[Federal Register: June 26, 2003 (Volume 68, Number 123)]
[Notices]               
[Page 38068-38071]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26jn03-100]                         

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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.

ACTION: Notice.

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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-

[[Page 38069]]

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: tau@cdrh.fda.gov; 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: 
hrs@cdrh.fda.gov.
SUPPLEMENTARY INFORMATION:

I. Background

    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 
jurisdiction.
    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 
guidance.
    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 
pilot program.

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

[[Page 38070]]

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 
test.
    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 
pilot program.
    (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 
information.
    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 
standards.
    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 
document.
    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 
device.
    (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 
submission burden.
    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

[[Page 38071]]

510(k) when using the draft STED format as described in the final 
guidance document.
    (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.

V. Comments

    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 
through Friday.

    Dated: June 19, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-16108 Filed 6-25-03; 8:45 am]

BILLING CODE 4160-01-S