Guidelines for Ensuring the Quality of Information Disseminated to the Public
F. � Food and Drug Administration
- Agency Mission
- Scope and Applicability of Guidance
- Types of Information Disseminated to the Public by FDA
- Public Communications About Risk
- Rulemaking Documents
- Product Approvals
- Medical Products
- Food and Color Additives
- Guidance and Regulatory Assistance
- Citizen Petitions and Responses
- Press Items and Publications
- Types of Dissemination Methods
- Agency Quality Assurance Policies, Standards, and Processes
- Product Review Activities
- Food Safety Activities
- Adverse Events Analysis for Medical Products
- Research to Support the Regulatory Functions of FDA
- Agency Administrative Complaint Procedures
- Submission of Complaints and Requests for Correction
- Dispute Resolution Procedures
- Influential Scientific, Financial, and Statistical Information
- Definition of the Term Influential
- Risk Assessment
- Special Considerations for Agency Dissemination
This guidance represents the Food and Drug Administration's (FDA's) current
thinking on this topic. It does not create or confer any rights for or on
any person and does not operate to bind FDA or the public. An alternative
approach may be used if such approach satisfies the requirements of the applicable
statutes and regulations.
This guidance provides the information quality guidelines for the Food and Drug Administration (FDA)
requested under the Guidelines for Ensuring and Maximizing the Quality, Objectivity, Utility,
and Integrity of Information Disseminated by Federal Agencies (OMB Guideline).
The OMB Guidelines implement section 515 of the Treasury and General Government
Appropriations Act for Fiscal Year 2001 (Pub. L. 106-554; H.R. 5658). The
OMB Guidelines direct agencies to issue their own information quality guidelines
ensuring and maximizing the quality, objectivity, utility, and integrity
of information, including statistical information, disseminated by the agency.
This guidance is part of the U.S. Department of Health and Human Services
(HHS) implementation plan developed to comply with the OMB Guidelines. The
principles described in the HHS plan and OMB guidance are incorporated by
reference into this guidance.
This guidance describes the nature of the information disseminated
by the FDA and explains FDA's standards, policies, and procedures for ensuring
the quality of the information it disseminates. The guidance also explains
the administrative mechanisms that are in place to enable persons to seek
and obtain correction of information maintained and disseminated by the FDA
that they believe does not comply with the OMB and HHS Guidelines and this
I. � Agency Mission
The Agency's mission, as defined in Section
406 of the Food and Drug Administration (FDA) Modernization Act of 1997,
is as follows:
The Administration shall --
- promote the public health by promptly and efficiently reviewing clinical
research and taking appropriate action on the marketing of regulated products
in a timely manner;
- with respect to such products, protect the public health by ensuring that --
- foods are safe, wholesome, sanitary, and properly labeled;
- human and veterinary drugs are safe and effective;
- there is reasonable assurance of the safety and effectiveness of devices intended for human use;
- cosmetics are safe and properly labeled; and
- public health and safety are protected from electronic product radiation;
- participate through appropriate processes with representatives
of other countries to reduce the burden of regulation, harmonize regulatory
requirements, and achieve appropriate reciprocal arrangements; and
- as determined to be appropriate by the Secretary, carry out
paragraphs (1) through (3) in consultation with experts in science, medicine,
and public health, and in cooperation with consumers, users, manufacturers,
importers, packers, distributors, and retailers of regulated products.
II. � Scope and Applicability of Guidelines
FDA is a scientific
regulatory agency that regulates one trillion dollars worth of consumer goods
each year. This amounts to more than 20 percent of all consumer spending.
FDA regulates most food that we eat, all prescription drug and over-the-counter
drug products that we take, and all medical devices that we use. For foods,
we ensure that products are safe, wholesome, sanitary, and properly labeled.
For drugs, we ensure the products are both safe and effective for use; and
for medical devices, there is a reasonable assurance of their safety and
effectiveness. We also are responsible for ensuring that electronic and radiation-emitting
equipment, such as x-ray machines, microwave ovens, and metal detectors,
are safe for use. We certify and inspect annually all mammography facilities.
We regulate animal feed and most animal drugs. We ensure that cosmetics are
labeled honestly and cause no harm. Our regulatory activities include inspection
and surveillance of marketed products, standard setting, bioresearch monitoring,
and human subject protection. We also conduct research in support of our
FDA, which employs about 10,000 people, is organized primarily by centers:
- Center for Biologics Evaluation and Research (CBER)
- Center for Devices and Radiological Health (CDRH)
- Center for Drug Evaluation and Research (CDER)
- Center for Food Safety and Applied Nutrition (CFSAN)
- Center for Veterinary Medicine (CVM)
- National Center for Toxicological Research (NCTR)
- Office of the Commissioner (OC)
- Office of Regulatory Affairs (ORA)
Our Office of the Ombudsman, which is responsible for monitoring complaints
regarding information dissemination and our response to those complaints,
resides in the Office of the Commissioner.
As described in detail in the paragraphs that follow, we disseminate
many different types of information to a wide variety of audiences, including
the regulated industry, health care professionals and organizations, consumers,
patients, other governmental agencies, and international organizations and
agencies. Information dissemination is an important part of our mission to
promote and protect the public health. FDA recognizes that public access
to high quality information is critical to achieving this mission and public
input, in turn, improves the quality of the information we disseminate.
Because of the nature of this information, our goal has been and
remains to ensure that all the information we disseminate meets the high
standards of quality (including objectivity, utility, and integrity) described
in the OMB and HHS Guidelines. As discussed in detail in Section V,
we have established several policies, standards, and processes to ensure
the quality of the information we make available to the public. FDA also
will ensure that information collected under the Paperwork Reduction Act
of 1995, 44 U.S.C. chapter 35, will be collected, maintained, and used in
a manner consistent with the OMB and HHS Guidelines and this guidance document.
With the following specific exceptions, the OMB Guidelines apply to most
categories of FDA-disseminated information (see discussion in following sections):
- Documents relating to internal FDA procedures
- Internal government correspondence
- Correspondence with individuals that is not normally made public
- Press releases (unless they contain new substantive information not covered by previous information dissemination)
- Archival records
- Distributions intended to be limited to subpoenas or adjudicative
documents including findings and determinations made in the course of an
administrative proceeding pursuant to 21 CFR Parts 10, 12, 13, 14, 15, 16,
17 and 19.
- Scientific publications that only contain the views of the authors and are not used to support an official agency position
- Responses to requests for information under the Freedom of Information
Act (FOIA), the Privacy Act, the Federal Advisory Committee Act, or other
In the pages that follow, we describe the types of information we disseminate (Section III), the methods we use to disseminate this information (Section IV),
and the quality assurance policies, standards, and processes that have been
put in place to ensure the quality of the information we distribute (Section V).
Some of the information described below may include information that falls
under one of the types of information specifically excluded above. To the
extent that information in one of the categories listed below includes information
listed in one of the exceptions, the OMB Guidelines do not apply. In Section VI, we discuss the procedures to be used by persons who want to request that information we have disseminated be corrected. Section VII
discusses the types of information we have identified to be influential according
to the OMB Guidelines and the principles we apply to information that will
be disseminated regarding risks to human health, safety, and the environment.
The principles that are used have been adapted from the quality principles
applied by Congress to risk information pursuant to the Safe Drinking Water
Act Amendments of 1996 (42 U.S.C. 300g-1(b)(3)(A) and (B)). Section VIII describes some special circumstances that may apply to certain information dissemination activities.
The pre-dissemination review described in the HHS guidelines only
applies to information disseminated on or after October 1, 2002. The administrative
mechanism for correction applies to information that the agency disseminates
on or after October 1, 2002, regardless of when the agency first disseminated
III. � Types of Information Disseminated
We make a large number
of documents and information available to a variety of audiences. The major
types, with examples of each, are provided here.
- Public Communications About Risk
As part of our mission to protect the public health and safety, we provide
the public with a wide variety of information on risk, including information
on food safety and the risks involved with using medical products. Some examples
of our communications are listed here.
- Consumer advice and fact sheets (for example, News Release No. 0020.01,
January 2001 provides advice to consumers to reduce the risk of illness from
foodborne Listeria monocytogenes)
- "Dear Health Care Professional" letters (for example, Agency August
2001 letter to health care professionals warning about rhabdomyolsis, a serious,
potentially fatal adverse effect of all statin drugs)
- Public health
and safety alerts (for example, "FDA Announces New Alcohol Warnings for Pain
Relievers and Fever Reducers," October 1998; "Seniors and Food Safety --
Preventing Foodborne Illness," May 1999; "Learning About Lasik Eye Surgery,"
on the Internet; "FDA Patient Safety News," a video targeting hospitals;
"Tips and Warnings for Consumers About Buying Medicines and Medical Products
Online," on the Internet; "An Important Message for Pregnant Women and Women
of Childbearing Age About the Risk of Mercury in Fish," March 2001; "FDA
Public Health Notification: Reducing Radiation Risk from Computed Tomography
for Pediatric and Small Adult Patients," November 2001)
- FDA Talk Papers (for example, FDA Announces Availability of Vibrioparahaemolyticus Risk Assessment, January 18, 2001)
- Various subject matter brochures intended for consumers. Some are
produced as low-literacy brochures aimed at consumers with no more than a
fifth-grade reading level. Some are also produced in other languages, particularly
in Spanish. Some are mailed directly to specific audiences; some are disseminated
at large professional meetings (for example, "Reprocessing of Single-Use
Medical Devices by Hospitals" (November 2000), "Buying Contact Lenses on
the Internet, by Phone, or by Mail" (August 2001)).
- Posters are distributed to health clinics and schools with consumer information on FDA-related health issues.
Like many Federal agencies, we engage in rulemaking. This process
includes publishing a proposed rule and explanatory material in the Federal Register, obtaining public comment, and publishing a final rule and response to the comments. Some examples include:
- Additional Criteria for Classifying Over the Counter Drugs as Generally
Recognized as Safe and Effective and Not Misbranded, a final rule that published
on January 23, 2002
- Medical Devices; Device Tracking, a final rule that published on February 8, 2002
- State Certification of Mammography Facilities, a final rule that published on February 6, 2002
- Implantation or Injectable Dosage Form New Animal Drugs: Trenbolone
and Estradiol; a final rule that published on February 7, 2002
- Foreign Establishment Registration and Listing, a final rule that published on November 27, 2001
- Substances Affirmed as Generally Recognized as Safe: Menhaden Oil; a proposed rule that published on February 26, 2002
- Hazard Analysis and Critical Control Point (HACCP): Procedures for
the Safe and Sanitary Processing and Importing of Juice; a final rule that
published on January 19, 2001
As part of the rulemaking process, we may also publish advanced notice of
proposed rulemaking documents (ANPRs) and direct final rules.
- Medical Products
When we evaluate applications for approval to market medical products,
we produce reviews of the data collected, analyzed, and submitted by applicants.
On approval of drugs2,
we compile our reviews into an approval package that provides the basis for
the Agency clearance of a decision to approve a product. To provide as much
information as possible to health care practitioners and consumers so they
can make informed decisions about treatment, we make the medical product
approval packages, including generic drug approvals, available on the Internet.
An approval package can range from 100 to more than 1,000 pages, redacted
to remove confidential and trade secret information. Contents usually include
individual discipline reviews; correspondence between the company and FDA;
administrative documents; and labeling. For example, the package for Clarinex
[desloratadine], an antihistamine to treat seasonal allergic rhinitis, was
approved on December 21, 2001. We posted the 500-page package on the Internet
on February 12, 2002.
We also post on the Internet, for animal drug products, an FOI summary
of the approval and for device premarket approvals, a detailed summary
of safety and effectiveness, the approval order, and the draft labeling.
- Food and Color Additives
When we evaluate applications for premarket approval of food additives
and color additives, we produce reviews of the data and analyses submitted
by the applicant. For direct food additives and color additives, we publish
a final rule in the Federal Register
explaining the basis for Agency approval of the product and issuance of a
regulation in the U.S. Code of Federal Regulations. For other food additives,
we announce their approval via Internet listings that are updated at least
monthly. In all cases, the published listings include specifications and
use limitations necessary to ensure the safe use of the product. In addition,
the documents and information that form the basis for Agency approvals are
available under the Freedom of Information Act.
Guidance and Regulatory Assistance
We develop guidance and other policy documents usually with input
from the public, to assist industry, consumers, hospitals, reviewers, and
other health care related organizations and individuals interested in our
statutes and regulations. In addition, we provide procedural guidance to
our field offices. In compliance with our policy involving good guidance
practices, under 21 CFR 10.115, we publish notices announcing the availability
of guidances in the Federal Register, and make the guidances available in the public docket and on the Internet. Some examples of guidances are provided here:
- Guidance to Hospitals, Nursing Homes, and Other Health Care Organizations -- FDA Public Advisory on the risks of death and injury related to medical gas mix-ups (April 2001)
- Small Business Compliance Guides -- guidances to help small
businesses; required by the Regulatory Flexibility Act (5 U.S.C. 602) for
all rulemakings that will have a significant impact on small entities (for
example, Sterility Requirement for Aqueous-Based Drug Products for Oral Inhalation -- Small Entity Compliance Guide, November 2001)
- Formal Dispute Resolution: Appeals Above the Division Level (March 2001)
- Food Security Guidance (January 2002)
- Food Code; 2001 Revision (December 2001)
- Guidance for Industry: Studies to Evaluate the Safety of Residues
of Veterinary Drugs in Human Food: Genotoxicity Testing, VICH GL23
- Guidance on Enforcement Priorities for Single-Use Devices Reprocessed by Third Parties and Hospitals (August 2000)
- The Policy Guidance Help System (January 2000; revised November
2001) -- a computerized system containing all Mammography Quality Standards
Act regulations and final guidance (Internet and as a stand-alone downloadable
- CDRH develops "Plain Talk" guidance on how to comply with our regulations
and provides a unique interactive Website called "Device Advice" to answer
specific device related questions.
- Compliance Policy Guides are issued to the field offices to ensure
that our regulations and policies are followed consistently. These Compliance
Policy Guides are made public and treated as guidances.
- Regulatory Procedures Manual provides FDA procedural guidance and
instruction for use by FDA and the public. The manual is publicly available
and is treated as guidance.
We also develop reports on a variety of topics. Some examples include:
- Managing the Risks From Medical Product Use -- Report to the FDA Commissioner from the Task Force on Risk Management (May 1999)
- Prescription Drug Marketing Act of 1987 -- Report to Congress (June 2001)
- FDA Fiscal Year 2002 Congressional Budget Request (annual report)
- Import Detentions Reports (IDRs) -- IDRs provide information
on the products detained by the Agency (that is, products for which our District
Offices have issued a "Notice of Detention and Hearing"). The IDR is generated
from data collected by FDA's Operational and Administrative System for Import
Support (OASIS) and is updated monthly and is posted on the FDA website for
a period of time (on the average of 12 months). Archived data are not available
on the Internet but is available under the Freedom of Information Act.
- FDA Enforcement Report -- Published weekly, this online
publication contains information on recalls and other actions taken in connection
with Agency regulatory activities.
- Mammography Facility Adverse Event Report -- an annual report
of adverse actions taken against mammography facilities issued to help health
professionals and consumers in evaluating the performance of their mammography
Citizen Petitions and Responses
When citizens petition the FDA to address an issue, we write a response
to the petitioner explaining our position. Although these responses are letters
addressed to individuals or organizations, the petitions and our responses
are made available through the public docket and often on the Internet. In
recent years, we have responded to an average of 250 citizen petitions per
year. For example, on February 15, 2002, we issued a response to a petitioner
asking us to refrain from approving a generic version of an antibiotic (Ceftin)
if the generic drug product's active ingredient were wholly or partially
in crystalline form.
Press Items and Publications
The Agency releases much information through the press and related media. Some examples include:
- News releases (for example, HHS and USDA Release Listeria monocytogenes
Risk Assessment and Listeria monocytogenes Action Plan, Release No. 0020.01,
January 18, 2001; Cape May Foods Recalls Chopped Clams Because of Possible
Health Risk, January 15, 2002)
- FDA Consumer Magazine (bimonthly magazine targeting consumers) and reprints of selected feature articles from FDA Consumer.
- FDA Veterinarian (bimonthly newsletter targeting veterinarians and the food animal industry)
- Frequently Asked Questions: What Can I Do to Protect Myself from Food Poisoning? (Internet only)
IV. � Types of Dissemination Methods
Transparency is one of the
Agency's key goals. It is critical that our audience understand what we do,
how we do what we do, and why we do something. Because our audience is so
diverse, we use a variety of media to disseminate public health and safety
information. Some examples are provided here:
- Oral Presentations in public forums sponsored by FDA or outside
parties, such as professional societies or trade associations (for example,
the FDA Science Forum)
- Internet (medical product approval packages; device summaries
of safety and effectiveness; safety alerts; guidance documents; special issue
papers, such as those on "Online Medicine Sales" and the "Agency's Bioterrorism
- Federal Register (proposed and final rules; notices announcing the availability of guidances; meeting notices; other notices)
- The public docket (citizen petitions and responses; transcripts
of certain meetings; information about advisory committee meetings; public
comments on guidances, regulations, and any other documents that publish
in the Federal Register)
- Videos (on the Internet and for dissemination to outside
organizations and use in meetings and conferences. For example, "Science
and our Food Supply: Investigating Food Safety from Farm to Table")
- CD ROM (for example, Listeria monocytogenes draft risk assessment documents and models)
- FDA's E-mail lists (see topics at www.fda.gov/emaillist.html)
V. � Agency Quality Assurance Policies, Standards, and Processes
As described in the HHS Implementation Plan, as one of the HHS operating
divisions, we have established a number of quality assurance policies, standards,
and processes for ensuring the quality of the information we disseminate
to the public. Our documents undergo a rigorous review and clearance evaluation
according to pre-established procedures, documented in our regulations and
Generally, Agency documents are cleared as follows:
- Document is developed by an individual or team
- Document is circulated to working group members, and often an editor, and comments are incorporated
- Document is circulated and cleared by center managers
- We publish many documents (for example, guidances, proposed rules)
for comment by members of the public, and some documents are reviewed by
outside advisory committees comprising experts in the subject matter of the
- If required by regulation or policy, documents are circulated to
and cleared by the Office of the Chief Counsel, Office of Policy, Planning,
and Legislation, the Department (HHS), and the Office of Management and Budget
In addition to these clearance procedures, we use a number of mechanisms
to ensure the quality of the information we disseminate. FDA reviews the
quality (including the objectivity, utility, and integrity) of information
before it is disseminated and treats information quality as integral to every
step of the development of information, including its creation, collection,
maintenance, and dissemination. Quality, as defined in the OMB Guidelines,
encompasses (1) utility, the usefulness of the information to its intended
users, including the public; (2) objectivity, whether information is being
presented in an accurate, clear, complete, and unbiased manner; and (3) integrity,
the information is protected from unauthorized access or revision.
We only disseminate information that we believe will be useful to the
public or a segment of the public. In fact, often we disseminate information
because members of the public or the regulated industry have requested it.
We develop many guidances as a result of public questions about a specific
topic. We also have processes (21 CFR 10.30) by which members of the public
can petition us to take certain actions, such as initiating rulemaking or
taking specific administrative or enforcement actions. Requests for dissemination
of information also can be submitted through petitions.
We developed our good guidance practice (GGP) policy as a result of public
request. Congress later enacted the policy into law, and we codified our
GGP policy in our regulations at 21 CFR 10.115. The GGPs describe our procedures
for developing, issuing, and using guidance documents and include detailed
procedures on how members of the public can suggest areas for guidance development,
submit drafts of proposed guidance documents, and request the revision or
withdrawal of an existing guidance document. We also maintain a guidance
Agenda, which is a list of guidances we are planning to develop in the coming
year. We post the list on the Internet and publish it annually in the Federal Register.
We publish the Agenda to keep the public up-to-date on guidance development
plans and solicit input from the public on what guidances are needed.
In addition, we are subject to the Freedom of Information Act and
the Electronic Freedom of Information Act Amendments (5 U.S.C. 552), which
provide for the dissemination of information to members of the public and
posting on the Internet certain information that is, or is likely to be,
responsive to multiple information requests.
In accordance with the Regulatory Flexibility Act (5 U.S.C. 602),
the General Services Administration publishes a semiannual regulatory agenda
describing the regulatory actions being developed. The Secretary welcomes
comments on this agenda and suggestions for improvements and initiatives.
As already mentioned, we have many different systems in place to
ensure that the information we disseminate is presented in an accurate, clear,
and unbiased manner. We have a strong commitment to writing all our new documents
in plain English. We have provided plain English training to many of the
employees who write our documents. We also continue to solicit feedback from
stakeholders on our efforts to present written information clearly.
We also take steps to ensure that our regulatory decisions are based
on objective information. If we rely on information submitted to us by third
parties in support of an application for product approval or in a rulemaking
proceeding, we make sure that this information meets the appropriate standards
for quality and objectivity. We have a number of regulations and guidances
that set standards for the generation of information in support of regulatory
decisions. For example, the supporting data may be generated in new research
using good laboratory practices (GLPs)3, in clinical studies subject to Good Clinical Practices (GCPs)4,
in reviews of existing information obtained primarily from peer-reviewed
scientific literature, or obtained from surveys based on widely accepted
scientific survey techniques. Interpretations of quantitative results of
Agency studies are commonly subjected to statistical analyses. Even though
we may be unable to fully disclose the information on which our actions are
based because it has been submitted by a third party with a proprietary interest
in maintaining its confidentiality, we make special efforts to ensure that
the information submitted meets these standards for objectivity and is of
The methods by which we ensure the objectivity of the information
for some of our major regulatory activities are described here.
- Product Review Activities
One key FDA responsibility is the evaluation of data submitted to the
Agency in medical and veterinary medical product applications and in food
and color additive petitions or notifications. In general, firms that want
to market certain products (for example, drugs and medical devices) submit
applications to FDA. These applications contain data or information on which
the firm relies to claim that its product is safe and effective for its intended
uses. We base our decisions about safety and effectiveness primarily on our
analyses of the integrity of the submitted data. When we approve a product
and post a drug review package on the Internet, we are ensuring that our
analyses of the data submitted to us are available for public scrutiny.
We develop regulations and guidance documents to help ensure that
the data submitted to us result from the best available studies, that the
studies are conducted in accordance with sound and objective scientific practices,
and that the data are collected using scientifically accepted methods. For
example, FDA regulations specify the format and content of the clinical studies
that are submitted in support of an application to market a new drug product.
They specify how the data are to be collected and the types of analyses that
are to be performed. In the case of biological products, we have developed
guidance on the format and content of reports on clinical studies that are
submitted to the Agency. Other FDA guidances provide detailed descriptions
of appropriate methodologies, analyses, and procedures.
Since the early 1990s, we have been involved in an intensive international
effort to harmonize technical requirements for the conduct of studies in
support of marketing applications and the content and format of applications
with the goal of allowing the submission of a common application for marketing
around the world. The International Conference on Harmonisation for Technical
Requirements for Registration of Pharmaceuticals for Human Use (ICH) brings
together scientific experts from different countries to develop a consensus
on the appropriate requirements. We also are engaged in international activities
in the device, food, and animal drug areas. For example, International Cooperation
on Harmonisation of Technical Requirements for Registration of Veterinary
Products (VICH) is the veterinary counterpart to ICH. The Global Harmonization
Task Force (GHTF) is working to harmonize device regulations and guidance.
The Codex Alimentarius committees are working to harmonize international
food regulations. Many agreements reached are then embodied in regulations
issued through notice-and-comment rulemaking and in guidance documents that
describe in more detail appropriate ways to comply with the regulations.
As a result of these efforts, most of our actions on product approval applications
are consistent with international standards for data collection and quality
We also are in the process of developing good review practices (GRPs)
for drug reviews with the goal of making our drug product review process
consistent across all divisions in the Center for Drug Evaluation and Research.
A major emphasis of the GRP project is to ensure that the reviews we make
available to the public are consistently formatted and clearly written so
interested individuals can access important health and safety information.
We frequently consult with scientific experts on product approval
applications and broader issues. We have 31 standing Advisory Committees5,
whom we routinely consult on whether the data in particular applications
are sufficient to support an approval decision. As noted above, we incorporate
our approval decisions into drug approval packages and device summaries of
safety and effectiveness that contain our analyses of the submitted data.
These packages and summaries do not include confidential commercial, trade
secret, and other information exempt from disclosure when we place them on
- Food Safety Activities
One of FDA's major areas of responsibility is ensuring the safety
of the food we eat. Food safety activities include research, risk assessment,
inspections, surveillance, compliance, education, and system coordination
activities. We must make sure that the information we provide on food safety
is presented in an accurate, clear, complete and unbiased manner. This means
that the data on which we base our decisions must be collected in an objective
manner using sound scientific principles for data collection.
We collect information to support our food safety activities through
many sources, including research, risk assessment, inspection and surveillance,
peer-reviewed literature, and advisory committee opinions. We conduct in-house
research on a variety of food safety topics and also fund a substantial amount
of extramural research every year. The Center for Food Safety and Applied
Nutrition (CFSAN) participates in collaborative research on processing and
packaging through the National Center for Food Safety and Technology, which
is a consortium of government, industry, and academia, and we coordinate
food safety research activities through a cooperative program with the University
of Maryland. Topics of both internal and external research interest are determined
by CFSAN's 3-year research plan. This plan is developed in conjunction with
other federal agencies to prioritize our research to inform our most critical
food safety efforts and to avoid duplication of effort.
We also gather information for certain food safety activities through
risk assessment. Risk assessments are a very useful tool for evaluating the
benefits of pursuing various rulemaking strategies. To date, we have conducted
or been involved in four risk assessments related to food safety. We conducted
a joint risk assessment with USDA on Salmonella Enteritidis in shell eggs that was published in 1998. More recently, we published risk assessments on the Public Health Impact of Vibrio parahaemolyticus in Raw Molluscan Shellfish and the Relative Risk to Public Health from Foodborne Listeria monocytogenes Among Selected Ready-to-Eat Foods.
We also intend to use the risk assessment model developed for USDA by Harvard
University on bovine spongiform encephalopathy to determine the risk reduction
outcomes of various rulemaking efforts we are considering.
We gather data for FDA food safety activities through use of surveys
designed for specific purposes and advisory committee opinions. The surveys
include the Health and Diet Survey and the Total Diet Study, both of which
are used in our development of safety and exposure assessments for various
compounds. When information is not available through research or literature,
we have several advisory committees that are able to render expert opinions
on particular matters. These committees include the National Advisory Committee
on Microbiological Criteria for Foods, which considers a variety of food
safety issues for FDA and USDA, and FDA's Transmissible Spongiform Encephalopathy
Advisory Committee (TSEAC), which specifically considers issues related to
TSE diseases. Finally, our food safety activities are informed through the
participation of FDA scientists in a variety of professional organizations
such as Codex Alimentarius, International Commission on Microbiological Specifications
for Foods, Institute of Food Technologists, American Society for Microbiology,
the International Association for Food Protection, Society for Toxicology,
American Chemical Society, the National Academy of Sciences, International
Life Sciences Institute, and editorial review boards of several publications
including Journal of Food Protection and Journal of Food Science.
- Adverse Events Analysis for Medical Products
Once products are marketed, we continue to monitor their safety after
approval and disseminate information about their risks to health care providers,
patients, and consumers. We undertake a number of data collection activities
to ensure the objectivity of the information we disseminate on medical products.
- Human Drug and Biological Products
The Adverse Event Reporting System (AERS) is an Oracle-based computerized
information system designed to support the Agency's postmarketing safety
surveillance program for all approved drug and therapeutic biologic products.
The structure of the database complies with the international safety reporting
guidance (E2B Guidance on Data Elements for Transmission of Individual Case Safety Reports, January 19986),
including content and format for electronic submission of the reports from
the manufacturers. The ultimate goal of AERS is to help reduce the risks
associated with medical product use by providing the best available tools
for storing and analyzing safety reports. Information from this system is
used to support decisions to disseminate information of product safety. By
systematizing the submission of data to the Agency, we have greatly improved
the quality (and objectivity) of related decisions and information dissemination
A separate system is used to monitor the safety of vaccines after
approval. The Vaccine Adverse Events Reporting System (VAERS) is a cooperative
program for vaccine safety of the FDA and the Centers for Disease Control
and Prevention (CDC). VAERS is a postmarketing safety surveillance program,
collecting information about adverse events that occur after the administration
of U.S. licensed vaccines. Other systems are in place to monitor the quality
of manufacturing of drugs and biological products and blood related products.
- Medical Devices
We use a variety of tools to identify problems and safety issues
related to medical devices that are approved and being used by health care
practitioners and consumers. Tools include both voluntary and mandatory reporting
of adverse events; monitoring of product performance through other data sources,
such as registries and various research efforts; and the use of both mandatory
and voluntary postmarket studies aimed at examining specific safety issues.
Adverse events related to either product problems or issues associated with
the use of the device are reported by both manufacturers and device users.
Although both the manufacturing and user communities have mandatory reporting
requirements for device-related problems, this surveillance system is virtually
a passive system that depends on the reporter to recognize an event and follow
through in reporting. This passive surveillance system is augmented by a
more active reporting network composed of hospitals and other health care
facilities, where reporting is encouraged and supported through educational
activities and feedback. Adverse event reports are immediately triaged to
quickly identify problems that require urgent attention; all reports are
then reviewed by clinical analysts and others with appropriate expertise
to decide if further follow-up is needed.
- Animal Drugs
An Adverse Drug Event (ADE) report for veterinary medicinal products
consists of either an undesired side effect or the lack of a desired effect
associated with drugs administered to animals. Reports may also involve product
defects and potential harm posed to persons administering or using animal
drugs. For example, in the year 2000, FDA's Center forVeterinary Medicine
reviewed 14,497 ADE reports consisting of: 13,757 undesired side effects
and lack of desired effect; and 740 product defects.
Adverse event reports related to animal drugs are maintained in
a separate database, the Center for Veterinary Medicine's adverse drug event
reporting system (ADERS). This database is used to identify adverse effects
not detected during pre-market testing of FDA-approved animal drugs and to
monitor the performance of drugs not approved for use in animals. The ADERS
depends upon the detection of an adverse clinical event by veterinarians
and animal owners, the attribution of the clinical event to the use of a
particular drug ("suspect" drug), and the reporting of the ADE either to
the manufacturer of the suspected drug or directly to FDA. Data from these
ADE reports are reviewed, coded and entered into the computerized ADERS.
The ADE for veterinary drugs generates current information on the
safety and efficacy of veterinary drugs. These data expand the knowledge
base used in animal drug approvals and ultimately contribute to reducing
the risks associated with veterinary medical products. Summary information
from this system is available to support decisions about disseminating information
on product safety.
- Foods, Including Dietary Supplements, and Cosmetics
We use several reporting systems to identify problems associated with foods, including dietary supplements, and cosmetics.
- The Adverse Reaction Monitoring System (ARMS) collects spontaneous reports
from consumers and health professionals regarding alleged adverse effects
from food products.
- The Special Nutritional Adverse Event Monitoring System
(SN/AEMS) collects spontaneous reports from consumers and health professionals
regarding adverse effects from special nutritional.
- The Cosmetic Adverse Reaction Monitoring System (CARMS)
collects spontaneous reports from consumers and health professionals regarding
alleged adverse effects from cosmetic products.
- CFSAN receives adverse event reports linked to the products it regulates through FDA's MedWatch program.
- Research to Support the Regulatory Functions of FDA
FDA conducts peer-reviewed research that supports the regulatory
functions of the Agency. To accomplish this mission, the FDA seeks feedback
from its stakeholders and partners, including its center scientists, other
government agencies, industry, and academia. In addition, the FDA Science
Board (SB) provides guidance on specific complex and technical issues as
well as emerging issues within the scientific community, in industry, and
academia. The SB conducts ongoing reviews of the research programs themselves
and how these programs are keeping pace with technical and scientific evolutions
in the fields of regulatory science. Their review includes advice on developing
an appropriate research agenda and on upgrading FDA's scientific and research
facilities to keep pace with these changes. The SB is composed of non-governmental
scientists from industry, academia, and consumer organizations. This board
is further supplemented with subject matter experts and scientists representing
all FDA centers. Research programs can be via collaborations through partnerships
with other scientific organizations. Scientific and monetary collaborations
include interagency agreements with other government agencies, Cooperative
Research and Development Agreements and technology transfer with industry,
and grants or informal agreements with academic institutions.
Each FDA Center and Office also uses several strategies to ensure
the quality (including objectivity) of its extramural research and the accuracy
of data collected in association with these studies. For example, study protocols
may be developed collaboratively by principal investigators and program officials.
A project advisory group (PAG) consisting of experts who oversee extramural
research projects in a particular field may be appointed.
To ensure the data are accurate and timely, FDA monitors research
progress at the project level on a recurring basis. FDA quality assurance
staff assess experiments that fall within the scope of FDA's Good Laboratory
practice guidelines for compliance. Additionally, agency scientists publish
research manuscripts, book chapters, and abstracts in recognized, peer-reviewed
scientific journals. FDA's research findings are also presented at national
and international scientific meetings, many of which are sponsored or co-sponsored
by FDA. Many FDA scientists also serve on international scientific advisory
We strive to maintain the integrity of the information we collect
and use, and protect it against disclosure, alteration, loss, or destruction.
We require all of our operating divisions to adhere to a series of Agency
guidelines to ensure our data integrity operations. Guidelines include:
- FDA Staff Manual Guide 3250.17 Data Security\Data Integrity
- Computer Security Act of 1987
- Computer Fraud and Abuse Act of 1986
- Clinger-Cohen Act of 1996
- Federal Managers Financial Integrity Act
- Government Information Security Reform Act (GISRA)
- Office of Management and Budget (OMB) Circular A-130, Appendix III, Management of Federal Information Resources, Revised 2/96
- HHS Automated Information Systems Security Program Handbook (Release 2.0), 5/94
- NIST Special Publication 800-14, Generally Accepted Principles and
Practices for Securing Information Technology Systems (September 1996)
All data submitted for inclusion in our systems must be accompanied by
information about origin, sensitivity, reliability, and the date of most
recent revision. We have systems in place to ensure that data modifications
are accomplished in a managed and controlled manner and that all information
is protected from unauthorized access, revision, corruption, or falsification.
Transactions affecting sensitive or valuable information can only
be processed if the originating individual or system has been validated as
authorized to submit such transactions. Additionally, transactions must be
initiated only through source documents or computerized messages in which
the originating individual or system is clearly identified. All transactions
intended for input into a multi-user production computer system must first
be subjected to reasonableness checks, edit checks, and/or validation checks.
Transactions that fail such checks must either be:
- Rejected with a notification of the rejection sent to the submitter
- Corrected and resubmitted or
- Suspended pending further investigation
Management has established and maintains preventive and detective security
measures that ensure that our information is protected from undetected alteration.
All rejected input transactions are placed in a suspense file and listed
in exception reports until they are successfully resubmitted for processing.
Resubmission and corrections are subject to the same validation procedures
that original input transactions receive. Management reviews the reasonableness
and accuracy of all changes to internal records. If a client or customer
brings record errors to our attention, an investigation of the errors is
The Office of Public Affairs provides guidance to the Agency on
best communications principles and practices to help assure that public messages
are accurate, understandable and consistent with current Agency policies.
The quality, objectivity, utility and integrity of information posted on
the FDA Internet is assured by the internal clearance process used to clear
VI. � Agency Administrative Complaint Procedures
- Format for Submitting Complaints
As described below, we intend to use existing complaint mechanisms to
address complaints from the public concerning our information dissemination
activities. You may use any of the mechanisms outlined below to request correction
of information disseminated by FDA that you believe does not meet the applicable
OMB or HHS Information Quality Guidelines, or this Guidance.
If you request a correction of any information disseminated by us,
we would appreciate it if you clearly designate the request as a request
for correction of information under this guidance and the OMB and HHS Guidelines.
You should use the following format for your request:
- Your name, mailing address, fax number or e-mail address, telephone number,
and organizational affiliation, if any, of the requestor,
- A detailed description of the specific material that needs to be
corrected including where the material is located, i.e., the publication
title, date, and publication number, if any, or the website and web page
address (Uniform Resource Locator or url),
- The specific reasons for believing the information does not meet
applicable OMB, HHS, or FDA guidelines and is in error, and supporting documentation,
- The specific recommendations for correcting the information,
- A description of how the person submitting the complaint is affected
by the information error.
Procedures for Submitting Complaints
We have clear procedures in place to address complaints from the
public. Requests should be submitted to the Agency in accordance with the
procedures described below for dispute resolution (i.e., beginning with the
employee or division that disseminated the information, or by contacting
the center, the Agency, or an ombudsman). To help us track and monitor complaints,
regardless of which procedures you use, we ask that you also send a copy
of your request for correction to:
Office of the Ombudsman
Food and Drug Administration
5600 Fishers Lane
Room 14B03, HF-7
Rockville, MD 20857
FDA regulations at 21 CFR 10.75 provide a mechanism for any interested
person (a person who submits a petition, comment, or objection, or otherwise
asks to participate in an informal or formal administrative proceeding or
court action) to obtain formal review of any Agency decision or action by
raising the matter with the supervisor of the employee who made the decision.
These procedures can be used to submit an initial complaint about an FDA
information dissemination. If the issue is not resolved at the primary supervisory
level, the interested person may request that the matter be reviewed at the
next higher supervisory level. This process may continue throughout the Agency's
chain of command, through the centers to the Commissioner of the FDA.
Regulations for dispute resolution during the application review
process (21 CFR 312.48; 314.103; and 814.42 (d), 814.46(c), 814.112(b), and
808.25 (e)) specify procedures similar to those outlined above. CDRH also
established a Medical Devices Dispute Resolution Panel to hear scientific
disputes. Regulations for CDER and CBER also provide that a sponsor may request
that we seek the advice of outside experts. In addition, we may refer major
issues to an appropriate advisory committee for its recommendations (�� 312.48(c)(3)
Several guidances explaining the dispute resolution process also are available:
- Formal Dispute Resolution: Appeals Above the Division Level (for drug and biological products, February 2000),
- Resolving Scientific Disputes Concerning the Regulation of Medical
Devices, a Guide to Use of the Medical Devices Dispute Resolution Panel (July 2001)
- Medical Device Appeals and Complaints: Guidance on Dispute Resolution (February 1998)
- A Suggested Approach to Resolving Least Burdensome Issues (September 2000)
Finally, 21 CFR 5.200 provides for the establishment of an Agency ombudsman.
We have established an Ombudsman Office within the Office of the Commissioner,
and each center has identified or is identifying an ombudsman. Information
about when and how to contact an Agency or center ombudsman can be found
on our Internet site7.
We encourage interested parties who may be reluctant to contact a program
person in a specific program, division, office or center to feel free to
contact a center or Agency ombudsman.
Existing public comment procedures for rule-makings and other formal
agency actions already provide well established procedural safeguards that
allow affected persons to raise information quality issues on a timely basis.
Accordingly, FDA will use these existing procedures to respond to information
quality complaints that arise in this process.
In cases where the agency disseminates a study, analysis, or other
information prior to the final agency action or information product, requests
for correction will be considered prior to the final agency action or information
product in those cases where in the agency's judgment issuing an earlier
response would not unduly delay issuance of the agency action or information
product and the complainant has shown a reasonable likelihood of suffering
actual harm from the agency's dissemination if the agency does not resolve
the complaint prior to the final agency action or information product.
You should be aware that you bear the "burden of proof" with respect to your request for correction.
FDA's Response to Complaints
Based on a review of the information you provide in your complaint,
we will determine whether a correction is warranted and, if so, what action,
if any, we will take. We will respond to you in a manner appropriate to the
nature and extent of your complaint (for example, by letter, e-mail, fax,
press release, mass mailing) and will indicate whether, and if so how, we
intend to correct the information. We will respond in accordance with the
time frame specified in the complaint mechanism you use. Where a procedure
does not specify a time frame for a response, we will respond within 60 days,
in accordance with the OMB and HHS Guidelines. We will respond by either
issuing a decision or by informing you that more time is required, explaining
why, and providing you with an estimated decision date. In deciding how to
respond, we will consider all of our legal obligations and policies.
Requests for Reconsideration
If you do not agree with FDA's decision about your complaint (including
any corrective action), you may send a request for reconsideration within
30 days of receipt of our decision. You may use any of the Procedures for Submitting Complaints
described above. A request for reconsideration should state the reasons why
you believe the response is inadequate, should be designated as an "Information
Quality Appeal," and should include a copy of your original request and the
agency's decision. The agency will respond to all requests for appeals within
the time frame specified in the procedure you use. Where a procedure does
not specify a time frame for a response to your appeal, we will respond in
a timely manner, in accordance with the OMB and HHS Guidelines.
VII. � Influential Scientific, Financial, and Statistical Information
As illustrated by the number and types of information we disseminate and
the variety of methods we use to disseminate them, it is clear that we strive
for a high degree of transparency with regard to all of our information dissemination
activities. The OMB Guidelines, however, apply special quality standards
to the dissemination of information that is considered influential. Such
information must meet high standards of transparency of the data and methods
used to facilitate the reproducibility of such information by third parties.
As defined below, influential scientific, financial and statistical information
that FDA disseminates will meet the high standards in the OMB Guidelines
for such information.
- Definition of the Term Influential
The term influential information, when used in the OMB Guideline
in the phrase "influential scientific, financial, or statistical information,"
applies when the agency can "reasonably determine that dissemination of the
information will have or does have a clear and substantial impact
on important public policies or important private sector decisions" (67 FR
8452; February 22, 2002). However, because each agency is different, and
there are vast differences in the types of information they disseminate,
each agency has been asked to elaborate on the definition of influential
in the context of their missions and duties, "with due consideration of the
nature of the information they disseminate." As stated in the OMB Guideline
(V.9), "[e]ach agency is authorized to define 'influential' in ways appropriate
for it given the nature and multiplicity of issues for which the agency is
For purposes of this guidance, influential information is
defined as disseminated information that results from or is used in support
of agency actions that are expected to have an annual effect on the economy
of $100 million or more or will adversely affect in a material way the economy,
a sector of the economy, productivity, competition, jobs, the environment,
public health or safety, or State, local or tribal governments or communities.
It should be noted that the definition applies to "information" itself, not
to decisions that the information may support. Even if a decision or action
by FDA is itself very important, a particular piece of information supporting
it may or may not be "influential."
Two examples of what FDA considers to be influential information follow.
- Quality Mammography Standards
On October 28, 1997, we issued a final rule (62 FR 55852) amending our
regulations governing mammography to provide increased assurance of adequate
and consistent evaluation of mammography facilities on a nationwide level
and compliance of the facilities with quality standards. Costs of the regulation
include replacing below standard mammography units and film processors, providing
written results of tests to patients, providing telephone results of tests
to referring physicians, and conducting required weekly image quality tests.
Because this rulemaking was expected to have an annual effect on the economy
of more than $100 million, the information FDA disseminated in support of
this rulemaking would be considered influential information.
- Hazard Analysis and Critical Control Point (HACCP); Procedures for the Safe and Sanitary Processing and Importing of Juice
On January 19, 2001, we adopted a final rule (66 FR 6138) to ensure the
safe and sanitary processing of fruit and vegetable juices. The regulations
mandate the application of HACCP principles to the processing of these foods.
HACCP is a preventive system of hazards control. FDA adopted this rule in
response to a number of food hazards associated with juice products and because
preventive control measures are the most effective and efficient way to ensure
that these products are safe. The final regulation involves costs to the
manufacturers and processors of juice products for implementing procedures
consistent with the regulation that exceeded $100 million. Therefore, the
information disseminated in connection with this rulemaking would be considered
If information that meets the criteria for influential information
is disseminated, the OMB Guidelines provide that it must meet certain higher
standards of transparency and methods to facilitate the reproducibility of
information by qualified third parties. When we disseminate information,
but particularly in those cases involving influential information, we strive
to ensure that the information is accurate and unbiased, as well as substantially
reproducible and replicable. This goal is accomplished by using reliable
data sources and sound analytical techniques, and by employing a high degree
of transparency about the data, methods, measures, assumptions and limitations
used to develop the information to facilitate reproducibility by third parties.
Our goal is to provide a clear explanation of the assumptions and data upon
which we base our conclusions, the criteria used to determine the suitability
of the data for use, the methods used in our analysis, and the conclusions
we have drawn.
Because of legal obligations to maintain the confidentiality of
data supplied by third parties, there may be instances when original or supporting
data may not be available to the public. In such cases, we will disclose
the specific data sources used and the specific quantitative methods and
assumptions employed. We will also conduct especially rigorous robustness
checks of any models used in the analysis and the analytic results so that
there will be a high degree of confidence in the results.
Biases, if any, will be revealed. All assumptions used in the analysis,
the scientific rationale, and data used to estimate the impact of the various
factors influencing the analysis should be clearly stated. This ensures that
biases will be eliminated or minimized and that any introduced biases will
be clearly identified.
Clarity includes ensuring the information disseminated is clear and
understandable. When detailed technical information is needed to provide
sufficient information so that a qualified third party could reproduce the
analysis, the resulting document may be lengthy and difficult the public
to understand. One approach that can provide additional transparency in such
cases is to develop an interpretative summary document as a companion to
the technical analysis. The summary document can provide a non-technical
explanation of the data, process, results, and conclusions in a manner that
the public can understand. As discussed under "Objectivity," we have a strong
commitment to writing all our new documents in plain English. As we revise
and update existing documents, we will ensure that they are written in plain
English. Our goal is to make our written communications more understandable.
A participatory process should be used. The process for
generating information defined as influential should be transparent. One
approach is to invite public comment on the information to be disseminated
and encourage stakeholders to submit scientific data and information that
can be used in preparing the information. As appropriate, we will solicit
advice and opinions of advisory committees as well as peer review from experts
within and outside of the agency. To the extent practicable under confidentiality
laws, we will strive to make supporting data and analyses available to the
public for technical review and comment. This can be accomplished by posting
the information on our web pages and providing printed copies as requested.
Some of the influential information that we disseminate is based
on an analysis of the risks to the public of certain actions or exposures
to hazardous substances. For purposes of this guidance, we are defining risk
as the likelihood that injury or damage is or can be caused by a substance,
technology, or activity. We use risk analysis (the integration of risk assessment
with risk management and risk communication) as a tool to enhance the scientific
basis for all of our regulatory decisions.
The OMB Guidelines provide that in addition to the ordinary standards for
utility, objectivity, and integrity that apply to dissemination of information,
special considerations must be taken into account in certain risk assessments,
i.e., those that provide the basis for the dissemination of influential information.
The Guidelines state that "With regard to analysis of risks to human health,
safety, and the environment maintained or disseminated by the agencies, agencies
shall either adopt or adapt the quality principles applied by Congress to
risk information used and disseminated pursuant to the Safe Drinking Water
Act Amendments of 1996 (SDWA) (42 U.S.C. 300g-1(b)(3)(A) and (B)).
The SDWA risk assessment principles are as follows:
- To the degree that the agency action is based on science, the agency shall use
- the best available, peer-reviewed science and supporting studies conducted
in accordance with sound and objective scientific practices
- data collected by accepted methods (if reliability of the method
and the nature of the decision justify use of the data)
- In the dissemination of public information about risks, the
agency shall ensure that the presentation of information about risk effects
is comprehensive, informative, and understandable.
- In a document made available to the public in support of a regulation, the agency shall specify, to the extent practicable
- Each population addressed by any estimate of applicable risk effects
- The expected risk or central estimate of risk for the specific populations affected
- Each appropriate upper-bound or lower-bound estimate of risk
- Each significant uncertainty identified in the process of the assessment
of risk effects and the studies that would assist in resolving the uncertainty
- Peer-reviewed studies known to the agency that support, are directly
relevant to, or fail to support any estimate of risk effects and the methodology
used to reconcile the inconsistencies in the scientific data
Many of our actions are based on scientific experts' judgments using
available data, are essentially qualitative, and are generally carried out
for non-cancer-causing hazards. Such assessments provide useful answers in
most instances that are sufficient for regulatory purposes, and much more
elaborate, quantitative estimates extrapolating beyond the data are unnecessary.
For example, we may issue regulations on submission requirements for product
approval applications, electronic submission of product labeling, or periodic
reporting by manufacturers of adverse events from drugs; devices; and biologics,
including blood, vaccines, and tissues. Regulations like these do not always
lend themselves to the types of quantitative risk assessments contemplated
by the Safe Drinking Water Act principles.
Other actions are based on research and supporting data that are
generated outside FDA. For example, most product approval actions are based
on scientific studies conducted by sponsors seeking marketing approval in
accordance with our regulations and guidance documents. Our regulations and
guidance documents describe sound scientific practices for conducting human
and animal studies of medical products and analyzing the resulting data.
Most information in these studies is considered confidential commercial information
and is closely held by the sponsors. As a result, formal peer-review of the
data is rare. However, for certain drug approval applications, the safety
and/or effectiveness information is presented to scientific advisory committees
for recommendations. Evaluations of food safety and nutritional data are
also presented to scientific advisory committees.
As a result, we have adapted the general principles for risk assessments
from the SDWA to fit these situations. The principles we intend to apply
to risk assessments involving the dissemination of influential information
affecting product approval actions or regulations that do not lend themselves
to quantitative risk assessment are as follows:
- The Agency will use
- the best available science and supporting studies conducted in accordance
with sound and objective scientific practices, including peer reviewed science
and supporting studies when available
- data collected by accepted methods (if reliability of the method and the nature of the decision justify use of the data)
- In the dissemination of public information about risks, the
Agency will ensure that the presentation of information about risk effects
is comprehensive, informative, and understandable.
In situations requiring a quantitative risk assessment, we generally
follow basic risk assessment principles in the NAS paradigm of 1983. Our
needs for quantitative risk assessments range over a wide variety of hazards
including physical hazards encountered during use of a medical device, food
chemical residues, and antimicrobial resistance genes in bacteria. Thus,
we also ascribe to the statement from NAS when it revisited the risk assessment
process in 1994 (Science and Judgment in Risk Assessment,
NAS 1994): "Risk assessment is not a single process, but a systematic approach
to organizing and analyzing scientific knowledge and information. "In each
of the areas we regulate, we apply risk assessment practices to the specific
task that are widely accepted among relevant domestic and international public
For quantitative risk assessments in support of the dissemination
of influential information, FDA intends to apply the following principles:
- The agency will use-
- the best available science and supporting studies conducted in accordance
with sound and objective scientific practices, including peer reviewed science
and supporting studies when available;
- data collected by accepted methods (if reliability of the method and the nature of the decision justifies use of the data)
- In the dissemination of public information about health risks,
the agency shall ensure that the presentation of information is comprehensive,
informative, and understandable, within the context of its intended purpose.
- In a risk assessment document made available to the public, the agency shall specify, to the extent practicable-
- Each population addressed by any estimate of applicable effects;
- The expected or central estimate of risk for the specific populations affected;
- Each appropriate upper-bound and/or lower-bound risk estimate and
the methodology used to reconcile the inconsistencies in the scientific data;
- Data gaps and other significant uncertainties identified in the
process of the risk assessment and the studies that would assist in characterizing
the uncertainties; and
- Additional studies not used to produce the risk estimate that support
or fail to support the findings of the assessment, and the rationale of why
they were not used.
VIII. � Special Considerations for Agency Dissemination
circumstances, we may need to disseminate information without fully applying
the principles for ensuring the quality, objectivity, utility and integrity
of the information outlined above. Even in these cases, however, FDA intends
to use its internal review process to evaluate the data received and the
information it plans to disseminate to ensure to the degree practicable the
accuracy, objectivity, and transparency of the relevant information, and
will entertain requests for correction after the exigent circumstances have
passed. The specific situations where this may occur are as follows:
- Public Health Emergencies: In the case of a public health emergency,
there may not be time for the Agency to submit relevant information to all
levels of review or review by an Advisory Committee prior to dissemination
of the information.
- Statutory or Other Legal Requirement: If a statutory
requirement, Executive Order, or court order requires immediate implementation
of a policy, we may have insufficient time to apply the OMB requirements
prior to disseminating information relevant to that policy.
- Other Circumstances: There may be unforeseen circumstances
in carrying out our mission that could prevent the Agency from applying all
of the OMB guidelines when disseminating information to the public.
As mentioned above, in all such special circumstances, the Agency will
be particularly careful to use its internal review processes to the extent
practicable when considering the dissemination of relevant information to
IX. � References
Clinger-Cohen Act of 1996.
Code of Federal Regulations (CFR), Title 21, Parts 5, 10, 50, 56, 58, 312, and 314.
Computer Fraud and Abuse Act of 1986.
Computer Security Act of 1987.
Consolidated Appropriations Act, 2001 (Public Law 106-554), Appendix C -- H.R. 5658.
HHS Automated Information Systems Security Program Handbook (Release 2.0), May 1994.
FDA guidance, Formal Dispute Resolution: Appeals Above the Division Level, February 2000.
FDA guidance, Medical Device Appeals and Complaints: Guidance on Dispute Resolution, February 1998.
FDA guidance, Resolving
Scientific Disputes Concerning the Regulation of Medical Devices, a Guide
to Use of the Medical Devices Dispute Resolution Panel, July 2001.
FDA Internet world Wide Web Site Guidelines, rev. March 23, 2001.
FDA Staff Manual Guide 3250.17,Data Security\Data Integrity.
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 et seq.).
Federal Managers Financial Integrity Act.
Food and Drug Administration Modernization Act of 1995 (Public Law 105-115).
Freedom of Information Act and Electronic Freedom of Information Act Amendments (5 U.S.C. 552).
Government Information Security Reform Act (GISRA).
ICH guidance, E2B Guidance on Data Elements for Transmission of Individual Case Safety Reports, January 1998.
NIST Special Publication 800-14, Generally Accepted Principles and Practices
for Securing Information Technology Systems, September 1996.
Office of Management and Budget (OMB) Circular A-130, Appendix III, Management
of Federal Information Resources, rev. February 1996.
Public Health Service Act (42 U.S.C. 201 et seq.).
Regulatory Flexibility Act (5 U.S.C. 601-612).
Safe Drinking Water Act Amendments (Public Law 104-182).
Treasury and General Government Appropriations Act, 2001.
- These guidelines published in the Federal Register on January 3, 2002
(67 FR 369) and were republished with corrections on February 22, 2002 (57
- All product reviews undergo extensive review through a hierarchical process (see Section V).
- Good laboratory practices (GLPs) for nonclinical laboratory studies are discussed in 21 CFR 58.
- Regulations at 21 CFR 312, guidances developed as part of the
Agency's international harmonization efforts (for example, E6 and E8), and
guidances developed by FDA that address clinical development of drugs to
treat specific indications provide requirements and recommendations on good
clinical practice (GCP). In addition 21 CFR parts 50 and 56 address issues
related to informed consent and investigational review boards (IRBs), respectively.
- FDA also administers an HHS Advisory Committee that has 18 panels.
- This guidance is being updated and should be available soon.
- Information on the FDA Ombudsman Program can be found at www.fda.gov/oc/ombudsman/homepage.htm.
Last revised: November 12, 2003