[Federal Register Volume 63, Number 215 (Friday, November 6, 1998)]
[Rules and Regulations]
[Pages 60122-60164]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-29609]
[[Page 60121]]
_______________________________________________________________________
Part IV
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
21 CFR Part 26
Mutual Recognition of Pharmaceutical Good Manufacturing Practice
Inspection Reports, Medical Device Quality System Audit Reports, and
Certain Medical Device Product Evaluation Reports Between the United
States and the European Community; Final Rule
Memorandum of Understanding Between the Food and Drug Administration
and the Office of the United States Trade Representative; Notice
Federal Register / Vol. 63, No. 215 / Friday, November 6, 1998 /
Rules and Regulations
[[Page 60122]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 26
[Docket No. 98N-0185]
RIN 0910-ZA11
Mutual Recognition of Pharmaceutical Good Manufacturing Practice
Inspection Reports, Medical Device Quality System Audit Reports, and
Certain Medical Device Product Evaluation Reports Between the United
States and the European Community
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is amending its
regulations pursuant to an international agreement between the United
States and the European Community (EC). The agreement is entitled
``Agreement on Mutual Recognition Between the United States of America
and the European Community'' (MRA). Under the terms of that agreement,
the importing country authority may normally endorse good manufacturing
practice (GMP) inspection reports for pharmaceuticals provided by the
exporting authority determined by the importing authority to have an
equivalent regulatory system. Likewise, the importing country authority
may normally endorse medical device quality system evaluation reports
and certain medical device product evaluation reports provided by
conformity assessment bodies (CAB's) determined by the importing
country authority to have equivalent assessment procedures. FDA is
taking this action to enhance its ability to ensure the safety and
effectiveness of pharmaceuticals and medical devices through more
efficient and effective utilization of its regulatory resources. The
proposed rule which published in the Federal Register on April 10, 1998
(63 FR 17744), carried an incorrect docket number in its heading. This
final rule carries the correct docket number.
DATES: This regulation is effective on December 7, 1998. The Director
of the Office of the Federal Register approves the incorporation by
reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51 of a
certain publication listed in new Sec. 26.60(b), effective December 7,
1998. Written comments and information relevant to implementation of
the MRA and this regulation may be submitted at anytime.
ADDRESSES: Submit written comments and information relevant to
implementation of the MRA and this regulation to the Dockets Management
Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Merton V. Smith, Office of
International Affairs (HFG-1), Office of External Affairs, Food and
Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-
0910, or E-mail: ``MSmith@oc.fda.gov''.
SUPPLEMENTARY INFORMATION:
I. Background
On June 20, 1997, the United States and the EC concluded an
agreement on the MRA. The MRA includes two sectoral annexes covering
products regulated by FDA. The sectoral annex on medical devices covers
medical device quality system-related inspection reports and certain
product evaluation reports. The sectoral annex for pharmaceutical GMP's
covers pharmaceutical GMP inspection reports. The MRA also includes
sectoral annexes covering products regulated by other U.S. regulatory
agencies, including telecommunication equipment, electromagnetic
compatibility, electrical safety, and recreational craft. Finally, the
MRA includes a ``framework'' agreement that contains general
provisions.
At the conclusion of negotiations, the United States and the EC
submitted the text of the MRA to their respective authorities to
complete the necessary procedures for approval and implementation. For
FDA, these procedures included publishing a proposed rule that was
published in the Federal Register of April 10, 1998 (63 FR 17744). The
proposed rule was based on the provisions contained in the two FDA
sectoral annexes and the ``framework'' agreement of the MRA concluded
on June 20, 1997. FDA received comments from 14 persons in response to
this proposed rule. Many of these comments supported the proposed rule.
Some comments raised significant issues but none that, in FDA's view,
necessitated any substantive changes to the proposed rule. On May 14,
1998, FDA informed the Office of the U.S. Trade Representative (USTR)
that it supported the signing of the MRA. The MRA was signed in London
on May 18, 1998. Provisions of the MRA are between the United States
and EC, and do not create rights in third parties.
II. Summary of Comments
A. General Comments and Issues
Most comments by industry associations and pharmaceutical and
medical device manufacturers generally were supportive of the MRA and
the proposed rule. Some comments by others expressed concern about
possible diminished public health and safety if certain precautions are
not taken.
1. Five comments strongly supported the MRA and the proposed rule,
citing its potential to improve patient access to safe and effective
technologies, reduce unnecessary regulatory redundancies, enhance the
access of United States and EC companies to each other's markets,
provide significant savings to both companies and regulators, and set
the stage for further regulatory cooperation and harmonization. They
indicated that the proposed rule and the MRA allow for incorporation of
the best regulatory attributes.
FDA agrees with these comments. FDA takes the view that equivalence
of GMP reports and other conformity assessment reports and evaluations
between the FDA and EC Member State authorities and CAB's can be relied
on to help ensure the safety, quality, and effectiveness of products
exported to the United States while also reducing the regulatory burden
on manufacturers. For the United States, the MRA and this regulation
also permit FDA to redirect some of its inspectional resources from
countries whose systems are found equivalent to, or higher to, risk
priorities not covered under the MRA. The agency may thus better target
its limited foreign inspection and other resources devoted to imports
and other regulatory concerns. Thus, FDA will be able to leverage its
resources by relying on information from its counterpart regulatory
authorities in foreign countries that have demonstrated equivalence.
Under the MRA and this regulation, as equivalence is achieved between
regulatory systems of EC Member State authorities, or CAB's, and FDA,
there will be reduced need for importing countries to engage in
resource-intensive foreign inspection, sampling, and examination of
products being for entry from countries with equivalent systems. This
can assist in speedier approvals of safe and effective products and in
more comprehensive and effective surveillance of GMP's and quality
systems. In addition, during the transition period, collaborative
confidence-building activities between FDA and EC Member State
authorities and CAB's can result in harmonization of requirements at a
high level of
[[Page 60123]]
consumer protection, thus enhancing regulatory controls.
2. One comment described three fundamental principles which
underlie the comment's concerns about the MRA and the proposed rule:
(1) The paramount goal for FDA implementation of the MRA and the
proposed rule must be to safeguard public health of U.S. consumers; (2)
equivalence determinations performed by FDA must improve or at least
maintain current U.S. public health protections; and (3) the United
States' democratically accountable, policy-making process must be
maintained.
FDA agrees with these comments. FDA has consistently articulated
these same principles in its policies relating to international
cooperative agreements over the last decade. In 1988, the FDA and
Directorate-General III (Industrial Affairs) of the European Commission
began early discussions in consideration of agreements in the areas of
pharmaceutical and medical device GMP inspections. The FDA's primary
motivation in seeking such agreements was at that time, and still is, a
desire to leverage its limited inspectional resources and to enhance
public health protection through increased assurance that regulatory
counterparts are applying similar controls. FDA described the value of
pursuing international cooperative agreements with selected foreign
regulatory bodies in its 1992 ``Report of the Task Force on
International Harmonization'' (Ref. 1). The Task Force concluded that
such international agreements are an effective means of facilitating
the safety, effectiveness, and/or quality of products that are offered
for import into the United States and of efficiently setting priorities
for the agency's inspectional resources. The Task Force concluded that
a properly conceived and executed agreement would permit FDA's use of
foreign government inspectional information to assist in the agency's
regulatory decision-making and could help FDA to set priorities for
foreign inspection or import surveillance programs. As a result of
specific Task Force recommendations, in 1995 FDA revised its Compliance
Policy Guide (Ref. 2) to emphasize that the agency's primary goals for
entering into agreements with foreign governments are for the purposes
of better utilizing its regulatory resources and furthering its mission
of protecting the U.S. consumer.
The significant increase of international commerce in
pharmaceuticals and medical devices and the question of how FDA can
continue to ensure the safety and effectiveness of these medical
products prompted the agency to convene a Foreign Inspection Working
Group in 1995 to evaluate the agency's foreign inspection program and
related import product monitoring. In 1997, this group issued its
``Summary Report of the Foreign Inspection Working Group'' (Ref. 3)
that recognized the need for inspectional approaches that involve
cooperative activities such as the development of international
agreements between FDA and counterpart regulatory authorities in other
countries.
Section 26.21 of this rule provides that the importing country has
the right to fulfill its legal responsibilities by taking actions
necessary to ensure the protection of human and animal health at the
level of protection it deems appropriate. In addition, under Sec. 26.74
nothing in this part limits the authority of FDA to take appropriate
and immediate measures that it determines necessary to prevent
compromising human health and safety, or to fulfill its legislative,
regulatory, or administrative responsibilities.
To ensure a democratic and open process, the FDA will make
available in a public docket the complete administrative file that
constitutes the basis for FDA's equivalence determinations. In
addition, any other related documents the agency receives under the MRA
and this regulation will be releasable to the public (or not
releasable) according to current Freedom of Information Act (FOIA)
provisions. FDA also will assess the degree to which a foreign
regulatory system or CAB is accountable to consumers and other
interested parties as part of its equivalence determinations. (App. D
of subpart A, criteria I.F.). A regulatory system that is not
sufficiently transparent to assess accountability may not be found
equivalent.
3. One comment stated that the MRA and the proposed rule would
replace FDA-conducted inspections of foreign pharmaceutical plants and
FDA reviews of foreign medical devices with inspections and evaluations
performed by EC Member State authorities and CAB's located in EC Member
States.
The implementation of the MRA and this regulation may or may not
result in the replacement of some FDA inspections and product
evaluations of medical devices produced by manufacturers located in EC
Member States. Inspection reports and product evaluations may normally
be endorsed under certain conditions only if, after a comprehensive
assessment during the 3-year transition period, FDA determines that
such reports will provide the information that FDA needs for its
regulatory decision making.
4. One comment stated that the MRA negotiation took place primarily
for trade facilitation purposes. Evidence of this conclusion was
offered by the fact that the negotiations were co-chaired by USTR and
the Department of Commerce (DOC) and that press releases and other
public statements have characterized the discussions as ``trade
negotiations.''
FDA participated in the negotiations leading to the MRA under its
own authority to enter agreements with foreign authorities (see, inter
alia, sections 519 and 803 of the Federal Food, Drug, and Cosmetic Act
(the act) (21 U.S.C. 360(i), 383)). Furthermore, the agency believes
that the MRA and this regulation, properly based on a rigorous
determination of equivalence of regulatory systems, can help ensure the
safety, quality, and effectiveness of these imports while also reducing
the regulatory burden on manufacturers, thereby facilitating
availability of these important medical products. The goals of
facilitating trade and protection of the public health are not
necessarily incompatible. The role of USTR and DOC was one of
coordination. FDA's ability to reach decisions on the basis of its
public health priorities was upheld, and never compromised, during the
negotiations. FDA officials led the negotiations concerning the FDA
annexes, and FDA's views were incorporated into the portions of the
``framework'' agreement where FDA's interests were affected. USTR and
DOC as well as European trade counterparts undoubtedly desired an MRA
for trade reasons. Those agencies, however, supported FDA's position in
the negotiations and did not interfere with FDA's desire to maintain
health and safety protections. FDA believes that this degree of FDA
autonomy will continue as the MRA and this regulation are implemented.
Furthermore, FDA has entered into an interagency Memorandum of
Understanding (MOU) with the USTR that ensures that any decisions about
the MRA that relate to matters under FDA's jurisdiction will be made
only by FDA (see the notice of availability for this MOU published
elsewhere in this issue of the Federal Register). Specifically, the MOU
requires that USTR notify FDA of matters that the Joint Committee will
be considering. The MOU states that while USTR would normally speak and
vote for the U.S. Government in the Joint Committee, subject to
arrangements with other agencies covered by the MRA, FDA will speak
for, and vote on behalf of, the U.S.
[[Page 60124]]
Government on any matter pertaining to FDA's statutory or regulatory
authority raised within the Joint Committee or within any other bodies
established under the MRA. In addition, the Sectoral Annex for
Pharmaceutical GMP's is specifically exempted from certain provisions
of the ``framework'' agreement, in order to avoid any possible
confusion about the use of CAB's that are not utilized in the Annex.
Finally, throughout the ``framework'' agreement and the FDA product-
related annexes there are clear safeguard requirements that stipulate
if there are health and safety concerns on the part of the importing
authority, the importing authority may take appropriate action.
5. One comment stated that the goal of the MRA and the proposed
rule appears to be to harmonize health, safety, and environmental
standards to the lowest acceptable levels.
While the process of confidence-building and equivalence
determination may lead to harmonization of some standards, FDA
disagrees that lowest common denominator standards will result. During
the transition period, collaborative activities and joint equivalence
determinations by FDA-EC Member State authorities and CAB's may result
in harmonization of requirements that will enhance consumer protection.
By law, section 803(c)(1) of the act requires the Commissioner of Food
and Drugs (by delegation under 21 CFR 5.10) to work to ``harmonize
regulatory requirements,'' but conditions these actions on findings by
the Commissioner that ``such harmonization continues consumer
protections consistent with the purposes of this Act.'' FDA's
experience in working as a party to the Global Harmonization Task Force
(GHTF), the International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use, and the
International Cooperation on Harmonisation of Technical Requirements
for Registration of Veterinary Medicinal Products has demonstrated that
regulatory public health authorities do not compromise health and
safety as standards are harmonized, because the relevant discussions
and and the resulting documents have been thorough, science-based, and
protective of public health. (Harmonization can lead to higher
standards because in instances where one regulator has a requirement
that others lack, the ensuing discussions of why one regulator has such
a requirement often leads to understanding, acceptance, and inclusion
of a corresponding provision in the harmonized standard.)
6. One comment expressed the belief that the MRA and the proposed
rule put U.S. consumer protection at risk of compromise and cited as
evidence the fact that the negotiations extended well beyond their
original deadlines, and were reportedly near collapse due to concerns
about whether EC regulation is as stringent for pharmaceuticals and
medical devices as U.S. regulation.
The comment is correct in stating that the MRA negotiations took
longer than expected and that FDA had concerns during the early stages
of MRA discussions that early MRA drafts would not provide appropriate
public health protections for U.S. consumers. For example, the
provision for a 3-year confidence-building transition period was not
considered during early MRA discussions. Acceptance of the need for a
transition period during which time equivalence would be assessed was
one of the keys to moving the MRA negotiations ahead. Indeed, Article 2
of the Sectoral Annex for Pharmaceutical GMP's states that the
determination of equivalence of the regulatory systems by the parties
is the cornerstone of that Annex. FDA believes that the requirement of
a comprehensive assessment of equivalence before inspection reports and
product evaluations will be normally accepted, and other safeguard
clauses such as Secs. 26.21 and 26.74, as discussed previously, provide
strong public health protections. In the medical device provisions, EC
acceptance that FDA must, as a matter of law and policy, maintain final
decision making authority over premarket notifications, and that the
MRA could cover premarket notifications only for certain devices,
enabled conclusion of the MRA.
7. One comment stated that FDA must make a commitment to seek
additional resources to accomplish the activities required by the MRA
and the proposed rule.
In the preamble to the proposed rule, FDA acknowledged that neither
startup costs nor operational costs are being covered by additional FDA
funding in FDA's current budget and that startup costs will have to be
absorbed by current funding. Certain key activities of the MRA and this
regulation, such as joint inspections of manufacturers located in EC
Member States, may be accomplished as part of FDA's inspections of
these manufacturers that have been scheduled for the next fiscal year
as part of FDA's normal budget process. Other activities of the MRA and
this regulation will likely result in new costs. These additional costs
are difficult to estimate because they depend significantly on the
initial findings from FDA's equivalence assessments of EC Member State
authorities and CAB's. FDA will likely be better able to estimate these
additional costs as experience is gained during the first year of the
transition period. After the first year, FDA will reassess its need to
seek additional funding for the activities required by the MRA and this
regulation.
8. One comment stated that a failure to devote adequate resources
to the programs of the MRA and the proposed rule during the
implementation stage would endanger their success.
FDA agrees with this comment. FDA will engage in activities during
implementation as its resources permit. FDA recognizes the critical
need to undertake a number of activities during the transition process
as part of its assessment of the equivalence of CAB's located in EC
Member States, including participating in seminars, workshops, joint
training exercises, and observed inspections, as well as the analysis
required for the equivalence determination process. In addition, any
significant problem that is identified may require additional
activities to address and resolve it. Finally, the parties will need to
develop a consensus on what must be present in quality system and
product evaluation reports (or, where harmonization cannot be achieved,
each side will need to identify what it needs). Further, the parties
will develop a notification and alert system for defects, recalls, and
similar problems. All of these activities will require resources, and
FDA recognizes their completion is critical to the success of the MRA
and the implementation of this regulation.
9. One comment stated that the number of repetitive inspections
must actually decrease if the potential value of the MRA and the
proposed rule is to be realized.
FDA's interest in the MRA is its view that public health protection
can be better assured through enhanced regulatory cooperation. Although
FDA agrees that cost savings to industry and to government regulatory
authorities can be realized by an actual decrease in the number of
inspections that are unnecessarily duplicative, there are additional
benefits that may be achieved by the activities required under the MRA
and this regulation that make the MRA endeavor worthwhile. For example,
the cooperative activities between FDA and EC Member State authorities
that will of necessity be part of the equivalence determination
[[Page 60125]]
process may result in harmonization or congruence of requirements
resulting in strengthened consumer protection, more effective
regulatory approaches, and reduced regulatory burden on each side of
the Atlantic.
10. One comment suggested that FDA must use the inspectional
savings anticipated by the MRA and the proposed rule for increased
surveillance activities.
Any resource savings resulting from the MRA and this regulation
will be used by FDA as necessary and appropriate to enhance the
effectiveness of FDA's regulatory programs.
11. One comment stated that FDA should complete confidence building
activities as expeditiously as possible and should devote adequate
resources to that job.
FDA agrees with this comment and, as stated previously, will devote
resources to this program to the best of its ability.
12. One comment noted that the proposed rule did not address FDA
guidance documents and asked how guidance documents would be handled
under the MRA and this regulation. The comment implied that some FDA
guidance documents contain requirements.
FDA will handle guidance documents under this MRA as it handles all
guidance documents, according to FDA's Good Guidance Practices (62 FR
8961, February 27, 1997). If FDA determines that there is a need for
guidance documents under the MRA, it will publish them or refer to them
as appropriate. FDA periodically makes available to the public lists of
guidance documents and those that are relevant to the implementation of
the MRA or this regulation will be referred to during such
implementation. Guidance documents do not themselves contain
requirements; they do sometimes refer to or explain requirements that
exist in statutes or regulations.
13. One comment expressed concern that the MRA and the proposed
rule might result in lower health, safety, and environmental standards
in both the United States and the EC. The comment expressed concern
that the ``framework'' agreement might allow undue pressure to relax
regulation in one sector of commercial activity in order to secure
market access in another unrelated sector. Consequently, the comment
asked FDA to seek ``the elimination of the umbrella framework
agreement'' to ensure that U.S. health and safety standards are not
compromised.
FDA declines to take the action requested by the comment. The
``framework'' agreement will not result in lower health or safety
standards for FDA-regulated products. The MRA and this regulation
expressly preserve the authority of a party to determine, ``through its
legislative, regulatory, and administrative measures, the level of
protection it considers appropriate for safety; for protection of
human, animal, or plant life or health; for the environment; for
consumers; and otherwise with regard to risks'' (MRA Article 15,
``Preservation of Regulatory Authority,'' and Sec. 26.74 of this
regulation).
Additionally, this regulation expressly recognizes, at several
places, that statutory and regulatory requirements applicable to drugs
and devices remain in place unchanged (see, e.g., Sec. 26.1(b)
(definition of ``equivalence'') see also Sec. 26.32(c) and
Sec. 26.62(c) and that each party may take actions necessary to ensure
the protection of human and animal health ``at the level of protection
it deems appropriate'' (see Sec. 26.21; see also Sec. 26.74(a) and (b)
(preservation of regulatory authority)).
This position is consistent with both the statutes FDA administers
and international agreements such as the Agreement on Technical
Barriers to Trade which expressly recognizes that ``no country should
be prevented from taking measures necessary to ensure the quality of
its imports, or for the protection of human, animal or plant life or
health, of the environment, or for the prevention of deceptive
practices, at the levels it considers appropriate, subject to the
requirement that they are not applied in a manner which would
constitute a means of arbitrary or unjustifiable discrimination between
countries where the same conditions prevail or a disguised restriction
on international trade * * *.'' (See paragraph 6 of the preamble to the
Agreement on Technical Barriers to Trade).
FDA further notes that, under an MOU with USTR concerning the MRA
(see the notice of availability for this MOU published elsewhere in
this Federal Register), USTR will notify FDA of matters to be
considered by the Joint Committee, which will be established to
consider issues relating to the effective functioning of the MRA. While
USTR normally will speak and vote for the United States in the Joint
Committee, subject to arrangements with other agencies covered by the
MRA, FDA will speak for and vote on behalf of the United States on any
matter pertaining to FDA's statutory and regulatory authority. FDA will
also represent the U.S. Government on such matters in any other
committee or bodies with similar functions established under the MRA or
its annexes. This MOU will ensure that, insofar as FDA-regulated
products and issues are concerned, public health and safety issues are
adequately considered and addressed.
14. One comment strongly disagreed with FDA's position that a 30-
day comment period for the proposed rule was adequate. The comment was
characterized as ``a preliminary identification of key issues involved
in the [MRA or the proposed rule] process'' and requested that the
comments be viewed as ``the beginning of an ongoing open process in
which public comments will be considered at later junctures'' with
future opportunities to discuss issues with FDA and other government
officials.
As stated in the preamble to the proposed rule (63 FR at 17744 at
17747), FDA provided a 30-day comment period because a longer comment
period was unnecessary in light of the numerous opportunities for
public input the agency provided during the MRA negotiations. These
opportunities included the creation of a public docket for MRA-related
issues on May 9, 1996, dissemination of a document concerning the MRA
on October 18, 1996 (including an opportunity for public comment on
that document), public exchange meetings on March 31, 1995, and October
30, 1996, a Transatlantic Business Dialogue (TABD) meeting on November
8 and 9, 1996, which included a discussion of the MRA, and other public
meetings on March 14, 1997, and September 23, 1997. The MRA itself was
initialed by governmental representatives on June 20, 1997, and has
been available on the World Wide Web (WWW) for over a year. Therefore,
the agreement upon which the proposed rule was based had been available
for analysis and comment by interested members of the public for some
months. In view of these opportunities for public discussion and
consideration of the MRA, the 30-day comment period for the proposed
rule was adequate.
FDA also stated that it was in the public interest to proceed
expeditiously to implement the MRA, and that the 30-day comment period
was not contrary to Executive Order 12889 (63 FR 17744 at 17747).
As for the comment's remarks concerning future opportunities for
public comment, the agency shares this interest and notes that the
public has many avenues for contacting FDA on almost any issue. For
example, a person may send a letter to the agency, request a meeting,
submit a citizen petition to request issuance or revision of a
[[Page 60126]]
regulation or to request agency action or reconsideration on a
particular matter, or submit comments on a document published in the
Federal Register (see, e.g, 21 CFR 10.20, 10.30, 10.33, 10.65).
In sum, FDA agrees that the agency will need to communicate with
the public, on a regular basis, as the MRA is being implemented.
Interested persons may submit comments on the MRA, or implementation of
the MRA, to the agency at any time. In addition, as noted previously
FDA's administrative practices and procedures regulations (21 CFR part
10) provide a range of processes for interaction with the agency.
Furthermore, the agency contemplates frequent meetings and other
communications with the public as MRA implementation progresses.
B. Composition and Operation of the Joint Committees
Several comments encouraged, or would revise the rule to provide
for, opportunities for public, industry, or specific agency involvement
in various programs or bodies established by the MRA and the proposed
rule or by their operation.
1. Four comments said that FDA should ensure industry or public
access to and participation in the activities of the MRA and the
proposed rule. Three comments advocated industry participation and
suggested that FDA and the EC consult the industry during the
transitional and operational phases of the confidence building stage.
Two of these three comments specifically identified TABD as being
critical or essential to implementing the MRA and the proposed rule.
Another comment expressed the opposite view, i.e., concern about what
the comment described as the TABD's involvement in the MRA
negotiations. One comment asked FDA to ensure greater public
participation and access for nongovernmental organizations in future
mutual recognition agreement negotiations and throughout their
implementation.
The agency appreciates and values public and industry input and
advice on many matters and intends to employ a variety of means to seek
input from the public on the implementation of the MRA and this
regulation. However, the MRA and its sectoral annexes represent an
agreement between governments that contemplates examination of one
another's equivalence in specific areas of regulation. Although FDA
believes it would be inappropriate to amend the rule to require
industry or consumer participation or the participation of specific
industry or consumer representatives on delegations to meetings or to
require FDA or the EC to consult industry, FDA plans to consult
interested persons--whether they represent the industry, public
interest groups, or any other interested person--at appropriate stages
of implementation of the MRA and this regulation.
As for the comment requesting greater public participation in
future mutual recognition agreement negotiations and implementation,
that request is outside the scope of this rule. However, we refer
interested persons to ``A Plan that Establishes a Framework for
Achieving Mutual Recognition of Good Manufacturing Practices
Inspections,'' dated May 20, 1998 (see ``What's New on the FDA
Website'') (``www.fda.gov/opacom/newonweb.html'').
2. Four comments discussed representatives to either the Joint
Committee or the Joint Sectoral Committee in proposed Secs. 26.17 and
26.47 (``Role and Composition of the Joint Sectoral Committee'') and
26.73 (``Joint Committee''). Three comments requested clarification as
to which U.S. Government agencies would be represented on the Joint
Committee or the Joint Sectoral Committees; two comments advocated
including officials of USTR and the Department of Commerce on the Joint
Sectoral Committees; and one comment recommended including EC trade
offices on the Joint Sectoral Committees. All four comments advocated
industry representation, or regular participation, in the Joint
Committee and/or the Joint Sectoral Committees.
FDA declines to amend the rule to describe which U.S. or EC
governmental bodies will send representatives to meetings of the Joint
Committee or Joint Sectoral Committees as requested by the comments. In
general, the government representatives to either the Joint Committee
or the Joint Sectoral Committees will vary depending upon the issues
presented to those committees (see, e.g., Sec. 26.73(a) (stating that
the Joint Committee consists of ``representatives'' of both parties)
and Sec. 26.73(b) (authorizing the Joint Committee to establish Joint
Sectoral Committees ``comprised of appropriate regulatory authorities
and others deemed necessary''). Thus, each party has the flexibility to
determine which government authorities should be present and to match a
particular governmental authority's expertise to the issue or issues
before a committee. Amending the rule so that either committee would
have to include specific representatives of U.S. Government authorities
would unnecessarily impair such flexibility, and it would be especially
inappropriate for FDA to amend the rule to specify what representatives
the EC would send to the committees.
In any case, as explained in section II of this document, the USTR
will normally speak for and vote on behalf of the United States in the
Joint Committee, subject to arrangements with other agencies covered by
the MRA, and FDA will speak for and vote on behalf of the United States
on any matter pertaining to FDA's statutory or regulatory authority.
Furthermore, the Joint Committee (when FDA is representing the United
States) and the Joint Sectoral Committee likely will be addressing
technical issues of the sort that FDA, not USTR or DOC, will be
considering. The agency is confident that, in all cases, the
composition of the Joint Committee or Joint Sectoral Committees will be
appropriate for the topics being discussed.
As for the comments seeking industry representation or
participation in the Joint Committee or the Joint Sectoral Committees,
FDA declines to revise the rule to require such industry representation
or participation. Because the MRA, including its sectoral annexes, is
an agreement between governments, it is neither necessary nor
appropriate to amend the rule to include or to require nongovernmental
entities or organizations on the Joint Committee or the Joint Sectoral
Committees.
3. One comment asked for clarification about the composition of the
Joint Committee and asked whether U.S. citizenship is required for U.S.
members.
U.S. representatives addressing FDA topics will be FDA officials.
Except in extremely rare circumstances, U.S. citizenship is a
requirement for employment by FDA. European representatives will be
European Commission officials, possibly accompanied by officials of
member country regulatory authorities.
C. Transparency and Confidentiality Issues
Several comments discussed the need for ensuring public or industry
participation in equivalence or other regulatory matters under the
rule. Other comments emphasized a need for withholding certain
information, such as trade secrets and confidential commercial
information, from public disclosure.
1. One comment suggested that the rule contain a mechanism for
public participation in the equivalence determination process. The
comment would provide the opportunity for public comment or input
throughout the 3-year transition period, as soon as FDA
[[Page 60127]]
decides which foreign regulatory systems and CAB's it will review to
determine whether they are equivalent, and again when FDA makes a
preliminary determination of equivalence. The comment also called for
public notice in the Federal Register and a response to any public
comments when FDA issues a final determination.
FDA intends to hold periodic meetings with interested parties. FDA
also plans to prepare and to make public summaries of key meetings held
with its EC counterparts concerning implementation of the MRA and this
regulation. Further, FDA will make available to the public the
administrative file that constitutes the basis for any of FDA's
equivalence determinations subject to exemptions from disclosure
provided in the FOIA and restrictions in related statutory provisions
discussed in the response to comment 2 in section II.C of this
document. These approaches should give interested persons insight as to
the information FDA considered when making an equivalence
determination.
FDA also will use the Federal Register and its Internet home page
to make available information on equivalence determinations under the
MRA and this regulation. Interested persons can submit comments on
these determinations.
The agency believes it is important that all interested parties
have an opportunity to contribute to the equivalence assessment
process. To facilitate such contribution, FDA intends to hold public
meetings during the 3-year transition period. In addition, FDA invites
all interested persons to provide the agency with information that is:
(1) Generally relevant to implementation of the MRA and this
regulation; and, (2) of particular relevance to equivalence criteria in
Appendix D of subpart A of this rule, and their application to the
authorities listed in Appendix B of subpart A of this rule. Information
should be sent to the Dockets Management Branch (address above), and
should be identified with docket number 95N-0185.
2. Three comments would revise the proposed rule to ensure that the
public has access to: Draft programs for assessing equivalence of a
regulatory system under proposed Sec. 26.6(b); information provided by
a foreign government concerning that government's regulatory activities
under proposed Sec. 26.6(c); ``audit'' reports by European authorities
submitted to FDA; or records of CAB's reviewed by a foreign government
to the extent that such records would be publicly available if they
were reviewed by FDA. One comment explained that public disclosure
would ensure accountability and enable U.S. consumers to maintain
confidence in an ``equivalent'' inspection system. One comment would
also revise the proposed rule to state expressly that neither party may
obstruct public access to information that is publicly available under
the laws or regulations of that party.
In contrast, four comments sought clarification concerning
disclosure or confidentiality issues and proposed Sec. 26.76, such as
whether reports between the parties would be subject to public
disclosure under the FOIA; whether information provided to the EC would
be subject to EC confidentiality policies; and whether alert or
vigilance reports (required by proposed Sec. 26.50) exchanged between
the parties as part of an ongoing investigation would be subject to
public disclosure.
FDA declines to revise the rule as suggested by the comments. Under
Sec. 26.76(a) of this regulation and Article 17 of the MRA, each party
agrees to maintain, to the extent required under its laws, the
confidentiality of information exchanged under this regulation and the
MRA. Trade secrets, confidential commercial or financial information,
and information relating to an ongoing investigation are not subject to
public disclosure (see Sec. 26.76(b)). Additionally, the parties may
designate portions of information that it considers to be exempt from
disclosure, and parties are to take all precautions reasonably
necessary to protect information exchanged under the MRA and this
regulation from public disclosure (see Sec. 26.76(c) and (d)).
Those receiving information under the MRA will treat the
information according to their domestic laws and policies. FDA will
treat information it receives consistent with the FOIA, Privacy Act,
and FDA's regulations and policies. EC Member States will treat
information they receive according to the applicable laws in their
respective territories. Therefore, information supplied to FDA by a
foreign government or CAB and other information or documents discussed
by the comments are subject to the rules on public disclosure (or
nondisclosure) in the FOIA, the Privacy Act, parts 20 and 21 (21 CFR
parts 20 and 21). FDA further notes that other laws, regulations, and
agreements may provide additional safeguards against public disclosure
of trade secrets and confidential commercial information. For example,
section 301(j) of the act (21 U.S.C. 331(j)), in brief, prohibits any
person from using to his or her own advantage or revealing trade secret
information acquired by FDA under various provisions of the act.
Article 39 of the Agreement on Trade-Related Aspects of Intellectual
Property Rights (better known as the ``TRIPS'' agreement), to which the
United States is a signatory, states that:
Members, when requiring, as a condition of approving the
marketing of pharmaceutical or of agricultural chemical products
which utilize new chemical entities, the submission of undisclosed
test or other data, the origination of which involves a considerable
effort, shall protect such data against unfair commercial use. In
addition, Members shall protect such data against disclosure, except
where necessary to protect the public, or unless steps are taken to
ensure that the data are protected against unfair commercial use.
These laws and agreements would also be applicable to information and
documents acquired by FDA under the MRA and this regulation.
Consequently, given the existence of various agreements, laws, and
regulations pertaining to public disclosure and confidentiality, no
revision to this rule is necessary.
The public availability of the documents or information identified
in the comments would, therefore, depend on whether they contained
information that, under U.S. laws, regulations, or other obligations,
is exempt from public disclosure. In some instances, portions of a
document may be publicly available. For example, alert or vigilance
reports under Sec. 26.50, when provided to FDA, would be available for
public disclosure under Sec. 20.111 if the investigation of the
reported incident has been completed; however, personal identifiers
would be redacted, as FDA currently does under Sec. 20.111.
3. Two comments would revise proposed Sec. 26.76 so that a person
submitting information to FDA could decide whether all or part of the
information is confidential or trade secret and therefore not subject
to public disclosure.
FDA declines to revise the rule as suggested by the comments. The
agency believes this issue is handled adequately under current FDA
regulations and policies. FDA policy is to make the fullest possible
disclosure of records to the public, consistent with the rights of
individuals to privacy, property rights in trade secrets and
confidential commercial or financial information, and FDA's need to
promote frank internal policy deliberations and to pursue regulatory
activities without disruption (see Sec. 20.20). Under FDA regulations,
marking records submitted to FDA as confidential raises no obligation
by FDA to regard such records as confidential, to return them
[[Page 60128]]
to the person submitting the records, to review the records to
determine whether all or part of them are available for public
disclosure, or to withhold them from public disclosure (see
Sec. 20.27). FDA determines whether data or other information are
confidential and not subject to public disclosure, consistent with
Sec. 20.28.
4. One comment would revise proposed Sec. 26.76 so that trade
secrets, ongoing investigations, and patient records are confidential.
FDA declines to amend the rule as requested by the comment. Such a
revision is unnecessary given current statutory and regulatory
requirements involving public disclosure and confidentiality, including
the prohibition in section 301(j) of the act against disclosure of
trade secrets, all of which apply to information FDA receives from the
regulatory authorities and CAB's.
5. One comment would revise the rule so that a foreign country
receiving documents from FDA would have to make those documents
available to the U.S. public, even if the foreign country's laws would
not make those documents publicly available. The comment would make
information submitted to a foreign country available to the public if
that information were publicly available in the United States.
FDA declines to revise the rule as suggested by the comment.
Requiring a foreign country to make information available to U.S.
citizens when such disclosure would be contrary to the foreign
country's own laws and regulations is beyond the scope of this
rulemaking and beyond FDA's regulatory authority. In addition, the
public availability in the United States of information provided to EC
officials is already dealt with in FDA's regulations, particularly
Sec. 20.89. (Under Sec. 20.89, disclosure of nonpublic information to
foreign officials does not automatically result in that information
being available to the public generally.)
6. One comment would revise proposed Sec. 26.20 as it pertains to
the application of the alert system against individual companies. The
comment expressed concern about lack of transparency and due process
before a company is placed in or removed from ``a negative regulatory
status'' and suggested that the elements to be considered as part of
the alert system be described.
The comment misunderstands the purpose of the alert system
provisions of the MRA and this regulation. The agency wishes to clarify
that the purpose of the alert system is to implement a timely exchange
of product quality information and not information on the regulatory
status of inspected firms. The agency is keenly aware of the need to
avoid predecisional or otherwise inappropriate regulatory
classification of a firm or product. In implementing Sec. 26.20, FDA
intends to apply the same standard of fairness and due process it
currently affords to manufacturers with respect to regulatory matters.
While keeping in mind the need to be fair to manufacturers, however,
the agency must keep public health and safety paramount in ensuring
that the alert system functions effectively to protect consumers from
unsafe or ineffective products. Regarding ``transparency,'' as
discussed in section II of this document, FDA will apply to the alert
system established by the MRA and this regulation the applicable
requirements as to disclosure and nondisclosure.
The proposed rule did set forth the elements to be considered in
developing a two-way alert system (see 63 FR 17744 at 17752), and the
alert system is designed to serve as a means for notifying each party
of crises and emergencies. For example, the documentation element for
the two-way alert system refers to elements such as ``definition of
crisis/emergency and under what circumstances an alert is required''
and ``mechanism of health hazards evaluation and classification''
(id.). The crisis management system element mentions ``crisis
management and communication mechanisms,'' ``establishment of contact
points,'' and ``reporting mechanisms.'' In short, the alert system does
not place specific firms in a ``negative regulatory status'' or
otherwise punish firms as the comment suggests.
7. One comment asked about the confidentiality of submissions under
the MRA, particularly submissions to medical device CAB's.
Confidentiality by FDA and EC regulatory authorities is addressed
under Article 17 of the MRA. Confidentiality concerns are also
addressed in FDA's regulations (e.g., part 20) and guidance materials.
FDA urges manufacturers to include clear and definitive language
regarding their views on the confidentiality of submissions in
contracts developed with CAB's. Just as submitters currently identify
information they believe to be confidential commercial or trade secret
information in submissions to the agency, they should clearly mark the
same types of information in submissions to CAB's. Although FDA needs
to make the final decisions as to confidentiality, as discussed
previously in comment 3 in section II.C of this document, the
contractual agreement between submitters and the CAB's should address
the desired handling of information marked in this manner and
contractual provisions should specifically address the need to share
information with regulatory agencies participating in the MRA,
including FDA.
D. Equivalence issues
1. One comment recommended that equivalence determinations and
suspensions of equivalence determinations should be made by the
importing authority only, rather than jointly by the parties to the MRA
and the proposed rule. The exporting country should develop the case
for equivalence, while the importing country should have complete
control over the final equivalence decision. This would maintain the
importing country's sovereign prerogative to protect the health and
safety of its citizens.
FDA agrees that the importing authority must have control over the
decision as to whether the exporting authority is equivalent, and the
agency believes that the decision-making process set up by the MRA and
this regulation provides adequately for this. The MRA and this
regulation stipulate that equivalence determinations will be made by
the Joint Sectoral Committee, which consists of representatives of the
parties. This regulation states that decisions of the Joint Sectoral
Committee ``will be taken by unanimous consent'' (Secs. 26.17(b) and
26.47(b)). Therefore, no equivalence determinations can be reached in
the Joint Sectoral Committee without concurrence by both sides. Hence,
in all cases, the relevant authority of the importing country (FDA, in
the case of imports into the United States) will have definitive
decision making authority.
Similarly, the importing party's right to determine that an
equivalence determination should be suspended is also protected by the
MRA and this regulation. Decisions to suspend equivalence are taken in
the Joint Sectoral Committee, and when that Committee cannot reach
unanimous consent on the appropriate action, the matter is referred to
the Joint Committee. (As discussed earlier, FDA officials will speak
for, and vote on behalf of, the U.S. Government on any matter
pertaining to FDA's statutory or regulatory authority raised within the
Joint Committee or Joint Sectoral Committees.) If unanimous consent is
not reached within a set time period in the Joint Committee, the
contested authority must be suspended. Thus, if
[[Page 60129]]
during these deliberations, the importing authority remains convinced
that an exporting authority's equivalence determination should be
suspended, the contested authority will be suspended even if the other
party disagrees.
Furthermore, the importing country's sovereign prerogative to
protect the health and safety of its citizens is further protected for
pharmaceuticals by Sec. 26.21 and for medical devices by Sec. 26.67(f).
Section 26.21 provides that a party may, if necessary to ensure the
protection of human and animal health at the level of protection it
deems appropriate, take actions such as suspension of the distribution
of the pharmaceutical, product detention at the border of the importing
country, withdrawal of the batches and any request for additional
information or inspection as provided in Sec. 26.12. Section 26.67(f)
provides that a party may, prior to the suspension of a CAB, cease
accepting the results of conformity assessment procedures performed by
that CAB if the decision for such action is made on the basis of
health, safety or environmental considerations, among others. The
``framework'' of the MRA and this regulation also contain a provision
(Article 15 and Sec. 26.74, respectively) preserving domestic
legislation.
2. One comment stated that equivalence determinations must be based
on an exacting review of the foreign regulatory system. This comment
emphasized that equivalence should be determined to exist only where a
finding can be made that the foreign system meets or exceeds the level
of public health protection, enforceability, transparency, and
effectiveness of the U.S. system.
FDA agrees with this comment, and intends to carry out a careful,
detailed, and complete review of foreign regulatory systems in order to
determine whether equivalence does, in fact, exist. FDA's review will
examine whether the foreign system, as it is implemented by the
exporting authority, provides the same (or a higher) level of public
health assurance as the FDA system. The enforcement activities of the
foreign regulatory system and the foreign system's effectiveness in
assuring public health protection are very important components of the
overall equivalence analyses. For pharmaceuticals, they are
specifically covered in subpart A of this regulation, Appendix D,
Subsection I (Criteria for Assessing Equivalence for Post- and
Preapproval). Criterion I. (Ability to enforce requirements and to
remove products found in violation of such requirements from the
market) and Criterion V. (Execution of regulatory enforcement actions
to achieve corrections, designed to prevent future violations, and to
remove products found in violation of requirements from the market)
focus on the execution of regulatory enforcement actions. All of the
criteria taken as a whole cover the public health protection and
effectiveness of the foreign system. In addition, Criterion I. F.
(Accountability of the regulatory authority) relates to transparency,
in that there must be a system through which the regulatory authority
is accountable for its actions. Similar criteria will be developed and
applied for competent authority oversight of medical devices. FDA
expectations as to medical device CABs' reviews of premarket
evaluations are set forth in a guidance document announced in the
Federal Register of July 2, 1998 (63 FR 36240).
3. One comment requested clarification of equivalence assessment
(Sec. 26.6) and asserted that enforcement and regulatory compliance
systems between the United States and the EC need to be comparable. The
comment explained further that, before assessments can be made, local
regulations for pharmaceutical manufacturing should be in place. The
comment added that EC countries have not issued and made public such
regulatory documents as warning letters, to identify unacceptable
manufacturers.
The agency emphasizes that, as stated in the definition of
equivalence, to be equivalent to the United States, EC regulatory
authorities need to be ``sufficiently comparable to assure that the
process of inspection and the ensuing inspection reports will provide
adequate information to determine whether respective statutory and
regulatory requirements of the authorities have been fulfilled.''
(Sec. 26.1(c)). However, ``[E]quivalence does not require that the
respective regulatory systems have identical procedures.'' Furthermore,
among the criteria for assessing equivalence, contained in Appendix D
of subpart A, is the ``[A]bility to enforce requirements and to remove
products found in violation of such requirements from the market'' and
``[A]ccountability of the regulatory authority.'' The agency expects
that these two criteria, in combination with others in Appendix D,
should address the comment's concerns.
The agency does not understand the comment's apparent premise that,
before assessment can commence, regulatory systems must already be
comparable. The agency intends to assess the equivalence of an
authority based upon the criteria in Appendix D of subpart B as they
exist at the time the agency makes the assessment, and needed steps can
be taken to address any shortcoming noted.
4. One comment emphasized the need to assure a level playing field
in terms of inspectional activity (i.e., the length and frequency of
inspections and the number of auditors). This comment recommended
collection of statistics about these activities during the transition
period and then steps to ensure a reasonable harmonization in
approaches between European and FDA audits.
FDA agrees with this comment. Equivalence must exist not only in
the foreign authority's legislation and written procedures (including
those concerning audits), but also in the manner in which these
policies are actually implemented. Under the MRA and this regulation,
the conduct of inspections is one of the criteria (Criteria IV) that
must be considered in reaching equivalence determinations for
pharmaceuticals.
5. One comment questioned how the MRA and the proposed rule would
stop a country from relaxing its standards to create an industry-
friendly regulatory environment within its jurisdiction, resulting in
movement of industry from countries with strict enforcement to
countries of less strict enforcement.
There are limits to what governments can do to influence corporate
choices about location or relocation of manufacturing sites; many
factors play a part in these corporate choices. In any case, the MRA
and this regulation have several mechanisms to help prevent ``a race to
the bottom'' with respect to regulatory controls. First, the process
for ascertaining equivalence will be rigorous. Second, after an
equivalence determination has been made, Article 18 of the Sectoral
Annex for Pharmaceutical GMP's (Sec. 26.18 of this regulation) and
Article 19 of the Sectoral Annex for Medical Devices (Sec. 26.49 of
this regulation) provide that the parties and authorities are to inform
and consult one another, as permitted by law, on proposals to introduce
new controls or to change existing technical regulations or inspection
procedures, and to provide the opportunity to comment on such
proposals. Furthermore, the parties must notify each other in writing
of any changes to relevant legislation, regulations, and procedures.
Third, Article 15 of the MRA and Sec. 26.15 of this regulation provide
for monitoring activities for the purpose of maintaining equivalence.
Fourth, either side may refrain from ``normally endorsing'' audit
reports or device evaluation reports if regulation is
[[Page 60130]]
insufficiently strict. Fifth, if FDA believes that the foreign
authority has made changes to its control system that lessen the
equivalence of that system, FDA has the right to contest the
equivalence of that regulatory authority.
Although the MRA and this regulation cannot prevent an exporting
country from relaxing its standards, the MRA and this regulation ensure
that the importing country must be notified, the equivalence
determination of the exporting country can be suspended, and importing
countries can take needed actions to protect their citizens.
6. One comment offered support for the proposed rule's recognition
that an equivalence assessment must include joint training and joint
inspections. This comment emphasized that the MRA and the proposed rule
should provide for monitoring and verification of on-going equivalence,
including on-going training, on-going joint inspections, and periodic
on-going visits.
FDA agrees with this comment. This regulation, as currently
drafted, provides for such monitoring and verification in Sec. 26.15
for pharmaceuticals and Sec. 26.69 for medical devices. In the case of
medical devices, Sec. 26.69 does not specifically mention training, but
also does not exclude it. Joint training exercises are listed in
Sec. 26.37 as a confidence building activity during the transition
period, and FDA considers monitoring and verification of on-going
training to be an essential element of verifying that equivalence
continues to exist.
7. One comment stated that the MRA and the proposed rule should
provide for periodic expiration of an equivalence determination within
3 to 5 years following the initial determination. FDA should then
publish a notice in the Federal Register for public comment on whether
the equivalence determination has worked and should be renewed. Before
renewing the equivalence determination, the United States should verify
that the foreign country's or CAB's procedure continues to be
equivalent.
FDA agrees that periodic reexamination of a foreign system that has
been found equivalent is a prudent practice to ensure that equivalence
continues to exist. The agency intends to provide for monitoring of
continued equivalence in its implementation of equivalence
determinations arrived at under the MRA and this regulation. However,
the agency does not believe it necessary to require a ``sunset''
provision for periodic reexamination of equivalence in the MRA or this
regulation. FDA will consider how to provide for reexamination of
equivalence during implementation of the MRA.
E. ``Piggy back'' Agreements
1. One comment suggested that the MRA and the proposed rule should
prohibit the development of what the comment called the ``piggy-back
dilemma'' because they would set a precedent for these types of
arrangements. The comment described an example of such a ``piggy-back''
arrangement as FDA establishing a mutual recognition agreement with
country A, country A then establishing a mutual recognition agreement
with country B, and then FDA automatically granting a mutual
recognition with country B on the basis of its mutual recognition
agreement with country A.
FDA disagrees with the comment's conclusion that the MRA and this
regulation would set a precedent for entering into such ``piggy-back''
arrangements. The MRA and this regulation require a determination of
equivalence be made by FDA of each EC Member State regulatory authority
and each device CAB located in EC Member States before any inspectional
or evaluation reports would be ``normally endorsed'' by FDA under
certain conditions. There are no provisions in the MRA or this
regulation for the ``normal endorsement'' of reports from any countries
or CAB's that have not been determined to be equivalent by FDA.
2. One comment strongly opposed what the comment called ``piggy
back equivalence'' as described in the proposed rule under
Sec. 26.11(b) because it would take away FDA's authority to make its
own equivalence determinations and otherwise compromise its ability to
ensure public health.
The so-called ``piggy-back'' or ``surrogate'' inspections described
in Sec. 26.11(b) provide that FDA may ``normally endorse'' inspection
reports resulting from joint inspections by an equivalent authority and
a nonequivalent authority of manufacturers located in the nonequivalent
authority's territory. Under the provisions of the MRA and this
regulation, FDA has the option of participating in all ``surrogate''
inspections and expects to exercise this right as necessary.
Furthermore, the MRA and this regulation have other safeguards in place
for these types of inspections, and more generally as described
previously, that ensure public health protections are maintained.
F. Pharmaceutical issues
1. One comment stated that if FDA has confidence that the EC can
regulate drug substances, biologics should also be included in the
scope of the document.
Many biological products, such as vaccines and therapeutic drug
products, are included in the scope of the MRA and this regulation.
Other biological products, specifically human blood, plasma, tissues
and organs, were excluded from the scope of the MRA. In order for there
to be a finding of equivalence, the parties to the MRA and this
regulation must have sufficiently comparable regulatory systems for the
products. Not all EC Member States have established regulatory systems
for human blood, plasma, tissues, and organs at this time, so it would
not be possible to have a finding of equivalence during the transition
period for these products. Plasma derivatives were excluded from
initial consideration because the U.S. regulation of plasma derivative
products has recently undergone intense scrutiny and regulatory change;
therefore, the FDA did not believe it appropriate at this time to
include plasma derivatives within the scope of the MRA and this
regulation.
2. One comment suggested that Sec. 26.1 of the proposed rule be
amended to include a definition for the term ``normally endorsed.''
The agency believes that a codified definition of ``normally
endorsed'' is not needed because the rule (at Sec. 26.12) exemplifies
circumstances in which the reports would not be normally endorsed.
However, FDA wishes to clarify that normal endorsement generally means
that an authority will accept the information contained in the
inspection report to evaluate and determine a manufacturer's compliance
with that authority's requirements, and FDA expects to endorse the
finding in the reports most of the time. FDA is not, however, prevented
from reaching different conclusions in appropriate circumstances.
3. One comment suggested revisions to the definition of GMP's
(Sec. 26.1(c)(1)) to explicitly include packaging, labeling, testing,
and quality control.
FDA believes the suggested revisions are unnecessary. Labeling,
testing, quality control, and packaging are part of manufacturing. FDA
believes that the proposed definition meets the needs of part 26
because it is consistent with FDA's statutes and regulations.
4. One comment said that the proposed definition of ``inspection
report'' (Sec. 26.1(e)) was inconsistent with
[[Page 60131]]
the definition of ``inspection'' because it lacked reference to report
coverage of commitments made as part of the approval to market a
product. The comment suggested added wording to include such
commitments.
The agency believes it unnecessary to modify the definition of
``inspection report,'' as suggested, because it should be clear from
other sections of the rule (such as Secs. 26.2, 26.3, and 26.14), that
FDA fully expects that reports covering preapproval inspections of drug
manufacturers will, as a matter of course, include information relating
to commitments made as part of the marketing approval. In addition, as
stated in Sec. 26.8, the agency intends to work quickly with
counterpart authorities under the MRA to determine inspection report
contents and format.
5. One comment suggested that the proposed rule clarify that it
would apply only to inspection of firms that are exporting covered
pharmaceutical products from either of the two regions to the other.
The agency believes that the current wording in Sec. 26.3 is
sufficiently clear to limit the scope of inspections to only those
firms located in the two regions. The rule states in relevant part that
the ``provisions of this subpart shall apply to pharmaceutical
inspections carried out in the United States and Member States of the
European Community* * *.'' Furthermore, Sec. 26.12 refers to inspection
reports being normally endorsed by the importing (emphasis added)
party. Clearly, the importing party is interested in only inspection
reports because of products being imported into its territory.
6. One comment suggested changing the word ``both'' to ``either''
in Sec. 26.4(a) on the grounds that a product regulated as a drug by
one party but not the other should not be excluded from this regulation
because at least one party will apply current GMP standards to the
product.
The agency disagrees with the suggestion. If an importing country
regulates an article as a drug, but the exporting country does not, the
importing country would likely hold the article to a different (higher)
set of manufacturing standards. In such a situation, it is unlikely
that the importing country would find the exporting country's
inspection report of value in assessing the manufacturer's compliance.
7. One comment objected to the provision in Sec. 26.6(c) that
equivalence assessments mandate joint inspections. The comment
suggested that they be minimized or replaced by ``accompanied
inspections'' where the lead authority is clearly designated.
FDA believes that the conduct of joint inspections is an essential
part of the equivalence assessment process. Such assessments would be
incomplete without first hand observation of how an authority conducts
an inspection. The agency wishes to clarify that, as stated in the
rule, the conduct of joint inspections is ``for the purpose of
assessing regulatory systems and the authorities' capabilities.'' The
actual format of the joint inspections has not yet been determined, and
may include inspections where one party observes the other party's
inspectional conduct or where each party has responsibility for part of
the inspection. As part of the preparation for implementation of the
MRA and this regulation, FDA expects to jointly develop with the EC a
standard operating procedure for joint inspection that embodies this
approach.
8. One comment said the second sentence in Sec. 26.6(a) (stating
that the EC will provide information pertaining to criteria under EC
competence) was problematic because the equivalence criteria in
Appendix D should be complete, as is, or else augmented, as needed.
The agency believes the comment may have misinterpreted the
proposed rule to mean the EC will be held to different, yet to be
specified, equivalence criteria. The agency wishes to clarify that the
equivalence criteria in Appendix D apply equally and fully to both
parties. The sentence at issue addresses information (e.g., European
Commission Directives) that the EC will provide relating to these
criteria that applies to all Member State authorities, versus
information that is specific to a particular Member State as to how
Member State authorities meet these criteria.
9. One comment said Sec. 26.6(b) should address the mechanism by
which the parties establish and communicate their draft equivalence
assessment programs. The comment called for interested parties to have
the opportunity to comment on the draft programs before they become
official. The comment also suggested that the phrase ``as deemed
necessary'' would for FDA be in conflict with legislative mandates that
require certain pre- and postapproval inspections.
The agency does not believe it is necessary to codify the mechanism
by which the parties establish and communicate their draft equivalence
assessment programs. The parties have yet to establish those logistics.
Regarding the opportunity for public input on such programs, as
discussed in section II of this document, the agency intends to provide
for such input in a manner consistent with current policy development
and FOIA requirements. The agency is fully aware of its legislative
mandates regarding establishment inspections and does not believe the
wording of the MRA or the rule is inconsistent with those
responsibilities. FDA intends to carry out all activities that it deems
necessary to be consistent with its responsibilities.
10. One comment suggested adding wording to Sec. 26.8 to state that
FDA will use its current inspection report format, or some modification
thereof, until the parties develop and agree upon an inspection report
format.
The agency believes the suggested wording is unnecessary because it
is confident that the parties will develop and agree upon a mutually
acceptable report format in a timely manner.
11. One comment suggested that Sec. 26.9(a) be revised to
explicitly require FDA to use International Organization for
Standardization (ISO) 9000 and ISO 10000 standards to determine that an
authority has demonstrated a pattern of consistent performance with the
criteria in Appendix D.
The agency believes it is unnecessary to apply precise statistical
methods in demonstrating a pattern of consistent performance, in the
context of complying with Appendix D. The agency intends to apply
objective and fair criteria in evaluating whether an authority has
demonstrated a pattern of consistent performance but does not believe
its already rigorous GMP and inspection requirements need an added
``layer'' of requirements based upon the ISO standards mentioned.
12. One comment suggested that Sec. 26.11(c) be amended to include
a manufacturer's certification that the product was manufactured in
accordance with applicable GMP's.
FDA's view is that such a certification is unwarranted. The agency
expects that, in the context of this agreement, authorities would rely
upon inspectional reports to determine a manufacturer's current GMP
compliance rather than relying upon the manufacturer's own declaration.
The agency therefore declines to adopt the suggestion.
13. One comment suggested adding a new paragraph, to complement
Sec. 26.11(c), that would exempt U.S. manufacturers from carrying out
all of the quality controls specified in the current GMP regulations,
provided that the controls specified in Article 22 paragraph 1(b) of
Council Directive 73/319/EEC have been carried out in the EC and each
batch or lot is accompanied by
[[Page 60132]]
certificates of current GMP and marketing authorization compliance.
FDA does not believe it is in the public interest to exempt
manufacturers from performing currently required current GMP quality
control measures, or to allow products to be released for distribution
without requisite laboratory determination of conformance to
established specifications. The suggested changes are not adopted.
14. One comment suggested revisions to Sec. 26.13 to explicitly
require that: (1) Requests for postapproval inspections include the
product and the requester's areas of special concern; and (2) when new
inspections are needed the authority receiving the request should state
the reasons why a new inspection is needed along with the estimated
completion date.
The agency does not believe it is necessary to make the suggested
modifications. The agency anticipates that, as a matter of course,
inspection requests and corresponding communication will identify
products, areas of concern, and other relevant information, as needed.
15. One comment suggested revising Sec. 26.14(b) to require the
notified authority to advise the requesting authority of approximately
when the inspection will be completed, and to require the requesting
authority at that point to detail what issues need to be addressed
during the inspection.
The agency declines to accept the suggestion because it believes
such operational logistics will be performed as a matter of course, and
need not be codified.
16. One comment suggested revising Sec. 26.15 to specify that
review of reports includes evaluation mechanisms such as tracking
trends and problems and to state that review studies be used to focus
on needed training and program improvements.
The agency agrees that report evaluation and trending, along with
coordination among the authorities to ensure program improvements, have
merit. The agency does not, however, believe it is necessary to codify
details of how equivalence monitoring will be performed.
17. With regard to Sec. 26.18, one comment asked how changes in
current GMP regulations and initiation of new programs, such as the
First Party Audit Program (FPAP), would affect the implementation of
the MRA and the proposed rule.
The agency advises that, under Sec. 26.18, FDA will inform, consult
with, and offer the opportunity for comment by, the other party, as
permitted by law, regarding changes in current GMP regulations or
inspection procedures. The mechanisms for conducting that collaboration
have yet to be developed. Regarding the FPAP, the subject of an FDA
public meeting held on June 23, 1998 (see 63 FR 27583, May 19, 1998),
the agency advises that this initiative is currently in very early
stages of development. However, conceptually, FPAP is intended to
gather information from selected human use pharmaceutical manufacturers
regarding their quality assurance measures; the information would be
submitted to FDA by those firms and could substitute, in some measure,
for information the agency would otherwise obtain from its direct
inspectional activities. The agency cannot predict how these
initiatives will affect the nature and volume of current GMP
inspections performed under the MRA and this regulation. However, the
agency will consult with the other party, in accordance with the
provisions of this rule and the MRA itself.
18. One comment suggested revising Sec. 26.18(b) to establish a 30-
day timeframe for the United States to notify the EC of any changes to
Appendix B, and a 5-day timeframe where such notification can be made
electronically.
The agency intends to promptly notify the EC of changes to Appendix
B, and to use electronic means of doing so whenever feasible. However,
FDA believes it is unnecessary to codify specific timeframes.
19. One comment suggested revising Sec. 26.19 to add reporting
timeframes of 15 days for paper correspondence or 3 days for electronic
correspondence.
FDA shares the comment's concern regarding the timeliness of
exchanging information relating to quality problems, and intends to
implement such exchange in a prompt manner to be arranged in concert
with the EC. FDA does not, however, believe it is necessary to codify a
specific timeframe.
20. One comment suggested revising Sec. 26.20(a) to establish
reporting timeframes of 5 days for paper correspondence or 3 days for
electronic communications.
As discussed in response to comments on Sec. 26.19, the agency
agrees that reporting needs to be done promptly, but does not agree
with the suggestion.
21. One comment asked if, and how, the MRA and the proposed rule
will accommodate the collection of regulatory samples during
pharmaceutical inspections.
The agency advises that the MRA and this regulation do not specify
how regulatory samples collected during establishment inspections will
be handled. However, FDA anticipates that both parties will handle such
samples as they currently do, and that information about such samples
would be contained in the inspection report or related documents. The
agency is prepared to work with the regulatory authorities should it
become necessary to develop procedures relating to sample collection.
22. One comment noted that a recent U.S. General Accounting Office
(GAO) report on FDA's foreign inspection program included
recommendations intended to improve management of the agency's overseas
inspection program. The comment asked if FDA's consideration of the
report would affect the MRA or the proposed rule.
The agency has, in response to the GAO report, already initiated
several modifications in the management of its overseas inspection
program. The agency does not at this point anticipate that
implementation of those changes will have a significant effect on the
MRA or this regulation.
23. One comment suggested adding a new paragraph to subpart C,
Sec. 26.76 that would explicitly prohibit the parties from obstructing
public access to information which, by U.S. law, is disclosable to the
public.
The agency does not agree that this section is needed because part
26 does not conflict with U.S. laws regarding public access to
information. The agency is fully aware of its legal obligations to
abide by those applicable statutes, as discussed in section II of this
document.
24. One comment suggested numerous editorial changes to add clarity
throughout the rule.
The agency has carefully considered the suggested revisions and
believes that although some have merit, on balance, the need to retain
wording in part 26 that is as close as possible to the MRA itself
outweighs the advantages that the changes might afford.
G. Medical Device Issues
The Food and Drug Administration Modernization Act of 1997 (FDAMA),
Pub. L. 105-115, 111 Stat. 2296 (1997), included a number of amendments
to the act relevant to the MRA's Sectoral Annex on Medical Devices
(Medical Devices Annex). First, an FDA pilot program for third-party
review of medical devices (see 61 FR 14789, April 3, 1996) was codified
in the act as new section 523 (21 U.S.C. 360m), entitled ``Accredited
Persons.'' In the Federal Register of May 22, 1998 (63 FR 28392), FDA
published a notice of availability of a draft guidance on its third-
party
[[Page 60133]]
accredited persons program under this new section of the act.
Interested persons should also refer to a related notice of
availability published in the Federal Register of July 2, 1998 (63 FR
36240), entitled ``Draft Guidance for Staff, Industry and Third
Parties, Third Party Programs under the Sectoral Annex on Medical
Devices to the Agreement on Mutual Recognition Between the United
States of America and the European Community; Availability'' (MRA).
This guidance document is also available in FDA's Home Page on the WWW
(``www.fda.gov'').
Second, due to amendments made by FDAMA, FDA has exempted a number
of devices from premarket notifications under section 510(k) of the act
(21 U.S.C. 360(k)) (see 63 FR 3142, January 21, 1998 (Class II
devices), and 63 FR 5387, February 2, 1998 (Class I devices)). On May
20, 1998, FDA made available a list of devices which are eligible for
third party review under new section 523 of the act. FDA plans to
propose to the European Commission that the tables attached to the
Medical Devices Annex to the MRA, listing devices eligible for review
during the transitional period of the MRA, be revised to reflect the
changes in U.S. requirements made by FDAMA and the FDA implementing
actions described previously. The EC may also suggest changes
concerning devices eligible for the MRA. These adjustments will be made
during the transitional period under the MRA.
Third, as discussed in comment 9 of section II.F of this document,
FDA now has explicit authority to recognized voluntary consensus
standards for devices due to a FDAMA amendment to section 514 (c) of
the act (21 U.S.C. 360d(c)).
1. One comment identified a typographical error in Table 1 of the
Sectoral Annex on Medical Devices (Annex) of the proposed rule
concerning radiographic screens Sec. 892.1960 (21 CFR 892.1960).
FDA agrees with the comment and in the final rule has corrected
this typographical error. Also, several minor typographical errors in
the device lists were identified by the European Commission and FDA
just prior to the signing of the MRA on May 18, 1998. These corrections
are also being made in corresponding provisions in this rule.
2. One comment from a manufacturer questioned whether condoms are
covered by the MRA.
The list of devices that FDA made available on May 20, 1998, for
eligibility in the accredited persons program under section 523 of the
act includes condoms, with and without spermicidal lubricant.
Therefore, FDA is willing to consider condoms with or without
spermicidal lubricant as eligible for participation in the premarket
assessment component of the device MRA, if the EC agrees. Condoms
without spermicidal lubricant are listed in Table 3 of the Annex for
possible inclusion in the scope of product coverage during the
Operational Period. However, condoms with spermicidal lubricants may be
regulated by the EC, or certain EC Member States, as pharmaceuticals
and hence may be outside the scope of the Medical Devices Annex.
3. One comment asked whether clearance of a 510(k) will be
equivalent to CE marking.
Clearance of a 510(k) will not be considered equivalent to the CE
marking, nor will CE marking be considered equivalent to a 510(k).
Under the MRA and this regulation, the exporting country's CAB's
perform specified conformity assessments in accordance with the
importing country's requirements. The MRA and this regulation are
intended to enable determinations: (1) Whether CAB's in the EC are
capable of conducting certain premarket and quality system evaluations
in accordance with U.S. regulatory requirements in a manner equivalent
to how those evaluations are conducted by FDA (with FDA making the
final decision, but with an expectation that FDA would ``normally
endorse'' a CAB's assessment), and (2) whether CAB's in the United
States are capable of conducting certain premarket and quality system
evaluations in accordance with EC regulatory requirements in a manner
equivalent to those conducted by European CAB's, also referred to as
``notified bodies.''
4. One comment requested implementation of a system by which U.S.
manufacturers can obtain government documents for presentation to the
EC.
Appendix A of subpart B contains addresses the relevant
legislation, regulations, and procedures for the EC and the United
States. In addition, the European Commission has a site on the WWW for
direct access to EC documents (``http://Europa.eu.int/eur-lex''). Also,
just as European notified bodies are frequently a manufacturer's first
point of contact regarding the process for meeting the European
requirements, it is expected that, under the MRA and this regulation,
U.S.-based CAB's will be able to provide manufacturers with information
on EC requirements and copies of necessary European documents needed to
meet European requirements.
5. One comment stated that industry would like to encourage
observed audits. The comment explained that, in an observed audit, a
U.S. manufacturer would allow an EC Notified Body representative to
accompany an FDA inspector during an inspection of its plant.
FDA agrees that joint industry audits are necessary to demonstrate
that CAB's are competent to assess medical devices to each country's
requirements and level of public health protection. FDA encourages
manufacturers to support observed audits.
6. One comment suggested that, to further strengthen confidence in
CAB's, training on auditing should be conducted by the United States
and EC, and industry should be encouraged to participate in FDA's third
party system, i.e., the accredited persons program.
FDA agrees with the suggestions. Training on premarket and quality
system evaluations is planned for CAB's participating in the MRA and in
FDA's third-party accredited persons program. FDA has made tentative
plans to conduct training for EC CAB's on October 14 to 16, 1998, in
the Washington, DC area. Representatives of EC CAB's interested in
participating in the MRA should begin making plans to attend this
training, which is also being provided to participants in the
accredited persons program. This training is intended to address the
scope, content, and expectations of the evaluations sufficient to
determine the equivalence of the assessments.
7. One comment requested that FDA consider IV catheters, under 21
CFR 880.5200, for inclusion in Table 2, ``Class II Medical Devices
Included in Scope of Product Coverage at Beginning of Transition
Period.''
During the negotiation of the Annex, there were no expressions of
interest in adding IV catheters to any of the tables of eligible
medical devices. FDA is willing to consider that issue in the future,
but at this time does not intend to include IV catheters in Table 2 at
this time.
8. Several comments suggested that the MRA be expanded to include
more devices, including class II devices.
As discussed previously, FDA plans to propose expansion of the list
of eligible devices to include all devices eligible for third party
review under FDAMA, except those medical devices regulated as in vitro
diagnostics. (The EC does not yet have legislation in place on in vitro
diagnostics.) The agency is considering specific suggestions by
industry comments for inclusion of specific devices. These suggestions
are extremely useful for future decisions,
[[Page 60134]]
although neither the FDA nor the European Commission can, at this time,
respond to these industry suggestions by including additional devices
under the MRA. Revision of the list will, however, be a step taken
early during the transition stage. The pace at which devices can be
added to the device premarket assessment aspect of the MRA depends on
the availability of guidance documents or FDA-recognized standards, as
discussed in comment 8 of section II.G of this document.
9. Several comments urged FDA to accept international standards,
instead of developing FDA guidance documents, for the third party
review of class II devices. One comment proposed use of 81
international and regional standards to support premarket evaluations
and quality system evaluations.
FDA, under FDAMA, has begun to recognize consensus standards for
use in its various medical device activities (see 63 FR 9561, February
25, 1998). FDA very much appreciates the submission identifying
potentially useful standards. Communications such as this that relate
to the use of standards in MRA implementation and other device
activities are being considered in regard to FDA's consensus standards
initiative announced on February 25, 1998. FDA plans to update the
guidance for the recognition and use of consensus standards, as
described in the February 25, 1998, document, and in doing so the
agency will take into account the suggestions received and the
information and experience to be gained during the implementation of
the MRA.
FDA's views on the appropriateness of including a device under the
premarket evaluation component of the MRA will depend, in part, on
whether FDA-recognized standards or review guidance documents exist to
provide a basis for product evaluation. Recognized standards or review
guidance do not currently exist for many of the additional devices
suggested for inclusion in the MRA by certain industry comments. FDA
plans to develop guidance documents only where recognized consensus
standards fail to address sufficiently the requirements for
demonstrating substantial equivalence or other U.S. requirements.
10. One comment suggested that FDA take aggressive steps to
identify and designate third party review organizations.
FDA is proceeding in a timely and transparent manner to describe
processes and expectations for third parties to participate in both the
accredited persons program and the MRA. For example, the agency, in the
Federal Register of July 2, 1998 (63 FR 36240), issued a comprehensive
guidance document entitled ``Draft Guidance for Staff, Industry and
Third Parties, Third Party Programs Under the Sectoral Annex on Medical
Devices to the Agreement on Mutual Recognition Between the United
States of America and the European Community (MRA),'' to assist
interested parties to understand the designation process for CAB's and
to prepare their applications. This document has been made available on
the CDRH Home Page on the WWW. FDA officials also have discussed the
third party programs under FDAMA and the MRA at trade shows and public
meetings.
11. Two comments suggested that both quality system evaluation
reports and premarket evaluation reports should be harmonized between
the United States and EC. Another comment stated that one of the issues
to be resolved is determining what duration of an audit is satisfactory
to the designating authorities as well as the scope, content, and
degree of rigor expected from such audits. One comment further
suggested incorporating efforts by an international harmonization group
known as the GHTF and its Study Groups I and IV in developing the
format for reports. FDA officials, European government officials, and
industry representatives are among those active in the GHTF, which is
comprised of government and industry representatives from North
America, Europe, Asia, and Australia, as well as observers from other
countries and international organizations (see International
Harmonization, Policy on Standards, in the Federal Register of October
11, 1995 (60 FR 53081)).
The comment also suggested that, in the interest of efficiency and
to minimize translation costs, such reports should be in an abbreviated
form in most circumstances. It further suggested that the reporting
forms be limited to certification by the CAB that applicable
requirements of the other party's regulations are met and that this
certification may reference those documents which were examined to
demonstrate compliance. The comment also recommended use of FDA's
initiative known as the ``510(k) Paradigm'' that offers other ways of
streamlining decisions on 510(k)'s.
FDA expects to use relevant GHTF documents, as appropriate, in
implementing the MRA. Study Group I of GHTF is developing a universal
format which provides guidance on technical documentation with a view
to first identifying similarities and divergences among various
regulatory systems and then striving to achieve, to the extent
possible, harmonization of requirements. At this time, this study group
has reviewed requirements of existing systems and is now developing the
essential principles which could facilitate harmonization of
requirements, particularly as to premarket submissions. FDA is hopeful
that it will be able to use guidance developed by Study Group I as
guidance to MRA participants on the development of premarket evaluation
reports.
Study Group IV of GHTF is preparing guidelines for auditing quality
systems of medical device manufacturers. These GHTF guidelines are now
being made available for comments by principal participants in GHTF,
e.g., by the EC United Kingdoms' Medical Devices Agency's Home Page and
the United States through a future publication as a guidance in the
Federal Register and in the FDA Home Page. FDA anticipates using audit
guidance developed by Study Group IV in the implementation of the MRA.
It is too soon to say precisely what formats will be used for
premarket evaluation reports and quality system evaluation reports
under the MRA. FDA intends to take into account the concerns expressed
in the comment about minimizing the required documentation to that
which is necessary. The formats for such reports will be developed
during the MRA transition period, and FDA expects guidance from the
GHTF study groups to be extremely helpful in this respect. During
format development, FDA will work to develop formats that will not be
unduly burdensome, so that forms and reports will include information
sufficient for the parties to determine if normal endorsement is
warranted. FDA will consider the use by third parties of FDA
streamlining initiatives such as the 510(k) Paradigm in review of
applications under the accredited persons program and the MRA.
Information on the 510(k) paradigm can be accessed on the CDRH Home
Page under ``Re-engineering Efforts'' (www.fda.gov/cdrh).
12. Two comments raised the concern that the exchange of post
market vigilance reports might create an administrative burden for
industry if reports are not kept simple. One of the comments noted that
industry has wanted to avoid multiple reporting and wishes to report
only when there is a real and imminent danger to public health.
FDA believes that adverse event reports need to be clear, concise,
and
[[Page 60135]]
addressed to public health needs. FDA, through its participation in the
GHTF Study Group II, is working toward a streamlined and harmonized
system of reporting adverse events that are required by EC and U.S.
laws and regulations. This effort is initially focused on harmonizing
the guidelines for the types of adverse events that medical device
manufacturers need to report. This guidance will make it easier for a
manufacturer to decide which events need to be reported to the
appropriate bodies in the EC and in the United States. The guidance
developed by Study Group II will also be used to institute a mechanism
for sharing adverse event data between the EC and United States under
the MRA.
13. Two comments expressed support for Sec. 26.48,
``Harmonization,'' and one suggested that FDA should continue to
participate in the efforts of the GHTF.
FDA agrees with this comment and intends to continue to participate
in these efforts, as resources allow.
14. One comment suggested that the FDA consider provisions by which
U.S. CAB's would perform domestic inspections under the act.
This comment addresses issues outside of the scope of the MRA and
of this rulemaking. Under the MRA and this regulation, U.S. CAB's will
be designated only to conduct product type-examination and verification
and/or quality system evaluations for products produced for export to
the EC.
15. One comment asked if the ``post market vigilance reports''
addressed under Sec. 26.33(a)(3) were the same as Medical Device
Reports (MDR's).
Post market vigilance reports and MDR's are similar mechanisms for
reporting adverse incidents in the EC and the United States
respectively. A system will be set up during the transition period and
maintained thereafter by which the parties will notify each other when
there is an immediate danger to public health. (See Sec. 26.50.) As
part of the alert system, each party shall notify the other party of
any confirmed problem reports, corrective actions, or recalls. The
United States and EC plan to develop the data elements of such reports
during the transition period, making use of draft documents already
being prepared by the GHTF's Study Group II.
16. One comment asked if the regulatory authorities mentioned in
Sec. 26.34 and the designating authorities mentioned in Sec. 26.65 are
the same.
``Regulatory Authority'' is defined in Sec. 26.60(a)(3) and
``Designating Authority'' is defined in Sec. 26.60(a)(1) of the final
rule. It is possible for these authorities to be different, or they may
be the same. For the purpose of the Sectoral Annex on Medical Devices,
regulatory authorities have the responsibility to implement the
provisions of the Annex, including the designation and monitoring of
CAB's.
17. One comment asked if the criteria to be used by FDA to
determine technical competence for product reviews is identical to that
which is to be used in the U.S. third party program for accredited
persons.
The technical competence, qualifications, and freedom from conflict
of interest for the product review (510(k)) part of the MRA are
essentially the same as those being applied in FDA's third-party
program for accredited persons. However, the MRA also includes quality
systems audits, and CAB's performing quality systems audits under the
MRA will need to have the additional training, expertise, and
experience to perform quality systems audits. In this respect, the MRA
is broader than the FDA third party accredited persons program.
18. One comment supported Sec. 26.31, which states that the
Sectoral Annex on Medical Devices should evolve and that the parties
will periodically review the program to assess progress and identify
enhancements. This comment also requested that timeframes be
established for specific actions during the transition period. The
comment also recommended that the regulatory authorities establish a
schedule for the execution of the specified confidence building
activities, under Sec. 26.35, that can serve to ``benchmark'' progress.
FDA finds these comments extremely useful. Specific confidence
building activities will depend on the nature of product evaluation and
the extent of CAB utilization, and available resources. A process for
scheduling confidence building activities and the schedule for
accomplishing them will be developed by the United States and EC.
19. One comment stressed the importance of defining the supporting
evidence necessary to demonstrate the technical competence and
independence of CAB's. This comment also requested that FDA make known
to the general public the date and process by which the CAB's will be
designated.
FDA issued a Federal Register of July 2, 1998 (63 FR 36240)
announcing the availability of a draft guidance entitled ``Draft
Guidance for Staff, Industry, and Third Parties, Third Party Programs
Under the Sectoral Annex on Medical Devices to the Agreement on Mutual
Recognition between the United States of America and the European
Community (MRA).'' This draft guidance addresses the criteria and
qualifications expected to demonstrate technical competence and
independence of CAB's. In addition, the draft guidance outlines the
process for designation of CAB's under the Medical Devices Annex to the
MRA. FDA will keep the public informed through the home page on the WWW
of events under the MRA, such as designation of CAB's.
20. One comment expressed concern that FDA stated that the
operational period will start at the end of the transition period, and
that FDA did not state that the transition period will be for a period
of 3 years. The comment sought clarification.
FDA disagrees that further clarification is needed. The duration of
the Transition Period is 3 years. This is clearly stated in Sec. 26.35
and in the Annex, Article 5.
21. One comment supported the process of the importing party's
regulatory authority routinely accepting or ``normally endorsing''
reports.
FDA observes that this was the criterion agreed to in the Annex and
stated in the regulation (Sec. 26.41(d), Exchange and endorsement of
quality system reports, and Sec. 26.42(c), Exchange and endorsement of
product evaluation reports).
22. One comment sought clarification of the term ``normally
endorse'' and expected that the importing party will endorse the vast
majority of quality system evaluation and premarket evaluation reports.
FDA anticipates that, once CAB's are designated, the importing
party (FDA, in the case of devices to be imported into the United
States) it is likely to endorse most reports. Sections 26.41(d) and
26.42(c) describe the expectation that reports will normally be
endorsed by the authority of the importing party, except under
circumstances delineated in those provisions.
23. One comment supported the need to continue to accept the
results of conformity assessment procedures performed by a CAB prior to
its suspension as a listed body, except in specified situations as
identified in Sec. 26.67(f).
FDA agrees with the comment's description of the Annex and the
regulation but would also point out the provisions in the framework
agreement and in Sec. 26.74 of this regulation allowing authorities on
either side to take appropriate and immediate measures to protect
public health.
24. One comment expressed concern that the conformity assessment
procedures performed by a CAB prior to
[[Page 60136]]
withdrawal remain valid subsequent to withdrawal.
FDA notes that Sec. 26.68, ``Withdrawal of Listed Conformity
Assessment Bodies,'' clearly delineates the circumstances under which a
party is no longer required to accept or recognize results of
conformity assessment procedures performed by CAB's (or, in the case of
this Annex, to no long normally endorse reports provided by CAB's). As
noted in the response in the preceding comment, however, nothing in the
MRA or this regulation supersedes a participating country's ability to
preclude shipments of products that present a concern under its laws.
Whether there will be ``normal endorsement'' of assessments done by a
CAB before its suspension or withdrawal would be determined, on the
merits, based on the facts in the particular case (see, also, the
discussion in comment 13 in section II.A of this document under the
heading ``General Comments and Issues'')
25. One comment suggested a definition section for subpart B.
FDA does not believe that it is necessary to change the regulation
to add a definition section. Guidance may be provided in the future, if
necessary.
26. One comment expected the list of CAB's would be published along
with the final rule, or that the final rule would state when the list
will be published.
At this time, FDA is not certain of the date when the designation
of CAB's will be made under the MRA. Once this occurs, however, the
list will be made public on the FDA Home Page on the WWW.
27. One comment requested availability of a description of the
information which must be presented in quality system and premarket
evaluation reports to be produced by CAB's. The comment suggested that
this information is needed in order to judge the adequacy of the work
of various CAB's.
FDA agrees. The information that FDA expects to be present in
quality system and product evaluation reports will be made public
through the FDA Home Page on the WWW during the transition period.
Comment 4 of the section II.F of this document describes how to obtain
EC documents.
28. One comment commented on the 90-day period provided for
obtaining an inspection and requested provision for extension of this
period for good cause.
FDA realizes that the CAB's may not be able to accommodate all
inspection requests within 60 or 90 days. Time extensions may be
needed, for good cause, but FDA believes procedures for such a request
need not be codified in this section.
29. One comment strongly recommended that FDA conduct an on-going
verification of the evaluation reports produced by the CAB's because
they are vital to ensuring the safety and effectiveness of medical
devices. This comment also raised concerns about the potential for
conflicts of interest in a system of private review. (Some EC CAB's are
private sector bodies.)
FDA is sensitive to the concerns raised in this comment and
recognizes the importance of adequate reports from CAB's regarding
product evaluations and quality system evaluations as well as FDA's
verifications. It is anticipated that FDA will rigorously evaluate both
the reports and the CAB's that produce them. In addition, FDA has
issued a notice announcing the availability of a draft guidance
entitled ``Draft Guidance for Staff, Industry, and Third Parties, Third
Party Programs Under the Sectoral Annex on Medical Devices to the
Agreement on Mutual Recognition between the United States of America
and the European Community (MRA),'' published in the Federal Register
of July 2, 1998 (63 FR 36240). This document addresses conflict of
interest concerns as well as technical competence criteria.
Also, it should be kept in mind that final decisions on 510(k)'s
will be made by FDA, ``normally endorsing'' submissions by CAB's,
during both the transitional stage and the operational stage of the
Medical Devices Annex.
33. One comment suggested that the wording of Secs. 26.39(b) and
26.46(b) be clarified. These sections address equivalence and listing
of CAB's.
FDA believes the wording of these sections is sufficiently clear.
Further clarification, if necessary, could be considered in the future
after experience is gained under these provisions.
34. One comment stated that CAB's should be designated within the
first 2 years of the transition period because sufficient accumulation
of evidence supporting equivalence would be unlikely if designation
occurred in the last year of the transition period.
FDA points out that Article 6 of the Annex and Sec. 26.36 of this
regulation states that ``each Party shall designate [CAB's] to
participate in confidence-building activities by transmitting to the
other Party a list of CAB's* * *.'' This transmission will be done at
the start of the transition period. However, determinations of
equivalence will be made following this exchange of lists and, indeed,
will be a continuous feature of MRA implementation.
35. One comment suggested that Sec. 26.37 be revised to include the
frequency of workshops and seminars throughout the transitional and
operational phases.
FDA agrees that workshops and seminars are important. However,
provisions for the frequency of workshops and seminars are not
appropriate for inclusion in a rule. Furthermore, available resources
will determine the frequency of joint training and seminars. FDA will
continue to explore cost effective means, such as audio/video
conferences and videotape training, to enhance the expertise of the CAB
representatives. As stated earlier, an FDA training program for EC
CAB's has been tentatively scheduled for October 14 to 16, 1998, in the
Washington, DC area.
36. One comment said that Sec. 26.46(c) implies that the
designation of additional CAB's in the operational phase will occur
only once each year. This comment went on to suggest that, if expansion
of the CAB list is expected to be an annual event, then Sec. 26.66(b)
should so state.
FDA believes the language in Sec. 26.46(b) is sufficiently clear,
and that there is no need for change in the regulatory provisions
cited.
37. One comment suggested that Sec. 26.65 be revised to state that,
``Designating authorities shall only designate CAB's where the primary
place of business is in the territory of the designating authority.''
FDA disagrees with the suggestion, as it would introduce an
unwarranted restriction into FDA's implementation of the MRA and this
regulation. In any case, even if FDA were to adopt the comment's
suggestion, the intended purpose of the suggested change could easily
be overcome if a U.S. division of a foreign CAB simply formed a new
corporation, under the law of a U.S. State, with the United States as
the principal place of business.
38. One comment noted that medical devices principally regulated by
FDA's Center for Biologics Evaluation and Research (CBER) appear to
have been excluded from the MRA.
The comment is correct in noting that no CBER-regulated devices are
included in the lists appended to the Sectoral Annex on Medical
Devices. CBER has the lead responsibility for 510(k) review for 23
medical device classifications. Adding some of these devices to the
list of devices that FDA wishes to make eligible for review under the
Annex, at this time, would require establishment of special handling
procedures, training, and monitoring within CBER without the
expectation of a meaningful number
[[Page 60137]]
of third party reviews. However, devices regulated by CBER under the
device premarket notification provisions of the act (21 CFR 360(k))
might be considered for eligibility in the MRA program as experience
and confidence develops.
39. A comment addressed issues of grammar and format and did not
deal with substantive matters relevant to the MRA that would have any
bearing on its content, issues, or outcome.
FDA declines to alter the text of the proposed rule in response to
this comment. Throughout this rulemaking process FDA has attempted to
adhere to the language contained in the MRA unless serious substantive
matters were identified having bearing on the content, issues, or
outcome of the MRA or this regulation. The nonsubstantive issues raised
by this comment do not justify any amendments to this regulation.
III. Summary of Changes
1. In response to a comment, the title of the proposed regulation
has been changed to the following: ``Part 26--Mutual Recognition of
Pharmaceutical Good Manufacturing Practice Reports, Medical Device
Quality System Audit Reports, and Certain Medical Device Product
Evaluation Reports: the United States and the European Community.''
2. On its own initiative, FDA has determined that the language of
proposed Sec. 26.0 should be amended to provide additional and more
precise explanation about the applicability of this regulation with
regard to other U.S. agencies and the EC. Therefore, proposed Sec. 26.0
has been amended to read as follows:
Section 26.0 General.
This part substantially reflects relevant provisions of the
framework agreement and its sectoral annexes on pharmaceutical good
manufacturing practices (GMP's) and medical devices entitled
``Agreement on Mutual Recognition Between the United States of
America and the European Community'' (the MRA), signed in London on
May 18, 1998. For codification purposes, certain provisions of the
MRA have been modified for use in this part. This modification is
done for purposes of clarity only and shall not affect the text of
the MRA concluded between the United States and the European
Community (EC), or the rights and obligations of the United States
or the EC under that agreement. Whereas the parties to the MRA are
the United States and the European Community (EC), this part is
relevant only to the Food and Drug Administration's (FDA's)
implementation of the MRA, including the sectoral annexes reflected
in subparts A and B of this part. This part does not govern
implementation of the MRA by the EC, which will implement the MRA in
accordance with its internal procedures, nor does this part address
implementation of the MRA by other concerned U.S. Federal agencies.
For purposes of this part, the terms ``party'' or ``parties,'' where
relevant to FDA's implementation of the MRA, should be considered as
referring to FDA only. If the parties to the MRA subsequently amend
or terminate the MRA, FDA will modify this part accordingly, using
appropriate administrative procedures.
3. On its own initiative FDA has amended several sections of the
proposed rule to more accurately describe the relationship between the
provisions of this part and the provisions of the MRA. Specifically,
Secs. 26.6(d), 26.61, 26.73, 26.78, 26.79, and 26.81(d) have been
appropriately changed to accomplish this purpose.
4. In response to one comment, Table 1 of the proposed rule
concerning the product code for radiographic screens, Sec. 892.1960, is
amended in the final rule to reflect the correction of a typographical
error: ``WAM'' is changed to read ``EAM.''
5. Other typographical errors and nonsubstantive changes in the MRA
have been identified by FDA and the EC since the FDA proposed rule was
published on April 10, 1998. Because FDA has endeavored to have this
regulation reflect the text of the MRA as accurately as possible, the
final rule has been amended to reflect all of these nonsubstantive
changes. For example, in Sec. 26.4, the reference is now ``European
Community (EC), rather than ``European Union'' or ``EU,'' in accordance
with the preference of the EC. The EC is the correct entity, as the EU
is not a juridical entity.
6. The agency has amended the authority citation to refer to U.S.
statutes on confidentiality (5 U.S.C. 552, 18 U.S.C. 1905, and 21
U.S.C. 331) as well as the new accredited persons provisions of the act
(section 523, 21 U.S.C. 360m) added by FDAMA.
7. Under Appendix E of Subpart A (Elements to be Considered in
Developing a Two-Way Alert System), for administrative reasons the
contact points for FDA are changed from ``FDA's Division of Emergency
and Investigational Operations'' to the following:
Biologics: Director, Office of Compliance and Biologics Quality
(HFM-600), 1401 Rockville Pike, Rockville, MD 20852, phone: 301-827-
6190, fax: 301-594-1944.
Human Drugs: Director, Office of Compliance (HFD-300), MPN I,
7520 Standish Pl., Rockville, MD 20855-2737, phone: 301-594-0054,
fax: 301-594-2114.
Veterinary Drugs: Director, Office of Surveillance and
Compliance (HFV-200), MPN II, 7500 Standish Pl., Rockville, MD
20855-2773, phone: 301-827-6644, fax: 301-594-1807.
8. Under Sec. 26.1(c), the definition of Good Manufacturing
Practices (GMP's) has been changed from the following:
(c) Good Manufacturing Practices (GMP's): [These GMP conceptual
definitions are to be merged by the parties at a future date.]
(1) GMP's mean the requirements found in the respective
legislations, regulations, and administrative provisions for methods
to be used in, and the facilities or controls to be used for, the
manufacturing, processing, packing, and/or holding of a drug to
assure that such drug meets the requirements as to safety, and has
the identity and strength, and meets the quality and purity
characteristics that it purports or is represented to possess.
(2) GMP's are that part of quality assurance which ensures that
products are consistently produced and controlled to quality
standards. For the purpose of this subpart, GMP's include,
therefore, the system whereby the manufacturer receives the
specifications of the product and/or process from the marketing
authorization/product authorization or license holder or applicant
and ensures the product is made in compliance with its
specifications (qualified person certification in the European
Community (EC)).
to the following:
(c) Good Manufacturing Practices (GMP's): [The United States
has clarified its interpretation that under the MRA, that only
paragraph (c)(1) of this section has to be understood as the U.S.
definition and paragraph (c)(2) as the EC definition.]
(1) GMP's mean the requirements found in the legislations,
regulations, and administrative provisions for methods to be used
in, and the facilities or controls to be used for, the
manufacturing, processing, packing, and/or holding of a drug to
assure that such drug meets the requirements as to safety, and has
the identity and strength, and meets the quality and purity
characteristics that it purports or is represented to possess.
(2) GMP's are that part of quality assurance which ensures that
products are consistently produced and controlled to quality
standards. For the purpose of this subpart, GMP's include,
therefore, the system whereby the manufacturer receives the
specifications of the product and/or process from the marketing
authorization/product authorization or license holder or applicant
and ensures the product is made in compliance with its
specifications (qualified person certification in the EC).
The previous changes reflect discussions between FDA and European
Commission officials. As a result of those discussions, the United
States has clarified its interpretation that the first paragraph of
Article 1(3) of the Sectoral Annex for Pharmaceutical GMP's, has to be
understood as the U.S. definition and the second as the EC definition.
The agency believes that these changes are appropriate because they
clarify that the applicable definition under the MRA
[[Page 60138]]
will be consistent with the act and regulations (see, e.g., section
501(a)(2)(B) of the act; 21 U.S.C. 351(a)(2)(B)). Furthermore, the
Sectoral Annex on Pharmaceutical GMP's, including its core concept of
``equivalence,'' does not require either party to change its definition
or application of GMP's.
9. Changes have been made to the list of regulatory authorities
contained in Appendix B of Subpart A (List of Authorities) as a result
of the legal review carried out in the EC prior to finalizing the MRA.
The European Commission amended its list of regulatory authorities
contained in Appendix 2 of the Pharmaceutical GMP Annex of the MRA
because the changes more correctly reflect the allocation of
administrative competencies in the EC and its Member States and do not
alter the activities to be carried out under the MRA.
10. Changes have been made to Table 2. of Appendix B of Subpart B
of the rule. That table listed 42 class II medical devices to be
included within the scope of product coverage at the beginning of the
transition period. Four of the devices that were on the list cannot be
reviewed by conformity assessment bodies under the MRA and this rule,
because of a statutory prohibition in the act. Accordingly, the
agreement will be brought into force without application to those four
devices. Section 523 of the act prohibits ``accredited persons'' from
performing review of a class II device that is intended to be
permanently implantable, life sustaining, or life supporting, and
review of such devices must be performed by FDA. This provision was
recently added to the act by FDAMA. The agency recently determined that
the following four devices are within the scope of the prohibition and
have been removed from Table 2: AN 868.5925, powered emergency
ventilator; OR 888.3020, intramedullary fixation rod; OR 888.3030,
single/multiple component metallic bone fixation appliances and
accessories; and OR 888.3040, smooth or threaded metallic bone fixation
fastener. The United States has informed the EC of this situation and
of the need to make appropriate amendments to the MRA promptly after
its entry into force.
IV. Analysis of Impacts
FDA has examined the impacts of the final rule under Executive
Order 12866, under the Regulatory Flexibility Act (Pub. L. 96-354, as
amended by Pub. L. 104-121), and under the Unfunded Mandates Reform Act
(Pub. L. 104-4). Executive Order 12866 directs agencies to assess all
costs and benefits of available regulatory alternatives and, when
regulation is necessary, to select regulatory approaches that maximize
net benefits (including potential economic, environmental, public
health and safety, and other advantages; distributive impacts; and
equity). The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant economic impact
of a rule on a substantial number of small entities. The Unfunded
Mandates Reform Act requires agencies to prepare an assessment of
anticipated costs and benefits before enacting any rule that may result
in an expenditure by State, local and tribal governments, in the
aggregate, or by the private sector, of $100 million (adjusted annually
for inflation) in any 1 year.
The agency believes that this final rule is consistent with the
regulatory philosophy and principles identified in the Executive Order
and in these two statutes. Through this regulation, the agency sets out
requirements through which it may normally endorse certain conformity
assessment procedure reports. Such reports would be provided by
equivalent EC Member State regulatory authorities for manufacturing
site inspections to ascertain conformity with pharmaceutical GMP's and
by equivalent CAB's for quality system audits and certain medical
device premarket evaluations. Obtaining conformity assessment
information in the manner described in the final rule is more efficient
and cost-effective than the existing approach, where additional
inspection efforts by FDA in foreign countries are necessary because
foreign regulatory systems have not been found equivalent. The primary
benefit of the final rule is to provide credible assurance that the
increasing volume of EC Member States' imports into the United States
meet pharmaceutical GMP requirements, and medical device quality system
evaluation and certain premarket evaluation requirements, as specified
in U.S. statutes and regulations. In the future, this credible
assurance must be achievable with FDA resource expenditures that rise
less than proportionately to the volume of trade.
In recent years, the credibility of the current approach has been
strained as FDA's essentially constant foreign inspection capacity has
been stretched over an expanding volume of imports from the EC. In the
3-year interval between 1994 and 1997, the value of EC pharmaceutical
and medical device imports into the United States has nearly doubled
from $5.5 billion to more than $10.7 billion. Growth has been greatest
in pharmaceuticals, where annual EC exports have increased by more than
$2 billion in each of the last 2 years. In 1997, FDA conducted one
inspection in the EC for every $60 million in pharmaceutical exports to
the United States, which is less than half the coverage intensity of
1994. In addition, the majority of these inspections have been
preapproval in nature. Continuation of the current trend would further
decrease FDA's coverage intensity to less than one inspection per $100
million in EC pharmaceutical exports by the year 2000. Equivalence with
EC Member State regulatory systems would leverage FDA's regulatory
resources so that necessary conformity assessments can be ensured
despite higher volumes of future trade.
In addition to helping FDA cope with higher trade volumes, mutual
recognition or equivalence-based agreements with exporting nations may
permit FDA to redirect some of its inspectional resources to risk
priorities not covered by such agreements. This flexibility would
provide a more responsive level of U.S. consumer protection in the face
of a changing global marketplace with inherently variable risk
management priorities.
Another important benefit of the final rule would be the cost
savings realized by the regulated industry, largely as a result of the
sharing of inspection reports among equivalent regulatory authorities.
This exchange, in turn, will minimize the need for duplicative
inspections and permit individual firms to undergo fewer inspections of
manufacturing sites. FDA does not have data on the average
administrative cost incurred by manufacturers of pharmaceuticals
(including biologicals) or medical devices as they participate in
regulatory inspections, but it is likely that the avoidance of
redundant inspections would generate cost savings. The final rule also
may shorten product review times for regulated products as a result of
the increased efficiency of premarket approval inspection activities
and the third-party evaluation of certain medical devices.
Quantification of these savings will be highly dependent on the
specific countries that achieve equivalence and on the number of
medical device audits and evaluations performed by CAB's under the MRA.
The costs of this regulation will have a greater impact on
governmental regulatory agencies than on the regulated industry. These
governmental costs involve both startup and operational components. FDA
has not received additional government funding earmarked for achieving
mutual
[[Page 60139]]
recognition agreements and, therefore, must proceed to implement these
agreements as a concurrent function within normal day-to-day regulatory
activities. The 3-year transition period reflects the necessity to
absorb these startup costs within existing regulatory budgets. Some
activities such as joint inspections may be reasonably easy to absorb
as concurrent functions that do not require additional funding, while
others such as developing and maintaining systems for routine
information exchange may involve new activities. These absorbed
governmental costs will fall heavily on FDA, as it must assess
equivalence of multiple EC Member States and notified bodies.
For FDA, the absorption of these startup costs will be easier with
respect to those EC Member States with which the United States already
has a large volume of trade in the products in question, where FDA
already conducts enough inspections to have gathered a general
understanding of the requirements and regulatory practices of the
exporting country. From this perspective, the pace and priorities for
mutual recognition agreements during the transition period will be
affected by FDA's ability to conduct these processes as concurrent
functions within current activities.
In the longer run, an operational system of mutual recognition
agreements could pose additional costs or problems for regulatory
authorities of exporting countries if equivalence requires a frequency,
focus or content of inspections not presently included in regulatory
requirements of the exporting nation. For example, Country A may not be
able to provide the frequency of medical device inspections desired by
Country B without conducting inspections beyond those required for
Country A's domestic inspection strategy. Conversely, Country B may not
be able to provide to Country A adequate details of the quality of
pharmaceutical source materials, because Country B does not have
inspectional authority over pharmaceutical starting materials. To the
extent that such costs or problems are insignificant or offset by other
savings, they will not be obstacles to reaching agreement on
equivalence.
This rule is not expected to involve any new incremental costs to
the affected industries. Although joint inspections during the
transition period may create the appearance of more regulatory effort,
they would not impose additional costs on the firms inspected. FDA does
not anticipate an increase in the total number of EC inspections, and
in fact, the coverage intensity of FDA inspections in the EC would be
expected to continue to fall during the transition period, as it has
for the past several years. Other activities related to equivalence
determinations, such as the procedures for exchanging information and
reports, focus on the interface and coordination among regulatory
agencies and, as such, will not affect industry in a cost context.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities unless the rule is not expected to have a significant
economic impact on a substantial number of small entities. As this
final regulation is not expected to impose costs on the regulated
industry, and FDA has received no comments that would indicate
otherwise, the agency certifies that this rule will not have a
significant impact on a substantial number of small entities.
Therefore, under the Regulatory Flexibility Act, no further analysis is
required.
The Unfunded Mandates Act of 1995 requires that agencies prepare
an assessment of the anticipated costs and benefits before issuing any
final rule that may result in expenditures by State, local, and tribal
governments, in the aggregate, or by the private sector, of $100
million or more (adjusted annually for inflation) in any 1 year. This
rule does not impose any mandates on State, local or tribal
governments, or the private sector that would result in an annual
expenditure of $100 million or more. Therefore, no further analysis is
appropriate for this requirement.
V. Paperwork Reduction Act of 1995
This final rule does not contain any information collection
provisions that would be subject to review by the Office of Management
and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C.
3501-3520).
VI. References
1. The 1992 ``Report of the Task Force on International
Harmonization'' is available from the National Technical Information
Service, Vienna, VA; Order # PB93128155.
2. FDA's Compliance Policy Guides ``Sec. 100.900, International
Memoranda of Understanding (CPG 7150.19)'' is available from the
National Technical Information Service, Vienna, VA 22161 (Order # PB
96-915499INZ) or can be found on FDA's website at the following
location: ``www.fda.gov/ora/compliance__ref/cpg/
cpgch1.htm#sec.100.900''.
3. The 1997 ``Summary Report of the Foreign Inspection Working
Group'' is available from the Freedom of Information Staff (HFI-35),
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD
20857.
VII. Comparison Table
The following table shows the relationship of the MRA Articles and
the sections of the Code of Federal Regulations (CFR) under this rule:
Table 1.-- Relationship of the MRA Articles to sections in the CFR
------------------------------------------------------------------------
MRA Article CFR Section
------------------------------------------------------------------------
Sectoral Annex for Pharmaceutical GMP's Subpart A
------------------------------------------------------------------------
Article 1.............................. 26.1
Article 2.............................. 26.2
Article 3.............................. 26.3
Article 4.............................. 26.4
Article 5.............................. 26.5
Article 6.............................. 26.6
Article 7.............................. 26.7
Article 8.............................. 26.8
Article 9.............................. 26.9
Article 10............................. 26.10
Article 11............................. 26.11
Article 12............................. 26.12
Article 13............................. 26.13
Article 14............................. 26.14
Article 15............................. 26.15
[[Page 60140]]
Article 16............................. 26.16
Article 17............................. 26.17
Article 18............................. 26.18
Article 19............................. 26.19
Article 20............................. 26.20
Article 21............................. 26.21
Appendix 1............................. Appendix A
Appendix 2............................. Appendix B
Appendix 3............................. Appendix C
Appendix 4............................. Appendix D
Appendix 5............................. Appendix E
------------------------------------------------------------------------
------------------------------------------------------------------------
MRA Article CFR Section
------------------------------------------------------------------------
Sectoral Annex on Medical Devices Subpart B
------------------------------------------------------------------------
Article 1.............................. 26.31
Article 2.............................. 26.32
Article 3.............................. 26.33
Article 4.............................. 26.34
Article 5.............................. 26.35
Article 6.............................. 26.36
Article 7.............................. 26.37
Article 8.............................. 26.38
Article 9.............................. 26.39
Article 10............................. 26.40
Article 11............................. 26.41
Article 12............................. 26.42
Article 13............................. 26.43
Article 14............................. 26.44
Article 15............................. 26.45
Article 16............................. 26.46
Article 17............................. 26.47
Article 18............................. 26.48
Article 19............................. 26.49
Article 20............................. 26.50
Appendix 1............................. Appendix A
Appendix 2 and Tables 1-3.............. Appendix B and Tables 1-3
Appendix 3 [Reserved].................. Appendix C [Reserved]
Appendix 4 [Reserved].................. Appendix D [Reserved]
Appendix 5 [Reserved].................. Appendix E [Reserved]
Appendix 6 [Reserved].................. Appendix F [Reserved]
------------------------------------------------------------------------
------------------------------------------------------------------------
MRA Article CFR Section
------------------------------------------------------------------------
Framework Agreement Subpart C
------------------------------------------------------------------------
Article 1.............................. 26.60
Article 2.............................. 26.61
Article 3.............................. 26.62
Article 4.............................. 26.63
Article 5.............................. 26.64
Article 6.............................. 26.65
Article 7.............................. 26.66
Article 8.............................. 26.67
Article 9.............................. 26.68
Article 10............................. 26.69
Article 11............................. 26.70
Article 12............................. 26.71
Article 13............................. 26.72
Article 14............................. 26.73
Article 15............................. 26.74
Article 16............................. 26.75
Article 17............................. 26.76
Article 18............................. 26.77
[[Page 60141]]
Article 19............................. 26.78
Article 20............................. 26.79
Article 21............................. 26.80
Article 22............................. 26.81
------------------------------------------------------------------------
List of Subjects in 21 CFR Part 26
Animal and human drugs, Biologicals, Devices, Exports, Imports,
Incorporation by reference, and Inspections.
Therefore, under the Federal Food, Drug, and Cosmetic Act and the
Public Health Service Act and under authority delegated to the
Commissioner of Food and Drugs, 21 CFR chapter I is amended by adding
part 26 to read as follows:
PART 26--MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING
PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND
CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES
AND THE EUROPEAN COMMUNITY
Sec.
26.0 General.
Subpart A--Specific Sector Provisions for Pharmaceutical Good
Manufacturing Practices
26.1 Definitions.
26.2 Purpose.
26.3 Scope.
26.4 Product coverage.
26.5 Length of transition period.
26.6 Equivalence assessment.
26.7 Participation in the equivalence assessment and
determination.
26.8 Other transition activities.
26.9 Equivalence determination.
26.10 Regulatory authorities not listed as currently equivalent.
26.11 Start of operational period.
26.12 Nature of recognition of inspection reports.
26.13 Transmission of postapproval inspection reports.
26.14 Transmission of preapproval inspection reports.
26.15 Monitoring continued equivalence.
26.16 Suspension.
26.17 Role and composition of the Joint Sectoral Committee.
26.18 Regulatory collaboration.
26.19 Information relating to quality aspects.
26.20 Alert system.
26.21 Safeguard clause.
Appendix A of Subpart A--List of Applicable Laws, Regulations, and
Administrative Provisions.
Appendix B of Subpart A--List of Authorities.
Appendix C of Subpart A--Indicative List of Products Covered by
Subpart A.
Appendix D of Subpart A--Criteria for Assessing Equivalence for
Post- and Preapproval.
Appendix E of Subpart A--Elements to be Considered in Developing a
Two-Way Alert System.
Subpart B--Specific Sector Provisions for Medical Devices
26.31 Purpose.
26.32 Scope.
26.33 Product coverage.
26.34 Regulatory authorities.
26.35 Length and purpose of transition period.
26.36 Listing of CAB's.
26.37 Confidence building activities.
26.38 Other transition period activities.
26.39 Equivalence assessment.
26.40 Start of the operational period.
26.41 Exchange and endorsement of quality system evaluation
reports.
26.42 Exchange and endorsement of product evaluation reports.
26.43 Transmission of quality system evaluation reports.
26.44 Transmission of product evaluation reports.
26.45 Monitoring continued equivalence.
26.46 Listing of additional CAB's.
26.47 Role and composition of the Joint Sectoral Committee.
26.48 Harmonization.
26.49 Regulatory cooperation.
26.50 Alert system and exchange of postmarket vigilance reports.
Appendix A of Subpart B--Relevant Legislation, Regulations, and
Procedures.
Appendix B of Subpart B--Scope of Product Coverage.
Appendix C of Subpart B [Reserved].
Appendix D of Subpart B [Reserved].
Appendix E of Subpart B [Reserved].
Appendix F of Subpart B [Reserved].
Subpart C--``Framework'' Provisions
26.60 Definitions.
26.61 Purpose of this part.
26.62 General obligations.
26.63 General coverage of this part.
26.64 Transitional arrangements.
26.65 Designating authorities.
26.66 Designation and listing procedures.
26.67 Suspension of listed conformity assessment bodies.
26.68 Withdrawal of listed conformity assessment bodies.
26.69 Monitoring of conformity assessment bodies.
26.70 Conformity assessment bodies.
26.71 Exchange of information.
26.72 Sectoral contact points.
26.73 Joint Committee.
26.74 Preservation of regulatory authority.
26.75 Suspension of recognition obligations.
26.76 Confidentiality.
26.77 Fees.
26.78 Agreements with other countries.
26.79 Territorial application.
26.80 Entry into force, amendment, and termination.
26.81 Final provisions.
Authority: 5 U.S.C. 552; 15 U.S.C. 1453, 1454, 1455; 18 U.S.C.
1905; 21 U.S.C. 321, 331, 351, 352, 355, 360, 360b, 360c, 360d,
360e, 360f, 360g, 360h, 360i, 360j, 360l, 360m, 371, 374, 381, 382,
383, 393; 42 U.S.C. 216, 241, 242l, 262, 264, 265.
Sec. 26.0 General.
This part substantially reflects relevant provisions of the
framework agreement and its sectoral annexes on pharmaceutical good
manufacturing practices (GMP's) and medical devices of the ``Agreement
on Mutual Recognition Between the United States of America and the
European Community'' (the MRA), signed at London May 18, 1998. For
codification purposes, certain provisions of the MRA have been modified
for use in this part. This modification is done for purposes of clarity
only and shall not affect the text of the MRA concluded between the
United States and the European Community (EC), or the rights and
obligations of the United States or the EC under that agreement.
Whereas the parties to the MRA are the United States and EC, this part
is relevant only to the Food and Drug Administration's (FDA's)
implementation of the MRA, including the sectoral annexes reflected in
subparts A and B of this part. This part does not govern implementation
of the MRA by the EC, which will implement the MRA in accordance with
its internal procedures, nor does this part address implementation of
the MRA by other concerned U.S. Federal agencies. For purposes of this
part, the terms ``party'' or ``parties,'' where relevant to FDA's
implementation of the MRA, should be considered as referring to FDA
only. If the parties to the MRA subsequently amend or terminate the
MRA, FDA will modify this part accordingly, using appropriate
administrative procedures.
[[Page 60142]]
Subpart A--Specific Sector Provisions for Pharmaceutical Good
Manufacturing Practices
Sec. 26.1 Definitions.
(a) Enforcement means action taken by an authority to protect the
public from products of suspect quality, safety, and effectiveness or
to assure that products are manufactured in compliance with appropriate
laws, regulations, standards, and commitments made as part of the
approval to market a product.
(b) Equivalence of the regulatory systems means that the systems
are sufficiently comparable to assure that the process of inspection
and the ensuing inspection reports will provide adequate information to
determine whether respective statutory and regulatory requirements of
the authorities have been fulfilled. Equivalence does not require that
the respective regulatory systems have identical procedures.
(c) Good Manufacturing Practices (GMP's). [The United States has
clarified its interpretation that under the MRA, that only paragraph
(c)(1) of this section has to be understood as the U.S. definition and
paragraph (c)(2) as the EC definition.]
(1) GMP's mean the requirements found in the legislations,
regulations, and administrative provisions for methods to be used in,
and the facilities or controls to be used for, the manufacturing,
processing, packing, and/or holding of a drug to assure that such drug
meets the requirements as to safety, and has the identity and strength,
and meets the quality and purity characteristics that it purports or is
represented to possess.
(2) GMP's are that part of quality assurance which ensures that
products are consistently produced and controlled to quality standards.
For the purpose of this subpart, GMP's include, therefore, the system
whereby the manufacturer receives the specifications of the product
and/or process from the marketing authorization/product authorization
or license holder or applicant and ensures the product is made in
compliance with its specifications (qualified person certification in
the EC).
(d) Inspection means an onsite evaluation of a manufacturing
facility to determine whether such manufacturing facility is operating
in compliance with GMP's and/or commitments made as part of the
approval to market a product.
(e) Inspection report means the written observations and GMP's
compliance assessment completed by an authority listed in Appendix B of
this subpart.
(f) Regulatory system means the body of legal requirements for
GMP's, inspections, and enforcements that ensure public health
protection and legal authority to assure adherence to these
requirements.
Sec. 26.2 Purpose.
The provisions of this subpart govern the exchange between the
parties and normal endorsement by the receiving regulatory authority of
official good manufacturing practices (GMP's) inspection reports after
a transitional period aimed at determination of the equivalence of the
regulatory systems of the parties, which is the cornerstone of this
subpart.
Sec. 26.3 Scope.
(a) The provisions of this subpart shall apply to pharmaceutical
inspections carried out in the United States and Member States of the
European Community (EC) before products are marketed (hereafter
referred to as ``preapproval inspections'') as well as during their
marketing (hereafter referred to as ``postapproval inspections'').
(b) Appendix A of this subpart names the laws, regulations, and
administrative provisions governing these inspections and the good
manufacturing practices (GMP's) requirements.
(c) Appendix B of this subpart lists the authorities participating
in activities under this subpart.
(d) Sections 26.65, 26.66, 26.67, 26.68, 26.69, and 26.70 of
subpart C of this part do not apply to this subpart.
Sec. 26.4 Product coverage.
(a) The provisions of this subpart will apply to medicinal
products for human or animal use, intermediates and starting materials
(as referred to in the European Community (EC)) and to drugs for human
or animal use, biological products for human use, and active
pharmaceutical ingredients (as referred to in the United States), only
to the extent they are regulated by the authorities of both parties as
listed in Appendix B of this subpart.
(b) Human blood, human plasma, human tissues and organs, and
veterinary immunologicals (under 9 CFR 101.2, ``veterinary
immunologicals'' are referred to as ``veterinary biologicals'') are
excluded from the scope of this subpart. Human plasma derivatives (such
as immunoglobulins and albumin), investigational medicinal products/new
drugs, human radiopharmaceuticals, and medicinal gases are also
excluded during the transition phase; their situation will be
reconsidered at the end of the transition period. Products regulated by
the Food and Drug Administration's Center for Biologics Evaluation and
Research as devices are not covered under this subpart.
(c) Appendix C of this subpart contains an indicative list of
products covered by this subpart.
Sec. 26.5 Length of transition period.
A 3-year transition period will start immediately after the
effective date described in Sec. 26.80(a).
Sec. 26.6 Equivalence assessment.
(a) The criteria to be used by the parties to assess equivalence
are listed in Appendix D of this subpart. Information pertaining to the
criteria under European Community (EC) competence will be provided by
the EC.
(b) The authorities of the parties will establish and communicate
to each other their draft programs for assessing the equivalence of the
respective regulatory systems in terms of quality assurance of the
products and consumer protection. These programs will be carried out,
as deemed necessary by the regulatory authorities, for post- and
preapproval inspections and for various product classes or processes.
(c) The equivalence assessment shall include information exchanges
(including inspection reports), joint training, and joint inspections
for the purpose of assessing regulatory systems and the authorities'
capabilities. In conducting the equivalence assessment, the parties
will ensure that efforts are made to save resources.
(d) Equivalence assessment for authorities added to Appendix B of
this subpart after the effective date described in Sec. 26.80(a) will
be conducted as described in this subpart, as soon as practicable.
Sec. 26.7 Participation in the equivalence assessment and
determination.
The authorities listed in Appendix B of this subpart will actively
participate in these programs to build a sufficient body of evidence
for their equivalence determination. Both parties will exercise good
faith efforts to complete equivalence assessment as expeditiously as
possible to the extent the resources of the authorities allow.
Sec. 26.8 Other transition activities.
As soon as possible, the authorities will jointly determine the
essential information which must be present in inspection reports and
will cooperate to develop mutually agreed inspection report format(s).
[[Page 60143]]
Sec. 26.9 Equivalence determination.
(a) Equivalence is established by having in place regulatory
systems covering the criteria referred to in Appendix D of this
subpart, and a demonstrated pattern of consistent performance in
accordance with these criteria. A list of authorities determined as
equivalent shall be agreed to by the Joint Sectoral Committee at the
end of the transition period, with reference to any limitation in terms
of inspection type (e.g., postapproval or preapproval) or product
classes or processes.
(b) The parties will document insufficient evidence of
equivalence, lack of opportunity to assess equivalence or a
determination of nonequivalence, in sufficient detail to allow the
authority being assessed to know how to attain equivalence.
Sec. 26.10 Regulatory authorities not listed as currently equivalent.
Authorities not currently listed as equivalent, or not equivalent
for certain types of inspections, product classes or processes may
apply for reconsideration of their status once the necessary corrective
measures have been taken or additional experience is gained.
Sec. 26.11 Start of operational period.
(a) The operational period shall start at the end of the
transition period and its provisions apply to inspection reports
generated by authorities listed as equivalent for the inspections
performed in their territory.
(b) In addition, when an authority is not listed as equivalent
based on adequate experience gained during the transition period, the
Food and Drug Administration (FDA) will accept for normal endorsement
(as provided in Sec. 26.12) inspection reports generated as a result of
inspections conducted jointly by that authority on its territory and
another authority listed as equivalent, provided that the authority of
the Member State in which the inspection is performed can guarantee
enforcement of the findings of the inspection report and require that
corrective measures be taken when necessary. FDA has the option to
participate in these inspections, and based on experience gained during
the transition period, the parties will agree on procedures for
exercising this option.
(c) In the European Community (EC), the qualified person will be
relieved of responsibility for carrying the controls laid down in
Article 22 paragraph 1(b) of Council Directive 75/319/EEC (see Appendix
A of this subpart) provided that these controls have been carried out
in the United States and that each batch/lot is accompanied by a batch
certificate (in accordance with the World Health Organization
Certification Scheme on the Quality of Medicinal Products) issued by
the manufacturer certifying that the product complies with requirements
of the marketing authorization and signed by the person responsible for
releasing the batch/lot.
Sec. 26.12 Nature of recognition of inspection reports.
(a) Inspection reports (containing information as established
under Sec. 26.8), including a good manufacturing practice (GMP)
compliance assessment, prepared by authorities listed as equivalent,
will be provided to the authority of the importing party. Based on the
determination of equivalence in light of the experience gained, these
inspection reports will normally be endorsed by the authority of the
importing party, except under specific and delineated circumstances.
Examples of such circumstances include indications of material
inconsistencies or inadequacies in an inspection report, quality
defects identified in the postmarket surveillance or other specific
evidence of serious concern in relation to product quality or consumer
safety. In such cases, the authority of the importing party may request
clarification from the authority of the exporting party which may lead
to a request for reinspection. The authorities will endeavor to respond
to requests for clarification in a timely manner.
(b) Where divergence is not clarified in this process, an
authority of the importing country may carry out an inspection of the
production facility.
Sec. 26.13 Transmission of postapproval inspection reports.
Postapproval good manufacturing practice (GMP) inspection reports
concerning products covered by this subpart will be transmitted to the
authority of the importing country within 60-calendar days of the
request. Should a new inspection be needed, the inspection report will
be transmitted within 90-calendar days of the request.
Sec. 26.14 Transmission of preapproval inspection reports.
(a) A preliminary notification that an inspection may have to take
place will be made as soon as possible.
(b) Within 15-calendar days, the relevant authority will
acknowledge receipt of the request and confirm its ability to carry out
the inspection. In the European Community (EC), requests will be sent
directly to the relevant authority, with a copy to the European Agency
for the Evaluation of Medicinal Products (EMEA). If the authority
receiving the request cannot carry out the inspection as requested, the
requesting authority shall have the right to conduct the inspection.
(c) Reports of preapproval inspections will be sent within 45-
calendar days of the request that transmitted the appropriate
information and detailed the precise issues to be addressed during the
inspection. A shorter time may be necessary in exceptional cases and
these will be described in the request.
Sec. 26.15 Monitoring continued equivalence.
Monitoring activities for the purpose of maintaining equivalence
shall include review of the exchange of inspection reports and their
quality and timeliness; performance of a limited number of joint
inspections; and the conduct of common training sessions.
Sec. 26.16 Suspension.
(a) Each party has the right to contest the equivalence of a
regulatory authority. This right will be exercised in an objective and
reasoned manner in writing to the other party.
(b) The issue shall be discussed in the Joint Sectoral Committee
promptly upon such notification. Where the Joint Sectoral Committee
determines that verification of equivalence is required, it may be
carried out jointly by the parties in a timely manner, under Sec. 26.6.
(c) Efforts will be made by the Joint Sectoral Committee to reach
unanimous consent on the appropriate action. If agreement to suspend is
reached in the Joint Sectoral Committee, an authority may be suspended
immediately thereafter. If no agreement is reached in the Joint
Sectoral Committee, the matter is referred to the Joint Committee as
described in Sec. 26.73. If no unanimous consent is reached within 30
days after such notification, the contested authority will be
suspended.
(d) Upon the suspension of authority previously listed as
equivalent, a party is no longer obligated to normally endorse the
inspection reports of the suspended authority. A party shall continue
to normally endorse the inspection reports of that authority prior to
suspension, unless the authority of the receiving party decides
otherwise based on health or safety considerations. The suspension will
remain in effect until unanimous consent has been reached by the
parties on the future status of that authority.
Sec. 26.17 Role and composition of the Joint Sectoral Committee.
(a) A Joint Sectoral Committee is set up to monitor the activities
under both the transitional and operational phases of this subpart.
[[Page 60144]]
(b) The Joint Sectoral Committee will be cochaired by a
representative of the Food and Drug Administration (FDA) for the United
States and a representative of the European Community (EC) who each
will have one vote. Decisions will be taken by unanimous consent.
(c) The Joint Sectoral Committee's functions will include:
(1) Making a joint assessment, which must be agreed by both
parties, of the equivalence of the respective authorities;
(2) Developing and maintaining the list of equivalent authorities,
including any limitation in terms of inspecting type or products, and
communicating the list to all authorities and the Joint Committee;
(3) Providing a forum to discuss issues relating to this subpart,
including concerns that an authority may be no longer equivalent and
opportunity to review product coverage; and
(4) Consideration of the issue of suspension.
(d) The Joint Sectoral Committee shall meet at the request of
either party and, unless the cochairs otherwise agree, at least once
each year. The Joint Committee will be kept informed of the agenda and
conclusions of meetings of the Joint Sectoral Committee.
Sec. 26.18 Regulatory collaboration.
(a) The parties and authorities shall inform and consult one
another, as permitted by law, on proposals to introduce new controls or
to change existing technical regulations or inspection procedures and
to provide the opportunity to comment on such proposals.
(b) The parties shall notify each other in writing of any changes
to Appendix B of this subpart.
Sec. 26.19 Information relating to quality aspects.
The authorities will establish an appropriate means of exchanging
information on any confirmed problem reports, corrective actions,
recalls, rejected import consignments, and other regulatory and
enforcement problems for products subject to this subpart.
Sec. 26.20 Alert system.
(a) The details of an alert system will be developed during the
transitional period. The system will be maintained in place at all
times. Elements to be considered in developing such a system are
described in Appendix E of this subpart.
(b) Contact points will be agreed between both parties to permit
authorities to be made aware with the appropriate speed in case of
quality defect, recalls, counterfeiting, and other problems concerning
quality, which could necessitate additional controls or suspension of
the distribution of the product.
Sec. 26.21 Safeguard clause.
Each party recognizes that the importing country has a right to
fulfill its legal responsibilities by taking actions necessary to
ensure the protection of human and animal health at the level of
protection it deems appropriate. This includes the suspension of the
distribution, product detention at the border of the importing country,
withdrawal of the batches and any request for additional information or
inspection as provided in Sec. 26.12.
Appendix A of Subpart A--List of Applicable Laws, Regulations, and
Administrative Provisions.
1. For the European Community (EC):
[Copies of EC documents may be obtained from the European
Document Research, 1100 17th St. NW., suite 301, Washington, DC
20036. EC documents may be viewed on the European Commission
Pharmaceuticals Units web site at ``http://dg3.eudra.org''.]
Council Directive 65/65/EEC of 26 January 1965 on the approximation
of provisions laid down by law, regulation, or administrative action
relating to proprietary medicinal products as extended, widened, and
amended.
Council Directive 75/319/EEC of 20 May 1975 on the approximation of
provisions laid down by law, regulation or administrative action
relating to proprietary medicinal products as extended, widened and
amended.
Council Directive 81/851/EEC of 28 September 1981 on the
approximation of the laws of the Member States relating to
veterinary medicinal products, as widened and amended.
Commission Directive 91/356/EEC of 13 June 1991 laying down the
principles and guidelines of good manufacturing practice for
medicinal products for human use.
Commission Directive 91/412/EEC of 23 July 1991 laying down the
principles and guidelines of good manufacturing practice for
veterinary medicinal products.
Council Regulation EEC No 2309/93 of 22 July 1993 laying down
Community procedures for the authorization and supervision of
medicinal products for human and veterinary use and establishing a
European Agency for the Evaluation of Medicinal Products.
Council Directive 92/25/EEC of 31 March 1992 on the wholesale
distribution of medicinal products for human use.
Guide to Good Distribution Practice (94/C 63/03).
Current version of the Guide to Good Manufacturing Practice, Rules
Governing Medicinal Products in the European Community, Volume IV.
2. For the United States:
[Copies of FDA documents may be obtained from the Government
Printing Office, 1510 H St. NW., Washington, DC 20005. FDA
documents, except the FDA Compliance Program Guidance Manual, may be
viewed on FDA's Internet web site at ``http://www.FDA.gov''.]
Relevant sections of the United States Federal Food, Drug, and
Cosmetic Act and the United States Public Health Service Act.
Relevant sections of Title 21, United States Code of Federal
Regulations (CFR) Parts 1-99, Parts 200-299, Parts 500-599, and
Parts 600-799.
Relevant sections of the FDA Investigations Operations Manual, the
FDA Regulatory Procedures Manual, the FDA Compliance Policy Guidance
Manual, the FDA Compliance Program Guidance Manual, and other FDA
guidances.
Appendix B of Subpart A--List of Authorities.
1. For the United States: In the United States, the regulatory
authority is the Food and Drug Administration.
2. For the European Community: In the European Community, the
regulatory authorities are the following:
Belgium: Inspection generale de la Pharmacie, Algemene
Farmaceutische Inspectie.
Denmark: Laegemiddelstyrelsen.
Germany: Bundesministerium fur Gesundheit for immunologicals: Paul-
Ehrlich-Institut, Federal Agency for Sera and Vaccines.
Greece:
, Ministry of Health and Welfare, National Drug Organization
(E.O.F).
Spain: For medicinal products for human use: Ministerio de Sanidad y
Consumo, Subdireccion General de Control Farmaceutico. For medicinal
products for veterinary use: Ministerio de Agricultura, Pesca y
Alimentacion (MAPA), Direccion General de la Produccion Agraria.
France: For medicinal products for human use: Agence du Medicament.
For veterinary medicinal products: Agence Nationale du Medicament
Veterinaire.
Ireland: Irish Medicines Board.
Italy: For medicinal products for human use: Ministero della Sanita,
Dipartimento Farmaci e Farmacovigilanza. For medicinal products for
veterinary use: Ministero della Sanita, Dipartimento alimenti e
nutrizione e sanita pubblica veterinaria-Div. IX.
Luxembourg: Division de la Pharmacie et des Medicaments.
Netherlands: Staat der Nederlanden.
Austria: Bundesministerium fur Arbeit, Gesundheit und Soziales.
Portugal: Instituto da Farmacia e do Medicamento (INFARMED).
Finland: Laakelaitos/Lakemedelsverket (National Agency for
Medicines).
Sweden: Lakemedelsverket-Medical Products Agency.
United Kingdom: For human use and veterinary (non-immunologicals):
Medicines Control Agency. For veterinary immunologicals: Veterinary
Medicines Directorate.
European Community: Commission of the European Communities. European
Agency
[[Page 60145]]
for the Evaluation of Medicinal Products (EMEA).
Appendix C of Subpart A--Indicative List of Products Covered by
Subpart A.
Recognizing that precise definition of medicinal products and drugs
are to be found in the legislation referred to above, an indicative
list of products covered by this arrangement is given below:
- human medicinal products including prescription and
nonprescription drugs;
- human biologicals including vaccines, and immunologicals;
- veterinary pharmaceuticals, including prescription and
nonprescription drugs, with the exclusion of veterinary
immunologicals (Under 9 CFR 101.2 ``veterinary immunologicals'' are
referred to as ``veterinary biologicals'');
- premixes for the preparation of veterinary medicated feeds
(EC), Type A medicated articles for the preparation of veterinary
medicated feeds (United States);
- intermediate products and active pharmaceutical ingredients or
bulk pharmaceuticals (United States)/starting materials (EC).
Appendix D of Subpart A--Criteria for Assessing Equivalence for
Post- and Preapproval.
I. Legal/Regulatory authority and structures and procedures providing
for post- and preapproval:
A. Appropriate statutory mandate and jurisdiction.
B. Ability to issue and update binding requirements on GMP's and
guidance documents.
C. Authority to make inspections, review and copy documents, and to
take samples and collect other evidence.
D. Ability to enforce requirements and to remove products found in
violation of such requirements from the market.
E. Substantive current good manufacturing requirements.
F. Accountability of the regulatory authority.
G. Inventory of current products and manufacturers.
H. System for maintaining or accessing inspection reports, samples
and other analytical data, and other firm/product information
relating to matters covered by subpart A of this part.
II. Mechanisms in place to assure appropriate professional standards
and avoidance of conflicts of interest.
III. Administration of the regulatory authority:
A. Standards of education/qualification and training.
B. Effective quality assurance systems measures to ensure adequate
job performance.
C. Appropriate staffing and resources to enforce laws and
regulations.
IV. Conduct of inspections:
A. Adequate preinspection preparation, including appropriate
expertise of investigator/team, review of firm/product and
databases, and availability of appropriate inspection equipment.
B. Adequate conduct of inspection, including statutory access to
facilities, effective response to refusals, depth and competence of
evaluation of operations, systems and documentation; collection of
evidence; appropriate duration of inspection and completeness of
written report of observations to firm management.
C. Adequate postinspection activities, including completeness of
inspectors' report, inspection report review where appropriate, and
conduct of followup inspections and other activities where
appropriate, assurance of preservation and retrieval of records.
V. Execution of regulatory enforcement actions to achieve corrections,
designed to prevent future violations, and to remove products found in
violation of requirements from the market.
VI. Effective use of surveillance systems:
A. Sampling and analysis.
B. Recall monitoring.
C. Product defect reporting system.
D. Routine surveillance inspections.
E. Verification of approved manufacturing process changes to
marketing authorizations/approved applications.
VII. Additional specific criteria for preapproval inspections:
A. Satisfactory demonstration through a jointly developed and
administered training program and joint inspections to assess the
regulatory authorities' capabilities.
B. Preinspection preparation includes the review of appropriate
records, including site plans and drug master file or similar
documentation to enable adequate inspections.
C. Ability to verify chemistry, manufacturing, and control data
supporting an application is authentic and complete.
D. Ability to assess and evaluate research and development data as
scientifically sound, especially transfer technology of pilot, scale
up and full scale production batches.
E. Ability to verify conformity of the onsite processes and
procedures with those described in the application.
F. Review and evaluate equipment installation, operational and
performance qualification data, and evaluate test method validation.
Appendix E of Subpart A--Elements to be Considered in Developing a
Two-Way Alert System.
1. Documentation
- Definition of a crisis/emergency and under what circumstances an
alert is required
- Standard Operating Procedures (SOP's)
- Mechanism of health hazards evaluation and classification
- Language of communication and transmission of information
2. Crisis Management System
- Crisis analysis and communication mechanisms
- Establishment of contact points
- Reporting mechanisms
3. Enforcement Procedures
- Followup mechanisms
- Corrective action procedures
4. Quality Assurance System
- Pharmacovigilance programme
- Surveillance/monitoring of implementation of corrective action
5. Contact Points
For the purpose of subpart A of this part, the contact points for
the alert system will be:
A. For the European Community:
the Executive Director of the European Agency for the Evaluation of
Medicinal Products, 7, Westferry Circus, Canary Wharf, UK - London
E14 4HB, England. Telephone 44-171-418 8400, Fax 418-8416.
B. For the United States :
Biologics: Director, Office of Compliance and Biologics Quality
(HFM-600), 1401 Rockville Pike, Rockville, MD 20852, phone: 301-827-
6190, fax: 301-594-1944.
Human Drugs: Director, Office of Compliance (HFD-300), MPN I, 7520
Standish Pl., Rockville, MD 20855-2737, phone: 301-594-0054, fax:
301-594-2114.
Veterinary Drugs: Director, Office of Surveillance and Compliance
(HFV-200), MPN II, 7500 Standish Pl., Rockville, MD 20855-2773,
phone: 301-827-6644, fax: 301-594-1807.
Subpart B--Specific Sector Provisions for Medical Devices
Sec. 26.31 Purpose.
(a) The purpose of this subpart is to specify the conditions under
which a party will accept the results of quality system-related
evaluations and inspections and premarket evaluations of the other
party with regard to medical devices as conducted by listed conformity
assessment bodies (CAB's) and to provide for other related cooperative
activities.
(b) This subpart is intended to evolve as programs and policies of
the parties evolve. The parties will review this subpart periodically,
in order to assess progress and identify potential enhancements to this
subpart as Food and Drug Administration (FDA) and European Community
(EC) policies evolve over time.
Sec. 26.32 Scope.
(a) The provisions of this subpart shall apply to the exchange
and, where appropriate, endorsement of the following types of reports
from conformity assessment bodies (CAB's) assessed to be equivalent:
(1) Under the U.S. system, surveillance/postmarket and initial/
preapproval inspection reports;
(2) Under the U.S. system, premarket (510(k)) product evaluation
reports;
(3) Under the European Community (EC) system, quality system
evaluation reports; and
(4) Under the EC system, EC type examination and verification
reports.
[[Page 60146]]
(b) Appendix A of this subpart names the legislation, regulations,
and related procedures under which:
(1) Products are regulated as medical devices by each party;
(2) CAB's are designated and confirmed; and
(3) These reports are prepared.
(c) For purposes of this subpart, equivalence means that: CAB's in
the EC are capable of conducting product and quality systems
evaluations against U.S. regulatory requirements in a manner equivalent
to those conducted by FDA; and CAB's in the United States are capable
of conducting product and quality systems evaluations against EC
regulatory requirements in a manner equivalent to those conducted by EC
CAB's.
Sec. 26.33 Product coverage.
(a) There are three components to this subpart each covering a
discrete range of products:
(1) Quality System Evaluations. U.S.-type surveillance/postmarket
and initial/preapproval inspection reports and European Community (EC)-
type quality system evaluation reports will be exchanged with regard to
all products regulated under both U.S. and EC law as medical devices.
(2) Product Evaluation. U.S.-type premarket (510(k)) product
evaluation reports and EC-type-testing reports will be exchanged only
with regard to those products classified under the U.S. system as Class
I/Class II-Tier 2 medical devices which are listed in Appendix B of
this subpart.
(3) Postmarket Vigilance Reports. Postmarket vigilance reports
will be exchanged with regard to all products regulated under both U.S.
and EC law as medical devices.
(b) Additional products and procedures may be made subject to this
subpart by agreement of the parties.
Sec. 26.34 Regulatory authorities.
The regulatory authorities shall have the responsibility of
implementing the provisions of this subpart, including the designation
and monitoring of conformity assessment bodies (CAB's). Regulatory
authorities will be specified in Appendix C of this subpart. Each party
will promptly notify the other party in writing of any change in the
regulatory authority for a country.
Sec. 26.35 Length and purpose of transition period.
There will be a 3-year transition period immediately following the
date described in Sec. 26.80(a). During the transition period, the
parties will engage in confidence-building activities for the purpose
of obtaining sufficient evidence to make determinations concerning the
equivalence of conformity assessment bodies (CAB's) of the other party
with respect to the ability to perform quality system and product
evaluations or other reviews resulting in reports to be exchanged under
this subpart.
Sec. 26.36 Listing of CAB's.
Each party shall designate conformity assessment bodies (CAB's) to
participate in confidence building activities by transmitting to the
other party a list of CAB's which meet the criteria for technical
competence and independence, as identified in Appendix A of this
subpart. The list shall be accompanied by supporting evidence.
Designated CAB's will be listed in Appendix D of this subpart for
participation in the confidence building activities once confirmed by
the importing party. Nonconfirmation would have to be justified based
on documented evidence.
Sec. 26.37 Confidence building activities.
(a) At the beginning of the transitional period, the Joint
Sectoral Group will establish a joint confidence building program
calculated to provide sufficient evidence of the capabilities of the
designated conformity assessment bodies (CAB's) to perform quality
system or product evaluations to the specifications of the parties.
(b) The joint confidence building program should include the
following actions and activities:
(1) Seminars designed to inform the parties and CAB's about each
party's regulatory system, procedures, and requirements;
(2) Workshops designed to provide the parties with information
regarding requirements and procedures for the designation and
surveillance of CAB's;
(3) Exchange of information about reports prepared during the
transition period;
(4) Joint training exercises; and
(5) Observed inspections.
(c) During the transition period, any significant problem that is
identified with a CAB may be the subject of cooperative activities, as
resources allow and as agreed to by the regulatory authorities, aimed
at resolving the problem.
(d) Both parties will exercise good faith efforts to complete the
confidence building activities as expeditiously as possible to the
extent that the resources of the parties allow.
(e) Both the parties will each prepare annual progress reports
which will describe the confidence building activities undertaken
during each year of the transition period. The form and content of the
reports will be determined by the parties through the Joint Sectoral
Committee.
Sec. 26.38 Other transition period activities.
(a) During the transition period, the parties will jointly
determine the necessary information which must be present in quality
system and product evaluation reports.
(b) The parties will jointly develop a notification and alert
system to be used in case of defects, recalls, and other problems
concerning product quality that could necessitate additional actions
(e.g., inspections by the parties of the importing country) or
suspension of the distribution of the product.
Sec. 26.39 Equivalence assessment.
(a) In the final 6 months of the transition period, the parties
shall proceed to a joint assessment of the equivalence of the
conformity assessment bodies (CAB's) that participated in the
confidence building activities. CAB's will be determined to be
equivalent provided they have demonstrated proficiency through the
submission of a sufficient number of adequate reports. CAB's may be
determined to be equivalent with regard to the ability to perform any
type of quality system or product evaluation covered by this subpart
and with regard to any type of product covered by this subpart. The
parties shall develop a list contained in Appendix E of this subpart of
CAB's determined to be equivalent, which shall contain a full
explanation of the scope of the equivalency determination, including
any appropriate limitations, with regard to performing any type of
quality system or product evaluation.
(b) The parties shall allow CAB's not listed for participation in
this subpart, or listed for participation only as to certain types of
evaluations, to apply for participation in this subpart once the
necessary measures have been taken or sufficient experience has been
gained, in accordance with Sec. 26.46.
(c) Decisions concerning the equivalence of CAB's must be agreed
to by both parties.
Sec. 26.40 Start of the operational period.
(a) The operational period will start at the end of the transition
period after the parties have developed the list of conformity
assessment bodies (CAB's) found to be equivalent. The provisions of
Secs. 26.40, 26.41, 26.42, 26.43, 26.44, 26.45, and 26.46 will apply
only with regard to listed CAB's and only to the extent of any
specifications and
[[Page 60147]]
limitations contained on the list with regard to a CAB.
(b) The operational period will apply to quality system evaluation
reports and product evaluation reports generated by CAB's listed in
accordance with this subpart for the evaluations performed in the
respective territories of the parties, except if the parties agree
otherwise.
Sec. 26.41 Exchange and endorsement of quality system evaluation
reports.
(a) Listed European Community (EC) conformity assessment bodies
(CAB's) will provide FDA with reports of quality system evaluations, as
follows:
(1) For preapproval quality system evaluations, EC CAB's will
provide full reports; and
(2) For surveillance quality system evaluations, EC CAB's will
provide abbreviated reports.
(b) Listed U.S. CAB's will provide to the EC Notified Body of the
manufacturer's choice:
(1) Full reports of initial quality system evaluations;
(2) Abbreviated reports of quality systems surveillance audits.
(c) If the abbreviated reports do not provide sufficient
information, the importing party may request additional clarification
from the CAB.
(d) Based on the determination of equivalence in light of the
experience gained, the quality system evaluation reports prepared by
the CAB's listed as equivalent will normally be endorsed by the
importing party, except under specific and delineated circumstances.
Examples of such circumstances include indications of material
inconsistencies or inadequacies in a report, quality defects identified
in postmarket surveillance or other specific evidence of serious
concern in relation to product quality or consumer safety. In such
cases, the importing party may request clarification from the exporting
party which may lead to a request for reinspection. The parties will
endeavor to respond to requests for clarification in a timely manner.
Where divergence is not clarified in this process, the importing party
may carry out the quality system evaluation.
Sec. 26.42 Exchange and endorsement of product evaluation reports.
(a) European Community (EC) conformity assessment bodies (CAB's)
listed for this purpose will, subject to the specifications and
limitations on the list, provide to FDA 510(k) premarket notification
assessment reports prepared to U.S. medical device requirements.
(b) U.S. CAB's will, subject to the specifications and limitations
on the list, provide to the EC Notified Body of the manufacturer's
choice, type examination, and verification reports prepared to EC
medical device requirements.
(c) Based on the determination of equivalence in light of the
experience gained, the product evaluation reports prepared by the CAB's
listed as equivalent will normally be endorsed by the importing party,
except under specific and delineated circumstances. Examples of such
circumstances include indications of material inconsistencies,
inadequacies, or incompleteness in a product evaluation report, or
other specific evidence of serious concern in relation to product
safety, performance, or quality. In such cases, the importing party may
request clarification from the exporting party which may lead to a
request for a reevaluation. The parties will endeavor to respond to
requests for clarification in a timely manner. Endorsement remains the
responsibility of the importing party.
Sec. 26.43 Transmission of quality system evaluation reports.
Quality system evaluation reports covered by Sec. 26.41 concerning
products covered by this subpart shall be transmitted to the importing
party within 60-calendar days of a request by the importing party.
Should a new inspection be requested, the time period shall be extended
by an additional 30-calendar days. A party may request a new
inspection, for cause, identified to the other party. If the exporting
party cannot perform an inspection within a specified period of time,
the importing party may perform an inspection on its own.
Sec. 26.44 Transmission of product evaluation reports.
Transmission of product evaluation reports will take place
according to the importing party's specified procedures.
Sec. 26.45 Monitoring continued equivalence.
Monitoring activities will be carried out in accordance with
Sec. 26.69.
Sec. 26.46 Listing of additional CAB's.
(a) During the operational period, additional conformity
assessment bodies (CAB's) will be considered for equivalence using the
procedures and criteria described in Secs. 26.36, 26.37, and 26.39,
taking into account the level of confidence gained in the overall
regulatory system of the other party.
(b) Once a designating authority considers that such CAB's, having
undergone the procedures of Secs. 26.36, 26.37, and 26.39, may be
determined to be equivalent, it will then designate those bodies on an
annual basis. Such procedures satisfy the procedures of Sec. 26.66(a)
and (b).
(c) Following such annual designations, the procedures for
confirmation of CAB's under Sec. 26.66(c) and (d) shall apply.
Sec. 26.47 Role and composition of the Joint Sectoral Committee.
(a) The Joint Sectoral Committee for this subpart is set up to
monitor the activities under both the transitional and operational
phases of this subpart.
(b) The Joint Sectoral Committee will be cochaired by a
representative of the Food and Drug Administration (FDA) for the United
States and a representative of the European Community (EC) who will
each have one vote. Decisions will be taken by unanimous consent.
(c) The Joint Sectoral Committee's functions will include:
(1) Making a joint assessment of the equivalence of conformity
assessment bodies (CAB's);
(2) Developing and maintaining the list of equivalent CAB's,
including any limitation in terms of their scope of activities and
communicating the list to all authorities and the Joint Committee
described in subpart C of this part;
(3) Providing a forum to discuss issues relating to this subpart,
including concerns that a CAB may no longer be equivalent and
opportunity to review product coverage; and
(4) Consideration of the issue of suspension.
Sec. 26.48 Harmonization.
During both the transitional and operational phases of this
subpart, both parties intend to continue to participate in the
activities of the Global Harmonization Task Force (GHTF) and utilize
the results of those activities to the extent possible. Such
participation involves developing and reviewing documents developed by
the GHTF and jointly determining whether they are applicable to the
implementation of this subpart.
Sec. 26.49 Regulatory cooperation.
(a) The parties and authorities shall inform and consult with one
another, as permitted by law, of proposals to introduce new controls or
to change existing technical regulations or inspection procedures and
to provide the opportunity to comment on such proposals.
(b) The parties shall notify each other in writing of any changes
to Appendix A of this subpart.
[[Page 60148]]
Sec. 26.50 Alert system and exchange of postmarket vigilance reports.
(a) An alert system will be set up during the transition period
and maintained thereafter by which the parties will notify each other
when there is an immediate danger to public health. Elements of such a
system will be described in an Appendix F of this subpart. As part of
that system, each party shall notify the other party of any confirmed
problem reports, corrective actions, or recalls. These reports are
regarded as part of ongoing investigations.
(b) Contact points will be agreed between both parties to permit
authorities to be made aware with the appropriate speed in case of
quality defect, batch recalls, counterfeiting and other problems
concerning quality, which could necessitate additional controls or
suspension of the distribution of the product.
Appendix A of Subpart B--Relevant Legislation, Regulations, and
Procedures.
1. For the European Community (EC) the following legislation applies to
Sec. 26.42(a) of this subpart:
[Copies of EC documents may be obtained from the European
Document Research, 1100 17th St. NW., suite 301, Washington, DC
20036.]
a. Council Directive 90/385/EEC of 20 June 1990 on active
implantable medical devices
OJ No. L 189, 20.7. 1990, p. 17. Conformity assessment
procedures.
Annex 2 (with the exception of section 4)
Annex 4
Annex 5
b. Council Directive 93/42/EEC of 14 June 1993 on Medical Devices OJ
No. L 169,12.7.1993, p.1. Conformity assessment procedures.
Annex 2 (with the exception of section 4)
Annex 3
Annex 4
Annex 5
Annex 6
2. For the United States, the following legislation applies to
Sec. 26.32(a):
[Copies of FDA documents may be obtained from the Government
Printing Office, 1510 H St. NW., Washington, DC 20005. FDA documents
may be viewed on FDA's Internet web site at ``http://www.fda.gov''.]
a. The Federal Food, Drug and Cosmetic Act, 21 U.S.C. 321 et seq.
b. The Public Health Service Act, 42 U.S.C. 201 et seq.
c. Regulations of the United States Food and Drug Administration
found at 21 CFR, in particular, Parts 800 to 1299.
d. Medical Devices; Third Party Review of Selected Premarket
Notifications; Pilot Program, 61 FR 14789-14796 (April 3, 1996).
e. Draft Guidance Document on Accredited Persons Program, 63 FR
28392 (May 22, 1998).
f. Draft Guidance for Staff, Industry and Third Parties, Third Party
Programs under the Sectoral Annex on Medical Devices to the
Agreement on Mutual Recognition Between the United States of America
and the European Community (MRA), 63 FR 36240 (July 2, 1998).
g. Guidance Document on Use of Standards, 63 FR 9561 (February 25,
1998).
Appendix B of Subpart B--Scope of Product Coverage.
1. Initial Coverage of the Transition Period
Upon entry into force of this subpart as described in Sec. 26.80 (it
is understood that the date of entry into force will not occur prior
to June 1, 1998, unless the parties decide otherwise), products
qualifying for the transitional arrangements under this subpart
include:
a. All Class I products requiring premarket evaluations in the
United States--see Table 1.
b. Those Class II products listed in Table 2.
2. During the Transition Period
The parties will jointly identify additional product groups,
including their related accessories, in line with their respective
priorities as follows:
a. Those for which review may be based primarily on written
guidance which the parties will use their best efforts to prepare
expeditiously; and
b. Those for which review may be based primarily on
international standards, in order for the parties to gain the
requisite experience.
The corresponding additional product lists will be phased in on an
annual basis. The parties may consult with industry and other
interested parties in determining which products will be added.
3. Commencement of the Operational Period
a. At the commencement of the operational period, product
coverage shall extend to all Class I/II products covered during the
transition period.
b. FDA will expand the program to categories of Class II devices
as is consistent with the results of the pilot, and with FDA's
ability to write guidance documents if the device pilot for the
third party review of medical devices is successful. The MRA will
cover to the maximum extent feasible all Class II devices listed in
Table 3 for which FDA-accredited third party review is available in
the United States.
4. Unless explicitly included by joint decision of the parties, this
part does not cover any U.S. Class II-tier 3 or any Class III product
under either system.
[The lists of medical devices included in these tables are
subject to change as a result of the Food and Drug Administration
Modernization Act of 1997.]
Table 1.--Class I Products Requiring Premarket Evaluations in the United
States, Included in Scope of Product Coverage at Beginning of Transition
Period\1\
------------------------------------------------------------------------
21 CFR Section No. Regulation Name
------------------------------------------------------------------------
Product Code--Device Name
------------------------------------------------------------------------
Anesthesiology Panel (21 CFR Part
868)
868.1910 Esophageal Stethoscope
BZW--Stethoscope, Esophageal
868.5620 Breathing Mouthpiece
BYP--Mouthpiece, Breathing
868.5640 Medicinal Nonventilatory
Nebulizer (Atomizer)
CCQ--Nebulizer, Medicinal,
Nonventilatory (Atomizer)
868.5675 Rebreathing Device
BYW--Device, Rebreathing
868.5700 Nonpowered Oxygen Tent
FOG--Hood, Oxygen, Infant
BYL--Tent, Oxygen
868.6810 Tracheobronchial Suction Catheter
BSY--Catheters, Suction,
Tracheobronchial
Cardiovascular Panel
(None)
Dental Panel (21 CFR Part 872)
872.3400 Karaya and Sodium Borate With or
Without Acacia Denture Adhesive
KOM--Adhesive, Denture, Acacia
and Karaya With Sodium Borate
[[Page 60149]]
872.3700 Dental Mercury (U.S.P.)
ELY--Mercury
872.4200 Dental Handpiece and Accessories
EBW--Controller, Food, Handpiece
and Cord
EFB--Handpiece, Air-Powered,
Dental
EFA--Handpiece, Belt and/or Gear
Driven, Dental
EGS--Handpiece, Contra- and Right-
Angle Attachment, Dental
EKX--Handpiece, Direct Drive, AC-
Powered
EKY--Handpiece, Water-Powered
872.6640 Dental Operative Unit and
Accessories
EIA--Unit, Operative Dental
Ear, Nose, and Throat Panel (21 CFR
Part 874)
874.1070 Short Increment Sensitivity Index
(SISI) Adapter
ETR--Adapter, Short Increment
Sensitivity Index (SISI)
874.1500 Gustometer
ETM--Gustometer
874.1800 Air or Water Caloric Stimulator
KHH--Stimulator, Caloric-Air
ETP--Stimulator, Caloric-Water
874.1925 Toynbee Diagnostic Tube
ETK--Tube, Toynbee Diagnostic
874.3300 Hearing Aid
LRB--Face Plate Hearing-Aid
ESD--Hearing-aid, Air-Conduction
874.4100 Epistaxis Balloon
EMX--Balloon, Epistaxis
874.5300 ENT Examination and Treatment
Unit
ETF--Unit, Examining/Treatment,
ENT
874.5550 Powered Nasal Irrigator
KMA--Irrigator, Powered Nasal
874.5840 Antistammering Device
KTH--Device, Anti-Stammering
Gastroenterology--Urology Panel (21
CFR Part 876)
876.5160 Urological Clamp for Males
FHA--Clamp, Penile
876.5210 Enema Kit
FCE--Kit, Enema, (for Cleaning
Purpose)
876.5250 Urine Collector and Accessories
FAQ--Bag, Urine Collection, Leg,
for External Use
General Hospital Panel (21 CFR Part
880)
880.5270 Neonatal Eye Pad
FOK--Pad, Neonatal Eye
880.5420 Pressure Infusor for an I.V. Bag
KZD--Infusor, Pressure, for I.V.
Bags
880.5680 Pediatric Position Holder
FRP--Holder, Infant Position
880.6250 Patient Examination Glove
LZB--Finger Cot
FMC--Glove, Patient Examination
LYY--Glove, Patient Examination,
Latex
LZA--Glove, Patient Examination,
Poly
LZC--Glove, Patient Examination,
Speciality
LYZ--Glove, Patient Examination,
Vinyl
880.6375 Patient Lubricant
KMJ--Lubricant, Patient
880.6760 Protective Restraint
BRT--Restraint, Patient,
Conductive
FMQ--Restraint, Protective
Neurology Panel (21 CFR Part 882)
882.1030 Ataxiagraph
GWW--Ataxiagraph
882.1420 Electroencephalogram (EEG) Signal
Spectrum Analyzer
GWS--Analyzer, Spectrum,
Electroencephalogram Signal
882.4060 Ventricular Cannula
HCD--Cannula, Ventricular
882.4545 Shunt System Implantation
Instrument
GYK--Instrument, Shunt System
Implantation
882.4650 Neurosurgical Suture Needle
HAS--Needle, Neurosurgical Suture
[[Page 60150]]
882.4750 Skull Punch
GXJ--Punch, Skull
Obstetrics and Gynecology Panel
(None)
Ophthalmology Panel (21 CFR Part 886)
886.1780 Retinoscope
HKM--Retinoscope, Battery-Powered
886.1940 Tonometer Sterilizer
HKZ--Sterilizer, Tonometer
886.4070 Powered Corneal Burr
HQS--Burr, Corneal, AC-Powered
HOG--Burr, Corneal, Battery-
Powered
HRG--Engine, Trephine,
Accessories, AC-Powered
HFR--Engine, Trephine,
Accessories, Battery-Powered
HLD--Engine, Trephine,
Accessories, Gas-Powered
886.4370 Keratome
HNO--Keratome, AC-Powered
HMY--Keratome, Battery-Powered
886.5850 Sunglasses (Nonprescription)
HQY--Sunglasses (Nonprescription
Including Photosensitive)
Orthopedic Panel (21 CFR Part 888)
888.1500 Goniometer
KQX--Goniometer, AC-Powered
888.4150 Calipers for Clinical Use
KTZ--Caliper
Physical Medicine Panel (21 CFR Part
890)
890.3850 Mechanical Wheelchair
LBE--Stroller, Adaptive
IOR--Wheelchair, Mechanical
890.5180 Manual Patient Rotation Bed
INY--Bed, Patient Rotation,
Manual
890.5710 Hot or Cold Disposable Pack
IMD--Pack, Hot or Cold,
Disposable
Radiology Panel (21 CFR Part 892)
892.1100 Scintillation (Gamma) Camera
IYX--Camera, Scintillation
(Gamma)
892.1110 Positron Camera
IZC--Camera, Positron
892.1300 Nuclear Rectilinear Scanner
IYW--Scanner, Rectilinear,
Nuclear
892.1320 Nuclear Uptake Probe
IZD--Probe, Uptake, Nuclear
892.1330 Nuclear Whole Body Scanner
JAM--Scanner, Whole Body, Nuclear
892.1410 Nuclear Electrocardiograph
Synchronizer
IVY--Synchronizer,
Electrocardiograph, Nuclear
892.1890 Radiographic Film Illuminator
IXC--Illuminator, Radiographic-
Film
JAG--Illuminator, Radiographic-
Film, Explosion-Proof
892.1910 Radiographic Grid
IXJ--Grid, Radiographic
892.1960 Radiographic Intensifying Screen
EAM--Screen, Intensifying,
Radiographic
892.1970 Radiographic ECG/Respirator
Synchronizer
IXO--Synchronizer, ECG/
Respirator, Radiographic
892.5650 Manual Radionuclide Applicator
System
IWG--System, Applicator,
Radionuclide, Manual
General and Plastic Surgery Panel (21
CFR Part 878)
878.4200 Introduction/Drainage Catheter
and Accessories
KGZ--Accessories, Catheter
GCE--Adaptor, Catheter
FGY--Cannula, Injection
GBA--Catheter, Balloon Type
GBZ--Catheter, Cholangiography
GBQ--Catheter, Continuous
Irrigation
GBY--Catheter, Eustachian,
General & Plastic Surgery
JCY--Catheter, Infusion
GBX--Catheter, Irrigation
GBP--Catheter, Multiple Lumen
[[Page 60151]]
GBO--Catheter, Nephrostomy,
General & Plastic Surgery
GBN--Catheter, Pediatric, General
& Plastic Surgery
GBW--Catheter, Peritoneal
GBS--Catheter, Ventricular,
General & Plastic Surgery
GCD--Connector, Catheter
GCC--Dilator, Catheter
GCB--Needle, Catheter
878.4320 Removable Skin Clip
FZQ--Clip, Removable (Skin)
878.4460 Surgeon's Gloves
KGO--Surgeon's Gloves
878.4680 Nonpowered, Single Patient,
Portable Suction Apparatus
GCY--Apparatus, Suction, Single
Patient Use, Portable,
Nonpowered
878.4760 Removable Skin Staple
GDT--Staple, Removable (Skin)
878.4820 AC-Powered, Battery-Powered, and
Pneumatically Powered Surgical
Instrument Motors and
Accessories/Attachments
GFG--Bit, Surgical
GFA--Blade, Saw, General &
Plastic Surgery
DWH--Blade, Saw, Surgical,
Cardiovascular
BRZ--Board, Arm (With Cover)
GFE--Brush, Dermabrasion
GFF--Bur, Surgical, General &
Plastic Surgery
KDG--Chisel (Osteotome)
GFD--Dermatome
GFC--Driver, Surgical, Pin
GFB--Head, Surgical, Hammer
GEY--Motor, Surgical Instrument,
AC-Powered
GET--Motor, Surgical Instrument,
Pneumatic Powered
DWI--Saw, Electrically Powered
KFK--Saw, Pneumatically Powered
HAB--Saw, Powered, and
Accessories
878.4960 Air or AC-Powered Operating Table
and Air or AC-Powered Operating
Chair & Accessories
GBB--Chair, Surgical, AC-Powered
FQO--Table, Operating-Room, AC-
Powered
GDC--Table, Operating-Room,
Electrical
FWW--Table, Operating-Room,
Pneumatic
JEA--Table, Surgical with
Orthopedic Accessories, AC-
Powered
880.5090 Liquid Bandage
KMF--Bandage, Liquid
------------------------------------------------------------------------
\1\Descriptive information on product codes, panel codes, and other
medical device identifiers may be viewed on FDA's Internet Web Site at
``http://www.fda.gov/cdrh/prodcode.html''.
Table 2.--Class II Medical Devices Included in Scope of Product Coverage
at Beginning of Transition Period (United States to develop guidance
documents identifying U.S. requirements and European Community (EC) to
identify standards needed to meet EC requirements)\1\
------------------------------------------------------------------------
Panel 21 CFR Section Regulation Name
---------------- No. --------------------------------------
------------------
Product Code--Device Name
------------------------------------------------------------------------
RA 892.1000 Magnetic Resonance Diagnostic Device
MOS--COIL, Magnetic Resonance,
Specialty
LNH--System, Nuclear Magnetic
Resonance Imaging
LNI--System, Nuclear Magnetic
Resonance Spectroscopic
Diagnostic
Ultrasound:
RA 892.1540 Nonfetal Ultrasonic Monitor
JAF--Monitor, Ultrasonic, Nonfetal
RA 892.1550 Ultrasonic Pulsed Doppler Imaging
System
IYN--System, Imaging, Pulsed Doppler,
Ultrasonic
RA 892.1560 Ultrasonic Pulsed Echo Imaging System
................ IYO--System, Imaging, Pulsed Echo,
Ultrasonic
RA 892.1570 Diagnostic Ultrasonic Transducer
................ ITX--Transducer, Ultrasonic,
Diagnostic
[[Page 60152]]
Diagnostic X-
Ray Imaging
Devices
(except
mammographic x-
ray systems):
RA 892.1600 Angiographic X-Ray System
IZI--System, X-Ray, Angiographic
RA 892.1650 Image-Intensified Fluoroscopic X-Ray
System
MQB--Solid State X-Ray Imager (Flat
Panel/Digital Imager)
JAA--System, X-Ray, Fluoroscopic,
Image-Intensified
RA 892.1680 Stationary X-Ray System
KPR--System, X-Ray, Stationary
RA 892.1720 Mobile X-Ray System
IZL--System, X-Ray, Mobile
RA 892.1740 Tomographic X-Ray System
IZF--System, X-Ray, Tomographic
RA 892.1750 Computed Tomography X-Ray System
JAK--System, X-Ray, Tomography,
Computed
ECG-Related
Devices:
CV 870.2340 Electrocardiograph
................ DPS--Electrocardiograph
................ MLC--Monitor, ST Segment
CV 870.2350 Electrocardiograph Lead Switching
Adaptor
DRW--Adaptor, Lead Switching,
Electrocardiograph
CV 870.2360 Electrocardiograph Electrode
DRX--Electrode, Electrocardiograph
CV 870.2370 Electrocardiograph Surface Electrode
Tester
KRC--Tester, Electrode, Surface,
Electrocardiographic
NE 882.1400 Electroencephalograph
GWQ--Electroencephalograph
HO 880.5725 Infusion Pump (external only)
MRZ--Accessories, Pump, Infusion
FRN--Pump, Infusion
LZF--Pump, Infusion, Analytical
Sampling
MEB--Pump, Infusion, Elastomeric
LZH--Pump, Infusion, Enteral
MHD--Pump, Infusion, Gallstone
Dissolution
LZG--Pump, Infusion, Insulin
MEA--Pump, Infusion, PCA
Ophthalmic
Instruments:
OP 886.1570 Ophthalmoscope
HLI--Ophthalmoscope, AC-Powered
HLJ--Ophthalmoscope, Battery-Powered
OP 886.1780 Retinoscope
HKL--Retinoscope, AC-Powered
OP 886.1850 AC-Powered Slit-Lamp Biomicroscope
HJO--Biomicroscope, Slit-Lamp, AC-
Powered
OP 886.4150 Vitreous Aspiration and Cutting
Instrument
MMC--Dilator, Expansive Iris
(Accessory)
HQE--Instrument, Vitreous Aspiration
and Cutting, AC-Powered
HKP--Instrument, Vitreous Aspiration
and Cutting, Battery-Powered
MLZ--Vitrectomy, Instrument Cutter
OP 886.4670 Phacofragmentation System
HQC--Unit, Phacofragmentation
SU 878.4580 Surgical Lamp
HBI--Illuminator, Fiberoptic,
Surgical Field
FTF--Illuminator, Nonremote
FTG--Illuminator, Remote
HJE--Lamp, Fluorescein, AC-Powered
FQP--Lamp, Operating-Room
FTD--Lamp, Surgical
GBC--Lamp, Surgical, Incandescent
FTA--Light, Surgical, Accessories
FSZ--Light, Surgical, Carrier
FSY--Light, Surgical, Ceiling Mounted
FSX--Light, Surgical, Connector
FSW--Light, Surgical, Endoscopic
FST--Light, Surgical, Fiberoptic
FSS--Light, Surgical, Floor Standing
[[Page 60153]]
FSQ--Light, Surgical, Instrument
NE 882.5890 Transcutaneous Electrical Nerve
Stimulator for Pain Relief
GZJ--Stimulator, Nerve,
Transcutaneous, For Pain Relief
Noninvasive Blood Pressure
Measurement Devices:
CV 870.1120 Blood Pressure Cuff
DXQ--Cuff, Blood-Pressure
CV 870.1130 Noninvasive Blood Pressure
Measurement System (except
nonoscillometric)
DXN--System, Measurement, Blood-
Pressure, Noninvasive
HO 880.6880 Steam Sterilizer (greater than 2
cubic feet)
FLE--Sterilizer, Steam
Clinical
Thermometers:
HO 880.2910 Clinical Electronic Thermometer
(except tympanic or pacifier)
FLL--Thermometer, Electronic,
Clinical
AN 868.5630 Nebulizer
CAF--Nebulizer (Direct Patient
Interface)
AN 868.5925 Powered Emergency Ventilator
Hypodermic
Needles and
Syringes
(except
antistick and
self-
destruct):
HO 880.5570 Hypodermic Single Lumen Needle
MMK--Container, Sharpes
FMI--Needle, Hypodermic, Single Lumen
MHC--Port, Intraosseous, Implanted
HO 880.5860 Piston Syringe
FMF--Syringe, Piston
OR 888.3020 Intramedullary Fixation Rod
HSB--ROD, Fixation, Intramedullary
and Accessories
External
Fixators
(except
devices with
no external
components):
OR 888.3030 Single/Multiple Component Metallic
Bone Fixation Appliances and
Accessories
KTT--Appliance, Fixation, Nail/Blade/
Plate Combination, Multiple
Component
OR 888.3040 Smooth or Threaded Metallic Bone
Fixation Fastener
JEC--Component, Traction, Invasive
HTY--Pin, Fixation, Smooth
JDW--Pin, Fixation, Threaded
Selected Dental
Materials:
DE 872.3060 Gold-Based Alloys and Precious Metal
Alloys for Clinical Use
EJT--Alloy, Gold Based, For Clinical
Use
EJS--Alloy, Precious Metal, For
Clinical Use
DE 872.3200 Resin Tooth Bonding Agent
KLE--Agent, Tooth Bonding, Resin
DE 872.3275 Dental Cement
EMA--Cement, Dental
EMB--Zinc Oxide Eugenol
DE 872.3660 Impression Material
ELW--Material, Impression
DE 872.3690 Tooth Shade Resin Material
EBF--Material, Tooth Shade, Resin
DE 872.3710 Base Metal Alloy
EJH--Metal, Base
Latex Condoms:
OB 884.5300 Condom
HIS--Condom
------------------------------------------------------------------------
\1\Descriptive information on product codes, panel codes, and other
medical device identifiers may be viewed on FDA's Internet Web Site at
``http://www.fda.gov/cdrh/prodcode.html''.
Table 3.--Medical Devices for Possible Inclusion in Scope of Product
Coverage During Operational Period\1\
------------------------------------------------------------------------
Product Family 21 CFR Section No Device Name Tier
------------------------------------------------------------------------
Anesthesiology
Panel
Anesthesia 868.5160 Gas machine for 2
Devices anesthesia or
analgesia
868.5270 Breathing system 2
heater
[[Page 60154]]
868.5440 Portable oxygen 2
generator
868.5450 Respiratory gas 2
humidifier
868.5630 Nebulizer 2
868.5710 Electrically 2
powered oxygen
tent
868.5880 Anesthetic 2
vaporizer
Gas Analyser 868.1040 Powered 2
Algesimeter
868.1075 Argon gas 2
analyzer
868.1400 Carbon dioxide 2
gas analyzer
868.1430 Carbon monoxide 2
gas analyzer
868.1500 Enflurane gas 2
analyzer
868.1620 Halothane gas 2
analyzer
868.1640 Helium gas 2
analyzer
868.1670 Neon gas 2
analyzer
868.1690 Nitrogen gas 2
analyzer
868.1700 Nitrous oxide 2
gas analyzer
868.1720 Oxygen gas 2
analyzer
868.1730 Oxygen uptake 2
computer
Peripheral 868.2775 Electrical 2
Nerve peripheral
Stimulators nerve
stimulator
Respiratory 868.1750 Pressure 2
Monitoring plethysmograph
868.1760 Volume 2
plethysmograph
868.1780 Inspiratory 2
airway pressure
meter
868.1800 Rhinoanemometer 2
868.1840 Diagnostic 2
spirometer
868.1850 Monitoring 2
spirometer
868.1860 Peak-flow meter 2
for spirometry
868.1880 Pulmonary- 2
function data
calculator
868.1890 Predictive 2
pulmonary-
function value
calculator
868.1900 Diagnostic 2
pulmonary-
function
interpretation
calculator
868.2025 Ultrasonic air 2
embolism
monitor
868.2375 Breathing 2
frequency
monitor (except
apnea
detectors)
868.2480 Cutaneous carbon 2
dioxide (PcCO2)
monitor
868.2500 Cutaneous oxygen 2
monitor (for an
infant not
under gas
anesthesia)
868.2550 Pneumotachomomet 2
er
868.2600 Airway pressure 2
monitor
868.5665 Powered 2
percussor
868.5690 Incentive 2
spirometer
Ventilator 868.5905 Noncontinuous 2
ventilator
(IPPB)
868.5925 Powered 2
emergency
ventilator
868.5935 External 2
negative
pressure
ventilator
868.5895 Continuous 2
ventilator
868.5955 Intermittent 2
mandatory
ventilation
attachment
868.6250 Portable air 2
compressor
Cardiovascular
Panel
Cardiovascula 870.1425 Programmable 2
r Diagnostic diagnostic
computer
870.1450 Densitometer 2
870.2310 Apex cardiograph 2
(vibrocardiogra
ph)
870.2320 Ballistocardiogr 2
aph
870.2340 Electrocardiogra 2
ph
870.2350 Electrocardiogra 1
ph lead
switching
adaptor
870.2360 Electrocardiogra 2
ph electrode
870.2370 Electrocardiogra 2
ph surface
electrode
tester
870.2400 Vectorcardiograp 1
h
870.2450 Medical cathode- 1
ray tube
display
870.2675 Oscillometer 2
870.2840 Apex 2
cardiographic
transducer
870.2860 Heart sound 2
transducer
[[Page 60155]]
Cardiovascula Valve, pressure
r Monitoring relief,
cardiopulmonary
bypass
870.1100 Blood pressure 2
alarm
870.1110 Blood pressure 2
computer
870.1120 Blood pressure 2
cuff
870.1130 Noninvasive 2
blood pressure
measurement
system
870.1140 Venous blood 2
pressure
manometer
870.1220 Electrode 2
recording
catheter or
electrode
recording probe
870.1270 Intracavitary 2
phonocatheter
system
870.1875 Stethoscope 2
(electronic)
870.2050 Biopotential 2
amplifier and
signal
conditioner
870.2060 Transducer 2
signal
amplifier and
conditioner
870.2100 Cardiovascular 2
blood flow-
meter
870.2120 Extravascular 2
blood flow
probe
870.2300 Cardiac monitor 2
(including
cardiotachomete
r and rate
alarm)
870.2700 Oximeter 2
870.2710 Ear oximeter 2
870.2750 Impedance 2
phlebograph
870.2770 Impedance 2
plethysmograph
870.2780 Hydraulic, 2
pneumatic, or
photoelectric
plethysmographs
870.2850 Extravascular 2
blood pressure
transducer
870.2870 Catheter tip 2
pressure
transducer
870.2880 Ultrasonic 2
transducer
870.2890 Vessel occlusion 2
transducer
870.2900 Patient 2
transducer and
electrode cable
(including
connector)
870.2910 Radiofrequency 2
physiological
signal
transmitter and
receiver
870.2920 Telephone 2
electrocardiogr
aph transmitter
and receiver
870.4205 Cardiopulmonary 2
bypass bubble
detector
870.4220 Cardiopulmonary 2
bypass heart-
lung machine
console
870.4240 Cardiovascular 2
bypass heat
exchanger
870.4250 Cardiopulmonary 2
bypass
temperature
controller
870.4300 Cardiopulmonary 2
bypass gas
control unit
870.4310 Cardiopulmonary 2
bypass coronary
pressure gauge
870.4330 Cardiopulmonary 2
bypass on-line
blood gas
monitor
870.4340 Cardiopulmonary 2
bypass level
sensing monitor
and/or control
870.4370 Roller-type 2
cardiopulmonary
bypass blood
pump
870.4380 Cardiopulmonary 2
bypass pump
speed control
870.4410 Cardiopulmonary 2
bypass in-line
blood gas
sensor
Cardiovascula 870.5050 Patient care 2
r suction
Therapeutic apparatus
870.5900 Thermal 2
regulation
system
Defibrillator 870.5300 DC-defibrillator 2
(including
paddles)
870.5325 Defibrillator 2
tester
Echocardiogra 870.2330 Echocardiograph 2
ph
Pacemaker & 870.1750 External 2
Accessories programmable
pacemaker pulse
generator
870.3630 Pacemaker 2
generator
function
analyzer
[[Page 60156]]
870.3640 Indirect 2
pacemaker
generator
function
analyzer
870.3720 Pacemaker 2
electrode
function tester
Miscellaneous 870.1800 Withdrawal- 2
infusion pump
870.2800 Medical magnetic 2
tape recorder
None Batteries,
rechargeable,
class II
devices
Dental Panel
Dental 872.1720 Pulp tester 2
Equipment
872.1740 Caries detection 2
device
872.4120 Bone cutting 2
instrument and
accessories
872.4465 Gas-powered jet 2
injector
872.4475 Spring-powered 2
jet injector
872.4600 Intraoral 2
ligature and
wire lock
872.4840 Rotary scaler 2
872.4850 Ultrasonic 2
scaler
872.4920 Dental 2
electrosurgical
unit and
accessories
872.6070 Ultraviolet 2
activator for
polymerization
872.6350 Ultraviolet 2
detector
Dental 872.3050 Amalgam alloy 2
Material
872.3060 Gold-based 2
alloys and
precious metal
alloys for
clinical use
872.3200 Resin tooth 2
bonding agent
872.3250 Calcium 2
hydroxide
cavity liner
872.3260 Cavity varnish 2
872.3275 Dental cement 2
(other than
zinc oxide-
eugenol)
872.3300 Hydrophilic 2
resin coating
for dentures
872.3310 Coating material 2
for resin
fillings
872.3590 Preformed 2
plastic denture
tooth
872.3660 Impression 2
material
872.3690 Tooth shade 2
resin material
872.3710 Base metal alloy 2
872.3750 Bracket adhesive 2
resin and tooth
conditioner
872.3760 Denture 2
relining,
repairing, or
rebasing resin
872.3765 Pit and fissure 2
sealant and
conditioner
872.3770 Temporary crown 2
and bridge
resin
872.3820 Root canal 2
filling resin
(other than
chloroform use)
872.3920 Porcelain tooth 2
Dental X-ray 872.1800 Extraoral source 2
x-ray system
872.1810 Intraoral source 2
x-ray system
Dental 872.4880 Intraosseous 2
Implants fixation screw
or wire
872.3890 Endodontic 2
stabilizing
splint
Orthodontic 872.5470 Orthodontic 2
plastic bracket
Ear/Nose/Throat
Panel
Diagnostic 874.1050 Audiometer 2
Equipment
874.1090 Auditory 2
impedance
tester
874.1120 Electronic noise 2
generator for
audiometric
testing
874.1325 Electroglottogra 2
ph
874.1820 Surgical nerve 2
stimulator/
locator
Hearing Aids 874.3300 Hearing aid (for 2
bone-
conduction)
874.3310 Hearing aid 2
calibrator and
analysis system
874.3320 Group hearing 2
aid or group
auditory
trainer
874.3330 Master hearing 2
aid
Surgical 874.4250 Ear, nose, and 1
Equipment throat electric
or pneumatic
surgical drill
874.4490 Argon laser for 2
otology,
rhinology, and
laryngology
[[Page 60157]]
874.4500 Ear, nose, and 2
throat
microsurgical
carbon dioxide
laser
Gastroenterology/
Urology Panel
Endoscope 876.1500 Endoscope and 2
(including accessories
angioscopes,
laparscopes,
ophthalmic
endoscopes)
876.4300 Endoscopic 2
electrosurgical
unit and
accessories
Gastroenterol 876.1725 Gastrointestinal 1
ogy motility
monitoring
system
Hemodialysis 876.5600 Sorbent 2
regenerated
dialysate
delivery system
for
hemodialysis
876.5630 Peritoneal 2
dialysis system
and accessories
876.5665 Water 2
purification
system for
hemodialysis
876.5820 Hemodialysis 2
system and
accessories
876.5830 Hemodialyzer 2
with disposable
insert (kiil-
type)
Lithotriptor 876.4500 Mechanical 2
lithotriptor
Urology 876.1620 Urodynamics 2
Equipment measurement
system
876.5320 Nonimplanted 2
electrical
continence
device
876.5880 Isolated kidney 2
perfusion and
transport
system and
accessories
General Hospital
Panel
Infusion 880.2420 Electronic 2
Pumps and monitor for
Systems gravity flow
infusion
systems
880.2460 Electrically 2
powered spinal
fluid pressure
monitor
880.5430 Nonelectrically 2
powered fluid
injector
880.5725 Infusion pump 2
Neonatal 880.5400 Neonatal 2
Incubators incubator
880.5410 Neonatal 2
transport
incubator
880.5700 Neonatal 2
phototherapy
unit
Piston 880.5570 Hypodermic 1
Syringes single lumen
needle
880.5860 Piston syringe 1
(except
antistick)
880.6920 Syringe needle 2
introducer
Miscellaneous 880.2910 Clinical 2
electronic
thermometer
880.2920 Clinical mercury 2
thermometer
880.5100 AC-powered 1
adjustable
hospital bed
880.5500 AC-powered 2
patient lift
880.6880 Steam sterilizer 2
(greater than 2
cubic feet)
Neurology Panel
882.1020 Rigidity 2
analyzer
882.1610 Alpha monitor 2
Neuro- 882.1320 Cutaneous 2
Diagnostic electrode
882.1340 Nasopharyngeal 2
electrode
882.1350 Needle electrode 2
882.1400 Electroencephalo 2
graph
882.1460 Nystagmograph 2
882.1480 Neurological 2
endoscope
882.1540 Galvanic skin 2
response
measurement
device
882.1550 Nerve conduction 2
velocity
measurement
device
882.1560 Skin potential 2
measurement
device
882.1570 Powered direct- 2
contact
temperature
measurement
device
882.1620 Intracranial 2
pressure
monitoring
device
882.1835 Physiological 2
signal
amplifier
882.1845 Physiological 2
signal
conditioner
[[Page 60158]]
882.1855 Electroencephalo 2
gram (EEG)
telemetry
system
882.5050 Biofeedback 2
device
Echoencephalo 882.1240 Echoencephalogra 2
graphy ph
RPG 882.4400 Radiofrequency 2
lesion
generator
Neuro Surgery none Electrode, 2
spinal epidural
882.4305 Powered compound 2
cranial drills,
burrs,
trephines, and
their
accessories
882.4310 Powered simple 2
cranial drills
burrs,
trephines, and
their
accessories
882.4360 Electric cranial 2
drill motor
882.4370 Pneumatic 2
cranial drill
motor
882.4560 Stereotaxic 2
instrument
882.4725 Radiofrequency 2
lesion probe
882.4845 Powered rongeur 2
882.5500 Lesion 2
temperature
monitor
Stimulators 882.1870 Evoked response 2
electrical
stimulator
882.1880 Evoked response 2
mechanical
stimulator
882.1890 Evoked response 2
photic
stimulator
882.1900 Evoked response 2
auditory
stimulator
882.1950 Tremor 2
transducer
882.5890 Transcutaneous 2
electrical
nerve
stimulator for
pain relief
Obstetrics/
Gynecology Panel
Fetal 884.1660 Transcervical 2
Monitoring endoscope
(amnioscope)
and accessories
884.1690 Hysteroscope and 2
accessories
(for
performance
standards)
884.2225 Obstetric- 2
gynecologic
ultrasonic
imager
884.2600 Fetal cardiac 2
monitor
884.2640 Fetal 2
phonocardiograp
hic monitor and
accessories
884.2660 Fetal ultrasonic 2
monitor and
accessories
884.2675 Fetal scalp 1
circular
(spiral)
electrode and
applicator
884.2700 Intrauterine 2
pressure
monitor and
accessories
884.2720 External uterine 2
contraction
monitor and
accessories
884.2740 Perinatal 2
monitoring
system and
accessories
884.2960 Obstetric 2
ultrasonic
transducer and
accessories
Gynecological 884.1720 Gynecologic 2
Surgery laparoscope and
Equipment accessories
884.4160 Unipolar 2
endoscopic
coagulator-
cutter and
accessories
884.4550 Gynecologic 2
surgical laser
884.4120 Gynecologic 2
electrocautery
and accessories
884.5300 Condom 2
Ophthalmic 886.3320 Eye sphere 2
Implants implant
Contact Lens 886.1385 Polymethylmethac 2
rylate (PMMA)
diagnostic
contact lens
886.5916 Rigid gas 2
permeable
contact lens
(daily wear
only)
Diagnostic 886.1120 Opthalmic camera 1
Equipment
886.1220 Corneal 1
electrode
886.1250 Euthyscope (AC- 1
powered)
886.1360 Visual field 1
laser
instrument
886.1510 Eye movement 1
monitor
886.1570 Ophthalmoscope 1
886.1630 AC-powered 1
photostimulator
886.1640 Ophthalmic 1
preamplifier
[[Page 60159]]
886.1670 Ophthalmic 2
isotope uptake
probe
886.1780 Retinoscope (AC- 1
powered device)
886.1850 AC-powered slit 1
lamp
biomicroscope
886.1930 Tonometer and 2
accessories
886.1945 Transilluminator 1
(AC-powered
device)
886.3130 Ophthalmic 2
conformer
(Diagnostic/ 886.4670 Phacofragmentati 2
Surgery on system
Equipment)
Ophthalmic 886.3340 Extraocular 2
Implants orbital implant
886.3800 Scleral shell 2
Surgical 880.5725 Infusion pump 2
Equipment (performance
standards)
886.3100 Ophthalmic 2
tantalum clip
886.3300 Absorbable 2
implant
(scleral
buckling
method)
886.4100 Radiofrequency 2
electrosurgical
cautery
apparatus
886.4115 Thermal cautery 2
unit
886.4150 Vitreous 2
aspiration and
cutting
instrument
886.4170 Cryophthalmic 2
unit
886.4250 Ophthalmic 1
electrolysis
unit (AC-
powered device)
886.4335 Operating 1
headlamp (AC-
powered device)
886.4390 Ophthalmic laser 2
886.4392 Nd:YAG laser for 2
posterior
capsulotomy
886.4400 Electronic metal 1
locator
886.4440 AC-powered 1
magnet
886.4610 Ocular pressure 2
applicator
886.4690 Ophthalmic 2
photocoagulator
886.4790 Ophthalmic 2
sponge
886.5100 Ophthalmic beta 2
radiation
source
none Ophthalmoscopes, 1
replacement
batteries, hand-
held
Orthopedic Panel
Implants 888.3010 Bone fixation 2
cerclage
888.3020 Intramedullary 2
fixation rod
888.3030 Single/multiple 2
component
metallic bone
fixation
appliances and
accessories
888.3040 Smooth or 2
threaded
metallic bone
fixation
fastener
888.3050 Spinal 2
interlaminal
fixation
orthosis
888.3060 Spinal 2
intervertebral
body fixation
orthosis
Surgical 888.1240 AC-powered 2
Equipment dynamometer
888.4580 Sonic surgical 2
instrument and
accessories/
attachments
none Accessories, 2
fixation,
spinal
interlaminal
none Accessories, 2
fixation,
spinal
intervertebral
body
none Monitor, 1
pressure,
intracompartmen
tal
none Orthosis, 2
fixation,
spinal
intervertebral
fusion
none Orthosis, spinal
pedicle
fixation
none System, cement 1
removal
extraction
Physical Medicine
Panel
Diagnostic 890.1225 Chronaximeter 2
Equipment or
(Therapy)
Therapeutic
Equipment
890.1375 Diagnostic 2
electromyograph
890.1385 Diagnostic 2
electromyograph
needle
electrode
[[Page 60160]]
890.1450 Powered reflex 2
hammer
890.1850 Diagnostic 2
muscle
stimulator
or (Therapy) 890.5850 Powered muscle 2
stimulator
Therapeutic 890.5100 Immersion 2
Equipment hydrobath
890.5110 Paraffin bath 2
890.5500 Infrared lamp 2
890.5720 Water 2
circulating hot
or cold pack
890.5740 Powered heating 2
pad
Radiology Panel
MRI 892.1000 Magnetic 2
resonance
diagnostic
device
Ultrasound 884.2660 Fetal ultrasonic 2
Diagnostic monitor and
accessories
892.1540 Nonfetal
ultrasonic
monitor
892.1560 Ultrasonic 2
pulsed echo
imaging system
892.1570 Diagnostic 2
ultrasonic
transducer
892.1550 Ultrasonic
pulsed doppler
imaging system
Angiographic 892.1600 Angiographic x- 2
ray system
Diagnostic X- 892.1610 Diagnostic x-ray 2
Ray beam-limiting
device
892.1620 Cine or spot 2
fluorographic x-
ray camera
892.1630 Electrostatic x- 2
ray imaging
system
892.1650 Image- 2
intensified
fluoroscopic x-
ray system
892.1670 Spot film device 2
892.1680 Stationary x-ray 2
system
892.1710 Mammographic x- 2
ray system
892.1720 Mobile x-ray 2
system
892.1740 Tomographic x- 1
ray system
892.1820 Pneumoencephalog 2
raphic chair
892.1850 Radiographic 1
film cassette
892.1860 Radiographic 1
film/cassette
changer
892.1870 Radiographic 2
film/cassette
changer
programmer
892.1900 Automatic 2
radiographic
film processor
892.1980 Radiologic table 1
CT Scanner 892.1750 Computed 2
tomography x-
ray system
Radiation 892.5050 Medical charged- 2
Therapy particle
radiation
therapy system
892.5300 Medical neutron 2
radiation
therapy system
892.5700 Remote 2
controlled
radionuclide
applicator
system
892.5710 Radiation 2
therapy beam-
shaping block
892.5730 Radionuclide 2
brachytherapy
source
892.5750 Radionuclide 2
radiation
therapy system
892.5770 Powered 2
radiation
therapy patient
support
assembly
892.5840 Radiation 2
therapy
simulation
system
892.5930 Therapeutic x- 1
ray tube
housing
assembly
Nuclear 892.1170 Bone 2
Medicine densitometer
892.1200 Emission 2
computed
tomography
system
892.1310 Nuclear 1
tomography
system
892.1390 Radionuclide 2
rebreathing
system
General/Plastic
Surgery Panel
Surgical 878.4630 Ultraviolet lamp 2
Lamps for
dermatologic
disorders
890.5500 Infrared lamp 2
878.4580 Surgical lamp 2
[[Page 60161]]
Electrosurgic 878.4810 Laser surgical 2
al Cutting instrument for
Equipment use in general
and plastic
surgery and in
dermatology
878.4400 Electrosurgical 2
cutting and
coagulation
device and
accessories
Miscellaneous 878.4780 Powered suction 2
pump
------------------------------------------------------------------------
\1\Descriptive information on product codes, panel codes, and other
medical device identifiers may be viewed on FDA's Internet Web Site at
``http://www.fda.gov/cdrh/prodcode.html''.
Appendix C of Subpart B [Reserved].
Appendix D of Subpart B [Reserved].
Appendix E of Subpart B [Reserved].
Appendix F of Subpart B [Reserved].
Subpart C--``Framework'' Provisions
Sec. 26.60 Definitions.
(a) The following terms and definitions shall apply to this
subpart only:
(1) Designating Authority means a body with power to designate,
monitor, suspend, remove suspension of, or withdraw conformity
assessment bodies as specified under this part.
(2) Designation means the identification by a designating
authority of a conformity assessment body to perform conformity
assessment procedures under this part.
(3) Regulatory Authority means a government agency or entity that
exercises a legal right to control the use or sale of products within a
party's jurisdiction and may take enforcement action to ensure that
products marketed within its jurisdiction comply with legal
requirements.
(b) Other terms concerning conformity assessment used in this part
shall have the meaning given elsewhere in this part or in the
definitions contained in ``Guide 2: Standardization and Related
Activities--General Vocabulary of the International Organization for
Standardization (ISO) and the International Electrotechnical Commission
(IEC)'' (ISO/IEC Guide 2) (1996 edition), which is incorporated by
reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies
are available from the International Organization for Standardization,
1, rue de Varembe, Case postale 56, CH-1211 Geneve 20, Switzerland, or
on the Internet at ``http://www.iso.ch'' or may be examined at the Food
and Drug Administration's Medical Library, 5600 Fishers Lane, rm. 11B-
40, Rockville, MD 20857, or the Office of the Federal Register, 800
North Capitol St. NW., suite 700, Washington, DC. In the event of an
inconsistency between the ISO/IEC Guide 2 and definitions in this part,
the definitions in this part shall prevail.
Sec. 26.61 Purpose of this part.
This part specifies the conditions by which each party will accept
or recognize results of conformity assessment procedures, produced by
the other party's conformity assessment bodies (CAB's) or authorities,
in assessing conformity to the importing party's requirements, as
specified on a sector-specific basis in subparts A and B of this part,
and to provide for other related cooperative activities. The objective
of such mutual recognition is to provide effective market access
throughout the territories of the parties with regard to conformity
assessment for all products covered under this part. If any obstacles
to such access arise, consultations will promptly be held. In the
absence of a satisfactory outcome of such consultations, the party
alleging its market access has been denied may, within 90 days of such
consultation, invoke its right to terminate the ``Agreement on Mutual
Recognition Between the United States of America and the European
Community,'' from which this part is derived, in accordance with
Sec. 26.80.
Sec. 26.62 General obligations.
(a) The United States shall, as specified in subparts A and B of
this part, accept or recognize results of specified procedures, used in
assessing conformity to specified legislative, regulatory, and
administrative provisions of the United States, produced by the other
party's conformity assessment bodies (CAB's) and/or authorities.
(b) The European Community (EC) and its Member States shall, as
specified in subparts A and B of this part, accept or recognize results
of specified procedures, used in assessing conformity to specified
legislative, regulatory, and administrative provisions of the EC and
its Member States, produced by the other party's CAB's and/or
authorities.
(c) Where sectoral transition arrangements have been specified in
subparts A and B of this part, the obligations in paragraphs (a) and
(b) of this section will apply following the successful completion of
those sectoral transition arrangements, with the understanding that the
conformity assessment procedures utilized assure conformity to the
satisfaction of the receiving party, with applicable legislative,
regulatory, and administrative provisions of that party, equivalent to
the assurance offered by the receiving party's own procedures.
Sec. 26.63 General coverage of this part.
(a) This part applies to conformity assessment procedures for
products and/or processes and to other related cooperative activities
as described in this part.
(b) Subparts A and B of this part may include:
(1) A description of the relevant legislative, regulatory, and
administrative provisions pertaining to the conformity assessment
procedures and technical regulations;
(2) A statement on the product scope and coverage;
(3) A list of designating authorities;
(4) A list of agreed conformity assessment bodies (CAB's) or
authorities or a source from which to obtain a list of such bodies or
authorities and a statement of the scope of the conformity assessment
procedures for which each has been agreed;
(5) The procedures and criteria for designating the CAB's;
(6) A description of the mutual recognition obligations;
(7) A sectoral transition arrangement;
(8) The identity of a sectoral contact point in each party's
territory; and
(9) A statement regarding the establishment of a Joint Sectoral
Committee.
(c) This part shall not be construed to entail mutual acceptance
of standards or technical regulations of the parties and, unless
otherwise specified in subpart A or B of this part, shall not entail
the
[[Page 60162]]
mutual recognition of the equivalence of standards or technical
regulations.
Sec. 26.64 Transitional arrangements.
The parties agree to implement the transitional commitments on
confidence building as specified in subparts A and B of this part.
(a) The parties agree that each sectoral transitional arrangement
shall specify a time period for completion.
(b) The parties may amend any transitional arrangement by mutual
agreement.
(c) Passage from the transitional phase to the operational phase
shall proceed as specified in subparts A and B of this part, unless
either party documents that the conditions provided in such subpart for
a successful transition are not met.
Sec. 26.65 Designating authorities.
The parties shall ensure that the designating authorities
specified in subpart B of this part have the power and competence in
their respective territories to carry out decisions under this part to
designate, monitor, suspend, remove suspension of, or withdraw
conformity assessment bodies (CAB's).
Sec. 26.66 Designation and listing procedures.
The following procedures shall apply with regard to the
designation of conformity assessment bodies (CAB's) and the inclusion
of such bodies in the list of CAB's in subpart B of this part:
(a) The designating authority identified in subpart B of this part
shall designate CAB's in accordance with the procedures and criteria
set forth in subpart B of this part;
(b) A party proposing to add a CAB to the list of such bodies in
subpart B of this part shall forward its proposal of one or more
designated CAB's in writing to the other party with a view to a
decision by the Joint Committee;
(c) Within 60 days following receipt of the proposal, the other
party shall indicate its position regarding either its confirmation or
its opposition. Upon confirmation, the inclusion in subpart B of this
part of the proposed CAB or CAB's shall take effect; and
(d) In the event that the other party contests on the basis of
documented evidence the technical competence or compliance of a
proposed CAB, or indicates in writing that it requires an additional 30
days to more fully verify such evidence, such CAB shall not be included
on the list of CAB's in subpart B of this part. In this instance, the
Joint Committee may decide that the body concerned be verified. After
the completion of such verification, the proposal to list the CAB in
subpart B may be resubmitted to the other party.
Sec. 26.67 Suspension of listed conformity assessment bodies.
The following procedures shall apply with regard to the suspension
of a conformity assessment body (CAB) listed in subpart B of this part.
(a) A party shall notify the other party of its contestation of
the technical competence or compliance of a CAB listed in subpart B of
this part and the contesting party's intent to suspend such CAB. Such
contestation shall be exercised when justified in an objective and
reasoned manner in writing to the other party;
(b) The CAB shall be given prompt notice by the other party and an
opportunity to present information in order to refute the contestation
or to correct the deficiencies which form the basis of the
contestation;
(c) Any such contestation shall be discussed between the parties
in the Joint Sectoral Committee described in subpart B of this part. If
there is no Joint Sectoral Committee, the contesting party shall refer
the matter directly to the Joint Committee. If agreement to suspend is
reached by the Joint Sectoral Committee or, if there is no Joint
Sectoral Committee, by the Joint Committee, the CAB shall be suspended;
(d) Where the Joint Sectoral Committee or Joint Committee decides
that verification of technical competence or compliance is required, it
shall normally be carried out in a timely manner by the party in whose
territory the body in question is located, but may be carried out
jointly by the parties in justified cases;
(e) If the matter has not been resolved by the Joint Sectoral
Committee within 10 days of the notice of contestation, the matter
shall be referred to the Joint Committee for a decision. If there is no
Joint Sectoral Committee, the matter shall be referred directly to the
Joint Committee. If no decision is reached by the Joint Committee
within 10 days of the referral to it, the CAB shall be suspended upon
the request of the contesting party;
(f) Upon the suspension of a CAB listed in subpart B of this part,
a party is no longer obligated to accept or recognize the results of
conformity assessment procedures performed by that CAB subsequent to
suspension. A party shall continue to accept the results of conformity
assessment procedures performed by that CAB prior to suspension, unless
a regulatory authority of the party decides otherwise based on health,
safety or environmental considerations or failure to satisfy other
requirements within the scope of subpart B of this part; and
(g) The suspension shall remain in effect until agreement has been
reached by the parties upon the future status of that body.
Sec. 26.68 Withdrawal of listed conformity assessment bodies.
The following procedures shall apply with regard to the withdrawal
from subpart B of this part of a conformity assessment body (CAB):
(a) A party proposing to withdraw a CAB listed in subpart B of
this part shall forward its proposal in writing to the other party;
(b) Such CAB shall be promptly notified by the other party and
shall be provided a period of at least 30 days from receipt to provide
information in order to refute or to correct the deficiencies which
form the basis of the proposed withdrawal;
(c) Within 60 days following receipt of the proposal, the other
party shall indicate its position regarding either its confirmation or
its opposition. Upon confirmation, the withdrawal from the list in
subpart B of this part of the CAB shall take effect;
(d) In the event the other party opposes the proposal to withdraw
by supporting the technical competence and compliance of the CAB, the
CAB shall not at that time be withdrawn from the list of CAB's in
subpart B of this part. In this instance, the Joint Sectoral Committee
or the Joint Committee may decide to carry out a joint verification of
the body concerned. After the completion of such verification, the
proposal for withdrawal of the CAB may be resubmitted to the other
party; and
(e) Subsequent to the withdrawal of a CAB listed in subpart B of
this part, a party shall continue to accept the results of conformity
assessment procedures performed by that CAB prior to withdrawal, unless
a regulatory authority of the party decides otherwise based on health,
safety, and environmental considerations or failure to satisfy other
requirements within the scope of subpart B of this part.
Sec. 26.69 Monitoring of conformity assessment bodies.
The following shall apply with regard to the monitoring of
conformity assessment bodies (CAB's) listed in subpart B of this part:
(a) Designating authorities shall assure that their CAB's listed
in subpart B of this part are capable and remain capable of properly
assessing conformity of products or processes, as applicable, and as
covered in subpart B of this part. In this regard, designating
authorities shall maintain, or cause to maintain, ongoing surveillance
over
[[Page 60163]]
their CAB's by means of regular audit or assessment;
(b) The parties undertake to compare methods used to verify that
the CAB's listed in subpart B of this part comply with the relevant
requirements of subpart B of this part. Existing systems for the
evaluation of CAB's may be used as part of such comparison procedures;
(c) Designating authorities shall consult as necessary with their
counterparts, to ensure the maintenance of confidence in conformity
assessment procedures. With the consent of both parties, this
consultation may include joint participation in audits/inspections
related to conformity assessment activities or other assessments of
CAB's listed in subpart B of this part; and
(d) Designating authorities shall consult, as necessary, with the
relevant regulatory authorities of the other party to ensure that all
technical requirements are identified and are satisfactorily addressed.
Sec. 26.70 Conformity assessment bodies.
Each party recognizes that the conformity assessment bodies
(CAB's) listed in subpart B of this part fulfill the conditions of
eligibility to assess conformity in relation to its requirements as
specified in subpart B of this part. The parties shall specify the
scope of the conformity assessment procedures for which such bodies are
listed.
Sec. 26.71 Exchange of information.
(a) The parties shall exchange information concerning the
implementation of the legislative, regulatory, and administrative
provisions identified in subparts A and B of this part.
(b) Each party shall notify the other party of legislative,
regulatory, and administrative changes related to the subject matter of
this part at least 60 days before their entry into force. Where
considerations of safety, health or environmental protection require
more urgent action, a party shall notify the other party as soon as
practicable.
(c) Each party shall promptly notify the other party of any
changes to its designating authorities and/or conformity assessment
bodies (CAB's).
(d) The parties shall exchange information concerning the
procedures used to ensure that the listed CAB's under their
responsibility comply with the legislative, regulatory, and
administrative provisions outlined in subpart B of this part.
(e) Regulatory authorities identified in subparts A and B of this
part shall consult as necessary with their counterparts, to ensure the
maintenance of confidence in conformity assessment procedures and to
ensure that all technical requirements are identified and are
satisfactorily addressed.
Sec. 26.72 Sectoral contact points.
Each party shall appoint and confirm in writing contact points to
be responsible for activities under subparts A and B of this part.
Sec. 26.73 Joint Committee.
(a) A Joint Committee consisting of representatives of the United
States and the European Community (EC) will be established. The Joint
Committee shall be responsible for the effective functioning of the
``Agreement on Mutual Recognition Between the United States of America
and the European Community,'' from which this part is derived.
(b) The Joint Committee may establish Joint Sectoral Committees
comprised of appropriate regulatory authorities and others deemed
necessary.
(c) The United States and the EC shall each have one vote in the
Joint Committee. The Joint Committee shall make its decisions by
unanimous consent. The Joint Committee shall determine its own rules
and procedures.
(d) The Joint Committee may consider any matter relating to the
effective functioning of that agreement. In particular it shall be
responsible for:
(1) Listing, suspension, withdrawal and verification of conformity
assessment bodies (CAB's) in accordance with that agreement;
(2) Amending transitional arrangements in the sectoral annexes to
that agreement;
(3) Resolving any questions relating to the application of that
agreement not otherwise resolved in the respective Joint Sectoral
Committees;
(4) Providing a forum for discussion of issues that may arise
concerning the implementation of that agreement;
(5) Considering ways to enhance the operation of that agreement;
(6) Coordinating the negotiation of additional sectoral annexes to
that agreement; and
(7) Considering whether to amend that agreement in accordance with
Sec. 26.80.
(e) When a party introduces new or additional conformity
assessment procedures affecting a sectoral annex to that agreement, the
parties shall discuss the matter in the Joint Committee with a view to
bringing such new or additional procedures within the scope of that
agreement and the relevant sectoral annex.
Sec. 26.74 Preservation of regulatory authority.
(a) Nothing in this part shall be construed to limit the authority
of a party to determine, through its legislative, regulatory, and
administrative measures, the level of protection it considers
appropriate for safety; for protection of human, animal, or plant life
or health; for the environment; for consumers; and otherwise with
regard to risks within the scope of the applicable subpart A or B of
this part.
(b) Nothing in this part shall be construed to limit the authority
of a regulatory authority to take all appropriate and immediate
measures whenever it ascertains that a product may:
(1) Compromise the health or safety of persons in its territory;
(2) Not meet the legislative, regulatory, or administrative
provisions within the scope of the applicable subpart A or B of this
part; or
(3) Otherwise fail to satisfy a requirement within the scope of
the applicable subpart A or B of this part. Such measures may include
withdrawing the products from the market, prohibiting their placement
on the market, restricting their free movement, initiating a product
recall, and preventing the recurrence of such problems, including
through a prohibition on imports. If the regulatory authority takes
such action, it shall inform its counterpart authority and the other
party within 15 days of taking such action, providing its reasons.
Sec. 26.75 Suspension of recognition obligations.
Either party may suspend its obligations under subpart A or B of
this part, in whole or in part, if:
(a) A party suffers a loss of market access for the party's
products within the scope of subpart A or B of this part as a result of
the failure of the other party to fulfill its obligations under this
part;
(b) The adoption of new or additional conformity assessment
requirements as referenced in Sec. 26.73(e) results in a loss of market
access for the party's products within the scope of subpart B of this
part because conformity assessment bodies (CAB's) designated by the
party in order to meet such requirements have not been recognized by
the party implementing the requirements; or
(c) The other party fails to maintain legal and regulatory
authorities capable of implementing the provisions of this part.
[[Page 60164]]
Sec. 26.76 Confidentiality.
(a) Each party agrees to maintain, to the extent required under
its laws, the confidentiality of information exchanged under this part.
(b) In particular, neither party shall disclose to the public, nor
permit a conformity assessment body (CAB) to disclose to the public,
information exchanged under this part that constitutes trade secrets,
confidential commercial or financial information, or information that
relates to an ongoing investigation.
(c) A party or a CAB may, upon exchanging information with the
other party or with a CAB of the other party, designate the portions of
the information that it considers to be exempt from disclosure.
(d) Each party shall take all precautions reasonably necessary to
protect information exchanged under this part from unauthorized
disclosure.
Sec. 26.77 Fees.
Each party shall endeavor to ensure that fees imposed for services
under this part shall be commensurate with the services provided. Each
party shall ensure that, for the sectors and conformity assessment
procedures covered under this part, it shall charge no fees with
respect to conformity assessment services provided by the other party.
Sec. 26.78 Agreements with other countries.
Except where there is written agreement between the parties,
obligations contained in mutual recognition agreements concluded by
either party with a party not a party to the agreement from which this
part is derived (a third party) shall have no force and effect with
regard to the other party in terms of acceptance of the results of
conformity assessment procedures in the third party.
Sec. 26.79 Territorial application.
The agreement from which this part is derived shall apply, on the
one hand, to the territories in which the Treaty establishing the
European Community (EC) is applied, and under the conditions laid down
in that Treaty and, on the other hand, to the territory of the United
States.
Sec. 26.80 Entry into force, amendment, and termination.
(a) The ``Agreement on Mutual Recognition Between the United
States of America and the European Community,'' from which this part is
derived, including its sectoral annexes on telecommunication equipment,
electromagnetic compatibility, electrical safety, recreational craft,
pharmaceutical Good Manufacturing Practices (GMP) inspections, and
medical devices shall enter into force on the first day of the second
month following the date on which the parties have exchanged letters
confirming the completion of their respective procedures for the entry
into force of that agreement.
(b) That agreement including any sectoral annex may, through the
Joint Committee, be amended in writing by the parties to that
agreement. Those parties may add a sectoral annex upon the exchange of
letters. Such annex shall enter into force 30 days following the date
on which those parties have exchanged letters confirming the completion
of their respective procedures for the entry into force of the sectoral
annex.
(c) Either party to that agreement may terminate that agreement in
its entirety or any individual sectoral annex thereof by giving the
other party to that agreement 6-months notice in writing. In the case
of termination of one or more sectoral annexes, the parties to that
agreement will seek to achieve by consensus to amend that agreement,
with a view to preserving the remaining Sectoral Annexes, in accordance
with the procedures in this section. Failing such consensus, that
agreement shall terminate at the end of 6 months from the date of
notice.
(d) Following termination of that agreement in its entirety or any
individual sectoral annex thereof, a party to that agreement shall
continue to accept the results of conformity assessment procedures
performed by conformity assessment bodies under that agreement prior to
termination, unless a regulatory authority in the party decides
otherwise based on health, safety and environmental considerations or
failure to satisfy other requirements within the scope of the
applicable sectoral annex.
Sec. 26.81 Final provisions.
(a) The sectoral annexes referred to in Sec. 26.80(a), as well as
any new sectoral annexes added pursuant to Sec. 26.80(b), shall form an
integral part of the ``Agreement on Mutual Recognition Between the
United States of America and the European Community,'' from which this
part is derived.
(b) For a given product or sector, the provisions contained in
subparts A and B of this part shall apply in the first place, and the
provisions of subpart C of this part in addition to those provisions.
In the case of any inconsistency between the provisions of subpart A or
B of this part and subpart C of this part, subpart A or B shall
prevail, to the extent of that inconsistency.
(c) The agreement from which this part is derived shall not affect
the rights and obligations of the parties under any other international
agreement.
(d) In the case of subpart B of this part, the parties shall review
the status of such subpart at the end of 3 years from the date
described in Sec. 26.80(a).
Dated: July 23, 1998.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 98-29609 Filed 11-5-98; 8:45 am]
BILLING CODE 4160-01-F
