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The New 510(k) Paradigm - Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications - Final Guidance |
This document is intended to provide guidance.
It represents the Agency's current thinking on the above. It
does not create or confer any 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.
Comments and suggestions may be submitted
at any time for Agency consideration to Heather Rosecrans, HFZ-404,
Office of Device Evaluation, 9200 Corporate Boulevard, Rockville,
MD 20850. Comments may not be acted upon by the Agency until
the document is next revised or updated. For questions regarding
the use or interpretation of this guidance, contact Heather Rosecrans at 240-276-4021 or e-mail heather.rosecrans@fda.hhs.gov.
For additional copies: World Wide Web/CDRH
home page: http://www.fda.gov/cdrh or CDRH Facts on Demand at
1-800-899-0381 or 301-827-0111.
As part of the Center for Devices and Radiological
Health's (CDRH) organizational transformation initiative, the
510(k) Process Reengineering Team examined the existing process
through which regulated industry demonstrates substantial equivalence
of medical devices in premarket notifications (510(k)s). On June
13, 1997, the Food and Drug Administration (FDA) released a draft
proposal entitled, "A New 510(k) Paradigm: Alternative Approaches
to Demonstrating Substantial Equivalence in Premarket Notifications"
for comment on the Internet. The proposal was the subject of
two videoconferences which were co-sponsored by FDA and the Food
and Drug Law Institute (FDLI) and was also discussed at several
trade and industry association meetings. On September 19, 1997,
the Agency published a Notice of Availability of the proposal
in the Federal Register (62 FR 49247) to formally solicit comments
from interested parties.
During this same period of time, the United States Congress was in the process of drafting the FDA Modernization Act of 1997 (the FDAMA)(Pub. L. 105-115), which amended the device provisions of the Federal Food, Drug, and Cosmetic Act (the Act). During its deliberations over the new law, several of the concepts in the New 510(k) Paradigm were discussed by members of Congress. On November 21, 1997, the President of the United States signed into law the FDAMA, which incorporated many of the changes proposed in the New Paradigm as well as many others that were envisioned in the Center's reengineering efforts. As a direct result of the enactment of this new law and the comments that were received during the period of public review, the 510(k) Process Reengineering Team developed this final guidance document.
TABLE OF CONTENTS:
Preface
Introduction
Background
The New 510(k) Paradigm
Conclusion
Attachments
Introduction
This document provides guidance to the regulated
industry and reviewers on two alternative approaches that may
be used, under appropriate circumstances, to demonstrate substantial
equivalence. It establishes procedures regarding the use of consensus
standards in the premarket review process (section 514 of the
Act, as amended by section 204 of the FDAMA) and reflects other
changes to the 510(k) Program that have resulted from enactment
of the new law, such as increased reliance on postmarket controls
to expedite premarket review (section 513 of the Act, as amended
by section 205 of the FDAMA). In addition, it incorporates concepts
that have arisen out of the Center's organizational transformation
initiative, including a new emphasis on the use of guidance documents
and special controls. The alternative approaches described in
this guidance document should streamline the 510(k) preparation
and review processes, thus conserving industry and Agency resources
while still protecting the public health.
Background
Under section 510(k) of the Act, a person
who intends to introduce a device into commercial distribution
is required to submit a premarket notification, or 510(k), to
FDA at least 90 days before commercial distribution is to begin.
Section 513(i) of the Act states that FDA may issue an order
of substantial equivalence only upon making a determination that
the device to be introduced into commercial distribution is as
safe and effective as a legally marketed device. Under 21 CFR
807.87, FDA established the content requirements for premarket
notifications to be submitted by device manufacturers in support
of the substantial equivalence decision. FDA has, however, discretion
in the type of information it deems necessary to meet those content
requirements. For example, to allocate review resources more
effectively to the highest risk devices, FDA developed a tiering
system based on the complexity and the level of risk posed by
medical devices. Under this system, the substantial equivalence
determination for low risk devices is based primarily on descriptive
information and a labeling review, while the decision for higher
risk devices relies on performance data.
In a further effort to manage FDA's workload and allocate resources most appropriately, the Agency exempted Class I devices for which it determined that premarket notification requirements were not necessary to provide reasonable assurance of safety and effectiveness.
Between the passage of the Medical Device
Amendments of 1976 and the FDAMA, FDA exempted 574 generic types
of Class I devices from the requirement of premarket notification.
As a result of the FDAMA, all Class I devices are exempt from
the requirement of premarket notification, unless the device is
intended for a use that is of substantial importance in preventing
impairment to human health or presents a potential unreasonable
risk of illness or injury ("reserved" criteria). Therefore,
only those Class I devices that meet the reserved criteria remain
subject to the premarket notification requirement. (See 63 FR
5387, February 2, 1998, for a listing of Class I "reserved"
devices.)
The FDAMA also gave FDA the authority to
directly exempt certain Class II devices rather than first down-classifying
them to Class I before they become eligible for exemption. On
January 21, 1998, FDA published a listing of Class II devices
that no longer require premarket notification. (See 63 FR 3142.)
In the future, additional Class II devices may become exempt
from the premarket notification requirement as FDA considers additional
devices for exemption.
The last phase of the Agency's effort to
evaluate which devices should be subject to 510(k) review involves
the preamendments Class III devices. Preamendments Class III
devices for which general controls or special controls are sufficient
to ensure safety and effectiveness will eventually be down-classified
to either Class I (510(k) exempt or reserved) or to Class II,
respectively. Those preamendments Class III devices that are
not appropriate for reclassification will remain in that class
and be subject to either premarket approval (PMA) or product development
protocol (PDP) requirements. It is anticipated that, as a result
of this reclassification effort, the premarket notification process
will be primarily reserved for Class II devices and a few "reserved"
Class I devices. Until a preamendments Class III device type
becomes subject to a regulation requiring premarket approval,
however, the device type will remain subject to the premarket
notification requirement.
The New 510(k) Paradigm
To streamline the evaluation of premarket
notifications for the reserved Class I devices, Class II devices
subject to premarket notification, and preamendments Class III
devices for which FDA has not yet called for PMAs, the Agency
has developed "The New 510(k) Paradigm." Attachment
1 outlines the New Paradigm, which presents device manufacturers
with two new optional approaches for obtaining marketing clearance
for devices subject to 510(k) requirements. While the New Paradigm
maintains the traditional method of demonstrating substantial
equivalence under section 510(k) of the Act, it also presents
the "Special 510(k): Device Modification" option, which
utilizes certain aspects of the Quality System Regulation, and
the "Abbreviated 510(k)" option, which relies on the
use of guidance documents, special controls, and recognized standards
to facilitate 510(k) review. Use of either alternative, however,
does not affect FDA's ability to obtain any information authorized
by the statute or regulations.
A.
Special 510(k): Device Modification
The Safe Medical Devices Act of 1990 (the
SMDA) (Pub. L. 101-629) amended section 520(f) of the Act, providing
FDA with the authority to issue regulations requiring pre-production
design controls. Specifically, section 520(f)(1)(A) states that
FDA may prescribe regulations to require "... that the methods
used in, and the facilities and controls used for, the manufacture,
pre-production design validation (including a process to assess
the performance of a device but not including an evaluation of
the safety or effectiveness of a device), packing, storage, and
installation of a device conform to current good manufacturing
practice, as prescribed in such regulations, to assure that the
device will be safe and effective and otherwise in compliance
with this Act." This change in the law was based on findings
that a significant proportion of device recalls were attributed
to faulty design. Under the authority provided by the SMDA, FDA
revised its current good manufacturing practice requirements to
include pre-production design controls that device manufacturers
must follow when initially designing devices or when making subsequent
modifications to those designs. (See 21 CFR 820.30 Subpart C
- Design Controls of the Quality System Regulation.)
Effective June 1, 1997, manufacturers of
Class II, Class III, and certain Class I devices are required
to follow design control procedures when originally developing
devices and for subsequent modifications. Product modifications
that could significantly affect safety and effectiveness are subject
to 510(k) submission requirements under 21 CFR 807 as well as
design control requirements under 21 CFR 820.30. In accordance
with the Quality System Regulation, manufacturers must have a
systematic set of requirements and activities for the management
of design and development, including documentation of design inputs,
risk analysis, design output, test procedures, verification and
validation procedures, and documentation of formal design reviews.
In this process, the manufacturer must ensure that design input
requirements are appropriate so the device will meet its intended
use and the needs of the user population. The manufacturer must
also establish and maintain procedures for defining and documenting
design output in terms that allow an adequate evaluation of conformance
to design input requirements. Thus, manufacturers may need to
refine their device design requirements as verification and validation
results are obtained. The design specifications that result from
this process are the design outputs, which form the basis for
the device master record (DMR). (See 21 CFR 820.3(i).) The DMR
is subject to inspection by FDA personnel.
Since design control requirements are now
in effect and require the manufacturer to conduct verification
and validation studies of a type that have traditionally been
included in 510(k) submissions, the Agency believes that it may
be appropriate to forgo a detailed review of the underlying data
normally required in 510(k)s. For this reason, FDA is allowing
an alternative to the traditional method of demonstrating substantial
equivalence for certain device modifications. For these well-defined
modifications, the Agency believes that the rigorous design control
procedure requirements produce highly reliable results that can
form, in addition to the other 510(k) content requirements specified
in Attachment 2, a basis for the substantial equivalence determination.
Under the Quality Systems Regulation, data that is generated
as a result of the design control procedures must be maintained
by the manufacturer and be available for FDA inspection.
Under the New 510(k) Paradigm, a manufacturer
should refer to 21 CFR 807.81(a)(3) and the FDA guidance document
entitled, "Deciding When to Submit a 510(k) for a Change
to an Existing Device" to decide if a device modification
may be implemented without submission of a new 510(k). If a new
510(k) is needed for the modification and if the modification
does not affect the intended use of the device or alter the fundamental
scientific technology of the device, then summary information
that results from the design control process can serve as the
basis for clearing the application.1
Under this option of the Paradigm, a manufacturer
who is intending to modify his/her own legally marketed device2
will conduct the risk analysis and the necessary verification
and validation activities to demonstrate that the design outputs
of the modified device meet the design input requirements. Once
the manufacturer has ensured the satisfactory completion of this
process, a "Special 510(k): Device Modification" may
be submitted. While the basic content requirements of the 510(k)
(21 CFR 807.87) will remain the same, this type of submission
should also reference the cleared 510(k) number3 and contain a
"Declaration of Conformity" with design control requirements.
Refer to Attachment 2 for the contents of a "Special 510(k):
Device Modification" with a "Declaration of Conformity"
to design controls.
2Although not subject to the design control procedure requirements of the Quality System Regulation, manufacturers of reserved Class I devices may elect to comply with this provision of the regulation and submit Special 510(k)s.
3Manufacturers of preamendments devices may submit Special 510(k)s. See footnote 6 of Attachment 2 for information that should be included in a Special 510(k) under this circumstance.
Under the Quality System Regulation, manufacturers
are responsible for performing internal audits to assess their
conformance with design controls. A manufacturer could, however,
use a third party4 to provide a supporting assessment of the conformance.
In this case, the third party will perform a conformance assessment
for the device manufacturer and provide the manufacturer with
a statement to this effect. The marketing application should
then include a declaration of conformity signed by the manufacturer,
while the statement from the third party should be maintained
in the DMR. As always, responsibility for conformance with design
control requirements rests with the manufacturer.
In order to provide an incentive for manufacturers
to choose this option for obtaining Agency clearance for device
modifications, the Office of Device Evaluation (ODE) intends to
process Special 510(k)s within 30 days of receipt by the Document
Mail Center (DMC). The Special 510(k) option will allow the Agency
to review modifications that do not affect the device's intended
use or alter the device's fundamental scientific technology within
this abbreviated time frame. The Agency does not believe that
modifications that affect the intended use or alter the fundamental
scientific technology of the device are appropriate for review
under this type of application, but rather should continue to
be subject to the traditional 510(k) procedures (i.e., "Traditional
510(k)") or may be subject to an Abbreviated 510(k)
as described below.
FDA believes that to ensure the success
of the Special 510(k) option of the Paradigm, there must be a
common understanding of the types of device modifications that
may gain marketing clearance by this path. In this vein, it is
critical that industry and Agency staff can easily determine whether
a modification is appropriate for submission as a Special 510(k).
To optimize the chance that a Special 510(k) will be accepted
and promptly cleared, 510(k) submitters should evaluate each modification
against the considerations described below to insure that the
particular change does not: (1) affect the intended use or (2)
alter the fundamental scientific technology of the device.
I. Intended Use
As discussed earlier, modifications to
the indications for use of the device or any labeling change that
affects the intended use of the device should not be submitted
as a Special 510(k). Therefore, FDA recommends that submitters
of Special 510(k)s highlight, or otherwise prominently identify,
all changes in the proposed labeling that may result from modifications
to their legally marketed device. In addition, it should be clearly
stated in the Special 510(k) that the intended use of the modified
device, as described in its labeling, has not changed as a result
of the modification(s).
II. Fundamental Scientific Technology
Special 510(k)s should also not be submitted
for modifications that have the potential to alter the fundamental
scientific technology of the device. These types of changes generally
include modifications to the device's operating principle(s) or
mechanism of action, such as automation of a manual device or
incorporation of a sensing or feedback circuit. Specific examples
that illustrate these types of changes that alter the fundamental
scientific technology and thus should not be submitted as Special
510(k)s include:
In addition, the Agency is concerned with
changes in materials in certain devices. While FDA acknowledges
that many such changes can be processed as Special 510(k)s, there
are certain types of changes in materials that may raise safety
or effectiveness issues that continue to warrant a more intensive
evaluation by the Agency. This includes a change in material(s)
in an implant, or other device that contacts body tissues or fluids,
to a material type that has not been used in other legally marketed
devices within the same classification regulation for the same
intended use (i.e., "legally marketed predicate device").
For example, a change in a material in a finger joint prosthesis
from a known metal alloy to a ceramic that has not been used in
a legally marketed predicate, should not be submitted as a Special
510(k). Similarly, a change in a device's active ingredient or
agent to one that has not been used in other legally marketed
predicate devices should not be submitted for review as a Special
510(k). For example, if a manufacturer of a contact lens disinfecting
solution wanted to change from hydrogen peroxide to an antiseptic
that had not been previously used in a legally marketed predicate,
such a change would not be appropriate for review as a Special
510(k). Both of the above types of modifications involve major
changes in the principle component of the device and thus would
be considered a change to the fundamental scientific technology
of the device and should be submitted for review as either Abbreviated
or Traditional 510(k)s.
A change, however, in formulation in a
material or a change to a type of material that has been used
in other legally marketed devices within the same classification
regulation for the same intended use could be reviewed as a Special
510(k). This should be true for both non-contacting devices as
well as implants and devices that contact body tissues or fluids.
Thus, a manufacturer of a hip implant could change from one alloy
to one that has been used in another legally marketed predicate
through the submission of a Special 510(k). Similarly, a contact
lens manufacturer could submit a Special 510(k) for a change in
their polymer to another material that has been used in a legally
marketed predicate. Finally, changes in an inactive or secondary
ingredient/agent should be appropriate for review as Special 510(k)s
as this should not be considered a major change to the fundamental
scientific technology of the device. For example, a manufacturer
of a urologic catheter could submit a Special 510(k) to add an
antimicrobial coating to the device if the coating has been used
on another legally marketed predicate of the same material.
Device modifications that should be appropriate
for review as Special 510(k)s also include those changes identified
below:
a. Energy type
b. Environmental specifications
c. Performance specifications
d. Ergonomics of the patient-user interface
e. Dimensional specifications
f. Software or firmware
g. Packaging or expiration dating
h. Sterilization
It should be noted that in cases where
FDA has issued guidance, established special controls, or recognized
standards that address issues such as device testing or performance,
manufacturers should consider this in their implementation of
design control requirements. For example, if a manufacturer is
modifying a contact lens, then the manufacturer's design control
inputs should include the special controls that FDA has established
for this device. Further, if a manufacturer modifies an in
vitro diagnostic, the manufacturer's design inputs should
include any recognized clinical standards such as those developed
by the National Committee of Clinical Laboratory Standards (NCCLS)
or a reasonable alternative. Thus, submitters of Special 510(k)s
need to be aware of any relevant guidance documents, special controls,
or recognized standards that apply to their device and that should
be addressed by their design control processes.
III. Clinical Considerations
FDA recognizes that clinical evaluation
may be involved in the validation of the design of a modified
device. Manufacturers are reminded that all clinical investigations
must conform to the applicable regulations, including 21 CFR Parts
812, 50 and 56. Therefore, collection of clinical data to support
a Special 510(k) may require submission of an investigational
device exemptions (IDE) application to FDA. The fact that a significant
risk device investigation was conducted to support any of the
activities listed above, however, does not necessarily preclude
the submission of a Special 510(k).
Manufacturers who intend to conduct
clinical investigations of a modified device as part of design
validation are encouraged to contact the appropriate ODE review
division before preparing a Special 510(k).
When a clinical investigation is necessary to answer safety and
effectiveness questions relating to a particular modification,
the Agency believes that the modification is likely to have gone
beyond that which is suitable for review as a Special 510(k).
In contrast, where design validation involves clinical evaluation
intended to ensure that the modified device meets user requirements
as opposed to patient safety and effectiveness or to demonstrate
continued conformance with a special control or recognized standard,
FDA believes that the Special 510(k) may be the appropriate submission.
B.
Abbreviated 510(k)
Over the past few years, FDA has been placing
greater emphasis on the development of guidance documents to communicate
regulatory and scientific expectations to industry. In the 510(k)
area, numerous guidance documents exist, while others are under
development for Class I, Class II and preamendments Class III
devices. With the advent of Good Guidance Practices, device璼pecific
guidance documents are developed with public participation. The
main focus of these guidance documents is the identification of
the information recognized as appropriate for marketing authorization.
FDA believes that use of these device-specific guidances may
provide an effective means of streamlining the review of 510(k)s
through a reliance on a "summary report" outlining adherence
to relevant guidance documents. A 510(k) submission that conforms
with an FDA guidance document should be easier to prepare and
review, thus resulting in a more expeditious evaluation and clearance
of the 510(k).
The SMDA introduced the concept of special
controls as a means by which the safety and effectiveness of Class
II devices can be assured. Special controls are defined in section
513(a)(1)(B) of the Act as those controls, such as performance
standards, postmarket surveillance, patient registries, development
and dissemination of guidelines, recommendations and other appropriate
actions that provide reasonable assurance of the device's safety
and effectiveness. As in the case of guidance documents, summary
information that describes how a special control(s) has been used
to address a specific risk or issue should reduce the time and
effort to prepare and review 510(k)s.
In addition to device-specific guidance
documents (hereinafter referred to as guidance documents) and
special controls, CDRH is committed to recognizing individual
consensus standards. In fact, the FDAMA amended section 514 of
the Act to specifically authorize the Agency to recognize all
or part of national and international standards through publication
of a notice in the Federal Register. Recognized standards could
be cited in guidance documents or individual policy statements,
or established as special controls that address specific risks
associated with a type of device. IEC 60601-1 is an example of
such a consensus standard. It has broad applicability to many
electromedical devices. FDA's recognition of this standard, combined
with modified review procedures, should streamline the review
of many 510(k)s for devices covered by the standard. Finally,
by using accompanying particular standards to adapt a general
standard to a specific device, the 510(k) review process may be
further expedited.
Therefore, device manufacturers may choose
to submit an Abbreviated 510(k) when: (1) a guidance documents
exists, (2) a special control has been established, or (3) FDA
has recognized a relevant consensus standard.5 An Abbreviated
510(k) submission must include the required elements identified
in 21 CFR 807.87. In addition, manufacturers submitting an Abbreviated
510(k) that relies on a guidance document and/or special control(s)
should include a summary report that describes how the guidance
document and/or special control(s) were used during device development
and testing. (See Attachment 3.) The summary report should include
information regarding the manufacturer's efforts to conform with
the guidance document and/or special control(s) and should outline
any deviations. Persons submitting an Abbreviated 510(k) that
relies on a recognized standard should provide the information
described in Attachment 3 (except for the summary report) and
a declaration of conformity to the recognized standard. (See
Attachment 4.) Such persons should also refer to the Agency's
guidance entitled, "Guidance on the Recognition and Use of
Consensus Standards."
In an Abbreviated 510(k), a manufacturer
will also have the option of using a third party to assess conformance
with the recognized standard. Under this scenario, the third
party will perform a conformance assessment to the standard for
the device manufacturer and should provide the manufacturer with
a statement to this effect. Like a Special 510(k), the marketing
application should include a declaration of conformity signed
by the manufacturer, while the statement from the third party
should be maintained in the DMR pursuant to the Quality System
Regulation. Responsibility for conformance with the recognized
standard, however, rests with the manufacturer, not the third
party.
The incentive for manufacturers to elect
to provide summary reports on the use of guidance documents and/or
special controls or declarations of conformity to recognized standards
will be an expedited review of their submissions. While abbreviated
submissions will compete with traditional 510(k) submissions,
it is anticipated that their review will be more efficient than
that of traditional submissions, which tend to be data intensive.
In addition, by allowing ODE reviewers to rely on a manufacturer's
summary report on the use of a guidance document and/or special
controls and declarations of conformity with recognized standards,
review resources can be directed at more complicated issues and
thus should expedite the process.
Conclusion
FDA believes that the New 510(k) Paradigm
will provide considerable flexibility for the medical device industry
in demonstrating substantial equivalence in 510(k) submissions.
The principles presented in this guidance document will be implemented
through changes in the administrative processes and do not require
changes to either the premarket notification regulation (21 CFR
807 Subpart E Premarket Notification Procedures) or to the Act.
As experience is gained by the industry in preparing Special
and Abbreviated 510(k)s and by FDA in evaluating these new types
of 510(k) submissions, this guidance document may be updated and
revised. CDRH will create and update a "New 510(k) Paradigm"
website on the CDRH home page with information regarding this
guidance as it becomes available. Device manufacturers should
access this website for copies of Special/Abbreviated 510(k) coversheets,
checklists, and additional information regarding implementation
of the New Paradigm.
Effective Date: This guidance document is effective March 20, 1998.
A Special 510(k): Device Modification should
include:
** The above two statements should
be signed by the designated individual(s) responsible for those
particular activities.
7 In cases where the referenced 510(k) was submitted under a different name than that of the submitter of the Special 510(k), the Agency recommends that a statement to this effect be included in the Special 510(k) and that the submitter maintain adequate information demonstrating his legal right to distribute the device.
8 If a recent Quality System inspection has resulted in the issuance of a violative inspection report, the manufacturer should be prepared to describe those corrective actions taken, if needed, that form the basis for the declaration of conformity.
An Abbreviated 510(k) should include:
In preparing a declaration of conformity
to recognized standards, manufacturers should refer to the guidance
document entitled, "Guidance on the Recognition and Use of
Consensus Standards." In accordance with this guidance,
declarations of conformity to recognized standards should include
the following:
Updated 3/20/98
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