[Federal Register: June 26, 2003 (Volume 68, Number 123)]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 01D-0281]
Medical Devices: A Pilot Program to Evaluate a Proposed Globally
Harmonized Alternative for Premarket Procedures; Final Guidance for
Industry and FDA Staff; Availability
AGENCY: Food and Drug Administration, HHS.
SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of final guidance entitled ``A Pilot Program to Evaluate a
Proposed Globally Harmonized Alternative for Premarket Procedures;
Guidance for Industry and FDA Staff.'' This guidance is intended to
assist the medical device industry and FDA staff in implementing a
voluntary pilot premarket review program that may reduce the burden on
manufacturers who face conflicting premarket submission format and
content requirements in different countries. The proposed pilot program
will evaluate the utility of an alternative submission procedure as
described in the document entitled ``Summary Technical Documentation
for Demonstrating Conformity to the Essential Principles of Safety and
Performance of Medical Devices,'' otherwise known as the ``draft STED
document.'' The draft STED document was developed by Study Group 1
(SG1) of the Global Harmonization Task Force (GHTF), and issued as a
working draft in December 2000. The GHTF is a voluntary group comprised
of medical device regulatory officials and industry representatives
from the United States, Canada, Australia, the European Union, and
Japan. Each of these member countries will participate in the pilot
program and will provide specific directions for implementing the
program within their respective jurisdictions. This guidance takes
effect upon the date of its publication.
DATES: Submit written comments at any time.
ADDRESSES: Submit written requests for single copies of the guidance
document entitled ``A Pilot Program to Evaluate a Proposed Globally
Harmonized Alternative for Premarket Procedures; Guidance for Industry
and FDA Staff'' to the Division of Small Manufacturers Assistance (HFZ-
220), Center for Devices and Radiological Health, Food and Drug
Administration, 1350 Piccard Dr., Rockville, MD 20850. Send two self-
addressed adhesive labels to assist that office in processing your
request, or fax your request to 301-443-8818.
Submit written comments concerning this guidance to the Division of
Dockets Management (HFA-305), Food and Drug Administration, 5630
Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments
to http://www.fda.gov/opacom/backgrounder/voice.html. Comments are to
be identified with the docket number found in brackets in the heading
of this document. See the SUPPLEMENTARY INFORMATION section for
information on electronic access to the guidance.
FOR FURTHER INFORMATION CONTACT: Timothy A. Ulatowski, Center for
Devices and Radiological Health (HFZ-300), Food and Drug
Administration, 2094 Gaither Rd., Rockville, MD 20850, 301-594-4692, e-
mail: firstname.lastname@example.org; or Harry R. Sauberman, Center for Devices and
Radiological Health (HFZ-480), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850, 301-443-8879, e-mail:
FDA is conducting a pilot premarket review program and is
soliciting participation from the medical device industry. The pilot
program is intended to evaluate the utility of an alternative
submission procedure as described in the draft STED document prepared
by SG1 of the GHTF. The document seeks to harmonize the different
requirements for premarket submissions in various countries.
The GHTF is a voluntary group comprised of medical device
regulatory officials and industry representatives from the United
States, Canada, Australia, the European Union, and Japan. The goals of
the GHTF are to: (1) Encourage convergence in regulatory practices with
respect to ensuring the safety, effectiveness, performance, and quality
of medical devices; (2) promote technological innovation; and (3)
facilitate international trade. The GHTF's Web site can be accessed at
http://www.ghtf.org. It provides further information concerning the
organization's structure, goals, and procedures.
The pilot premarket review program (STED pilot program) as
implemented in the United States by FDA, will rely on the FDA final
guidance that is the subject of this notice, and four related documents
that are appended to the guidance. These documents are: (1) A letter to
the global medical device industry announcing the pilot program
(Appendix 1); (2) the draft STED document created by SG1 of GHTF
(Appendix 2); (3) the GHTF SG1 final document entitled ``Essential
Principles of Safety and Performance of Medical Devices,'' known as
``Essential Principles'' (Appendix 3); and (4) the document entitled
``The Least Burdensome Provisions of the FDA Modernization Act of 1997:
Concept and Principles; Final Guidance for FDA and Industry,'' issued
in October 2002 (Appendix 4).
The FDA guidance document is intended to assist the medical device
industry in making submissions to FDA that use the draft STED document
format and are consistent with U.S. requirements. The announcement
letter provides useful background and summary information regarding the
proposed pilot premarket review program. The draft STED document
describes a proposed internationally harmonized format and content for
premarket submissions, e.g., PMA applications and 510(k) submissions in
the United States, based on conformity to the Essential Principles. The
Essential Principles are general and specific safety and performance
recommendations for medical devices. They were developed by GHTF and
are listed in the third document appended to the guidance. A discussion
of the least burdensome provisions is provided in the fourth document.
All five of the founding members of the GHTF are participating in
the pilot program. They include the United States, Canada, Australia,
the European Union, and Japan. Each of the participants will provide
specific directions for implementing the pilot program within its own
The GHTF seeks to assess the international utility of the draft
STED document. Therefore, SG1 of GHTF is encouraging manufacturers to
prepare submissions using the draft STED document for a particular
device to as many of the participating GHTF member countries as
possible. SG1 also encourages manufacturers to use the draft STED
document for submissions that cover a range of devices having different
regulatory classes. Candidate devices that have already been identified
to be of mutual interest to the GHTF members are set forth in the
FDA intends to process premarket submissions prepared using the
draft STED document within statutory time limits and with review times
comparable to other submissions for similar products. There will be no
expedited review of submissions unless the device merits such review
under current policies.
FDA plans to conduct the STED pilot program for a period of 1 year.
The pilot will begin on the date of publication of the final FDA
guidance document. FDA will assess the pilot during its course and may
choose to decline receipt of additional submissions using the format
described in the draft STED document (draft STED format) to assess the
initial experiences. At the end of the pilot, FDA and other GHTF
participants will analyze the outcome to determine whether the draft
STED document is a viable alternative to current premarket submission
procedures and whether the program should be continued or expanded. FDA
will post on its Web site a report of the outcome of the pilot program.
FDA published a draft of the FDA guidance document in the Federal
Register of July 25, 2001 (66 FR 38714). The comment period ended on
September 24, 2001. FDA received comments from five parties; in some
instances the parties submitted multiple comments. FDA's responses are
provided in section II of this document. In addition, FDA is planning
to have SG1 review the comments and provide recommendations at the time
it revises the draft STED document. This would occur at the end of the
II. Comments and Responses
(Comment 1) One comment states that harmonization is a barrier to
entry in the marketplace for smaller companies. The comment expresses
concern that the Essential Principles referenced in the draft STED
document will add more premarket notification (510(k)) requirements for
those seeking to obtain FDA clearance for their medical devices.
FDA believes the draft STED document, and the associated FDA
guidance document describing how FDA intends to implement the pilot
premarket program, do not present significant new impediments for
persons intending to market their devices using the 510(k) process.
There are no new requirements expected under the pilot program for
registration or quality systems implementation before a person submits
a 510(k) using the draft STED format. The example, manufacturing
information, is not ordinarily required in a 510(k) submission. The
same would be true for a submission using the draft STED format. A
manufacturer, however, must be registered and a quality system must be
in effect when a device is marketed.
(Comment 2) One comment supports the harmonization process and
requests that table 1 in the FDA guidance
document be revised to include computed tomography scanners and
magnetic resonance imaging devices.
FDA agrees to expand the candidates list as requested and has
amended table 1 of the FDA guidance document accordingly.
(Comment 3) Two comments requested that members of the GHTF
coordinate the execution of the pilot program in their respective
jurisdictions by including the same device categories and conducting
the pilot program simultaneously. The comments suggested posting
information about the pilot program on the GHTF Web site. Concern was
expressed that the draft STED document will lead to an increase in the
type and amount of information submitted in premarket applications.
FDA agrees that the pilot premarket program should be coordinated
with other members of GHTF to the extent possible, and has made efforts
to do so. FDA will work with the GHTF secretariat and the Chair of SG1
to post appropriate information regarding the pilot program on the GHTF
Web site. FDA is sensitive to the concern that a harmonized format may
recommend different or additional information from that customarily
submitted in premarket submissions. The draft STED format is one means
of normalizing the information submitted to many different regulatory
authorities. The short-term effect may indicate some imbalances in the
regulatory burden from one country to another, but the long-term
expectation is that the benefits will outweigh any short-term effects
and will be significant. FDA believes that harmonization of
administrative and technical requirements is desirable; the GHTF's role
in the STED pilot program is supplemented by the strength of its
efforts in standards development activities, bilateral partnerships,
and mutual recognition activities.
(Comment 4) Another comment requests clarification of the
information needed to be included in the premarket submission for each
Essential Principle and asks if every Essential Principle must be
addressed. The comment also requests clarifications on terminology with
respect to labeling.
The premarket submission should identify the Essential Principles
that are applicable to the device and provide conformity information as
explained in sections 7.1.1 and 7.1.2 of the draft STED document. It
will not necessarily be the case that all Essential Principles will be
applicable to a particular device. In addition, there may be more than
one way to conform to an Essential Principle, e.g., by meeting a
standard or demonstrating laboratory results from an appropriate bench
FDA agrees that the draft STED document should have clarifications
with respect to labeling terminology and instructions for use. FDA will
ask SG1 to consider this comment when it assesses the results of the
(Comment 5) Two comments ask FDA to clarify which of the Essential
Principles would be relevant in a premarket submission prepared using
the draft STED format. They ask whether FDA intends for premarket
submissions, based on the draft STED format, to be submitted in a
tabular format as shown in Appendix B of the draft STED document and,
if so, whether the table needs to be supplemented with supporting
FDA expects premarket submissions prepared using the draft STED
format to identify and reference all applicable Essential Principles,
as explained in sections 7.1.1 and 7.1.2 of the draft STED document.
Also, 510(k) submissions and premarket approval applictions (PMAs)
relying on the draft STED format must still address all applicable FDA
requirements for 510(k)s or PMAs. With regard to format, the basic
format for preparing a harmonized premarket submission is described in
sections 6.1 and 6.3 of the draft STED document (see also section VII
of the final FDA guidance). Each part of the submission can be
subgrouped as described in section 7.0 of the draft STED document.
Section 7.1.2 suggests that one method to format evidence of conformity
information may be in tabular form as shown in the sample table in
Appendix B of the draft STED document. Supporting information should be
provided as needed regardless of format, particularly if recommended in
a product-specific guidance. FDA accepts declarations or statements of
conformity to FDA-recognized standards. Use of such declarations or
statements may provide a benefit to a manufacturer by decreasing the
amount of supporting documentation that needs to be submitted.
(Comment 6) Another comment notes a possible incorrect cross-
reference in table 3 of the draft FDA guidance with regard to
FDA has eliminated table 3 and has clarified the section.
(Comment 7) Three comments state that a risk analysis is not
included in 510(k) and PMA submissions and therefore should not be
included in harmonized premarket submissions using the draft STED
FDA has announced new guidance that includes a risk analysis in
some 510(k) submissions. (See http://www.fda.gov/cdrh/modact/special-controls.html
). A goal of the premarket harmonization process is to
achieve a common submission in terms of format and content for all five
participating members of the GHTF. Although FDA may not require a risk
analysis for a new 510(k), it is a common request in other countries.
Therefore, it is prudent for a device manufacturer intending to market
a device globally, and who intends to use the draft STED format, to
include a risk analysis in the submission.
(Comment 8) One comment asks for clarification of the note under
table 2 of the draft FDA guidance concerning manufacturing information.
FDA has eliminated table 2 and clarified the information elsewhere
in the document. The FDA final guidance document notes that
manufacturing information will not be needed for 510(k)s using the
draft STED format during the pilot program, unless that information
would otherwise be submitted under current procedures for a particular
(Comment 9) One comment requests the draft STED document include
links between the class of a device and the parameters applicable to
the Essential Principles of safety and performance. The comment
suggests changing the title of section 7.3 from ``Summary of Design
Verification and Validation Documents'' to ``Summary of Design and
Verification Data.'' The comment notes the title could imply the need
for more documentation than what is intended.
FDA will ask SG1 to consider this comment when it assesses the
results of the pilot program.
(Comment 10) One comment recommends the use of promissory
statements when a regulatory authority requires country-specific
information beyond that described in the draft STED document.
FDA accepts statements of conformity to recognized standards. These
statements indicate a device meets a particular standard. FDA has no
other provisions for promissory statements.
(Comment 11) Another comment notes that the draft STED document and
appendices refer to data and information not usually submitted in
510(k)s and PMAs. It suggests there be an indication of the information
not applicable for these types of submissions to minimize the
FDA agrees with the comment and has noted that manufacturing
information is not ordinarily required in a 510(k) application. Hence
this information would not be needed in a
510(k) when using the draft STED format as described in the final
(Comment 12) One comment inquires about incentives for
manufacturers to participate in the pilot program. Related comments ask
that FDA reconsider the devices eligible for the pilot program.
FDA is committed to ensuring that the FDA review process will not
be unduly hindered if persons choose to follow the draft STED format.
However, FDA cannot assure shorter review timeframes if the draft STED
format is used. FDA believes that medical device companies with vision,
leadership, a desire to influence the accelerating global harmonization
effort, and the goal of ultimately reducing their regulatory burden,
will participate in the pilot program. FDA has increased the list of
eligible devices to provide more flexibility and believes the pilot
program will help achieve an international uniformity of submissions.
(Comment 13) One comment asks that the pilot program focus only on
510(k)s, PMAs, and PMA supplements that are for high risk devices.
FDA has exempted from premarket evaluation virtually all the low
risk devices that were subject to premarket requirements. Therefore,
the candidates for the pilot program are of a moderate to high degree
of risk. PMA supplements are not candidates for the pilot program.
(Comment 14) One comment asks that the same measures of success or
failure of the pilot program be identified for all countries conducting
the pilot and that FDA clearly define the criteria and analysis methods
that will be used.
FDA agrees that measures of success and analytical methods should
be clearly defined prior to initiation of the pilot. It is important to
determine whether the core of a premarket submission can be based on
the draft STED format. Both FDA and SG1 will track and assess whether:
(1) There are significant impediments to filing and review of
documents, (2) the STED harmonized format has utility for evaluating
different regulatory classes of devices having different complexities,
and (3) use of the STED harmonized format results in improved
regulatory review times. FDA will post a report summarizing the results
of its analysis of the pilot on its Web site.
(Comment 15) One comment notes that statutory and/or regulatory
changes may be needed to fully implement the draft STED document
concept of harmonized premarket submissions in the member countries.
Each of the five GHTF member countries has determined that the
pilot program can proceed without the need for statutory or regulatory
changes if current country-specific requirements are met. It remains to
be determined how a STED document would be implemented if it becomes an
alternative means of submission.
(Comment 16) One comment asks that FDA remove endosseous dental
implants from the list of candidate devices for the pilot program. The
comment notes that applying the harmonized process to these implants
will not provide the agency with the necessary information on their
safety and effectiveness.
FDA does not concur with the comment. The FDA draft guidance for
the pilot premarket review program and the draft STED document both
describe the need for applicants to consider country-specific
information, including guidance documents, when preparing their
premarket submissions for review. A premarket submission for an
endosseous dental implant based on the draft STED format should
consider all relevant available guidance documents.
III. Significance of Guidance
This guidance is being issued consistent with FDA's GGPs regulation
(21 CFR 10.115). The guidance represents the agency's current thinking
on a way to apply GHTF recommendations as related to premarket
submission to FDA. 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 and regulations.
IV. Electronic Access
You may obtain a copy of ``A Pilot Program to Evaluate a Proposed
Globally Harmonized Alternative for Premarket Procedures; Guidance for
Industry and FDA Staff,'' via fax machine by calling the CDRH Facts-On-
Demand system at 800-899-0381 or 301-827-0111 from a touch-tone
telephone. Press 1 to enter the system. At the second voice prompt
press 1 to order a document. Enter the document number (1347) followed
by the pound sign (). Follow the remaining voice prompts to
complete your request.
You may also obtain a copy of the guidance through the Internet.
CDRH maintains an entry on the Internet for easy access to information
including text, graphics, and files that may be downloaded to a
personal computer with Internet access. The CDRH home page is updated
on a regular basis and includes: Civil money penalty guidance
documents, device safety alerts, Federal Register reprints, information
on premarket submissions (including lists of approved applications and
manufacturers' addresses), assistance for small manufacturers,
information on video conferencing, electronic submissions, mammography
devices, and other device-related information. The CDRH home page may
be accessed at http://www.fda.gov/cdrh.
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper copy.
Comments are to be identified with the docket number found in brackets
in the heading of this document. Received comments may be seen in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
Dated: June 19, 2003.
Assistant Commissioner for Policy.
[FR Doc. 03-16108 Filed 6-25-03; 8:45 am]
BILLING CODE 4160-01-S