Medical Devices

Guidance on the CDRH Premarket Notification Review Program 6/30/86 (K86-3)

510(k) Memorandum #K86-3

This guidance was written prior to the February 27, 1997 implementation of FDA’s Good Guidance Practices, GGP’s. It does not create or confer rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both. This guidance will be updated in the next revision to include the standard elements of GGP’s. June 30, 1986

Premarket Notification Review Program

[NOTE: TWO ATTACHED FLOWCHARTS, "510(K) 'SUBSTANTIAL EQUIVALENCE DECISION-MAKING PROCESS" (OVERVIEW) AND (DETAILED), ARE LOCATED AT THE END OF THIS DOCUMENT]

The attached guidance document on the Center for Devices and Radiological Health's premarket notification review program results from several years of discussions on 510(k) issues, beginning with the work of the Center's Premarket Notification Criticism Task Force. The concepts appearing in the document were developed using the input from ODE Division Directors, Branch Chiefs, reviewers and other staff members. Mr. Villforth, Mr. Scarlett, Mr. Norris and Dr. Young have reviewed the guidance and concur with it. The guidance outlines the requirements for premarket notification review, and discusses some general points we normally consider when making a determination that a device is, or is not, "substantially equivalent."

The guidance describes practices that have been developed over many years of program operations; thus, the guidance is effective immediately. I recognize, however, that this program is very complex and that this guidance may need refinement or expansion over time. I will, therefore, arrange for seminars for all reviewers, not only to ensure that the guidance is clear, but to identify any changes that are necessary.

Attachment

ATTACHMENT

GUIDANCE ON THE CENTER FOR DEVICES AND RADIOLOGICAL HEALTH'S PREMARKET NOTIFICATION REVIEW PROGRAM

(June 30, 1986)

PURPOSE OF THE GUIDANCE

This guidance document outlines requirements for premarket notification review, and explains some points the Center for Devices and Radiological Health (CDRH) will consider when making a determination that a device is, or is not, "substantially equivalent." A consistent application of the principles set forth in the guidance should be useful to Center staff in conducting complete and expeditious reviews of 510(k) submissions.

PURPOSE OF THE PROGRAM

In brief, the premarket notification program is meant to:

identify new devices that must be placed automatically into class III and undergo premarket approval or reclassification before they are marketed;
classify new devices; a not substantially equivalent (NSE) new device is in class III, and a substantially equivalent (SE) new device is in the same regulatory class as the device to which it is found equivalent; and
achieve marketing equity by allowing manufacturers of new devices that are SE to pre-Amendments devices to market their devices without facing any greater regulatory burdens than faced by manufacturers of the pre-Amendments devices.

BACKGROUND

THE STATUTE: The Medical Device Amendments were enacted on May 28, 1976. They direct 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 must be met before a manufacturer may distribute the device in interstate commerce.

Class I devices are subject to a comprehensive set of regulatory authorities applicable to all classes of devices, e.g., premarket notification, registration and listing, prohibitions against adulteration and misbranding, and rules for good manufacturing practices. Class II devices also need performance standards, and class III devices need premarket approval.

The Act also specifies how a new device, i.e., a post-Amendments device, is to be classified. A 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 device within such type; 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 type. A SE device is in the same class, and is subject to the same requirements, as the device to which it is SE.

Section 510(k) of the Act requires a person who wishes to introduce a device into commerce to notify the Center at least ninety days in advance. This premarket notification is referred to as a "510(k)." The Agency uses 510(k)s to determine if new devices are, or are not, SE to either a pre-Amendments device or a reclassified post-Amendments device.

CONGRESSIONAL GUIDANCE: The statutory objectives for the 510(k) program are clear. Also, the Report by the Committee on Interstate and Foreign Commerce on the Medical Device Amendments of 1976 (House Report) offers some additional guidance on program implementation, describing the term "substantial equivalence" as follows:

The term "substantially equivalent" is not intended to be so narrow as to refer only to devices that are identical to marketed devices nor so broad as to refer to devices which are intended to be used for the same purposes as marketed products. The committee believes that the term should be construed narrowly where necessary to assure the safety and effectiveness of a device but not narrowly where differences between a new device and a marketed device do not relate to safety and effectiveness. Thus, differences between "new" and marketed devices in materials, design, or energy source, for example, would have a baring on the adequacy of information as to a new device's safety and effectiveness, and such devices should be automatically classified into class III. On the other hand, copies of devices marketed prior to enactment, or devices whose variations are immaterial to safety and effectiveness would not necessarily fall under the automatic classification scheme.1/

If substantial equivalence were judged too narrowly, the marketing of devices that would benefit the public would be delayed; the device industry would be unnecessarily exposed to the greater burdens of premarket approval; new devices would not be properly classified; and new manufacturers of pre-Amendments type devices would not have marketing equity. If substantial equivalence were judged too broadly, the statutory purpose may not be served, i.e., devices with new uses or those presenting new or different risks would be marketed without adequate regulatory control.

THE 510(K) REGULATION: On August 23, 1977, FDA issued a final regulation for Establishment Registration and Device Listing for Manufacturers of Devices (21 CFR Part 807). Subpart E describes premarket notification procedures. The 510(k) rules were incorporated into the registration and listing regulation because the 510(k) requirements apply only to those persons required to register.

The regulation describes the circumstances under which a 510(k) must be submitted, the information required, and the FDA rules for maintaining confidentiality of submitted information. Essentially, the regulation provides that a person required to register must submit a 510(k) at least ninety days before marketing a device that: (1) is being introduced into distribution for the first time by that person, or (2) is in distribution but is being significantly modified in design, or use, etc.2/

A 510(k) must contain, among other things:

proposed labeling sufficient to describe the device's intended use;
a description of how the device is similar to or different from other devices of comparable type, or information about what consequences a proposed device modification may have on the device's safety and effectiveness; and

any other information the Center needs to determine whether the device is SE
The statute provides that a new device can be SE to one of two type of devices (from hereon referred to as a "predicate device"). A predicate device is one that was in distribution prior to enactment of the Amendments, or it is a post-Amendments device that was subject to reclassification from class III to class I or II. The Center does not routinely require that manufacturers perform research to determine what specific predicate devices were available in 1976, or were available at the time a post-Amendments device was reclassified from class III to class I or II; nor does the Center routinely require that all 510(k)s initially provide information on a predicate device. Instead, the Center requires submitters to provide information that compares the new device to a marketed device of a similar type, regardless of whether this marketed device was marketed before or after enactment of the Amendments, or before or after a type of post-Amendments device was reclassified.

This means that the manufacturer can submit a 510(k) comparing a new device to a device that has been found to be SE. It does not mean, however, that the Center finds new devices SE to devices that have been found SE. It only reflects the agency's position that the similarity of a new device to a marketed device is evidence that can be considered in determining that the new device is, as is the marketed device to which it is compared, SE to a predicate device. Nevertheless, the ultimate burden of demonstrating the substantial equivalence of a new device to a predicate device remains with the 510(k) submitter, and in those occasions when the Center is unfamiliar with certain aspects of the predicate device, the submitter will be required to provide information that substantiates a claim of substantial equivalence.

The guidance that follows assumes that 510(k)s provide comparisons with marketed devices.

GENERAL POINTS CONSIDERED BY CDRH DURING THE REVIEW OF 510(K) SUBMISSIONS
CDRH normally approaches the review of 510(k)s by considering the following points:

Does the new device have the same intended use as a predicate device? Does the new device have the same technological characteristics, i.e., same materials, design, energy source, etc.? If it has new technological characteristics, could they affect safety or effectiveness?

If the new has a new intended use (what constitutes a new intended use is discussed below), it is considered NSE. If the new device has the same intended use as a predicate device and the same technological characteristics related to safety and effectiveness, the new device is considered SE. If the new device has the same intended use as a predicate device, and it has new technological features that could affect safety or effectiveness, additional issues are considered:

Do the new technological features pose the same type of questions about safety or effectiveness as are posed by the predicate device with the same intended use? Are there accepted scientific methods for evaluation whether safety or effectiveness has been adversely affected as a result of the use of new technological characteristics? Is there information to demonstrate that the new technological features have not diminished safety and effectiveness?

If the answers to any of the above questions are negative, the device is generally considered NSE.

Thus, as a matter of practice, CDRH generally considers a device to be SE to a predicate device if, in comparison to the predicate device:
the new device has the same intended use (as discussed below); and,
the new device has the same technological characteristics, (i.e., same materials, design, energy source, etc.); or, it has new technological characteristics that could not affect safety or effectiveness; or
it has new technological characteristics that could affect safety or effectiveness, and

-- there are accepted scientific methods for evaluating whether safety or effectiveness has been adversely affected as a result of the use of new technological characteristics; and

-- there are data to demonstrate that the new technological features have not diminished safety or effectiveness.

Premarket notification submissions should be designed to answer these questions. The guidance below describes how the Center draws conclusions about the questions. The guidance covers the meaning of "intended use," technological changes that can be reviewed under the 510(k) process, data that are required in a 510(k), and what "combination" devices can be 510(k)'ed. Also, flow charts on Attachments I and II illustrate the decision making process.

THE MEANING OF INTENDED USE

While a new device must have the same intended use as a predicate device in order to be SE, the Center does not require that a new device be labeled with precise therapeutic or diagnostic statements identical to those that appear on predicate device labeling in order for the new device to have the same intended use. Label statements may vary. Certain elements of a predicate device's labeled indication may not be critical to its intended therapeutic, diagnostic, prosthetic, surgical, etc., use. The Center's scientific expertise enables it to exercise considerable discretion in construing intended uses in the labeling and promotional materials for predicate and new devices.3/ Thus, a new device with the same intended use as a predicate device may have different specific indication statements, and, as long as these label indications do not introduce questions about safety or effectiveness different from those that were posed by the predicate device's intended use, the new device may be found SE.

For the purposes of determining whether or not the new device has the same intended use as a predicate device, the Center assesses any difference in label indications in terms of the safety and effectiveness questions they may raise. The Center considers such points as physiological purpose (e.g. removes water from blood, transports blood, cuts tissue), condition or disease to be treated or diagnosed, professional or lay use, parts of the body or types of tissue involved, frequency of use, etc. If a new device is determined to have the same intended use, the Center may then proceed to determine whether or not it is substantially equivalent. (Devices which do not have the same intended use cannot be substantially equivalent.) The following examples illustrate these concepts.

Nonimplanted Blood Access Device: This type of pre-Amendments class II device is intended to provide access to a patient's blood so that blood can, for example, be subjected to hemodialysis. Pre-1976 devices are labeled for insertion into the femoral vein. New devices that are labeled for insertion into the subclavian vein may have the same intended use to the extent that labeling for the new and predicate devices indicates that both are intended to provide access to a patient's blood for similar purposes. The differences in labeling described above do not undercut the fact that the new and predicate devices have the same intended use. CDRH was further able to conclude that, because the differences in labeling related only to a method of use not relevant to the effect that the insertion is to achieve (and therefore did not pose new safety or effectiveness questions) and because there were not other significant changes (in technology, design, etc.), the new device was substantially equivalent.

Conventional Dialyzer: This type of pre-Amendments device is in class II. The pre-Amendments devices are labeled for use as part of artificial kidney system for patients with renal failure. The principal purpose of the device is to remove excess water from the vascular system. Some new devices that have been found SE are labeled for use as part of a heart-lung machine to remove excess water from the vascular system at the end of surgery. Again, the Center concluded that this is not a different intended use. Differences in the labeling relate only to a nonessential condition that does not bear materially on the safe and effective use of the device, and moreover, there are no other significant changes (in technology, design, etc.); therefore, the devices are substantially equivalent.

Blood Tubing Set: This pre-Amendment class II device consists of tubing that enables blood to flow from a patient to a dialyzer and back to the patient. Some new devices that have been found SE are labeled for use in carrying blood to and from a plasmapheresis device. The Center concluded that this is not a different use for the two tubings.

The labeling differences relating to the subclavian catheter, the conventional dialyzer for use with the heart-lung machine, and the blood tubing set for plasmapheresis, are not significant enough to require a finding that the devices are for different intended uses. Moreover, the specific uses associated with the labeling modifications do not present issues of safety and effectiveness different from those posed by the use of their predicate devices, and therefore, the devices can be found SE in terms of intended use. On the other hand, for some new devices, modifications in label indications will not be found to represent the same intended use as a predicate device, even though the intended effect of the new device is very similar to that of the predicate device. This is because slight modifications in intended use can be significant to the claimed effect or purpose of the predicate device. If a device has a different intended use, there is no reason to proceed further to decide whether the devices are substantially equivalent. (Obviously, however, some of the same issues relevant to substantial equivalence determinations may arise in assessing whether or not devices are for the same intended use, i.e., differences in labeling are judged in terms of any safety and effectiveness questions they may raise.) Two examples follow:

Long-term Percutaneous Intravascular Catheter: This pre-Amendments, unclassified device consists of a slender tube labeled for insertion into the vascular system for extended periods in order to sample blood, monitor blood pressure, or administer drugs. A similarly designed device has been found NSE because it is labeled for use as a spinal canal access catheter. The new device was intended to deliver drugs over an extended period of time to the spinal canal. While both devices deliver drugs into the human body, each device relates to a different body system. The concern raised by this difference led to the conclusion that the intended uses of the devices are not the same. Inserting the device into, and maintaining it in, the spinal canal raises significantly different safety issues compared to the issues posed by intravascular insertion; namely, the new device potentially posed risks to the spinal cord, whereas the predicate device did not.

Powered Aspirators: These pre-Amendments devices, currently proposed for class II, were labeled to remove loose bone chips, blood, or tissue from the body during surgery. Similarly designed new devices have been found NSE when labeled for use in "suction lipectomy." In this new surgical procedure, the aspirating device is inserted under the skin to remove body fat, sometimes very large amounts of body fat, for cosmetic purposes. In suction lipectomy, the aspiration process performed by the device becomes the surgical procedure. It is no longer an aspirator merely used as an aid in performing another surgical procedure that is not aimed solely at the removal of fat. For these reasons, the new devices, as labeled, do not have the same intended uses as the predicate device. The difference in intended use is underscored by the fact that removal of large amounts of body fat through aspiration raises questions of safety and effectiveness not posed by the labeled use of pre-Amendments aspirators, e.g., possible metabolic changes, and permanent bagging of the skin resulting when the fat removed from the area exceed the ability of the skin to contract. Thus, the intended uses are not the same.

As the examples above illustrate, for a device to be found SE, it is important that a 510(k) for the device demonstrate that the intended use of the device does not differ from the intended use of marketed devices within the same type and that any changes in labeling are immaterial in terms of safety and effectiveness issues.

DEVICES WITH NEW TECHNOLOGICAL FEATURES

If a new device has the same intended use as a predicate device, and there are no technological differences between the new and a predicate device, the new device is SE. If the device has the same intended use and technological differences, but the technological differences could not affect safety or effectiveness, it is SE. If the device has the same intended use and technological differences that could affect safety or effectiveness, the new device may not be SE. Technological differences may include modifications in design, materials, or energy sources; for example, changes in the power levels of electrical surgical instruments, the use of new reagents in in vitro diagnostic devices, the use of new materials in orthopedic implants, and the use of new battery designs in implanted pacemakers. The Center finds devices with new technological features to be NSE when the new feature could adversely affect safety or effectiveness in a way that is consequential under the conditions of intended use.

In taking this approach, the Center focuses on the technological differences that are medically and scientifically significant and avoids the difficulties that would arise from a mechanistic application of rigid formal criteria to the wide variety of substantial equivalence questions posed by new devices proposed for marketing under a 510(k). Substantial equivalence determinations of necessity require the Center to exercise reasonable scientific judgment. For example, the strict application of a rule that would make devices NSE if they have a new material would be inappropriate for such devices as bed pans. For other devices, a "materials rule" may seem more appropriate, e.g. for implants. Even for implants, however, such a rule would be too encompassing if applied to substitute materials known to be, or easily shown to be, equivalent or superior; for example, if applied to a new post-Amendments hip made of titanium, which is generally known to be, and can easily be shown to be, stronger and less corrosive than some stainless steel that was used in pre-Amendments hips.

Thus, from a scientific perspective, to determine which technological changes are consequential, the Center considers whether:

the new device poses the same type of questions about safety or effectiveness as a predicate device.;
there are accepted scientific methods for evaluating whether safety or effectiveness has been adversely affected as a result of the use of new technological characteristics; and
there are data to demonstrate that new technological characteristics have not diminished safety or effectiveness

The examples below should help clarify these concepts.

Electrocardiographs: This device is in class II. Pre-Amendments electrocardiographs produce an analog visual display of the electrical signals produced by the heart. Some post-Amendments devices that have been found SE display these signals in a digital, rather than analog, form. This technological innovation could affect the effectiveness of the device, i.e., the electronic components used to produce the digital display might not achieve the accuracy of an analog display. The Center found the new devices SE because the modification presented the same question of effectiveness as posed by the predicate device, i.e., does the display accurately represent the electrical activity of the heart. Also, there are accepted bench test procedures to demonstrate comparability of accuracy between the new and predicate devices, and the necessary comparability information was presented in the 510(k).

Inflatable Penile Implant: This device is in class III. The pre-Amendments implants consist of inflatable cylinders implanted in the penis, connected to a reservoir filled with fluid and implanted in the abdomen, and a subcutaneous manual pump implanted in the scrotum. When the cylinders are inflated, they provide rigidity to the penis. The connections between the various parts of this system sometimes leaked. Manufacturers of post-Amendments versions of these devices modified the connector designs. These new devices have been found SE even though such a change would affect safety and effectiveness. This is because the new connectors presented the same questions of safety and effectiveness as posed by the predicate device, i.e., are the connector materials non-toxic and do the connectors leak? Since the material were the same, questions about the comparability of toxicity were obviated, and bench testing and clinical evidence easily and clearly demonstrated that the modified connectors were not more prone to leaks then the connectors in the predicate devices. Perimeter: This device is proposed for classification in class I or II, depending on whether it is manually or electrically operated. The pre-Amendments devices are AC-powered or manual devices that project light on various points of a curved surface, and the patient manually indicates whether he or she sees the light. The devices are designed to determine the extent of a patient's peripheral vision. Manufacturers of post-Amendments devices have incorporated software into the device. The software automatically lights various points on the curved surface, and keeps track of whether the patient indicates that the light has been seen by recording that the patient has or has not pressed a button. The new device posed the same safety and effectiveness questions as the predicate devices, i.e., are the light-point in the appropriate places, is there risk of shock, do the points light up when they are meant to, and can the patient's reaction be accurately recorded. Because the questions are the same, and obviously accepted testing procedures can ensure comparability of performance between the new and predicate device, and because clinical data showed comparability, the new devices with a software package were found to be SE.

Hemodialyzers: This is a class II device that is used as an artificial kidney system. The device allows the removal of water and waste from the patient's blood through a semipermeable membrane. Pre-Amendements devices used cellulose based semipermeable membranes.

Manufacturers of post-Amendments devices have used various other types of membranes in the filters and these devices have been found SE. This is because the new membranes raised the same questions of safety and effectiveness as the cellulose membrane, e.g., is the degree of permeability acceptable, is the material toxic, and is the degree of particulate contamination acceptable? Accepted preclinical tests, with clinical confirmation, demonstrated that the new membranes and the cellulose membranes were comparable.

On the other hand, there will be many technological changes that will make a device NSE. For example:

Heart Valves: This pre-Amendments type device is in class III. It is intended to perform the function of any of the heart's natural valves. It is constructed of prosthetic or biological materials, or both. The Center has found many new valves to be NSE even though the new valves, in some cases, incorporated only very slight design modifications in relation to predicate valves. This is not because the device is a high risk device. Rather, it is because of the nature of the device. A minor change in design can raise questions about safety and effectiveness that are inappropriate for evaluation under 510(k). Specifically, different valve designs can lead to a different balance in the performance factors related to valves. Minor changes in a valve may make it more susceptible to fractures than its predicate, but less susceptible to occlusion. In this case, it is difficult to compare the performance of one valve to another because they present different questions about safety; each valve tends to present different risk/benefit equations. As a result, there are no accepted methods for assessing comparability. Consequently, these devices are typically found NSE.

Electrohydraulic Lithotripter: This pre-Amendments device is in class III. The pre-Amendments device was used to fragment urinary bladder stones. It consists of a high voltage cable connected to a bipolar electrode introduced into the bladder through a cystoscope. The Center found an electrohydraulic lithotripter inserted into the ureter through a cystoscope for use on ureteral stones to be SE. The principle of operation for both devices are identical. The stone is fragmented by the discharge of electricity between the two electrical poles. Another post-Amendments device, known as the Extracorporeal Shock wave Lithotripter was NSE. This device breaks kidney stones through the use of a succession of externally generated shock waves focused on the stone. The shock waves are transmitted through water, in which the patient is sitting, and then transmitted through body tissue to the stone. The device raised questions about safety and effectiveness not present in the previous devices, e.g., the shock waves, which enter large portions of the body, could affect cardiopulmonary functions or could have had unknown effects on much of the tissue and organs in the abdomen. An evaluation of these questions was not appropriate for a 510(k) because they presented issues outside the questions of safety and effectiveness raised by the electrohydraulic lithotripter.

Femoral stem: This lower portion of a total artificial hip replacement is a pre-Amendments device proposed for class II. Some of these devices are uncemented and are fixed by impaction of the stem into the top of the femur. The pre-Amendments impact/fit stems had smooth, straight (uncontoured) surfaces on the stem that fit into the femur. The Center found SE some post-Amendments versions of the stem that have surface variations, i.e., grooves, irregular or regular contours, etc., that allow the bone to remodel over time. The Center found to be NSE post-Amendment stems with porous coatings (for uncemented use) that require bone ingrowth into the device fixation. The contoured stem relied on impact placement and bone remodeling to an essentially smooth surface. The health of the bone would still depend upon normal bone vascularization systems even if the bone conformed to some of the slightly wavy contours. The questions of safety and effectiveness were the same as those for the traditional impact fit stem. On the other hand, for bone to grow into, and remain viable in, a porous material, the bone would need to depend upon an intricate vascularization system not normally occurring in bone that may not, in fact, develop or be sustainable. Thus, the porous coated device was found NSE because it presented new scientific questions about long term fixation.

As the examples above illustrate, for a device to be found SE, it is important that a 510(k) for the device either demonstrate that the technology of the device does not differ from the technology of marketed devices within the same type; or, to the extent that the technology does differ: explain why the device does not present new questions about safety or effectiveness, describe what accepted methods exist to test comparability of performance, and present data, generated from such tests, that demonstrate comparability. (See the 510(k) data discussion below. 510(k)s for new devices that are different from predicate devices, but are not different from a marketed device within the same type, may not need to provide testing information.)

DATA REQUIREMENTS FOR 510(k)s

The requirements of section 510(k) of the act are intended not only to notify FDA that a device is about to be marketed but primarily to enable FDA to determine whether the device is SE to one already in commercial distribution. To fulfill this responsibility, the Center requires that a 510(k) include descriptive data needed to understand a new device's intended use, physical composition, method of operation, specifications, performance claims, etc. Similar information about the device to which the new device is being compared may also be required. In addition, under certain circumstances, the Center requires performance testing information, i.e., data from bench, animal, or clinical tests, in order to determine that a device performs according to its description.

While the Center has concluded that it should sometimes require performance testing data in order to confirm that a new device is SE, the 510(k) review process is not a substitute for premarket approval, and the Center does not attempt to address all of the issues would be answered in a PMA in its review of 510(k)s. Data in a 510(k) should show comparability of a new device to a predicate device, whereas demonstration, in an absolute sense, of a device's safety and effectiveness, is reserved for PMAs.

Although there are no hard and fast rules governing all the possible data collection issues that can arise in 510(k)s, the following guidance will govern many situations.

The Center will always require descriptive data necessary to understand a new device's intended use, physical composition, method of operation, specifications, performance claims, etc. Also, the Center will always require any descriptive data necessary to understand the same characteristics of the device to which the new device is being compared.

The Center normally will not require performance testing data to substantiate equivalence if a new device does not have an important descriptive difference in comparison to marketed devices within its type i.e., it does not have a new material, method of operation, etc., and it has descriptive characteristics that are precise enough to ensure that comparability will be achieved if the new device is manufactured according to its description. For example, the Center will accept the descriptive statement that a new surgical instrument will be made of surgical grade stainless steel, as are other marketed surgical instruments, as substantiation that the new instrument is equivalent in materials/composition to a predicate device. (See below for an explanation of how a comparison to any marketed device can lead to a conclusion about the substantial equivalence of a new device to a predicate device.)

The Center normally will require performance testing data to substantiate equivalence if a new device has an important descriptive difference in comparison to marketed devices within its type, and it is not clear from an initial review that the device has an intended use or technological change that makes it NSE; or, the new device has descriptive characteristics that are too imprecise to guarantee that comparability in performance will be achieved even if the new device is produced as described. Following is an example of when descriptive similarities are inadequate to ensure that comparability of performance will be achieved when a new device has the same descriptive characteristics as a marketed device. The fact that a new pacemaker lead and pre-marketed pacemaker lead are both in the polyurethane "family" does not ensure that both devices have the same chemical formulations, and differences in the chemical formulations of polyurethanes could affect safety or effectiveness. Differences in design, extrusion, and assembly of polyurethanes with the same chemical formulation could also affect safety or effectiveness. Thus, the Center would generally require performance testing information to confirm that the new lead in SE to the predicate.

If it is clear from an initial review that a new device has a intended use or technological feature that makes it NSE, the Center will not review or require performance information in the 510(k). Instead the applicant will be notified that the device is NSE, and any performance data will be reviewed in a PMA or reclassification petition.

Typically, 510(k) provides descriptive and testing data that compares the new device to another marketed device within the type, but does not necessarily compare the new device directly to a predicate device. In these cases, the Center can rely, as necessary, on performance data appearing in previously reviewed 510(k) files, in Center classification files, or in the literature, to determine that the device is not only comparable to another marketed device within its type, but is also SE to a predicate device.

Nevertheless, the ultimate burden of demonstrating the substantial equivalence of a new device to a predicate device remains with the 510(k) submitter, and in circumstances when the Center is unfamiliar with certain aspects of the predicate device, the submitter will be required to provide information that substantiates a claim of substantial equivalence.

NEW DEVICES THAT ARE COMBINATIONS OF OLD DEVICES

A new device is a so-called "combination" device when it claims to have the same intended uses as two or more different types of predicate devices. Normally, this is achieved by combining two or more predicate devices into a device that is sold as a unit, e.g., a urinary catheter may incorporate a temperature measuring device; or a cardiac monitor, electrocardiograph, and blood pressure computer that were sold separately prior to May 28, 1976, might be combined into one electronic monitoring device.

When a new device combines types of devices from different classes, questions have arisen about what classification the new device will have.

In its review of the 510(k), the Center will subject the combination device to the same sorts of questions and documentation requirements that are applied to a single device. When such a device is found to be SE, it combines devices from different classes and is classified in the highest of the predicate device classifications unless the combined devices are regulatable as separate articles, e.g., they are detachable. In that case, the separately regulatable articles will be regulated in separate classes.

1/ H.R. Rep. No. 94-853 pp. 36-37. The Amendments, as enacted, are comprised primarily of the bill H.R. 11124 as drafted by the Subcommittee on Health and the environment of the Committee on Interstate and Foreign Commerce and adopted by the House of Representatives. This report provides the only Congressional guidance on the criteria for substantial equivalence.

2/ This document does not provide guidance on what changes in marketed devices are significant enough to require the submission of a 510(k), but the Center plans to issue such guidance in the near future.

3/ Ordinarily, intended use is determined by reference to "labeling" or promotional claims; only in rare cases might it be necessary to infer intended use from other types of information.

510(k) Substantial Equivalence Decision Making Process Flow Chart Overview is available in pdf version or found directly below.