 807.92(a)(3)).
`
`
`The most commonly used method of demonstrating substantial equivalence is through the submission
`and FDA review and clearance of a Traditional 510(k). Under 21 CFR 807.87, FDA established
`basic content requirements for 510(k)s to be submitted by device manufacturers in support of
`substantial equivalence. The Agency has provided a general framework on how to format an original
`submission for a Traditional 510(k) in FDA’s Guidance for Industry and FDA Staff, “Format for
`
`
`9 Under 21 CFR 807.92(a)(3), a legally marketed device to which a new device may be compared for a determination
`regarding substantial equivalence is a device that was legally marketed prior to May 28, 1976, or a device which has been
`reclassified from class III to class II or I, or a device which has been found to be substantially equivalent through the
`510(k) premarket notification process.
`
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`5
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`Ex. 2040-0008
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`Contains Nonbinding Recommendations
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`Traditional and Abbreviated 510(k)s”
`(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm0843
`65.htm). Although the basic content requirements apply to all 510(k)s, the type of data and
`information necessary to establish substantial equivalence varies by the type of device and the
`differences between the new device and the predicate device. FDA has issued many device-specific
`guidance documents that clarify the data that should be included in 510(k)s for particular device
`types. If a manufacturer is unsure of what information to include within a 510(k) submission, the
`manufacturer may contact FDA and submit a pre-submission to seek additional feedback to ensure
`submissions contain appropriate data elements. For more information on the pre-submission process,
`see FDA’s Guidance for Industry and FDA Staff, “Requests for Feedback on Medical Device
`Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff”
`(http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocument
`s/UCM311176.pdf).
`
`
`Please note that the use of the Standards Data Report for 510(k)s (Form 3654)
`(http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM081667.pdf),
`recognized consensus standards, and device-specific guidance documents is not limited to
`Abbreviated 510(k) submissions. Appropriate reliance on these documents can facilitate the review
`of all 510(k) submissions and can help to make the review process more consistent. Medical device
`manufacturers should consider relying on and citing to standards and device-specific guidance
`documents wherever appropriate, regardless of the type of 510(k) submission.
`
` A
`
` new device does not need to be identical to the predicate device for it to be found substantially
`equivalent to the predicate device. In FDA’s experience, it is rare for a new device to be identical to
`a predicate device. Given the diversity of technologies evaluated under this review standard, this
`guidance adopts a flexible approach to determining “substantial equivalence” to accommodate
`evolving technology while maintaining predictability and consistency to promote confidence among
`device developers, practitioners, and patients.
`
`A. The 510(k) Review Standard
`
`1.
`
`The Statutory Standard
`
`The 510(k) review standard (substantial equivalence of a new device to a legally marketed (predicate)
`device) differs from the PMA review standard (reasonable assurance of safety and effectiveness).
`The 510(k) review standard is comparative, whereas the PMA standard relies on an independent
`demonstration of safety and effectiveness. Nonetheless, the principles of safety and effectiveness
`underlie the substantial equivalence determination in every 510(k) review. The standard for a
`determination of substantial equivalence in a 510(k) review is set out in section 513(i) of the FD&C
`Act, which states:
`
`Substantial Equivalence
`
`(i)(1)(A) For purposes of determinations of substantial equivalence under subsection (f) and
`section 520(l), the term "substantially equivalent" or "substantial equivalence" means, with
`respect to a device being compared to a predicate device, that the device has the same
`intended use as the predicate device and that the Secretary by order has found that the device
`
`
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`6
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`Ex. 2040-0009
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`(i) has the same technological characteristics as the predicate device, or
`
`Contains Nonbinding Recommendations
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`(ii)(I) has different technological characteristics and the information submitted that the device
`is substantially equivalent to the predicate device contains information, including appropriate
`clinical or scientific data if deemed necessary by the Secretary or a person accredited under
`section 523, that demonstrates that the device is as safe and effective as a legally marketed
`device, and (II) does not raise different questions of safety and effectiveness than the
`predicate device.
`
`(B) For purposes of subparagraph (A), the term “different technological characteristics”
`means, with respect to a device being compared to a predicate device, that there is a
`significant change in the materials, design, energy source, or other features of the device from
`those of the predicate device.
`
`Safety and effectiveness factor into both parts of the FDA’s review. First, FDA must find that the
`intended use of the device and its predicate are “the same.” As discussed in the Intended Use Section
`of this guidance, differences in the indications for use, such as the population for which a device is
`intended or the disease a device is intended to treat do not necessarily result in a new intended use.
`Such differences result in a new intended use when they affect (or may affect) the safety and/or
`effectiveness of the new device as compared to the predicate device and the differences cannot be
`adequately evaluated under the comparative standard of substantial equivalence. (See Section IV.D.)
`
`Second, when comparing a new device to a predicate device, FDA must find that the two devices
`have “the same technological characteristics,” or that a “significant change in the materials, design,
`energy source or other features of the device” does not raise different questions of safety and
`effectiveness and that the device is as safe and effective as a legally marketed device.
`
`Although the 510(k) process involves a comparison of a new device to a predicate device rather than
`an independent demonstration of the new device’s safety and effectiveness, as is required for
`approval of a PMA, in both cases FDA’s review decision reflects a determination of the level of
`control necessary to provide a “reasonable assurance of safety and effectiveness.”10 The evidentiary
`standard, however, is different. In the 510(k) context, FDA generally relies, in part, on FDA’s prior
`determination that a reasonable assurance of safety and effectiveness exists for the predicate device.
`Demonstrating basic similarities between a new device and a predicate device typically requires
`manufacturers to provide descriptive information such as a comparison of specifications, materials,
`and technology. In contrast, FDA generally evaluates differences between the new device and the
`predicate device to determine their effect on safety and effectiveness. It follows that the evidence
`necessary to show substantial equivalence will increase as differences between the new device and
`the predicate device increase if those differences significantly affect, or may significantly affect,
`safety or effectiveness (21 CFR 807.81).
`
`
`10 Under section 513(a)(2) of the FD&C Act, the safety and effectiveness of a device are to be determined:
`(A) with respect to the persons for whose use the device is represented or intended,
`(B) with respect to the conditions of use prescribed, recommended, or suggested in the labeling of the device, and
`(C) weighing any probable benefit to health from the use of the device against any probable risk of injury or illness from
`such use.
`
`
`
`7
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`Ex. 2040-0010
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`

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`
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`2.
`
`The Least Burdensome Principle
`
`Contains Nonbinding Recommendations
`
`The FDA Modernization Act of 1997 (FDAMA) added two provisions, commonly known as “the
`least burdensome provisions,” to the FD&C Act; these were amended by the FDA Safety and
`Innovation Act of 2012 (FDASIA) (Pub. L. 112-144; 126 Stat. 1051). The provision relating to
`substantial equivalence, section 513(i)(1)(D), states:
`
`
`(i) Whenever the Secretary requests information to demonstrate that devices with
`differing technological characteristics are substantially equivalent, the Secretary shall
`only request information that is necessary to making substantial equivalence
`determinations. In making such request, the Secretary shall consider the least
`burdensome means of demonstrating substantial equivalence and request information
`accordingly.
`For purposes of clause (i), the term “necessary” means the minimum required
`information that would support a determination of substantial equivalence between a
`new device and a predicate device.
`(iii) Nothing in this subparagraph shall alter the standard for determining substantial
`equivalence between a new device and a predicate device.
`
`(ii)
`
`
`Although the statutory provision refers only to information requests related to determining the
`substantial equivalence of technological characteristics of a device and its predicate, the underlying
`principle that information requests should relate to the review standard is a basic principle of good
`regulatory practice with broad applicability to the 510(k) decision-making process.
`
`FDA’s guidances, “The Least Burdensome Provisions of the FDA Modernization Act of 1997:
`Concept and Principles”
`(http://www.fda.gov/Medic