[Federal Register Volume 65, Number 182 (Tuesday, September 19, 2000)]
[Rules and Regulations]
[Pages 56468-56480]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-23887]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 7, 10, 14, 19, 25, 101, 107, 110, 114, 170, 310, 312, 
314, 316, 500, 514, 601, 803, 814, and 860

[Docket No. 99N-4783]


Administrative Practices and Procedures; Good Guidance Practices

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending its 
administrative regulations to codify its policies and procedures for 
the development, issuance, and use of guidance documents. This action 
is necessary to comply with requirements of the Food and Drug 
Administration Modernization Act of 1997 (the Modernization Act). The 
Modernization Act codified certain parts of the agency's current ``Good 
Guidance Practices'' (GGP's) and directed the agency to issue a 
regulation consistent with the act that specifies FDA's policies and 
procedures for the development, issuance, and use of guidance 
documents. The intended effect of this regulation is to make the 
agency's procedures for development, issuance, and use of guidance 
documents clear to the public.

DATES: This rule is effective October 19, 2000.

FOR FURTHER INFORMATION CONTACT: LaJuana D. Caldwell, Office of Policy 
(HF-27), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 
20857, 301-827-7010.

SUPPLEMENTARY INFORMATION:

I. Background

    Under section 405 of the Modernization Act (Public Law 105-115), 
statutory provisions on guidance documents were added to the Federal 
Food, Drug, and Cosmetic Act (the act) in section 701(h) (21 U.S.C. 
371(h)). In the Federal Register of February 14, 2000 (65 FR 7321), we 
(FDA) proposed changes to our existing part 10 (21 CFR part 10) 
regulations to clarify our procedures for the development, issuance, 
and use of guidance documents. Interested parties were given until May 
1, 2000, to comment on the proposal.

II. Description of the Final Rule

A. Comments and Agency Response

    We received 18 comments on the proposed rule, largely from trade 
organizations. The comments we received generally supported the 
policies and procedures described in the GGP's.
1. General Comment
    (Comment 1) One comment recommended that we include in this 
preamble a list of generally accepted principles of a good guidance 
document. The comment nominated several principles for inclusion on the 
list.
    We decline to develop a list of generally accepted principles of a 
``good'' guidance document because we believe that the procedures 
described in Sec. 10.115 reflect generally accepted principles for 
developing, issuing, and using guidance documents. For example, a good 
guidance document represents our current thinking on a matter and 
clearly states that it does not establish legally enforceable 
requirements. We expect each guidance document developed, issued, and 
used under the rule to have the characteristics of a good guidance 
document.
2. Definition of Guidance Documents
    (Comment 2) One comment suggested that we include in the definition 
of guidance documents those documents that describe our current 
policies regarding labeling and promotion.
    In our proposal, we defined guidance documents to include, among 
other kinds of documents, those that relate to the design, production, 
manufacturing, and testing of regulated products and those that relate 
to inspection or enforcement policies. We interpret our definition to 
include guidance documents about product labeling and promotion. We are 
amending the definition in Sec. 10.115(b)(2) to clarify our intent to 
include such topics as subjects for guidance documents.
3. Comprehensive List of Guidance Documents and Guidance Document 
Agenda
    (Comment 3) Several comments discussed the annual publication of 
the comprehensive list of guidance documents and the guidance document

[[Page 56469]]

agenda. Some suggested that we continue to publish these lists on a 
semiannual basis.
    Some comments stated that yearly publication of the comprehensive 
list is acceptable, particularly given that we maintain a current list 
on the Internet.
    One comment stated that annual publication of the guidance document 
agenda would be reasonable if we include the status of each item on the 
list and identify the highest priority guidance documents. Another 
comment recommended that the agenda be posted on the Internet.
    We believe that we provide adequate notice of and access to all 
available guidance documents through two mechanisms. We annually 
publish a comprehensive list of guidance documents in the Federal 
Register and we maintain current (i.e., updated within 30 days of the 
issuance of a new or newly revised guidance document or the deletion of 
an obsolete guidance document) lists of guidance documents on the 
Internet.
    We also believe that we provide adequate notice of the guidance 
document agenda through its annual publication in the Federal Register. 
We will not include the status of each document on the agenda. Each 
document listed on the agenda is being developed; further description 
of document status would not be practical because it would be too 
difficult to differentiate the stages of guidance document development. 
We also do not believe it would be feasible to prioritize the documents 
on the agenda. Often, resources allocated to the development of a 
particular document are diverted to creating guidance documents 
regarding other areas of greater public health need. As a result, our 
priorities may change throughout the year and priorities stated on the 
agenda would not remain accurate for an extended period of time. We try 
to maintain a current (i.e., updated at least semiannually) guidance 
document agenda on the Internet.
    In efforts separate from this rulemaking, we are considering ways 
to enhance our lists of guidance documents maintained on the Internet. 
For example, we are trying to make the lists easier to navigate and 
search. These enhancements may allow you to more efficiently find the 
information you seek on the comprehensive list and the agenda.
    (Comment 4) One comment suggested that we include a brief statement 
describing each document on the comprehensive list.
    We understand that much of the value of the comprehensive list lies 
in its ability to convey the subject matter of each document on the 
list. To provide this information adequately, we plan to ensure that 
the titles or subtitles of documents convey the subject of the document 
more precisely. The comprehensive list could become too cumbersome and 
difficult to use if we added a description of the subject of each 
document. Therefore, we will not include a separate statement 
describing each document on the comprehensive list.
    (Comment 5) A comment stated that the comprehensive list should 
identify guidance documents that have been revised or are currently 
being considered for revision.
    Through the lists that we publish under the procedures previously 
described, we already make the information requested in the comment 
available to the public. On the comprehensive list, we include the date 
of the last revision of a guidance document. This enables you to 
identify those guidance documents that have been revised and the date 
of the revision. In our guidance document agenda, we list guidance 
documents that are under consideration for development or revision.
    (Comment 6) In Sec. 10.115(c), we define two levels of guidance 
documents, Level 1 and Level 2. The two levels of guidance documents 
are subject to different procedures for public participation before 
issuance. One comment suggested that we include the designation for 
each document as Level 1 or Level 2 in the prospective list of guidance 
documents.
    We decline the suggestion to include the Level 1 or Level 2 
designation for all documents on the guidance document agenda. 
Generally, at the time we issue the agenda, we do not know the full 
content of the proposed documents. Thus, a determination of whether a 
document meets the criteria for a Level 1 designation 
(Sec. 10.115(c)(1)) would be premature.
    (Comment 7) One comment suggested that we make the guidance 
document agenda more user-friendly by separating guidance documents on 
cross-cutting issues from those that are technology-specific.
    The purpose of the guidance document agenda is to notify you of 
guidance documents we are developing so you may comment on topics for 
new documents and possible revisions to existing documents. We believe 
the guidance agenda is currently organized to disseminate this 
information most effectively. The documents on the agenda are organized 
by the issuing center or office and generally are further grouped by 
topic categories. By separating guidance documents according to the 
issuing center or office, we enable those of you who have interest in a 
particular issue or type of product (e.g., food products) to focus on 
documents that are being developed in one of the centers or offices 
(e.g., the Center for Food Safety and Applied Nutrition). Guidance 
documents that are being developed in more than one center or office 
will appear on the agenda for each participating center or office. 
Grouping documents on the agenda by subject category (e.g., electronic 
submissions) provides you greater ability to focus on specific areas of 
interest. After the effective date of the rule, we will group all 
guidance documents on the agenda by subject category. This format is 
consistent with the format of the comprehensive list of guidance 
documents. We believe that the format suggested in the comment could 
make the agenda difficult to use because you would not be able to 
concentrate effectively on a particular topic of interest.
4. Public Input
    (Comment 8) One comment suggested that we implement procedures to 
give you the opportunity to comment on designation of a document as a 
Level 1 or Level 2 guidance document before the decision is made.
    We decline to adopt this suggestion. It is in the best interest of 
promoting and preserving the public health that we be able to develop 
guidance documents in a timely and efficient manner. If we solicited 
comment on the level designation for each guidance document, we would 
create a procedural hurdle that could significantly slow the guidance 
development process. This delay in the development of guidance 
documents would not serve us or you.
    We determine whether a document is Level 1 or Level 2 based on the 
criteria described in Sec. 10.115(c). If you disagree with the 
designation of a document (e.g., if you believe that a guidance issued 
as a Level 2 should have been issued as a Level 1), you may send us an 
explanation of your reasons for disagreeing with our determination when 
you comment on the guidance document. If, after issuance, you still 
have a disagreement, you can appeal our designation using the dispute 
resolution process.
    (Comment 9) One comment suggested that we announce the development 
and issuance of Level 2 documents in the Federal Register. Another 
comment recommended that we receive comments on Level 2 guidance

[[Page 56470]]

documents before we issue them as final guidance.
    We decline to amend our procedures for announcing and receiving 
comment on Level 2 guidance documents. When we issue Level 2 documents, 
they are immediately posted on the Internet. Also, their issuance is 
announced in the comprehensive list of guidance documents that is 
published annually in the Federal Register and maintained on the 
Internet.
    Under section 701(h)(1)(D) of the act, we must solicit public 
comments ``upon implementation'' of guidance documents that describe 
existing practices or minor changes in agency policy. We believe the 
provisions of Sec. 10.115(g)(4) are consistent with the act and 
describe adequate provisions for developing and issuing Level 2 
guidance documents.
    (Comment 10) Under Sec. 10.115(g)(1)(v), we may issue a second 
draft of a guidance document and solicit comment on the document after 
providing an opportunity for comment on the first draft. One comment 
stated that two situations usually merit this procedure: When the first 
draft guidance on a medical or scientific topic is highly controversial 
and when the first draft guidance is in conflict with other widely 
recognized sources of scholarly guidance (e.g., International 
Conference on Harmonization guidance, pharmacopeial standards).
    We agree that it may be appropriate for us to issue a second draft 
of a guidance document in the two situations described in the comment. 
In addition, it may also be appropriate for us to issue a second draft 
guidance in other circumstances. For example, if we revise a document 
for clarification, we may want to issue a second draft guidance 
document to receive comment on whether our revisions made the document 
easier to understand.
    (Comment 11) One comment suggested that we allow the public to 
request the deletion of guidance documents that are no longer useful.
    Under Sec. 10.115(f), you can suggest that a document on the 
comprehensive list of guidance documents or on the guidance document 
agenda be revised or withdrawn if you find that the document is no 
longer relevant or accurate. We amended the final rule to explicitly 
state that you can suggest that a guidance be withdrawn 
(Sec. 10.115(f)(4)).
    (Comment 12) Many comments urged us to include a provision in the 
regulation requiring us to provide written responses to public comments 
or suggestions for revising guidance documents. One comment stated that 
we should respond to each suggestion for a revision to an existing 
guidance document within 90 days. Other comments stated that we should 
explain to the public why we changed, or why we did not change, a 
guidance document between the draft and final stages. Some comments 
recommended that we provide general responses to comments grouped by 
topic. Others suggested that we be required to issue a written response 
when certain criteria are met (e.g., when a majority of the comments on 
a guidance document concern the same issue).
    We believe that it is in the public interest to have an efficient 
process for developing guidance documents. The guidance document 
development process would be hampered if we were required to respond to 
each comment. When comments received are very significant or cause us 
to revise a guidance, we often discuss those comments in the notice of 
availability (NOA) for the final guidance or in the final guidance 
document. We intend to continue this practice. However, making a firm 
commitment to provide a written response to all comments when issuing a 
final guidance would unnecessarily delay the issuance of the document.
    (Comment 13) Two comments suggested that we be required to respond 
to your proposals for draft guidance documents.
    We agree with this comment. When you have taken the time to develop 
a guidance document and submit it to us for review, you should receive, 
at a minimum, an acknowledgment of receipt of the document. Therefore, 
we are now accepting guidance document submissions at the Dockets 
Management Branch. If you submit a document to us, you should designate 
it as a ``Guidance Document Submission,'' include the name of the 
center or office with oversight over the subject matter covered by the 
guidance document, and submit the document to the Dockets Management 
Branch (HFA-305), 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    The Dockets Management Branch will ensure that the document is 
assigned a public docket number and it is sent to the appropriate 
office or center. All proposed guidance documents will be available 
through the public docket. We will send you a written acknowledgment 
that we have received your document, and to the extent feasible, we 
also will inform you of our actions regarding the document you have 
submitted. These changes to the final rule are included in revised 
Sec. 10.115(f)(3).
    (Comment 14) We received many comments on early collaboration and 
meetings to discuss guidance documents as they are being developed. 
Generally, the comments were very supportive of our efforts to 
facilitate early interaction with you. Some comments suggested that we 
issue a clear policy about the procedures for collaboration and early 
meetings. One suggested that we provide a means for industry to 
recommend a particular collaborative approach for a guidance document 
under development. Another comment recommended that we provide 
opportunities for you to engage in ``real time dialogues'' with us 
before we begin to write a draft or final guidance. The comment noted a 
number of avenues for this type of collaboration, including joint task 
forces, public and private meetings, advisory committee meetings, and 
e-mail correspondence. Other comments stated that certain agency 
components had refused to meet about a guidance document before that 
document was issued in draft. One comment specifically requested that 
we use more mandatory language regarding preproposal collaboration with 
you.
    We agree that early collaboration (i.e., input from you in the 
early stage of developing the approach we will take in a new or revised 
guidance document) can be a very valuable tool in developing regulatory 
guidance. We have created several mechanisms to encourage early input, 
including the following:
     We provide an opportunity to suggest new or revised 
guidance.
     We publish an agenda of the guidance documents that we are 
working on and request your comments on the agenda.
     We notify you when we issue draft guidance documents and 
request your comments on the drafts.
     We may hold meetings or workshops even before we develop a 
draft document.
    We encourage your involvement in our development of guidance 
documents. Often, we develop guidance documents based on your 
suggestions. We solicit your comments on draft guidance documents 
because our views are not yet finalized and we want your input on the 
contents of the final guidance.
    We understand that you would like to meet with us more regarding 
the development of guidance documents. Our policies on meeting with the 
public on guidance development are evolving. In efforts separate from 
this rulemaking, we are exploring ways to increase this interaction 
within the confines of applicable statutes and regulations, and

[[Page 56471]]

are considering our need to provide all interested parties access to 
the process, our interest in issuing documents in a timely manner, and 
our resource constraints. We welcome your suggestions in this area.
    (Comment 15) One comment proposed establishing a mechanism in 
Sec. 10.115(g) whereby companies can fund a market research initiative 
that would permit us, through questionnaires, focus groups, and other 
techniques, to obtain input on proposed policies directly from 
patients, doctors, and other stakeholders.
    We welcome input from patients, doctors, and other stakeholders. We 
believe that the procedures described in Sec. 10.115, especially our 
increased use of the Internet to disseminate information, provide 
adequate avenues for patient, doctor, and stakeholder involvement in 
the development of our policies. We decline at this time to establish a 
funded market research initiative because administering such a program 
would divert personnel resources from other public health priorities.
    (Comment 16) One comment suggested that we consider interactive 
techniques, such as town hall meetings, that may encourage industry 
input on setting priorities for the development of guidance documents 
listed on the agenda.
    We welcome industry input on prioritizing our development of 
guidance documents. We believe that the procedures described in the 
GGP's on the guidance document agenda, especially our increased use of 
the Internet to disseminate the agenda and our request for comments on 
the agenda, provide adequate avenues for industry and others to assist 
us in prioritizing guidance documents. Furthermore, the agenda is only 
one of several mechanisms we use to solicit input on prioritizing the 
guidance documents we are developing. For example, we may participate 
in public meetings and public hearings and may raise guidance document 
issues at advisory committee meetings. At this time, we decline to 
change the GGP's in the manner suggested but will continue to consider 
avenues for encouraging input at all stages of guidance development.
    (Comment 17) One comment suggested that any proposed guidance 
documents submitted to advisory committees be made public in a manner 
that provides sufficient time for review before the meeting.
    We agree that proposed guidance documents submitted to advisory 
committees should be made public as soon as practicable to allow for a 
review of those materials. We are working to ensure that this 
information is made available in a timely manner.
5. Legal Effect of Guidance Documents
    (Comment 18) We received several comments on the legal effect of 
guidance documents. A number of comments referred to the statement in 
the proposed regulation that we are willing to discuss an alternative 
approach with you to ensure that it complies with the relevant statutes 
and regulations (Sec. 10.115(c)(3)). The comments stated that if a 
guidance document is not binding, the discussion of alternative 
approaches should not be required.
    The comments misinterpreted the intent of the statement in 
Sec. 10.115(c)(3). If you take an alternative approach, you are not 
required to discuss that approach with us. Instead, we are offering our 
assistance to make sure that any alternative approach you take meets 
the appropriate statutory or regulatory requirements. Discussing 
alternative approaches may help you understand our interpretation of 
the applicable statutes and regulations and may further our 
understanding of the merits of your approach.
    (Comment 19) Two comments suggested that compliance with a guidance 
document should provide a company with a safe harbor from FDA 
enforcement action. The comments recommended that we change the 
regulation to require us to amend, or at least publish a proposal to 
amend, a guidance document before initiating an enforcement action 
against a company that acted in accordance with a guidance. The 
comments also noted that if we do not provide a safe harbor from 
enforcement, at a minimum, a company's action in accordance with a 
guidance document should be evidence of the company's intent to comply 
with our regulations.
    Section 701(h)(1)(B) of the act provides that guidance documents 
``shall not be binding on the Secretary.'' Creating a ``safe harbor'' 
in a guidance document that would preclude us from taking action would 
impermissibly bind us. In issuing enforcement-related guidance 
documents, we express our current thinking regarding regulatory matters 
and believe this provides useful information. However, you always 
remain independently responsible for complying with applicable statutes 
and regulations. Whether you have complied with the law is determined 
from the facts of each case.
    (Comment 20) We received two comments suggesting that we clarify to 
our staff that FDA may not cite failure to follow a guidance document 
in any observation on Form FDA 483 (List of Inspectional Observations).
    We agree with this comment. Guidance documents are not binding. An 
enforcement action may be taken only when we find a violation of 
statutory or regulatory requirements. If a guidance document contains a 
reference to a regulatory or statutory requirement, then enforcement 
action may be taken if the regulation or statutory requirement is 
violated. Of course, enforcement action may be taken if a requirement 
in a regulation or statute is violated whether or not there is a 
reference to the requirements in any guidance document. We discuss this 
issue in the GGP training we provide employees under Sec. 10.115(l)(1).
    (Comment 21) We received one comment on how we should interpret a 
draft guidance document during the time that it is out for comment, 
before the document has been finalized. The comment suggested that we 
maintain three categories of guidance documents: Draft, approvable, and 
approved.
    We believe the provisions of Sec. 10.115(g) sufficiently describe 
both the process for issuing draft Level 1 guidance documents for 
comment and the process of implementing Level 1 guidance documents 
without comment when prior public participation is not feasible or 
appropriate. We do not believe that adding more categories will improve 
the process; instead, it could confuse the users of the documents. 
Early in the process of developing the GGP's, comments strongly urged 
the agency to streamline and simplify the nomenclature for guidance 
documents. We have done so. If you are concerned about FDA's thinking 
on an issue that is reflected only in a draft guidance, you should 
contact the appropriate office within FDA to discuss the issue.
    While a draft Level 1 guidance document is out for comment, you may 
be concerned that the guidance will change based on comments received. 
Because a guidance document represents the agency's current thinking on 
a subject but it is not ever binding on FDA or outside parties, you 
should not rely on any guidance document, draft or final. If you have 
questions about compliance with statutory or regulatory requirements, 
you can discuss those issues with an FDA employee.
6. Standard Elements
    (Comment 22) We received two comments suggesting that the 
designation as Level 1 or Level 2 be a standard element of each 
guidance document.

[[Page 56472]]

    We believe that the comment misinterpreted the significance of the 
Level 1 or Level 2 designation. The designation of a guidance as Level 
1 or Level 2 is only relevant when a guidance document or revision to a 
guidance document is being developed. The designation is used to 
indicate whether the proposed document or revision is significant 
enough to warrant public comment before implementation. If the Level 1 
or Level 2 determination remains with the document as a standard 
element, it may be confusing. For example, if we make a very minor 
revision to a guidance document that contains highly significant 
issues, this revision would warrant a Level 2 determination for the 
purposes of receiving comments. Affected parties should not assume that 
the document contains issues that are less significant because of the 
Level 2 designation, but rather that the change being made is not 
significant.
    (Comment 23) One comment suggested that we require as an element in 
each guidance document a statement that explains why the document is 
needed.
    Guidance documents should be issued only when a need for guidance 
exists. In each document, we generally include a background section 
that states the reason for its issuance. We will continue to do this in 
the future. However, although we acknowledge the utility of stating the 
need for each guidance, we do not believe the statement should be 
required. The advice we provide in a guidance document represents our 
current thinking, regardless of whether we adequately explain the need 
for the guidance. Therefore, we decline to make this information a 
required element in our guidance documents.
    (Comment 24) One comment suggested that statements of nonbinding 
effect be prominently displayed on all guidance documents.
    We agree with the comment. It is critical that all parties 
understand that guidance documents do not bind us or you. We are 
amending the regulation at Sec. 10.115(i)(1)(iv) to require that a 
statement of the guidance document's nonbinding effect be displayed on 
prominently each document. In the future, this statement will be placed 
immediately below the title of the guidance document on the first page 
of text and it will be in prominent (e.g., bold or italic) print.
7. Our Procedures
    (Comment 25) In the proposed rule, we stated that we would not seek 
public input prior to implementing a Level 1 guidance document if we 
determine that prior public participation is not feasible or 
appropriate (proposed Sec. 10.115(g)(2)). Several comments discussed 
this exception to the prior public participation requirement. Two 
comments stated that we should use the exception only in rare and 
extraordinary circumstances. Other comments suggested that we only use 
this exception in cases where there is a real, demonstrated public 
health emergency, not just a theoretical emergency. Another comment 
stated that when we use these procedures, we should provide a statement 
of our reasons for not soliciting prior public participation.
    Under section 701(h)(1)(C) of the act, we must ensure public 
participation prior to the implementation of guidance documents unless 
we determine that such prior public participation is not feasible or 
appropriate. As discussed in the preamble to the proposed rule, 
Sec. 10.115(g)(2) reflects the standard stated in the statute (65 FR 
7321 at 7324). We anticipate that this exception will generally be used 
when: (1) There are public health reasons for the immediate 
implementation of the guidance document; (2) there is a statutory 
requirement, executive order, or court order that requires immediate 
implementation; or (3) the guidance document presents a less burdensome 
policy that is consistent with public health. We agree that we should 
explain why a document is being issued without prior public 
participation when we issue the document. Generally, this explanation 
is included in the NOA for the guidance document. We will continue to 
follow this procedure in the future.
    (Comment 26) One comment suggested that we adopt a 30-day grace 
period for Level 1 guidance documents issued without prior public 
participation.
    A grace period would not be needed for a guidance document because 
guidance is not binding on us or you. We do not enforce guidance 
documents; we enforce applicable statutory and regulatory requirements.
    We are committed to ensuring that you have the opportunity to 
participate in guidance document development as much as possible. 
Therefore, we will issue a Level 1 guidance document without prior 
public participation only if it is not feasible or appropriate to 
solicit your comments (e.g., a public health emergency or a court order 
requires the issuance of the guidance and we need to make the document 
available to the public as quickly as possible). A delay in 
implementation would not be appropriate in such circumstances.
    (Comment 27) One comment noted that there are times when a Level 2 
guidance document may become controversial and suggested that we adopt 
procedures whereby a Level 2 document could be withdrawn, redesignated 
as a Level 1 document, and reissued in draft for public comment.
    We believe that the GGP's implicitly provide us with the ability to 
act as the comment describes. If our initial determination to issue a 
guidance document or amended guidance document using Level 2 procedures 
proves to be an incorrect decision because the document is highly 
controversial when issued, we may withdraw the guidance document and 
reissue it as a draft guidance document following Level 1 procedures 
(i.e., publish an NOA in the Federal Register for the draft guidance 
document and solicit comments on the draft). We do not believe the rule 
should be amended to reflect these procedures.
    (Comment 28) Two comments suggested that we use the Internet to the 
greatest extent possible to disseminate guidance documents. Several 
comments specifically requested that we allow submission of comments on 
guidance documents through e-mail.
    We use the Internet as our primary means of disseminating guidance 
documents. In most cases, newly issued or revised guidance documents 
are available on the Internet at the same time they are available 
through other means (e.g., through the Dockets Management Branch). We 
are developing new ways to use Internet technology to enhance our 
ability to disseminate information to the public. In particular, we are 
developing a system for providing access to all documents on the 
Internet and facilitating e-mail submission of comments on guidance 
documents.
    (Comment 29) One comment suggested that we publish a new guidance 
document within 30 days of changing our current thinking on a given 
subject. This comment also urged us to amend the regulations to clarify 
that the information in a guidance document may be relied on to be 
currently acceptable to FDA.
    We agree that guidance documents should reflect our current 
thinking on a given subject. We try to ensure that our documents are 
current. However, we allocate our limited resources to the areas of 
greatest public health need. Although GGP's help to ensure a greater 
level of public participation in guidance development, following these 
procedures often means that it takes

[[Page 56473]]

longer to issue guidance documents. Therefore, we will not commit 
ourselves to issuing guidance documents within a specific timeframe. We 
need flexibility to allocate our resources as we see fit, for example, 
to an area that presents more significant public health issues.
    In response to the second part of the comment, Sec. 10.115(d)(3) of 
the final rule clearly states that guidance documents represent the 
agency's current thinking on the subject of the document, and that FDA 
employees may depart from guidance documents only with appropriate 
justification and supervisory concurrence.
    (Comment 30) One comment stated that if we depart from a guidance 
document on multiple occasions, we should consider revising the 
document. A similar comment noted that when a change in policy allows 
deviation from a guidance document, we should amend the document to 
indicate the existence of limited exceptions.
    As discussed previously, guidance documents should represent our 
current thinking on the matters discussed in the documents. Our 
consistent deviation from a guidance document might suggest that we 
should revise it. Furthermore, we should amend guidance documents to 
clarify any changes in our interpretation of a guidance document. As 
resources allow, we will continue to update and revise guidance 
documents to reflect our current thinking.
    (Comment 31) One comment suggested that we provide written 
justification for deviating from a guidance document.
    As discussed in the preamble to the proposed rule (65 FR 7321 at 
7327), we agree that our employees should not deviate from guidance 
without appropriate justification and supervisory concurrence. However, 
because guidance documents are not legally binding, we do not believe 
that we should provide written notice stating the reasons for such 
deviations. If we are asked to explain why we are deviating from a 
guidance document, we will do so.
    (Comment 32) One comment suggested that we consolidate guidance 
documents addressing identical topics, those covering one topic that 
applies to several premarketing application types, and those containing 
identical premarketing application elements for similar product lines. 
This comment also noted that some currently available guidance 
documents are obsolete, redundant, or no longer appropriate.
    We consolidate similar guidance documents when feasible and 
appropriate. Our primary concern is to issue documents that represent 
our current thinking on a particular matter. On balance, the benefit of 
having consolidated guidance documents is often outweighed by the 
burden of reissuing the documents. Furthermore, consolidated documents 
may be too cumbersome to be user-friendly.
    We agree that documents that are obsolete, redundant, or no longer 
appropriate should be revised or withdrawn so they do not create 
confusion. During the past few years, we have tried to eliminate or 
revise documents when appropriate, given our resource constraints. We 
will continue this practice. Section 10.115(f) provides you with an 
opportunity to suggest documents that should be eliminated or revised.
    (Comment 33) One comment noted that we should not use guidance 
documents as a replacement for notice-and-comment rulemaking.
    We agree with this comment and believe that in certain 
circumstances regulations should be issued, while in other 
circumstances issuance of a guidance document is more appropriate. We 
carefully consider whether a document that contains binding 
requirements should be issued. This decision ultimately determines 
whether it is more appropriate for us to issue regulations or guidance 
on a given subject.
    (Comment 34) We received several comments on our dispute resolution 
process. One comment suggested that we establish a systematic review 
process for external auditors to examine the decisions of our staff and 
to determine whether the application of a guidance document was 
appropriate. One comment encouraged us to develop an appeals process to 
address complaints about our development and use of guidance documents, 
stating that this appeals process is required by the Modernization Act. 
Other comments suggested that we describe the normal appeals process 
for disputes about the content of a guidance document in this final 
rule.
    We appreciate the importance of providing effective mechanisms for 
dispute resolution and recognize that guidance documents need to be 
developed, issued, and used in a manner that is consistent with GGP's. 
However, we believe that an evaluation of our current dispute 
resolution system by an external auditor is unnecessary. We are 
required under section 405 of the Modernization Act to ensure that an 
effective appeals mechanism is in place to address complaints about our 
development and use of guidance documents. We believe that we have such 
a mechanism in place.
    If you believe that an FDA staff member did not follow the GGP's, 
including any situation where you believe a staff member treated a 
guidance document as binding, under Sec. 10.115(o) you can raise the 
issue with that staff member's supervisor. If the issue cannot be 
resolved, you can continue raising it through the chain of command. 
These procedures complement our dispute resolution regulation in 
Sec. 10.75 (internal review of decisions). You can also use the 
procedures in Sec. 10.75 to appeal a decision on the GGP's. We are 
amending the final rule to provide another means for raising an issue 
about our implementation of the GGP's. Under amended Sec. 10.115(o), 
you can contact the ombudsman of the center or office with which you 
have a dispute and seek the ombudsman's assistance in resolving the 
issue. Finally, if you feel that you are not making progress or if you 
are unable to resolve the issue at the center or office level, you can 
request that our Chief Mediator and Ombudsman become involved. Each 
center and office has made or will make available its own guidance 
documents on specific procedures for resolving disputes.
    You may also petition us under Sec. 10.30 (citizen petitions) and 
request that we formally resolve your issue.
    (Comment 35) One comment suggested that we explicitly state that 
guidance documents apply to all parties who work in the area addressed 
by the document. The comment stated that historically, we have not 
applied guidance documents uniformly to work undertaken by different 
individuals.
    In each document, we generally include an introductory section that 
states the intended audience of the guidance document (e.g., 
applicants, reviewers). The guidance document applies to all members of 
the intended audience. If you believe that an FDA staff member is not 
interpreting the document appropriately, you can follow the dispute 
resolution procedures described previously and in Sec. 10.115(o).
    (Comment 36) One comment suggested that we post the names and 
titles of the supervisors for each center/office on our Internet home 
page (www.fda.gov).
    We agree that information about the individuals to contact 
regarding the resolution of a dispute should be readily available. This 
information is currently on the Internet for all of the centers and 
offices. You can find the organizational charts at the following 
Internet addresses:

[[Page 56474]]



                                                     Table 1.
----------------------------------------------------------------------------------------------------------------
                    Center or Office                              Organizational Chart Internet address
----------------------------------------------------------------------------------------------------------------
Center for Biologics Evaluation and Research             www.fda.gov/cber/inside/orgchart.pdf
Center for Devices and Radiological Health               www.fda.gov/cdrh/organiz.html
Center for Drug Evaluation and Research                  www.fda.gov/cder/cderorg.htm
Center for Food Safety and Applied Nutrition             vm.cfsan.fda.gov/ centsdms/orgchart.html
Center for Veterinary Medicine                           www.fda.gov/cvm/fda/mappgs/contactcvm.html
Office of Regulatory Affairs                             www.fda.gov/ora/inspect__ref/iom/IOMORADIR.html
----------------------------------------------------------------------------------------------------------------

    (Comment 37) In Sec. 10.115(l)(2), we state that our centers and 
offices will monitor the development and issuance of guidance documents 
to ensure that GGP's are being followed. One comment suggested that we 
consider using a center ombudsman (e.g., the new ombudsman in the 
Center for Devices and Radiological Health) to perform this monitoring 
function.
    We agree that it is important to ensure that guidance documents are 
developed and issued consistently by all centers and offices. 
Therefore, each center and office will designate one or more persons to 
monitor the development and issuance of its guidance documents. The 
center or office can designate the ombudsman and/or other individuals 
to perform this function.
    As discussed previously, under Sec. 10.115(o) you may seek the 
assistance of a center or office ombudsman or the Office of the Chief 
Mediator and Ombudsman if you believe that someone at FDA is not 
following the GGP's.
    (Comment 38) One comment said that if we are serious about ensuring 
that our employees do not develop policy through speeches and other 
informal mechanisms, we should update and enforce internal written 
procedures on this subject. Another comment suggested that we state 
that our employees may not make statements at advisory committee 
meetings as a means to communicate new regulatory expectations.
    We stated in the proposed regulation at Sec. 10.115(e) that we may 
not use documents and other means of communication that are excluded 
from the definition of guidance document to informally communicate new 
or different regulatory expectations to the public for the first time. 
We are maintaining this language in the final rule. Part of our GGP 
training for employees includes the understanding that policy is not to 
be communicated initially to a broad audience through speeches. 
Statements at advisory committee meetings often depend on the context 
of the statement. If, for example, a marketing application under 
consideration raises a novel issue, it may be appropriate for an FDA 
employee to comment on that issue as it relates to a specific 
application during a public advisory committee meeting. If there are 
questions raised by an advisory committee member that are not about a 
specific application, an individual employee can express a view, but 
this would not reflect official agency policy.
    (Comment 39) One comment suggested that we examine our processes 
for training, evaluation, and related internal guidance to ensure that 
our directives to staff reinforce the appropriate use of guidance 
documents.
    Section 701(h)(1)(B) of the act requires us to provide training for 
employees on how to develop and use guidance documents. We train 
employees about guidance documents in new employee orientation and/or 
as part of continuing employee education and training programs. 
Internal procedural documents are examined before they are issued to 
ensure that they are consistent with our GGP policies.
    (Comment 40) Several comments recommended that there be better 
internal coordination among centers in the development, issuance, and 
use of guidance documents. In particular, one comment suggested that 
FDA ensure closer communication among centers, clarify the role of each 
center in oversight, and communicate clearly the enforcing center's 
expectation of a firm's responsibility for following a guidance 
document.
    One comment referred to the ``enforcing'' center. We note that 
guidance is not enforceable. It is not binding on you or us.
    In section 123 of the Modernization Act, Congress directed us to 
minimize differences in the review and approval of products required to 
have approved biologics license applications under section 351 of the 
Public Health Service Act (42 U.S.C. 262) and products required to have 
approved new drug applications under section 505(b)(1) of the act (21 
U.S.C. 355(b)(1)). We have made a concerted effort to minimize those 
differences and otherwise streamline the regulation of products that 
may involve dual jurisdiction of our centers. As part of this effort, 
we have issued numerous joint guidance documents.
    We also have several checks within the guidance document 
development process that help to ensure that there is communication 
among centers on multicenter topics. For example, Level 1 guidance 
documents that describe new legal interpretations or significant 
changes in our policy are reviewed by the Office of the Chief Counsel 
and the Office of Policy before issuance. These offices are aware of 
cross-cutting issues and can ensure appropriate coordination.
    (Comment 41) A comment suggested that we define the minimum levels 
of approval authority for sign-off on guidance documents.
    We understand that having the appropriate level of clearance on 
guidance documents is important for purposes of quality control and to 
achieve the greatest level of consistency across the agency. However, 
we believe that we should maintain flexibility by providing discretion 
to the various centers and offices to determine their appropriate 
levels of clearance. Therefore, we decline the suggestion to mandate 
minimum levels of approval authority for guidance documents.
    (Comment 42) One comment suggested that we clarify the status of 
advisory opinions and determine whether they are guidance documents.
    We issue advisory opinions under Sec. 10.85. We anticipate 
modifying Sec. 10.85 and explaining the effect of Sec. 10.115 on 
previously issued advisory opinions in a separate rulemaking effort. As 
such, the comment is outside the scope of this rulemaking.
    (Comment 43) Two comments suggested that we clarify the status of 
guidelines. One recommended that we designate them as Level 1 guidance.
    Our ability to issue guidelines was described in Sec. 10.90(b). In 
the conforming amendments to the proposed rule, we proposed to delete 
all references to guidelines in Sec. 10.90(b) and replace the provision 
with the statement that guidance documents will be developed, issued, 
and used

[[Page 56475]]

according to the requirements at Sec. 10.115. On further consideration, 
we have decided not to include a provision on guidance documents in 
Sec. 10.90(b) because it is not necessary to state that guidance 
documents will be regulated under Sec. 10.115. Therefore, we are 
removing and reserving Sec. 10.90(b).
    As described in the preamble to the proposed rule, all guidelines 
are now treated as guidance documents (65 FR 7321 at 7326). Because we 
no longer issue guidelines, we need not determine whether they would 
warrant a Level 1 or Level 2 determination. If any documents previously 
issued as guidelines are amended, we will follow the same procedures 
used for amending guidance documents (i.e., we will determine whether 
modifying the document meets the criteria for a Level 1 or Level 2 
change).
    (Comment 44) One comment asked whether we ensure that all broadly 
disseminated letters are posted on the Internet and whether we have 
procedures in place for quality control of this process.
    We currently post all broadly disseminated letters on the Internet, 
including ``Dear Doctor'' letters, and letters that are broadly 
circulated but do not provide the agency's current thinking on a 
regulatory issue. All broadly disseminated letters that fall under the 
definition of guidance documents are issued under the procedures 
described in this rule. Each center and office has personnel who 
determine whether a broadly disseminated letter meets the criteria for 
a guidance document and should be issued as such.
    (Comment 45) One comment asked whether we post on the Internet 
letters containing information about public health alerts.
    In Sec. 10.115(b)(3), we clarify that guidance documents do not 
include general information documents provided to consumers or health 
professionals. Public health alerts fall within this category of 
documents. While public health alerts are not guidance documents, and 
the comment is beyond the scope of this rulemaking, we do post such 
information on the Internet, as appropriate.
    (Comment 46) One comment questioned whether we have a mechanism in 
place for receiving and evaluating suggestions for novel or more 
efficient procedures. The same comment suggested that we create a data 
base that contains all correspondence issued to a company. The comment 
also requested that we post on the Internet all of our speeches and the 
preamble to the September 29, 1978, current good manufacturing 
practices (CGMP's) regulation.
    These comments are beyond the scope of this rulemaking.

B. Guidance Documents Resulting From International Negotiations

    In addition to amending the final rule as described previously in 
response to comments, we are making one revision that will improve our 
ability to participate in international negotiations on guidance 
documents. As described in Sec. 10.115(i)(1) and (i)(2), a guidance 
document must: (1) Include the term ``guidance,'' (2) identify the 
center(s) or office(s) issuing the document, (3) identify the activity 
to which and the people to whom the document applies, (4) include a 
statement of the document's nonbinding effect, (5) include the date of 
issuance, (6) note if it is a revision to a previously issued guidance, 
and (7) contain the word ``draft'' if the document is a draft guidance. 
Furthermore, guidance documents must not include mandatory language 
such as ``must'' or ``required'' unless we use those words to describe 
a statutory or regulatory requirement.
    In accordance with our mission, we actively participate in 
international efforts to reduce the burden of regulation, harmonize 
regulatory requirements, and achieve appropriate reciprocal 
arrangements (section 903(b)(3) of the act 21 U.S.C. 393(b)(3)). 
Through these efforts, we frequently negotiate guidance documents with 
representatives of other countries. For example, our participation in 
the International Conference on Harmonisation of Technical Requirements 
for Registration of Pharmaceuticals for Human Use (ICH) has allowed us 
to work with representatives of regulatory authorities from Europe, 
Japan, and the United States and experts from the pharmaceutical 
industry in the three regions to develop numerous guidance documents on 
the regulation of human drug and biological products.
    When draft documents are negotiated with representatives of other 
countries, we seek public comment on the resulting documents. We 
believe it is important to publish draft documents for comment at the 
same time as other countries so we may review the public comments and 
resume negotiations in a timely manner. However, other countries do not 
follow our GGP's; therefore internationally negotiated draft documents 
often do not comply with all of the provisions of Sec. 10.115(i)(1) and 
(i)(2). For example, documents negotiated through ICH do not include 
the Center for Drug Evaluation and Research or the Center for Biologics 
Evaluation and Research as issuing offices. Differences in language and 
use of certain terms often result in wording that implies the draft 
documents establish mandatory requirements. Therefore, to facilitate 
the development and issuance of draft documents resulting from 
international negotiations, we have modified the final rule to state 
that when issuing ``draft'' guidances that are the product of 
international negotiations, we need not apply the provisions of 
Sec. 10.115(i)(1) and (i)(2). However, we recognize and the final rule 
provides that final guidances that are the product of international 
negotiations must comply with all of the provisions of Sec. 10.115(i). 
We anticipate that this amendment will provide many advantages, 
including our ability to: (1) Provide more time for public comment on 
draft guidance documents that are the result of international 
negotiations, (2) receive more public comments on these draft 
documents, (3) negotiate based on issues raised in public comments more 
effectively, and (4) resume international negotiations in a timely 
manner.

III. Conforming Amendments

    We refer to guidelines issued under former Sec. 10.90(b) throughout 
our regulations. Because we are revising our administrative regulations 
by deleting guidelines and adding guidance documents issued under 
Sec. 10.115, we are making conforming amendments to 21 CFR parts 7, 10, 
14, 19, 25, 101, 107, 110, 114, 170, 310, 312, 314, 316, 500, 514, 601, 
803, 814, and 860 to reflect our changes. We are also adding 
Sec. 601.29, Guidance documents, to the biologics regulations, to be 
consistent with Secs. 312.145, 314.445, and 814.20. These conforming 
amendments will ensure the accuracy and consistency of the regulations.

IV. Environmental Impact

    The agency has determined under 21 CFR 25.30 that this action is of 
a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required statement 
would be required.

V. Analysis of Impact

    We have examined the impacts of the final rule under Executive 
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the 
Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive 
Order 12866 directs agencies to assess all costs and benefits of 
available regulatory alternatives and,

[[Page 56476]]

when regulation is necessary, to select regulatory approaches that 
maximize net benefits (including potential economic, environmental, 
public health and safety, and other advantages; distributive impacts; 
and equity). Under the Regulatory Flexibility Act, if a rule may have a 
significant economic impact on a substantial number of small entities, 
an agency must consider alternatives that would minimize the economic 
impact of the rule on small entities. Section 202(a) of the Unfunded 
Mandates Reform Act requires that agencies prepare a written assessment 
of anticipated costs and benefits before proposing any rule that may 
result in an expenditure by State, local, and tribal governments, in 
the aggregate, or by the private sector, of $100 million in any one 
year (adjusted annually for inflation).
    We believe that this final rule is consistent with the regulatory 
philosophy and principles identified in Executive Order 12866 and in 
these two statutes. This rule does not impose any mandates on State, 
local, or tribal governments. The rule will not be significant as 
defined by the Executive Order and will not require further analysis 
under the Regulatory Flexibility Act. The Unfunded Mandates Reform Act 
does not require us to prepare a statement of costs and benefits for 
the rule because the rule in any 1-year expenditure would not exceed 
$100 million adjusted for inflation. The current inflation-adjusted 
statutory threshold is $110 million.

VI. Paperwork Reduction Act of 1995

    This regulation would impose no additional reporting or 
recordkeeping requirements. Therefore, clearance by the Office of 
Management and Budget under the Paperwork Reduction Act of 1995 is not 
required.

VII. Federalism

    We have analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. We have determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between National Government and the States, 
or on the distribution of power and responsibilities among the various 
levels of government. Accordingly, we have concluded that the rule does 
not contain policies that have federalism implications as defined in 
the order and, consequently, a federalism summary impact statement is 
not required.

List of Subjects

21 CFR Part 7

    Administrative practice and procedure, Consumer protection, 
Reporting and recordkeeping requirements.

21 CFR Part 10

    Administrative practice and procedure, News media.

21 CFR Part 14

    Administrative practice and procedure, Advisory committees, Color 
additives, Drugs, Radiation protection.

21 CFR Part 19

    Conflict of interests.

21 CFR Part 25

    Environmental impact statements, Foreign relations, Reporting and 
recordkeeping requirements.

21 CFR Part 101

    Food labeling, Nutrition, Reporting and recordkeeping requirements.

21 CFR Part 107

    Food labeling, Infants and children, Nutrition, Reporting and 
recordkeeping requirements, Signs and symbols.

21 CFR Part 110

    Food packaging, Foods.

21 CFR Part 114

    Food packaging, Foods, Reporting and recordkeeping requirements.

21 CFR Part 170

    Administrative practice and procedure, Food additives, Reporting 
and recordkeeping requirements.

21 CFR Part 310

    Administrative practice and procedure, Drugs, Labeling, Medical 
devices, Reporting and recordkeeping requirements.

21 CFR Part 312

    Drugs, Exports, Imports, Investigations, Labeling, Medical 
research, Reporting and recordkeeping requirements, Safety.

21 CFR Part 314

    Administrative practice and procedure, Confidential business 
information, Drugs, Reporting and recordkeeping requirements.

21 CFR Part 316

    Administrative practice and procedure, Drugs, Reporting and 
recordkeeping requirements.

21 CFR Part 500

    Animal drugs, Animal feeds, Cancer, Labeling, Packaging and 
containers, Polychlorinated biphenyls (PCB's).

21 CFR Part 514

    Administrative practice and procedure, Animal drugs, Confidential 
business information, Reporting and recordkeeping requirements.

21 CFR Part 601

    Administrative practice and procedure, Biologics, Confidential 
business information.

21 CFR Part 803

    Imports, Medical devices, Reporting and recordkeeping requirements.

21 CFR Part 814

    Administrative practice and procedure, Confidential business 
information, Medical devices, Medical research, Reporting and 
recordkeeping requirements.

21 CFR Part 860

    Administrative practice and procedures, Medical devices.


    Therefore, under the Federal Food, Drug, and Cosmetic Act, the 
Public Health Service Act, and under authority delegated to the 
Commissioner of Food and Drugs, 21 CFR parts 7, 10, 14, 19, 25, 101, 
107, 110, 114, 170, 310, 312, 314, 316, 500, 514, 601, 803, 814, and 
860 are amended as follows:

PART 7--ENFORCEMENT POLICY

    1. The authority citation for 21 CFR part 7 continues to read as 
follows:

    Authority: 21 U.S.C. 321-393; 42 U.S.C. 241, 262, 263b-263n, 
264.


Sec. 7.1  [Amended]

    2. In Sec. 7.1, remove the word ``guidelines'' and add in its place 
the word ``guidance''.


Subpart C  [Amended]

    3. In the heading for subpart C, consisting of Secs. 7.40 through 
7.59, remove the word ``guidelines'' and add in its place the word 
``guidance''.


Sec. 7.40  [Amended]

    4. In 7.40(a), remove the word ``guidelines'' and add in its place 
the word ``guidance''.

PART 10--ADMINISTRATIVE PRACTICES AND PROCEDURES

    5. The authority citation for 21 CFR part 10 continues to read as 
follows:

    Authority: 5 U.S.C. 551-558, 701-706; 15 U.S.C. 1451-1461; 21 
U.S.C. 141-149, 321-

[[Page 56477]]

397, 467f, 679, 821, 1034; 28 U.S.C. 2112; 42 U.S.C. 201, 262, 263b, 
264.


Sec. 10.20  [Amended]

    6. In Sec. 10.20(j)(1)(v), remove the phrase ``guidelines filed 
under Sec. 10.90(b)'' and add in its place the words ``guidance 
documents developed under Sec. 10.115''.


Sec. 10.45  [Amended]

    7. In Sec. 10.45(d), remove the words ``on a guideline issued under 
Sec. 10.90,''.


Sec. 10.85  [Amended]

    8. In Sec. 10.85, remove paragraph (d)(5).


Sec. 10.90  [Amended]

    9. In Sec. 10.90, remove ``guidelines,'' from the section heading 
and remove and reserve paragraph (b).

    10. Add Sec. 10.115 to subpart B to read as follows:


Sec. 10.115  Good guidance practices.

    (a) What are good guidance practices? Good guidance practices 
(GGP's) are FDA's policies and procedures for developing, issuing, and 
using guidance documents.
    (b) What is a guidance document?
    (1) Guidance documents are documents prepared for FDA staff, 
applicants/sponsors, and the public that describe the agency's 
interpretation of or policy on a regulatory issue.
    (2) Guidance documents include, but are not limited to, documents 
that relate to: The design, production, labeling, promotion, 
manufacturing, and testing of regulated products; the processing, 
content, and evaluation or approval of submissions; and inspection and 
enforcement policies.
    (3) Guidance documents do not include: Documents relating to 
internal FDA procedures, agency reports, general information documents 
provided to consumers or health professionals, speeches, journal 
articles and editorials, media interviews, press materials, warning 
letters, memoranda of understanding, or other communications directed 
to individual persons or firms.
    (c) What other terms have a special meaning?
    (1) ``Level 1 guidance documents'' include guidance documents that:
    (i) Set forth initial interpretations of statutory or regulatory 
requirements;
    (ii) Set forth changes in interpretation or policy that are of more 
than a minor nature;
    (iii) Include complex scientific issues; or
    (iv) Cover highly controversial issues.
    (2) ``Level 2 guidance documents'' are guidance documents that set 
forth existing practices or minor changes in interpretation or policy. 
Level 2 guidance documents include all guidance documents that are not 
classified as Level 1.
    (3) ``You'' refers to all affected parties outside of FDA.
    (d) Are you or FDA required to follow a guidance document?
    (1) No. Guidance documents do not establish legally enforceable 
rights or responsibilities. They do not legally bind the public or FDA.
    (2) You may choose to use an approach other than the one set forth 
in a guidance document. However, your alternative approach must comply 
with the relevant statutes and regulations. FDA is willing to discuss 
an alternative approach with you to ensure that it complies with the 
relevant statutes and regulations.
    (3) Although guidance documents do not legally bind FDA, they 
represent the agency's current thinking. Therefore, FDA employees may 
depart from guidance documents only with appropriate justification and 
supervisory concurrence.
    (e) Can FDA use means other than a guidance document to communicate 
new agency policy or a new regulatory approach to a broad public 
audience? The agency may not use documents or other means of 
communication that are excluded from the definition of guidance 
document to informally communicate new or different regulatory 
expectations to a broad public audience for the first time. These GGP's 
must be followed whenever regulatory expectations that are not readily 
apparent from the statute or regulations are first communicated to a 
broad public audience.
    (f) How can you participate in the development and issuance of 
guidance documents?
    (1) You can provide input on guidance documents that FDA is 
developing under the procedures described in paragraph (g) of this 
section.
    (2) You can suggest areas for guidance document development. Your 
suggestions should address why a guidance document is necessary.
    (3) You can submit drafts of proposed guidance documents for FDA to 
consider. When you do so, you should mark the document ``Guidance 
Document Submission'' and submit it to Dockets Management Branch (HFA-
305), 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    (4) You can, at any time, suggest that FDA revise or withdraw an 
already existing guidance document. Your suggestion should address why 
the guidance document should be revised or withdrawn and, if 
applicable, how it should be revised.
    (5) Once a year, FDA will publish, both in the Federal Register and 
on the Internet, a list of possible topics for future guidance document 
development or revision during the next year. You can comment on this 
list (e.g., by suggesting alternatives or making recommendations on the 
topics that FDA is considering).
    (6) To participate in the development and issuance of guidance 
documents through one of the mechanisms described in paragraphs (f)(1), 
(f)(2), or (f)(4) of this section, you should contact the center or 
office that is responsible for the regulatory activity covered by the 
guidance document.
    (7) If FDA agrees to draft or revise a guidance document, under a 
suggestion made under paragraphs (f)(1), (f)(2), (f)(3) or (f)(4) of 
this section, you can participate in the development of that guidance 
document under the procedures described in paragraph (g) of this 
section.
    (g) What are FDA's procedures for developing and issuing guidance 
documents?
    (1) FDA's procedures for the development and issuance of Level 1 
guidance documents are as follows:
    (i) Before FDA prepares a draft of a Level 1 guidance document, FDA 
can seek or accept early input from individuals or groups outside the 
agency. For example, FDA can do this by participating in or holding 
public meetings and workshops.
    (ii) After FDA prepares a draft of a Level 1 guidance document, FDA 
will:
    (A) Publish a notice in the Federal Register announcing that the 
draft guidance document is available;
    (B) Post the draft guidance document on the Internet and make it 
available in hard copy; and
    (C) Invite your comment on the draft guidance document. Paragraph 
(h) of this section tells you how to submit your comments.
    (iii) After FDA prepares a draft of a Level 1 guidance document, 
FDA also can:
    (A) Hold public meetings or workshops; or
    (B) Present the draft guidance document to an advisory committee 
for review.
    (iv) After providing an opportunity for public comment on a Level 1 
guidance document, FDA will:
    (A) Review any comments received and prepare the final version of 
the guidance document that incorporates suggested changes, when 
appropriate;

[[Page 56478]]

    (B) Publish a notice in the Federal Register announcing that the 
guidance document is available;
    (C) Post the guidance document on the Internet and make it 
available in hard copy; and
    (D) Implement the guidance document.
    (v) After providing an opportunity for comment, FDA may decide that 
it should issue another draft of the guidance document. In this case, 
FDA will follow the steps in paragraphs (g)(1)(ii), (g)(1)(iii), and 
(g)(1)(iv) of this section.
    (2) FDA will not seek your comment before it implements a Level 1 
guidance document if the agency determines that prior public 
participation is not feasible or appropriate.
    (3) FDA will use the following procedures for developing and 
issuing Level 1 guidance documents under the circumstances described in 
paragraph (g)(2) of this section:
    (i) After FDA prepares a guidance document, FDA will:
    (A) Publish a notice in the Federal Register announcing that the 
guidance document is available;
    (B) Post the guidance document on the Internet and make it 
available in hard copy;
    (C) Immediately implement the guidance document; and
    (D) Invite your comment when it issues or publishes the guidance 
document. Paragraph (h) of this section tells you how to submit your 
comments.
    (ii) If FDA receives comments on the guidance document, FDA will 
review those comments and revise the guidance document when 
appropriate.
    (4) FDA will use the following procedures for developing and 
issuing Level 2 guidance documents:
    (i) After it prepares a guidance document, FDA will:
    (A) Post the guidance document on the Internet and make it 
available in hard copy;
    (B) Immediately implement the guidance document, unless FDA 
indicates otherwise when the document is made available; and
    (C) Invite your comment on the Level 2 guidance document. Paragraph 
(h) of this section tells you how to submit your comments.
    (ii) If FDA receives comments on the guidance document, FDA will 
review those comments and revise the document when appropriate. If a 
version is revised, the new version will be placed on the Internet.
    (5) You can comment on any guidance document at any time. Paragraph 
(h) of this section tells you how to submit your comments. FDA will 
revise guidance documents in response to your comments when 
appropriate.
    (h) How should you submit comments on a guidance document?
    (1) If you choose to submit comments on any guidance document under 
paragraph (g) of this section, you must send them to the Dockets 
Management Branch (HFA-305), 5630 Fishers Lane, rm. 1061, Rockville, MD 
20852.
    (2) Comments should identify the docket number on the guidance 
document, if such a docket number exists. For documents without a 
docket number, the title of the guidance document should be included.
    (3) Comments will be available to the public in accordance with 
FDA's regulations on submission of documents to the Dockets Management 
Branch specified in Sec. 10.20(j).
    (i) What standard elements must FDA include in a guidance document?
    (1) A guidance document must:
    (i) Include the term ``guidance,''
    (ii) Identify the center(s) or office(s) issuing the document,
    (iii) Identify the activity to which and the people to whom the 
document applies,
    (iv) Prominently display a statement of the document's nonbinding 
effect,
    (v) Include the date of issuance,
    (vi) Note if it is a revision to a previously issued guidance and 
identify the document that it replaces, and
    (vii) Contain the word ``draft'' if the document is a draft 
guidance.
    (2) Guidance documents must not include mandatory language such as 
``shall,'' ``must,'' ``required,'' or ``requirement,'' unless FDA is 
using these words to describe a statutory or regulatory requirement.
    (3) When issuing draft guidance documents that are the product of 
international negotiations (e.g., guidances resulting from the 
International Conference on Harmonisation), FDA need not apply 
paragraphs (i)(1) and (i)(2) of this section. However, any final 
guidance document issued according to this provision must contain the 
elements in paragraphs (i)(1) and (i)(2) of this section.
    (j) Who, within FDA, can approve issuance of guidance documents? 
Each center and office must have written procedures for the approval of 
guidance documents. Those procedures must ensure that issuance of all 
documents is approved by appropriate senior FDA officials.
    (k) How will FDA review and revise existing guidance documents?
    (1) The agency will periodically review existing guidance documents 
to determine whether they need to be changed or withdrawn.
    (2) When significant changes are made to the statute or 
regulations, the agency will review and, if appropriate, revise 
guidance documents relating to that changed statute or regulation.
    (3) As discussed in paragraph (f)(3) of this section, you may at 
any time suggest that FDA revise a guidance document.
    (l) How will FDA ensure that FDA staff are following GGP's?
    (1) All current and new FDA employees involved in the development, 
issuance, or application of guidance documents will be trained 
regarding the agency's GGP's.
    (2) FDA centers and offices will monitor the development and 
issuance of guidance documents to ensure that GGP's are being followed.
    (m) How can you get copies of FDA's guidance documents? FDA will 
make copies available in hard copy and, as feasible, through the 
Internet.
    (n) How will FDA keep you informed of the guidance documents that 
are available?
    (1) FDA will maintain on the Internet a current list of all 
guidance documents. New documents will be added to this list within 30 
days of issuance.
    (2) Once a year, FDA will publish in the Federal Register its 
comprehensive list of guidance documents. The comprehensive list will 
identify documents that have been added to the list or withdrawn from 
the list since the previous comprehensive list.
    (3) FDA's guidance document lists will include the name of the 
guidance document, issuance and revision dates, and information on how 
to obtain copies of the document.
    (o) What can you do if you believe that someone at FDA is not 
following these GGP's? If you believe that someone at FDA did not 
follow the procedures in this section or that someone at FDA treated a 
guidance document as a binding requirement, you should contact that 
person's supervisor in the center or office that issued the guidance 
document. If the issue cannot be resolved, you should contact the next 
highest supervisor. You can also contact the center or office ombudsman 
for assistance in resolving the issue. If you are unable to resolve the 
issue at the center or office level or if you feel that you are not 
making progress by going through the chain of command, you may ask the 
Office of the Chief Mediator and Ombudsman to become involved.

PART 14--PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE

    11. The authority citation for 21 CFR part 14 continues to read as 
follows:


[[Page 56479]]


    Authority: 5 U.S.C. App. 2; 15 U.S.C. 1451-1461; 21 U.S.C. 141-
149, 321-394, 467f, 679, 821, 1034; 28 U.S.C. 2112; 42 U.S.C. 201, 
262, 263b, 264.


Sec. 14.27  [Amended]

    12. In Sec. 14.27(b)(3), remove the word ``guidelines'' and add in 
its place the words ``guidance documents''.


Sec. 14.33  [Amended]

    13. In Sec. 14.33(c), remove the word ``guidelines'' and add in its 
place the words ``guidance documents''.

PART 19--STANDARDS OF CONDUCT AND CONFLICTS OF INTEREST

    14. The authority citation for 21 CFR part 19 continues to read as 
follows:

    Authority: 21 U.S.C. 371.


Sec. 19.10  [Amended]

    15. In Sec. 19.10(c), remove the word ``guidelines'' and add in its 
place the words ``guidance documents''.

PART 25--ENVIRONMENTAL IMPACT CONSIDERATIONS

    16. The authority citation for 21 CFR part 25 continues to read as 
follows:

    Authority: 21 U.S.C. 321-393; 42 U.S.C. 262, 263b-264; 42 U.S.C. 
4321, 4332; 40 CFR parts 1500-1508; E.O. 11514, 35 FR 4247, 3 CFR, 
1971 Comp., p. 531-533 as amended by E.O. 11991, 42 FR 26967, 3 CFR, 
1978 Comp., p. 123-124 and E.O. 12114, 44 FR 1957, 3 CFR, 1980 
Comp., p. 356-360.


Sec. 25.30  [Amended]

    17. In Sec. 25.30(h), remove the word ``guidelines'' and add in its 
place the words ``guidance documents''.

PART 101--FOOD LABELING

    18. The authority citation for 21 CFR part 101 continues to read as 
follows:

    Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342, 
343, 348, 371.


Sec. 101.9  [Amended]

    19. In Sec. 101.9(b)(7)(vi), remove the word ``guideline'' wherever 
it appears and add in its place the words ``guidance document''.

PART 107--INFANT FORMULA

    20. The authority citation for 21 CFR part 107 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 343, 350a, 371.


Sec. 107.270  [Amended]

    21. In Sec. 107.270, remove the word ``guidelines'' and add in its 
place the word ``guidance''.

PART 110--CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, 
PACKING, OR HOLDING HUMAN FOOD

    22. The authority citation for 21 CFR part 110 continues to read as 
follows:

    Authority: 21 U.S.C. 342, 371, 374; 42 U.S.C. 264.


Sec. 110.80  [Amended]

    23. In Sec. 110.80, remove the word ``guidelines,'' in paragraphs 
(a)(3) and (a)(4).

PART 114--ACIDIFIED FOODS

    24. The authority citation for 21 CFR part 114 continues to read as 
follows:

    Authority: 21 U.S.C. 342, 371, 374; 42 U.S.C. 264.


Sec. 114.100  [Amended]

    25. In Sec. 114.100(a), remove the word ``guidelines'' and add in 
its place the words ``guidance documents''.

PART 170--FOOD ADDITIVES

    26. The authority citation for 21 CFR part 170 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 341, 342, 346a, 348, 371.


Sec. 170.39  [Amended]

    27. In Sec. 170.39(h), remove the word ``guidelines'' wherever it 
appears and add in its place the words ``guidance documents''.

PART 310--NEW DRUGS

    28. The authority citation for 21 CFR part 310 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f, 
360j, 361(a), 371, 374, 375, 379(e); 42 U.S.C. 216, 241, 242(a), 
262, 263b-263n.


Sec. 310.500  [Amended]

    29. In Sec. 310.500(e), remove the words ``guidelines'' and 
``guideline'', respectively, and add in their place the words 
``guidance'' and ``guidance on'', respectively.

PART 312--INVESTIGATIONAL NEW DRUG APPLICATION

    30. The authority citation for 21 CFR part 312 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 371; 42 
U.S.C. 262.


Sec. 312.23  [Amended]

    31. In Sec. 312.23(a)(8), remove the word ``guidelines'' and add in 
its place the words ``guidance documents.''

    32. Revise Sec. 312.145 to read as follows:


Sec. 312.145  Guidance documents.

    (a) FDA has made available guidance documents under Sec. 10.115 of 
this chapter to help you to comply with certain requirements of this 
part.
    (b) The Center for Drug Evaluation and Research (CDER) and the 
Center for Biologics Evaluation and Research (CBER) maintain lists of 
guidance documents that apply to the centers' regulations. The lists 
are maintained on the Internet and are published annually in the 
Federal Register. A request for a copy of the CDER list should be 
directed to the Office of Training and Communications, Division of 
Communications Management, Drug Information Branch (HFD-210), Center 
for Drug Evaluation and Research, Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857. A request for a copy of the CBER 
list should be directed to the Office of Communication, Training, and 
Manufacturers Assistance (HFM-40), Center for Biologics Evaluation and 
Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, 
MD 20852-1448.

PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG

    33. The authority citation for 21 CFR part 314 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 371, 374, 
379e.


Sec. 314.50  [Amended]

    34. In Sec. 314.50, in the introductory text remove the word 
``guidelines'' and add in its place the words ``guidance documents''.


Sec. 314.70  [Amended]

    35. In Sec. 314.70(a), remove the words ``guideline, notice,'' and 
add in their place the word ``notice''.


Sec. 314.94  [Amended]

    36. In Sec. 314.94, in the introductory text remove the words 
``guidelines'' and add in its place the words ``guidance documents''.


Sec. 314.105  [Amended]

    37. In Sec. 314.105(c), remove the word ``guidelines'' and add in 
its place the words ``guidance documents''.


Sec. 314.420  [Amended]

    38. In Sec. 314.420(c), remove the words ``under Sec. 10.90(b) a 
guideline'' and add in their place the word ``guidance''.

    39. Revise Sec. 314.445 to read as follows:

[[Page 56480]]

Sec. 314.445  Guidance documents.

    (a) FDA has made available guidance documents under Sec. 10.115 of 
this chapter to help you to comply with certain requirements of this 
part.
    (b) The Center for Drug Evaluation and Research (CDER) maintains a 
list of guidance documents that apply to CDER's regulations. The list 
is maintained on the Internet and is published annually in the Federal 
Register. A request for a copy of the CDER list should be directed to 
the Office of Training and Communications, Division of Communications 
Management, Drug Information Branch (HFD-210), Center for Drug 
Evaluation and Research, Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857.

PART 316--ORPHAN DRUGS

    40. The authority citation for 21 CFR part 316 continues to read as 
follows:

    Authority: 21 U.S.C. 360aa, 360bb, 360cc, 360dd, 371.

    41. Revise Sec. 316.50 to read as follows:


Sec. 316.50  Guidance documents.

    FDA's Office of Orphan Products Development will maintain and make 
publicly available a list of guidance documents that apply to the 
regulations in this part. The list is maintained on the Internet and is 
published annually in the Federal Register. A request for a copy of the 
list should be directed to the Office of Orphan Products Development 
(HF-35), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 
20857.

PART 500--GENERAL

    42. The authority citation for 21 CFR part 500 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 342, 343, 348, 351, 352, 353, 
360b, 371.


Sec. 500.80  [Amended]

    43. In Sec. 500.80(a), remove the word ``guidelines'' wherever it 
appears and add in its place the words ``guidance documents''.

PART 514--NEW ANIMAL DRUG APPLICATIONS

    44. The authority citation for 21 CFR part 514 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 352, 360b, 371, 379e, 381.


Sec. 514.1  [Amended]

    45. In Sec. 514.1(d)(2), remove the word ``guidelines'' wherever it 
appears and add in its place the words ``guidance documents''.

PART 601--LICENSING

    46. The authority citation for 21 CFR part 601 continues to read as 
follows:

    Authority: 15 U.S.C. 1451-1561; 21 U.S.C. 321, 351, 352, 353, 
355, 360, 360c-360f, 360h-360j, 371, 374, 379e, 381; 42 U.S.C. 216, 
241, 262, 263; sec. 122, Pub. L. 105-115, 111 Stat. 2322 (21 U.S.C. 
355 note).

    47. Add Sec. 601.29 to subpart C to read as follows:


Sec. 601.29  Guidance documents.

    (a) FDA has made available guidance documents under Sec. 10.115 of 
this chapter to help you comply with certain requirements of this part.
    (b) The Center for Biologics Evaluation and Research (CBER) 
maintains a list of guidance documents that apply to the center's 
regulations. The lists are maintained on the Internet and are published 
annually in the Federal Register. You may request a copy of the CBER 
list from the Office of Communication, Training, and Manufacturers 
Assistance (HFM-40), Center for Biologics Evaluation and Research, Food 
and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852-1448.

PART 803--MEDICAL DEVICE REPORTING

    48. The authority citation for 21 CFR part 803 continues to read as 
follows:

    Authority: 21 U.S.C. 352, 360, 360i, 360j, 371, 374.


Sec. 803.14  [Amended]

    49. In Sec. 803.14(b), remove the word ``guidelines'' and add in 
its place the words ``guidance documents''.

PART 814--PREMARKET APPROVAL OF MEDICAL DEVICES

    50. The authority citation for 21 CFR part 814 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 352, 353, 360, 360c-360j, 371, 372, 
373, 374, 375, 379, 379e, 381.

    51. In Sec. 814.20, revise paragraph (g) to read as follows:


Sec. 814.20  Application.

* * * * *
    (g) FDA has issued a PMA guidance document to assist the applicant 
in the arrangement and content of a PMA. This guidance document is 
available on the Internet at http://www.fda.gov/cdrh/dsma/pmaman/front.html. This guidance document is also available upon request from 
the Center for Devices and Radiological Health, Division of Small 
Manufacturers Assistance (HFZ-220), 1350 Piccard Dr., Rockville, MD 
20850, FAX 301-443-8818.
* * * * *

PART 860--MEDICAL DEVICE CLASSIFICATION PROCEDURES

    52. The authority citation for 21 CFR part 860 continues to read as 
follows:

    Authority: 21 U.S.C. 360c, 360d, 360e, 360i, 360j, 371, 374.


Sec. 860.3  [Amended]

    53. In Sec. 860.3(c)(2), remove the words ``guidelines'' and 
``guidelines for'' and add in their place the words ``guidance 
documents'' and ``guidance on'', respectively.

    Dated: September 1, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-23887 Filed 9-18-00; 8:45 am]
BILLING CODE 4160-01-F