# International Harmonization; Policy on Standards

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URL: https://www.frixlaw.com/law-library/documents/fr%3A95-25070

## Record

- **Collection:** Federal Register
- **Document type:** Notice
- **Published:** October 11, 1995
- **Citation:** 60 FR 53078

## Text

[[Page 53078]]

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 94D-0300]

International Harmonization; Policy on Standards

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the
agency's policy on the development and use of standards with respect to
international harmonization of regulatory requirements and guidelines.
Specifically, the policy is intended to address the conditions under
which FDA plans to participate with standards bodies outside of FDA,
domestic or international, in the development of standards applicable
to products regulated by FDA. The policy also covers the conditions
under which FDA intends to use the resultant standards, or other
available domestic or international standards, in fulfilling its
statutory mandates for safeguarding the public health.

FOR FURTHER INFORMATION CONTACT: Linda R. Horton, International Policy
Staff (HF-23), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-3344.

SUPPLEMENTARY INFORMATION: In a notice published in the Federal
Register of November 28, 1994 (59 FR 60870), FDA published a draft
policy on international harmonization of regulatory requirements and
guidelines. The purpose of the draft policy was to articulate FDA's
policy on the development and use of standards with respect to
international harmonization of regulatory requirements and guidelines.
The agency gave interested persons an opportunity to comment on the
draft policy document. A discussion of the comments received and the
agency's responses is found in section III. of this document.
Background information as well as the text of the policy follow:

International Harmonization of Regulatory Requirements and Guidelines

I. Background

The purpose of this document is to articulate FDA's policy on
development and use of standards with respect to international
harmonization of regulatory requirements and guidelines. As used
throughout this document, the term ``standards'' includes what are
commonly referred to as ``consensus standards,'' ``voluntary
standards,'' and ``industry standards.'' Also, FDA sometimes accepts
standards and makes them mandatory regulatory requirements. Although
the draft policy focuses on international harmonization and
international standards, its principles are applicable as well to
domestic standards activities in which FDA participates.

A. Statutory Mandates for FDA-Regulated Products

FDA is the principal regulatory agency within the Public Health
Service (PHS). The agency protects the public health by, among other
things, implementing statutory provisions designed to ensure that
food is safe and otherwise not adulterated or misbranded; that human
and veterinary drugs, human biological products, and medical devices
are safe and effective; that cosmetics are safe; and that electronic
product radiation is properly controlled. FDA-regulated products
must be truthfully and accurately labeled and in compliance with all
applicable laws and regulations. The statutory mandates for
safeguarding the public health in these product sectors are
prescribed in several statutes, notably in the Federal Food, Drug,
and Cosmetic Act; the Public Health Service Act; and the Fair
Packaging and Labeling Act.

B. International Harmonization of Regulatory Requirements and
Guidelines

In recent decades, great changes in the world economy, together
with expanded working relationships of regulatory agencies around
the globe, have resulted in increased interest in international
harmonization of regulatory requirements. Increased international
commerce, opportunities to enhance public health through cooperative
endeavors, and scarcity of government resources for regulation have
resulted in efforts by the regulatory agencies of different nations
to work together on standards and harmonize their regulatory
requirements. Such harmonization enhances public health protection
and improves government efficiencies by reducing both unwarranted
contradictory regulatory requirements and redundant applications of
similar requirements by multiple regulatory bodies. Harmonization
facilitates cooperation in regulatory activities.
Harmonization of FDA's regulatory requirements and guidelines
with those of other countries was recently embraced as a pillar of
the President's and Vice President's National Performance Review. In
Reinventing Drug and Device Regulation (April 1995), international
harmonization was identified as a high priority initiative across
FDA programs. Recognizing the considerable synergy between its
domestic policy and its international policy priorities, FDA is
sharpening and focusing its planning for enhanced alignment of FDA
and international standards.
In 1992, an FDA Task Force on International Harmonization had
provided a broad assessment of the goals, scope, and direction of
FDA's international activities. These activities were found to
comprise a wide variety of efforts by FDA to retain and strengthen
its public health safeguards, while striving toward common ground
with its foreign government counterparts on product standards,
criteria for the assessment of test data, and enforcement
procedures. The task force's recommendations for the agency included
an overall FDA policy on international harmonization, which is to
encourage the initiation and support of efforts, consistent with the
agency's goals and principles, that will further the international
harmonization of standards and policies for the regulation of
products for which FDA has authority. Soon thereafter, FDA's
strategic plan began to recognize standards as the premier focus of
the agency's international activities.

1. Goals

FDA's goals in participating in international harmonization are:
To safeguard U.S. public health,
To assure that consumer protection standards and
requirements are met,
To facilitate the availability of safe and effective
products,
To develop and utilize product standards and other
requirements more effectively, and
To minimize or eliminate inconsistent standards
internationally.

2. General Principles

FDA participation in international harmonization efforts should
be guided by the following general principles:
The harmonization activity should be consistent with
U.S. Government policies and procedures and should promote U.S.
interests with foreign countries.
The harmonization activity should further FDA's mission
to protect the public health by, among other things, ensuring that
food is safe and otherwise not adulterated or misbranded; that human
and veterinary drugs, human biological products, and medical devices
are safe and effective as required by law and are not adulterated or
misbranded; that cosmetics are not adulterated or misbranded; that
electronic product radiation is properly controlled; and that all of
these products are labeled truthfully and informatively.
FDA's input into international standard setting
activities should be open to public scrutiny and should provide the
opportunity for the consideration of views of all parties concerned.
FDA should accept, where legally permissible, the
equivalent standards, compliance activities, and enforcement
programs of other countries, provided that FDA is satisfied such
standards, activities, and programs meet FDA's level of public
health protection.
Scientific and regulatory information and knowledge
should be exchanged with foreign government officials, to the extent
possible within legal constraints, to expedite the approval of
products and protect public health.
Thus, the agency's primary goal in all of its international
harmonization activities is to preserve and enhance its ability to
accomplish its public health mission. Global harmonization is also
approached with the aim of enhancing regulatory effectiveness, by
providing more consumer protection with scarce government resources,
and increasing worldwide consumer access to safe, effective, and
high quality products.

[[Page 53079]]

C. Other Obligations and Policies

1. International Agreements

The U.S. Government is a party to international trade
agreements. In the United States, such trade agreements become
effective only after implementing legislation is signed into law.
FDA has participated in recent international trade negotiations to
ensure that FDA's requirements are preserved and that regulatory
practices can remain focused on fulfilling the agency's mission to
protect the public health while being supportive of emerging,
broader U.S. Government obligations and policies. In addition, FDA
continues to be involved in work of the World Trade Organization
(WTO) as well as the North American Free Trade Agreement (NAFTA)
committees on sanitary and phytosanitary measures, and on technical
barriers to trade, in order to foster international harmonization of
regulatory requirements and to facilitate consultation on trade
issues. Recently FDA has begun to be involved in other regional
activities, e.g., the Forum on Asia Pacific Economic Cooperation
(APEC), work on initial steps toward a Free Trade Area of the
Americas (FTAA), and work towards a Transatlantic Area that
strengthens our ties with Europe.
The principal international trade agreement is the General
Agreement on Tariffs and Trade (GATT), which entered into force on
January 1, 1948. GATT has since been amended several times following
negotiation sessions known as rounds.
The GATT Agreement on Technical Barriers to Trade (TBT),
popularly known as the Standards Code, was negotiated during the
Tokyo Round of the GATT in the 1970's and entered into force on
January 1, 1980. As part of a general effort to reduce unnecessary
nontariff barriers to trade, the TBT agreement was intended to
promote use by countries of standards, technical regulations, and
conformity assessment procedures that are based on work done by
international standards bodies. The implementing legislation for the
TBT agreement, provided in the Trade Agreements Act of 1979 as
amended in 1994 (Pub. L. 103-465; 19 U.S.C 2531-2582), has thus
provided additional authority for FDA's international standards
activity. To assure that harmonization does not result in lowering
safety or quality standards for U.S. consumers, this law contains
the safeguard that:
``* * * No standard-related activity of any private person,
Federal agency, or State agency shall be deemed to constitute an
unnecessary obstacle to the foreign commerce of the United States if
the demonstrable purpose of the standards-related activity is to
achieve a legitimate domestic objective including, but not limited
to, the protection of legitimate health or safety, essential
security, environmental, or consumer interests and if such activity
does not operate to exclude imported products which fully meet the
objectives of such activity.''
The most recent GATT round, the Uruguay Round, was concluded on
December 15, 1993, and was formally signed at the Marrakech
Ministerial Meeting on April 15, 1994. The new WTO will administer
the new GATT and other Uruguay Round agreements, and every country
that is a member of the WTO will be required to adhere to all of
these agreements. On December 8, 1994, Pub. L. 103-465 was enacted
in the United States to approve and implement the Uruguay Round
agreements. This law included updating changes in the Trade
Agreements Act that reaffirmed the duty of Federal agencies to
participate in international standards activities, subject to
available resources.
One of the agreements of the Uruguay Round administered by the
WTO is the new agreement on TBT, which is similar in many respects
to the 1980 TBT agreement. As with the 1980 TBT agreement, the
purpose of the new TBT agreement is to ensure that product
standards, technical regulations, and related procedures do not
create unnecessary obstacles to trade. The new TBT agreement
ensures, and clearly states, that each country has the right to
establish and maintain technical regulations for the protection of
human, animal, and plant life and health and the environment, and
for prevention against deceptive practices.
In the new TBT agreement, the term ``standard'' is defined as:
``[A] document approved by a recognized body, that provides, for
common and repeated use, rules, guidelines or characteristics for
products or related processes and production methods, with which
compliance is not mandatory [emphasis added]. It may also include or
deal exclusively with terminology, symbols, packaging, marking or
labelling requirements as they apply to a product, process or
production method.''
Also, ``technical regulation'' is defined as:
``[A] document which lays down product characteristics or their
related processes and production methods, including applicable
administrative provisions, with which compliance is mandatory
[emphasis added]. It may also include or deal exclusively with
terminology, symbols, packaging, marking, or labelling requirements
as they apply to a product, process or production method.''
Thus, in the language of the new TBT agreement, when a
government acts to accept a voluntary standard to make it mandatory,
the resulting document is a technical regulation. A measure used to
ascertain compliance with a standard or technical regulation is a
conformity assessment procedure.
The new TBT agreement continues and strengthens the reference to
international standards found in the 1980 TBT agreement.
Specifically, the agreement states that, where technical regulations
are required and relevant international standards exist or their
completion is imminent, WTO-member countries shall use them, or the
relevant parts of them, as a basis for their technical regulations,
except when such international standards or relevant parts would be
an ineffective or inappropriate means for the fulfillment of the
legitimate objectives pursued. Further, the agreement states that,
with a view towards harmonizing technical regulations on as wide a
basis as possible, WTO-member countries shall play a full part
within the limits of their resources in the preparation by
appropriate international standards bodies of international
standards for products for which they either have adopted or expect
to adopt technical regulations.
Another agreement of the Uruguay Round administered by the WTO
is the Agreement on the Application of Sanitary and Phytosanitary
Measures (SPS agreement). This agreement pertains to those measures
intended: (1) To protect animal or plant life or health within a
territory from risks arising from the entry, establishment, or
spread of pests, diseases, disease-carrying organisms, or disease-
causing organisms; (2) to protect human or animal life or health
within a territory from risks arising from additives, contaminants,
toxins, or disease-causing organisms in foods, beverages, or
feedstuffs; (3) to protect human life or health within a territory
from risks arising from diseases carried by animals, plants, or
products thereof, or from entry, establishment, or spread of pests;
or (4) to prevent or limit other damage within a territory from the
entry, establishment, or spread of pests.
In order to harmonize SPS measures on as wide a basis as
possible, the SPS agreement encourages Members to base their SPS
measures on international standards, guidelines, or recommendations.
Thus, the SPS agreement, like the new TBT agreement, encourages use
of international standards. The SPS agreement refers specifically to
standards established by the Codex Alimentarius Commission, as
discussed below.
NAFTA also contains TBT and SPS agreements similar to those in
the new WTO agreements.

2. Internal U.S. Government Policy

The United States Office of Management and Budget (OMB), in its
revision to OMB Circular No. A-119 (58 FR 57643, October 26, 1993),
provides policy on Federal use of standards and agency participation
in voluntary standards bodies and standards-developing groups:
``It is the policy of the Federal Government in its procurement
and regulatory activities to:
a. Rely on voluntary standards, both domestic and international,
whenever feasible and consistent with the law and regulation
pursuant to law;
b. Participate in voluntary standards bodies when such
participation is in the public interest and is compatible with
agencies' missions, authorities, priorities, and budget resources;
and
c. Coordinate agency participation in voluntary standards bodies
so that: (1) The most effective use is made of agency resources and
representatives; and (2) the views expressed by such representatives
are in the public interest and, as a minimum, do not conflict with
the interests and established views of the agencies.''
OMB Circular No. A-119 also establishes additional policy
guidance and responsibilities for U.S. Government agencies. It is
applicable to all executive agency participation in voluntary
standards activities, domestic and international, but not to
activities carried out pursuant to treaties and international
standardization agreements.

[[Page 53080]]

The term ``standard,'' as defined in OMB Circular No. A-119,
means:
``* * * a prescribed set of rules, conditions, or requirements
concerned with the definition of terms; classification of
components; delineation of procedures; specification of dimensions,
materials, performance, design, or operations; measurement of
quality and quantity in describing materials, products, systems,
services, or practices; or descriptions of fit and measurement of
size.''
The circular defines ``voluntary standards'' as:
``* * * established generally by private sector bodies, both
domestic and international, and are available for use by any person
or organization, private or governmental. The term voluntary
standard includes what are commonly referred to as ``industry
standards'' as well as ``consensus standards,'' but does not include
professional standards of personal conduct, institutional codes of
ethics, private standards of individual firms, or standards mandated
by law, such as those contained in the United States Pharmacopeia
and the National Formulary, as referenced in 21 U.S.C. 351.''
These definitions in OMB Circular No. A-119 conform to common
usage and are consistent with the usage of these terms throughout
this policy document. It should be noted that, under the TBT,
``standards'' are considered to be nonmandatory (i.e., voluntary)
unless promulgated into mandatory technical regulations.

II. Standards Programs and Practices Within FDA

A. Purpose of FDA Involvement in Standards

The central purpose of FDA involvement in the development and
use of standards is to assist the agency in fulfilling its public
health, regulatory mission. The agency intends to participate in the
development of standards, domestic or international, and adopt or
use standards when such action will enhance its ability to protect
consumers and the effectiveness or efficiency of its regulatory
efforts. In doing so, FDA recognizes that standards often serve as
useful adjuncts to agency regulatory controls and that economies of
time and human resources are often realized in solving problems when
consensus-building activities are undertaken and conducted in open,
public arenas. The working together of FDA staff with other
professionals outside the agency in standards bodies effectively
multiplies the technical resources available to FDA. Further,
standards bodies generally have in place procedures for periodically
reviewing and updating completed standards, thus extending the
resource-multiplier effect, as well as keeping the solutions current
with the state of knowledge. The economy of effort translates into
monetary savings to the agency, regulated industries, and ultimately
consumers. Further, using standards, especially international ones,
is a means to facilitate the harmonization of FDA regulatory
requirements with those of foreign governments, to better serve
domestic and global public health.
Another benefit of participating in the development of standards
at both domestic and international levels is that in sharing
technical information with technical groups and professionals
outside FDA, staff members have opportunities to learn of other
viewpoints on an issue, to establish scientific leadership, and to
remain informed of state-of-the-art science and technology.

B. Past and Present Activities

FDA has been involved in standards activities for many years,
and on January 25, 1977, the agency promulgated a final regulation,
now found at 21 CFR 10.95 (Sec. 10.95), covering the participation
by FDA employees in standards-setting activities outside the agency.
This regulation encourages FDA participation in standard-setting
activities that are in the public interest and specifies the
circumstances under which FDA employees can participate in various
types of standards bodies.
Standards activities of multilateral organizations such as the
World Health Organization (WHO) and the Organization for Economic
Cooperation and Development (OECD, an international organization
with 25 member countries with advanced industrial economies) are
often important to FDA and frequently involve multiple product
types. For example, OECD is developing Genetic Toxicology Test
Guidelines that are of interest to all FDA Centers. Similarly,
guidelines developed under the International Programme on Chemical
Safety of the WHO relate to chemicals that may be in a wide variety
of FDA-regulated products, such as food additives, pesticides,
drugs, animal drugs, biologics, and devices. The United States
Pharmacopeia is a national standard setting body in which FDA
officials actively participate.
The principal standards organizations that are not connected
with a treaty are the International Organization for Standardization
(ISO) and the International Electrotechnical Commission (IEC).
Private organizations and government agencies, including FDA,
participate in ISO and IEC activities through the American National
Standards Institute (ANSI). ANSI represents the United States in the
ISO and IEC and coordinates much of the standards development
activity in the United States. As discussed below, FDA is active in
many ISO, IEC, ANSI, and standards development organization
activities. For example, FDA is represented on the Board of
Directors of ANSI and on several of its committees and working
groups.

1. Foods and Veterinary Medicine

FDA's Center for Food Safety and Applied Nutrition (CFSAN) and
Center for Veterinary Medicine (CVM) actively participate in the
development of international standards by the Codex Alimentarius
Commission (Codex). Codex is an international organization formed in
1962 to facilitate world trade in foods and to promote consumer
protection. It is a subsidiary of two United Nations components, the
Food and Agriculture Organization (FAO) and the WHO. Codex standards
cover food commodity standards (similar to FDA standards of
identity), food additives, food contaminants, and residues of
veterinary drugs in food. FDA officials chair two Codex committees,
the Food Hygiene Committee and the Residues of Veterinary Drugs in
Foods Committee, and participate in many others. Through its
involvement, FDA has been influential in the establishment of many
Codex standards. FDA's procedures for reviewing Codex standards for
purposes of regulation are codified in 21 CFR 130.6 and 564.6.
A provision of the United States implementing legislation for
the Uruguay Round Agreements, Pub. L. 103-465, requires the
President to designate an agency to inform the public, through a
notice published in the Federal Register each year by June 1, of
certain Codex Alimentarius standard-setting activities. The
President, pursuant to Proclamation No. 6780 of March 23, 1995 (60
FR 15845, March 27, 1995), designated the Department of Agriculture
to have this responsibility, and the first such notice of Codex
activities was published in the Federal Register of May 23, 1995 (60
FR 27250).
In 1988, the governments of the United States and Canada entered
into the Canada-United States Free Trade Agreement (now largely
superseded by NAFTA). Since then, officials from CFSAN and CVM have
participated in technical working groups responsible for
implementation of the chapter of the agreement that deals with
agriculture, food, beverage, and related goods (the CUSFTA Technical
Working Groups).
Officials from CFSAN and CVM also participate in the development
of standards by such domestic and international groups as the Food
Chemicals Codex (FCC), AOAC International (previously, the
Association of Official Analytical Chemists), expert committees of
the WHO, FAO, ISO, and other international consensus standards
bodies. Standards developed by these organizations are used by
industry, both in the United States and abroad. These standards
provide industry with guidance for food grade materials and
processes, and thus help elevate the quality of food and food
chemicals in domestic and international trade.
CFSAN has adopted many FCC and American Society for Testing and
Materials (ASTM) standards and AOAC methods, incorporating them into
regulations for both food additives and generally recognized as safe
food ingredients. CFSAN also refers industry to relevant FCC, Codex,
or ASTM standards when discussing particular issues related to good
manufacturing practices. CFSAN accepts many AOAC and equivalent
methods for use by laboratories in assaying food and in testing for
contaminants in food.
CVM accepts many AOAC and equivalent methods for use by
laboratories in testing for drug residues in animal tissues. CVM has
adopted the consumption estimates used by the FAO/WHO Joint Expert
Committee on Food Additives in the development of standards for drug
residues in animal tissues.
CVM is also an active participant in a new harmonization effort
under the auspices of the Office of International Epizooties (OIE).
This activity is known as the International Cooperation on
Harmonisation of Technical

[[Page 53081]]
Requirements for Registration of Veterinary Medicinal Products (VICH).

2. Biologics and Drugs

There has been active international standard setting for
biological products for more than 50 years. Officials from FDA's
Center for Biologics Evaluation and Research (CBER) serve as experts
or members of a variety of international committees that perform
standard-setting functions. Activities have encompassed
collaborative studies to establish international units of measure
and to develop internationally accepted standards for control of
biologics, including WHO standards. Efforts have been directed to
many kinds of biological products, including vaccines, human blood
and plasma products, blood testing reagents, and allergenic
extracts, and have extended to biotechnology-derived growth factors,
cytokines, and monoclonal antibody products.
FDA's Center for Drug Evaluation and Research (CDER), CBER, and
the National Center for Toxicological Research (NCTR) actively
participate in the International Conference on Harmonisation of
Technical Requirements for Registration of Pharmaceuticals for Human
Use (ICH). This ongoing project, begun in 1989, has been undertaken
by governmental agencies responsible for regulation of drugs and by
industry trade organizations from the European Union (EU), Japan,
and the United States. Specifically, ICH is sponsored jointly by the
Commission of the European Communities (CEC), the Japanese Ministry
of Health and Welfare (MHW), FDA, the European Federation of
Pharmaceutical Industries' Associations (EFPIA), the Japan
Pharmaceutical Manufacturers Association (JPMA), and the
Pharmaceutical Research and Manufacturers Association (PhRMA) of the
United States. In addition, the International Federation of
Pharmaceutical Manufacturers Associations (IFPMA) participates as an
umbrella organization for the pharmaceutical industry and provides
the secretariat function for ICH. ICH operates under the direction
of the ICH Steering Committee, which is comprised of representatives
of these organizations. Official observer status has been given to
WHO, the European Free Trade Area (EFTA), and the Health Protection
Branch of Canada.
The purposes of ICH are to: (1) Provide a forum for a dialogue
between regulatory agencies and the pharmaceutical industry on
differences in the technical requirements for product registration
(i.e., requirements for product marketing) in the EU, Japan, and the
United States; (2) identify areas where modifications in technical
requirements or greater mutual acceptance of research and
development procedures could lead to more efficient use of human,
animal, and material resources without compromising safety, quality,
and efficacy; and (3) make recommendations of practical ways to
achieve greater harmonization in the interpretation and application
of technical guidelines and requirements for registration. The work
products of ICH, created in working groups of experts from the
regulatory agencies and industry, consist of a series of consensus
guidance documents. These guidance documents, after successive ICH
steps of review and acceptance, including an opportunity for public
review and comment in the respective jurisdictions, are forwarded to
the regulatory agencies with the expectation that they will be
formally adopted by the agencies.
Officials from both CBER and CDER also participate in a
consensus standard setting activity sponsored by the Council for
International Organizations of Medical Sciences (CIOMS) that is
aimed at standardizing medical definitions and adverse experience
reporting.

3. Medical Devices and Radiation-Emitting Products

FDA's Center for Devices and Radiological Health (CDRH) has had
extensive involvement with standards in its regulation of medical
devices, as well as electronic products that emit radiation. The
development of standards to solve problems related to medical
devices involves many groups outside FDA. The interaction between
CDRH and the manufacturing and health care communities that
frequently occurs during the standards development process provides
knowledge and insight into the use of products, problems, and the
effectiveness of solutions. Frequently, the public discussion of the
problem that occurs in the consensus-building process results in the
manufacturers and the users of the subject medical device
implementing the solution before a standard is formally completed.
Thus, CDRH has encouraged participation in the development of
standards as a useful adjunct to regulatory controls. CDRH's
approach to use and participation in the development of consensus
standards was described in a letter dated June 29, 1993, to all
interested parties from the Director of CDRH. (This policy did not
apply to mandatory performance standards, i.e., technical
regulations, for class II medical devices as specified under the
Medical Device Amendments of 1976 (Pub. L. 94-295). The Safe Medical
Devices Act of 1990, SMDA (Pub. L. 101-629), puts the promulgation
of mandatory standards at the discretion of the agency.)
Over 200 completed consensus standards and selected sections of
additional draft standards that are not yet complete have been
incorporated into guidance documents for applications for conducting
clinical trials with investigational devices and applications for
permitting devices to be marketed. These guidance documents are
widely disseminated by CDRH to all interested parties. Other
standards used by CDRH, or which CDRH has helped to develop, concern
measurement or test methods, or support good manufacturing practices
and quality assurance.
A new ISO Committee, Technical Committee 210 (TC-210) is
developing harmonized standards in these areas. Also, CDRH is an
active participant in the Global Harmonization Task Force, in
cooperation with officials from Canada, the EU, Japan, and other
countries.
CDRH has published a notice of a working draft of a final rule
to revise the current good manufacturing practice regulations for
medical devices (60 FR 37856, July 24, 1995), in part to ensure that
they are compatible with specifications for quality systems
contained in an international quality standard developed by ISO,
namely ISO 9001 ``Quality Systems Part 1. Specification for Design/
Development, Production, Installation, and Servicing.'' This
standard (ISO 9001) is becoming widely recognized by medical device
regulatory authorities worldwide and is finding application in many
other industry sectors as well. CDRH officials, working with
counterpart foreign government officials, are pursuing in step-wise
fashion the harmonization of quality system inspection procedures
and enforcement.
The process of harmonizing regulatory requirements is
facilitated by using an international standard as a basis. Such
harmonization is not only recognized public policy, but for medical
devices, it is explicitly encouraged by provisions of SMDA (Pub. L.
101-629), which states, in part, that FDA ``* * * may enter into
agreements with foreign countries to facilitate commerce in devices
between the United States and [foreign] countries consistent with
the requirements of this Act.'' 21 U.S.C. 383.
In a recent (April 1995) program review, CDRH reported that in
1994, 192 Center staff members served as primary and alternate
liaison representatives on 440 committees and subcommittees in 38
standards developing organizations (domestic and foreign). CDRH
actively reviewed 286 draft standards; of these, 134 were with nine
international standards organizations. The experience CDRH has
acquired over the years has provided the foundation for the
standards policy it announced on June 29, 1993. The essential
features of that policy are reflected in the FDA policy presented in
section IV. below.

4. Regulatory Affairs

FDA's Office of Regulatory Affairs (ORA) is increasingly active
in international standards activities relevant to quality control
and conforming assessment, including activities relevant to ISO--
9001 and laboratory regulation.

III. Response to Comments

In response to its request for comments on the draft
international harmonization policy on standards, FDA received
comments from ten organizations (standards setting organizations,
trade and professional associations, a manufacturer, and a consumer
organization). A discussion of the comments received and the
agency's responses follow.
1. In general, the comments supported the agency's proposed
international harmonization policy on standards. For example, one
comment stated that the policy demonstrated the agency's commitment
to the international standards development process as well as
international harmonization. Another comment pointed out that the
policy will better enable the agency to establish agreements with
other global regulatory bodies, and ultimately permit FDA to carry
out its mandate to protect the public health in a more efficient and
cost effective manner. Other comments stated that the harmonization
of regulatory requirements and supportive standards could benefit
U.S. companies engaged in international trade. In addition, one of
these

[[Page 53082]]
comments pointed out that standards reflect technology, and that the
first priority with regard to standards should always be to develop
standards that represent the best available technological solutions,
adding that `harmony' and `consistency' can be achieved through the
general acceptance of excellent technological solutions. FDA agrees
with these comments.

A. Potential for Lowered Standards

2. Two comments stated that harmonization has the potential to
result in lowered standards, with potential adverse effects on
public health protection. One of the comments expressed concern that
FDA was subordinating the public interest in favor of voluntary
standards bodies and standards developing groups in a manner that is
inconsistent with the vital tasks assigned to the agency to protect
health. The second comment argued that the first priority with
regard to standards should be to develop standards that represent
the best available technological solutions, and that FDA should not
support international standards that reflect inferior or compromised
technological solutions that become obstacles, rather than benefits,
to U.S. industry. Another comment, while agreeing that international
standards should be adopted as national standards whenever possible,
stated that international standards may sometimes not meet the needs
of our health care community, adding that some may contain safety
standards only and no performance parameters, and that the
international standards may also be inconsistent with our country's
codes and regulations.
FDA wishes to reassure those who commented that FDA's
participation in international harmonization activities is intended
to safeguard the U.S. public health and to assure that consumer
protection standards and requirements are met. Indeed, a central
principle that guides the agency's international harmonization
activities is that the activities should further FDA's mission to
protect the public health. In addition, international agreements to
which the U.S. Government is a party have provisions that ensure
that harmonization activities will not result in lowered standards.
For example, the WTO Agreement on SPS provides that each country may
determine its appropriate level of protection; therefore, the
encouragement to use international standards as the basis for
technical regulations will not result in ``downward harmonization.''
Safeguards have been built into the TBT agreement and U.S.
implementing legislation that protect the ability of each country to
establish requirements necessary to fulfill a legitimate objective.
As stated in section I.C.1. above, the implementing legislation for
the new TBT agreement, which provides additional authority for FDA's
international standards activities, provides further assurance that
such harmonization would not result in lowering safety or quality
standards for U.S. consumers. Thus, the agency does not agree that
harmonization will result in inferior standards. Furthermore, FDA's
participation in standards development, consistent with Sec. 10.95
and OMB Circular No. A-119, and FDA's use of standards in its
regulatory programs, will be dependent not only on the substantive
aspects of the standards for ensuring the safety, effectiveness, and
quality of products, but also on the development process for the
standard. The standard itself must also comply with all applicable
statutes, regulations, and policies.

B. Regulatory Issues

3. One comment stated that any time a voluntary standard is used
in a regulation, the scope of that standard needs to be
unambiguously determined. The comment used a hypothetical case of a
voluntary standard intended to be used in the home environment being
inappropriately extended to the hospital environment. The comment
argued that if the regulatory need exceeds the scope of the existing
voluntary standard, it may indicate the need for yet another
voluntary standard that addresses the additional scope, or else
provisions may need to be added to the existing voluntary standard
so as to accommodate the broader scope in which the standard is to
be applied.
The agency agrees that when a voluntary standard is used in a
regulation, the scope of that standard should be unambiguously
expressed. As stated above, a basic tenet in the development and
adoption of a standard is that it contributes to safer, more
effective, and higher quality products. Inappropriate application of
a standard (voluntary or as part of a technical regulation) would
run counter to this notion.
4. Three comments questioned the need to make voluntary
standards mandatory regulations. One of the comments stated that if
the agency uses a voluntary standard as a ``referee'' standard,
which means that the agency uses the voluntary standard as a frame
of reference for determining safety and efficacy, there should be no
need for the agency to go through the procedures required for
creating a regulation. The second comment stated that if technical
standards are based on state-of-the-art science and are revised as
needed to incorporate advances, they should be voluntary standards
as opposed to regulatory requirements. The third comment asserted
that existence of a standard does not warrant a regulation and FDA
should avoid unnecessary regulations.
The agency agrees that it should avoid unnecessary regulations
but notes that there are times when it finds it is necessary to
propose and promulgate regulations for the efficient enforcement of
the laws it administers. Voluntary standards that will serve
agencies' purposes and are consistent with applicable laws and
regulations can be adopted and used by Federal agencies. This
principle is stated in both FDA's policy and in section 7(a) of OMB
Circular No. A-119 on Reliance on Voluntary Standards. Thus, when
appropriate, FDA will adopt voluntary standards by referencing them
in the regulations it promulgates. In all other instances, these
standards will remain voluntary.
As stated above, the purpose of FDA's involvement in the
development and use of standards is to assist the agency in
fulfilling its public health and regulatory missions. Thus, the
agency intends to participate in the development of domestic and
international standards, and to adopt or use standards, when such
action will enhance its ability to protect consumers and the
effectiveness or efficiency of its regulatory efforts.

C. Transparency

5. Four comments addressed the need for transparency during the
development of standards, in determining ``official'' use of a
standard, or when standards are used in a regulation or adopted as
regulations. The comments asserted that, if voluntary standards are
incorporated into guidance documents and compliance policy guides
and serve as the bases for mandatory standards and other regulations
promulgated by FDA, ample opportunity should be provided for
interested parties to comment through the established procedures of
notice and comment rulemaking. One comment further stated that the
policy should include a statement of assurance that FDA will engage
potentially affected parties whenever it intends formal inclusion of
a voluntary standard in an FDA document or process.
The agency agrees that the development of standards should be
conducted in an open fashion. Under Sec. 10.95, one of the criteria
for FDA participation in standards-setting bodies is that the group
or organization responsible for the standard-setting activity must
have a procedure by which an interested person will have an
opportunity to provide information and views on the activity and
standards involved, and that the information and views will be
considered. This is why FDA clearly states in its policy (section
IV. below) that one of the factors for FDA's participation in
standards development and use is the transparency of the process,
i.e., the process must be open to public scrutiny and provide the
opportunity for the consideration of views of all parties concerned.
With regard to transparency when standards are used in a
regulation or adopted as regulations, under the Administrative
Procedure Act (APA), an agency that issues, amends, or revokes a
regulation, whether on its own initiative or when petitioned by an
interested person, must act in an open manner with adequate time
provided for comment from interested parties, which will be
considered before a final regulation is promulgated. FDA's rule on
promulgation of regulations, found in 21 CFR 10.40, is explicit with
respect to the need for transparency of the process and opportunity
for participation in the process by interested persons. Other
procedural regulations govern guidelines and similar documents (21
CFR 10.90), and interested persons may use correspondence or
meetings (21 CFR 10.65), petitions (21 CFR 10.30), or reviews by
supervisors (21 CFR 10.75) to raise issues and present views about
other nonbinding guidance documents, which provide industry with
useful information about recommended or alternative ways to comply
with requirements. In fact, FDA has increasingly used public
meetings to elicit and share information with regard to its guidance
documents and it currently is reviewing the procedures it uses to
develop guidance documents to ensure sufficient transparency in the
process.
Thus, with regard to the comment that this policy should include
a statement of

[[Page 53083]]
assurance that FDA will engage potentially interested parties whenever
it intends formal inclusion of a voluntary standard in an FDA
document or process, the agency finds that it is not necessary to do
so as part of this document because there are established mechanisms
under the APA and the agency's administrative practices and
procedure regulations for obtaining and considering views of
interested persons. Of course, FDA is not foreclosing future
consideration of additional mechanisms toward this end.

D. Comments on Specific Issues

6. One comment suggested the alternative language, ``The
standard contributes to safe and effective products that meet
consumers' requirements for quality,'' instead of ``The standard
contributes to safer, more effective, and higher quality products''
(section III.A.1., proposed policy) and ``The standard, if adhered
to, would help ensure the safety, effectiveness, or quality of
products'' (section III.D.1., proposed policy). The alternative
language was offered to simplify future negotiations and to allow
the agency to participate more fully in standards development and
promulgation. The comment also questioned the use of the terms
`safer' and `more effective' in section III.A.1. of the proposed
policy (see above) because it is not clear what the measures for
`safer' and `more effective' are. The comment further stated that
the term ``higher quality'' is relative, leaving open to question
who determines higher quality. Finally, the comment added that an
international standard could conceivably result in requirements for
the same degree of safety, effectiveness, and quality as those
required by FDA.
The agency is revising the policy in a manner similar to that
suggested by the comment. FDA agrees that an international standard
could indeed result in requirements for the same degree of safety,
effectiveness, and quality as required by FDA. In fact, one of FDA's
guiding principles in its international harmonization activities is
that FDA should accept, where legally permissible, equivalent
standards of other countries provided such standards meet FDA's
goals to facilitate the availability of safe, effective, and
properly labeled products. The agency further agrees that the
alternative language would allow the agency more flexibility to
participate in standards development, without compromising public
health, and is therefore amending the policy accordingly.
7. One comment supported FDA's intent to develop standards on
the basis of sound scientific and technical information. The comment
added that the use of sound scientific and technical information
will permit the development of food regulations and standards that
cannot be misconstrued as unreasonable trade barriers. However, the
comment cautioned that a decision on participation in standards
development should be based on the purpose of the standard, not
whether the standard is based on sound scientific and technical
information.
The agency agrees that while all standards should be based on
sound scientific and technical information, not all scientifically
sound standards will serve purposes justifying the agency's
participation in developing them. FDA's regulation on participation
in outside standard-setting activities states that not only will the
activity be based upon consideration of sound scientific and
technological information, but it also will be designed to protect
the public against unsafe, ineffective, or deceptive products and
practices (21 CFR 10.95(d)(5)(i)). In addition, OMB Circular No. A-
119 states that it is the policy of the Federal Government to
participate in voluntary standards bodies when such participation is
in the public interest and is compatible with agencies' missions,
authorities, priorities, and budget resources. The OMB Circular adds
that the providing of agency support to a voluntary standards
activity should be limited to that which is clearly in furtherance
of an agency's mission and responsibility. These directives are
adequately reflected in the policy.
8. One comment suggested that proposed section III.A.4., ``The
development of an international standard that achieves the agency's
public health objectives is generally, but not always, given a
higher priority than the development of a domestic standard,'' be
deleted because it is made clear in other parts of the draft policy
that FDA complies with U.S. obligations under the GATT, other
international trade agreements, and OMB Circular No. A-119.
The agency agrees that the draft policy document does make clear
that FDA complies with U.S. obligations under international
agreements and the OMB Circular. However, the agency does not agree
that proposed section III.A.4. should be deleted. FDA's belief that
the development of an international standard that achieves the
agency's public health objectives is generally (but not always)
given a higher priority than the development of a domestic standard,
is an important factor on which agency participation in standards
development is based and merits being clearly delineated. This is
more so because proposed section III (section VI. of this document),
FDA Policy on Standards, is intended to stand on its own as the
agency's policy on harmonization of standards and, therefore, needs
to be as complete as possible.
FDA emphasizes that there are three routes to development of a
harmonized international standard, all of which are favored under
the FDA policy: (1) The U.S. voluntary standards community or an
agency, such as FDA, develops a U.S. standard and takes it to an
international forum so it can be made an international standard; (2)
a standard already developed in an international forum (or by
another country or a regional standards body) is adopted as a U.S.
voluntary or regulatory standard; or (3) a new international
standard is developed, ``from scratch,'' in an international forum.
Which of these routes is followed in the particular case will vary
with the facts of that case. While starting a standards activity in
an international forum offers many efficiencies in avoiding
duplication of effort, there will continue to be times when it makes
sense first to develop a domestic standard (voluntary or regulatory)
and then to take it, as appropriate, to an international forum.
9. One comment asserted that the intent of proposed factors
III.A.6. and III.D.6., which state: ``Wherever appropriate for the
product, the standard stresses product performance rather than
product design, but where necessary, covers all factors required to
ensure safety, effectiveness, and quality,'' was not clear. The
comment added that inspection can be used to prevent poor quality
products from being consumed but that safety cannot be inspected
into a product. The comment stated further that safety must be
designed into products during development, subsequent manufacturing,
packaging, and transport. Further, the comment stated that product
performance or product functionality issues with regard to safety
are the primary focus in the development of food regulations, and
therefore, the comment recommended alternative language to that in
the proposed policy: ``Wherever appropriate for the product, the
standard stresses product safety, performance, and functionality,
but where necessary, covers all factors required to ensure safety
and effectiveness, including product and process design, and process
performance.''
The agency believes that the suggested language is helpful in
capturing FDA's intentions in formulating these factors as the basis
for participation in standards development, and use of standards in
its regulatory programs. Therefore, the agency is making editorial
changes in the factors along the lines suggested in the comment.

E. Other Comments

10. One comment recommended that FDA review and revise current
U.S. guidelines for toxicity testing of food additives as outlined
in the Toxicological Principles for the Safety Assessment of Direct
Food Additives and Color Additives Used in Food (Redbook I), as well
as the proposed guidelines set forth in the revised draft, Redbook
II, and harmonize with those recommended by the OECD. The comment
added that this will allow more universal acceptance of results
performed throughout the world and will minimize the need to repeat
expensive testing to meet different testing standards in different
countries.
The agency has stated that standards activities of organizations
such as OECD are often important to FDA, and that the development of
international standards, and harmonization with international
standards if they achieve the agency's public health objectives,
will in most instances be given a high priority.
The agency announced that the draft Redbook II was available
(March 29, 1993, 58 FR 16536) and solicited comments on the draft
revised guidelines. Redbook II is being finalized in light of
comments received by the agency, including a comment that the
guidelines should be harmonized with those of the OECD; the final
revised Redbook II has yet to be issued. The agency notes that, in
revising the guidelines in the Redbook, it took into account the
fact that differences among guidelines can result in unnecessary
duplication of effort and inefficient use of

[[Page 53084]]
scarce testing resources. The agency also wants to make clear that the
Redbook is designed to provide guidance. Strict adherence to Redbook
guidelines is not a requirement for toxicological studies conducted
to establish the safety of an additive.
11. One comment indicated concern that a long standing
participation by the United States Public Health Service in the 3-A
Sanitary Standards (for dairy and related food industries) is not
mentioned in the text of the draft policy. The comment also stated
that it is necessary that, as international agreements anticipate
trade and importation of equipment, compliance with 3-A Sanitary
Standards should be applied by reference to assure receipt of
acceptable equipment.
The domestic and international standards-setting organizations
or bodies listed under section II.B. of this document are those in
which FDA has been or is most actively involved in developing
standards. The listing is not meant to be exhaustive nor is it meant
to list all standards setting bodies in which FDA has an interest.
12. One comment urged FDA to reference voluntary standards
rather than adopting and publishing standards, to maintain
appropriate support for standards development. The comment argued
that referencing rather than publishing the text of voluntary
standards as regulations or guidance protects the standards
organizations' copyrights which provide the financial support for
national and international programs.
FDA uses standards in the manner described in OMB Circular No.
A-119, which states that while voluntary standards adopted by
Federal agencies should be referenced along with their dates of
issuance and sources of availability in appropriate publications,
regulatory orders, and in related in-house documents, such adoption
should take into account any applicable requirements of copyright
law and other similar restrictions.
13. One comment advised that the value of standards is that they
are the consensus product of all technology experts, not just the
consensus of experts from government. Therefore, care should be
exercised that government participation in voluntary standards
organizations and its use of voluntary standards does not lead to an
appearance that voluntary standards organizations are unduly
directed or influenced by government.
The agency is sensitive to the need for balanced participation
in voluntary standards bodies and works within OMB's guidelines
regarding policy to be followed by executive agencies in working
with voluntary standards bodies. OMB Circular No. A-119 states that
agency representatives serving as members of standard-developing
groups should participate actively and on a basis of equality with
private sector representatives but that, in doing so, agency
representatives should not seek to dominate such groups. In
addition, the number of individual agency participants in a given
voluntary standards activity should be kept to the minimum required
for effective presentation of the various program, technical, or
other concerns of Federal agencies. Finally, while the circular
encourages agency representatives to participate in the policy-
making process of voluntary standards bodies, particularly in
matters such as establishing priorities, developing procedures for
preparing, reviewing and approving standards, and creating
standards-developing groups, it also states that in order to
maintain the private, nongovernmental nature of such bodies, agency
representatives should refrain from decisionmaking involvement in
the internal day-to-day management of such bodies.

F. Conclusion

Therefore, after considering the comments received, FDA is
issuing this statement of policy.

IV. FDA Policy on Standards\1\

\1\This policy document does not create or confer any rights,
privileges, or benefits, for or on any person, nor does it operate
to bind FDA in any way.
---------------------------------------------------------------------------

It is the intent of this policy to enable FDA to: (1) Continue
to participate in international standards activities that assist it
in implementing statutory provisions for safeguarding the public
health, (2) increase its efforts to harmonize its regulatory
requirements with those of foreign governments, including setting
new standards that better serve public health, and (3) respond to
laws and policies such as the Trade Agreements Act and OMB Circular
No. A-119 that encourage agencies to use international standards
that provide the desired degree of protection. Accordingly, it is
the policy of FDA, concerning the development and use of standards,
that:
A. FDA participation in standards development will be based on
the extent to which the development activity and expected standard
conform to certain factors, with consideration also being given to
the resources available in FDA to devote to the effort and expected
efficiencies to be gained as a result of the effort; the factors are
as follows:
1. The standard stresses product safety and effectiveness and
therefore contributes to safe, effective, and high quality products;
when necessary, the standard also covers all factors required to
ensure safety and effectiveness, including product and process
design, and process performance;
2. The standard is based on sound scientific and technical
information and permits revision on the basis of new information;
3. The development process for the standard is transparent
(i.e., open to public scrutiny), complies with applicable statutes,
regulations, and policies, specifically including Sec. 10.95 and OMB
Circular A-119, and is consistent with the codes of ethics that must
be followed by FDA employees;
4. The development of an international standard that achieves
the agency's public health objectives is generally, but not always,
given a higher priority than the development of a domestic standard;
and
5. The development of a horizontal standard which applies to
multiple types of products is generally, but not always, given
higher priority than the development of a vertical standard which
applies to a limited range of types of products.
B. FDA is not bound to use standards developed with FDA
participation. For example, the agency will not use a standard when,
in the judgment of FDA, doing so will compromise the public health.
C. The uses of final (and selected draft or proposed) standards,
or selected relevant parts, will include, where appropriate: (1)
Incorporating such standards into guidance documents for nonclinical
testing, applications for conducting clinical trials with
investigational products, and applications for permitting products
to be marketed; (2) conducting reviews of such applications; (3)
incorporating such standards into compliance policy guides; (4)
conducting reviews of test protocols used by firms as part of good
manufacturing practices; (5) conducting reviews of study protocols
submitted by firms as required for postmarket surveillance studies
or programs; (6) serving as the basis for mandatory standards or
other regulations promulgated by FDA; and (7) serving as the basis
for reference (e.g., evaluation criteria) in a memorandum of
understanding with other government agencies.
D. The use of a standard in the regulatory programs of FDA is
dependent upon the following factors:
1. The standard stresses product safety and effectiveness and
therefore, if adhered to, would help ensure the safety,
effectiveness, or quality of products; when necessary, the standard
also covers all factors required to ensure safety and effectiveness,
including product and process design, and process performance;
2. The standard is based on sound scientific and technical
information and is current;
3. The development process for the standard was transparent
(i.e., open to public scrutiny), was consistent with the codes of
ethics that must be followed by FDA employees, and the standard is
not in conflict with any statute, regulation, or policy under which
FDA operates;
4. Where a relevant international standard exists or completion
is imminent, it will generally be used in preference to a domestic
standard, except when the international standard would be, in FDA's
judgment, insufficiently protective, ineffective, or otherwise
inappropriate; and
5. Where a relevant horizontal standard which applies to
multiple types of products exists or its completion is imminent, it
will generally be used in preference to a vertical standard, which
applies to a limited range of types of products, except when such
horizontal standard would be insufficiently protective, ineffective
or otherwise inappropriate.
E. FDA employees will comply with agency regulations
(Sec. 10.95) covering participation in standard setting activities
outside the agency.

Dated: October 4, 1995.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 95-25070 Filed 10-10-95; 8:45 am]
BILLING CODE 4160-01-F

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Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/fr%3A95-25070. Public record. Not legal advice.