International Harmonization; Policy on Standards

[[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.

-----------------------------------------------------------------------

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