56468 Federal Register / Vol. 65, No. 182 / Tuesday, September 19, 2000 / Rules and Regulations adding, in their place, the words ‘‘FAA notice confirms that this direct final rule changes to our existing part 10 (21 CFR Order 7400.9H’’. will become effective on that date. part 10) regulations to clarify our procedures for the development, § 71.79 [Amended] Dated: Issued in Kansas City, MO on September 6, 2000. issuance, and use of guidance 10. Section 71.79 is amended by Richard L. Day, documents. Interested parties were removing the words ‘‘FAA Order given until May 1, 2000, to comment on 7400.9G’’ and adding, in their place, the Acting Manager, Air Traffic Division, Central Region. the proposal. words ‘‘FAA Order 7400.9H’’. [FR Doc. 00–2394 Filed 9–18–00; 8:45 am] II. Description of the Final Rule § 71.901 [Amended] BILLING CODE 4910±13±M A. Comments and Agency Response 11. Paragraph (a) of § 71.901 is amended by removing the words ‘‘FAA We received 18 comments on the Order 7400.9G’’ and adding, in their DEPARTMENT OF HEALTH AND proposed rule, largely from trade place, the words ‘‘FAA Order 7400.9H’’. HUMAN SERVICES organizations. The comments we received generally supported the Issued in Washington, DC, September 8, Food and Drug Administration policies and procedures described in the 2000. GGP’s. Reginald C. Matthews, 21 CFR Parts 7, 10, 14, 19, 25, 101, 107, 1. General Comment Manager, Airspace and Rules Division. 110, 114, 170, 310, 312, 314, 316, 500, [FR Doc. 00–23673 Filed 9–18–00; 8:45 am] 514, 601, 803, 814, and 860 (Comment 1) One comment BILLING CODE 4910±13±P recommended that we include in this [Docket No. 99N±4783] preamble a list of generally accepted principles of a good guidance DEPARTMENT OF TRANSPORTATION Administrative Practices and document. The comment nominated Procedures; Good Guidance Practices several principles for inclusion on the Federal Aviation Administration AGENCY: Food and Drug Administration, list. HHS. We decline to develop a list of 14 CFR Part 71 generally accepted principles of a ACTION: Final rule. [Airspace Docket No. 00±ACE±13] ‘‘good’’ guidance document because we SUMMARY: The Food and Drug believe that the procedures described in Amendment to Class E Airspace; Administration (FDA) is amending its § 10.115 reflect generally accepted Fairfield, IA administrative regulations to codify its principles for developing, issuing, and policies and procedures for the using guidance documents. For AGENCY: Federal Aviation development, issuance, and use of example, a good guidance document Administration, DOT. guidance documents. This action is represents our current thinking on a ACTION: Direct final rule; confirmation of necessary to comply with requirements matter and clearly states that it does not effective date. of the Food and Drug Administration establish legally enforceable Modernization Act of 1997 (the requirements. We expect each guidance SUMMARY: This document confirms the Modernization Act). The Modernization document developed, issued, and used effective date of a direct final rule which Act codified certain parts of the under the rule to have the revises Class E airspace at Fairfield, IA. agency’s current ‘‘Good Guidance characteristics of a good guidance DATES: The direct final rule published at Practices’’ (GGP’s) and directed the document. 65 FR 40991 is effective on 0901 UTC, agency to issue a regulation consistent 2. Definition of Guidance Documents November 30, 2000. with the act that specifies FDA’s (Comment 2) One comment suggested FOR FURTHER INFORMATION CONTACT: policies and procedures for the that we include in the definition of Kathy Randolph, Air Traffic Division, development, issuance, and use of guidance documents those documents Airspace Branch, ACE–520C, DOT guidance documents. The intended that describe our current policies Regional Headquarters Building, Federal effect of this regulation is to make the regarding labeling and promotion. agency’s procedures for development, Aviation Administration, 901 Locust, In our proposal, we defined guidance issuance, and use of guidance Kansas City, MO 64106; telephone: documents to include, among other documents clear to the public. (861) 329–2525. kinds of documents, those that relate to SUPPLEMENTARY INFORMATION: The FAA DATES: This rule is effective October 19, the design, production, manufacturing, published this direct final rule with a 2000. and testing of regulated products and request for comments in the Federal FOR FURTHER INFORMATION CONTACT: those that relate to inspection or Register on July 3, 2000 (65 FR 40991). LaJuana D. Caldwell, Office of Policy enforcement policies. We interpret our The FAA uses the direct final (HF–27), Food and Drug definition to include guidance rulemaking procedure for a non- Administration, 5600 Fishers Lane, documents about product labeling and controversial rule where the FAA Rockville, MD 20857, 301–827–7010. promotion. We are amending the believes that there will be no adverse SUPPLEMENTARY INFORMATION: definition in § 10.115(b)(2) to clarify our public comment. This direct final rule intent to include such topics as subjects I. Background advised the public that no adverse for guidance documents. comments were anticipated, and that Under section 405 of the unless a written adverse comment, or a Modernization Act (Public Law 105– 3. Comprehensive List of Guidance written notice of intent to submit such 115), statutory provisions on guidance Documents and Guidance Document an adverse comment, were received documents were added to the Federal Agenda within the comment period, the Food, Drug, and Cosmetic Act (the act) (Comment 3) Several comments regulation would become effective on in section 701(h) (21 U.S.C. 371(h)). In discussed the annual publication of the November 30, 2000. No adverse the Federal Register of February 14, comprehensive list of guidance comments were received, and thus this 2000 (65 FR 7321), we (FDA) proposed documents and the guidance document

VerDate 112000 09:40 Sep 18, 2000 Jkt 190000 PO 00000 Frm 00006 Fmt 4700 Sfmt 4700 E:\FR\FM\19SER1.SGM pfrm08 PsN: 19SER1 Federal Register / Vol. 65, No. 182 / Tuesday, September 19, 2000 / Rules and Regulations 56469 agenda. Some suggested that we ability to convey the subject matter of grouped by topic categories. By continue to publish these lists on a each document on the list. To provide separating guidance documents semiannual basis. this information adequately, we plan to according to the issuing center or office, Some comments stated that yearly ensure that the titles or subtitles of we enable those of you who have publication of the comprehensive list is documents convey the subject of the interest in a particular issue or type of acceptable, particularly given that we document more precisely. The product (e.g., food products) to focus on maintain a current list on the Internet. comprehensive list could become too documents that are being developed in One comment stated that annual cumbersome and difficult to use if we one of the centers or offices (e.g., the publication of the guidance document added a description of the subject of Center for Food Safety and Applied agenda would be reasonable if we each document. Therefore, we will not Nutrition). Guidance documents that are include the status of each item on the include a separate statement describing being developed in more than one list and identify the highest priority each document on the comprehensive center or office will appear on the guidance documents. Another comment list. agenda for each participating center or recommended that the agenda be posted (Comment 5) A comment stated that office. Grouping documents on the on the Internet. the comprehensive list should identify agenda by subject category (e.g., We believe that we provide adequate guidance documents that have been electronic submissions) provides you notice of and access to all available revised or are currently being greater ability to focus on specific areas guidance documents through two considered for revision. of interest. After the effective date of the mechanisms. We annually publish a Through the lists that we publish rule, we will group all guidance comprehensive list of guidance under the procedures previously documents on the agenda by subject documents in the Federal Register and described, we already make the category. This format is consistent with we maintain current (i.e., updated information requested in the comment the format of the comprehensive list of within 30 days of the issuance of a new available to the public. On the guidance documents. We believe that or newly revised guidance document or comprehensive list, we include the date the format suggested in the comment the deletion of an obsolete guidance of the last revision of a guidance could make the agenda difficult to use document) lists of guidance documents document. This enables you to identify because you would not be able to on the Internet. those guidance documents that have concentrate effectively on a particular We also believe that we provide been revised and the date of the topic of interest. adequate notice of the guidance revision. In our guidance document document agenda through its annual agenda, we list guidance documents that 4. Public Input publication in the Federal Register. We are under consideration for (Comment 8) One comment suggested will not include the status of each development or revision. that we implement procedures to give document on the agenda. Each (Comment 6) In § 10.115(c), we define you the opportunity to comment on document listed on the agenda is being two levels of guidance documents, Level designation of a document as a Level 1 developed; further description of 1 and Level 2. The two levels of or Level 2 guidance document before document status would not be practical guidance documents are subject to the decision is made. because it would be too difficult to different procedures for public We decline to adopt this suggestion. differentiate the stages of guidance participation before issuance. One It is in the best interest of promoting document development. We also do not comment suggested that we include the and preserving the public health that we believe it would be feasible to prioritize designation for each document as Level be able to develop guidance documents the documents on the agenda. Often, 1 or Level 2 in the prospective list of in a timely and efficient manner. If we resources allocated to the development guidance documents. solicited comment on the level of a particular document are diverted to We decline the suggestion to include designation for each guidance creating guidance documents regarding the Level 1 or Level 2 designation for all document, we would create a other areas of greater public health documents on the guidance document procedural hurdle that could need. As a result, our priorities may agenda. Generally, at the time we issue significantly slow the guidance change throughout the year and the agenda, we do not know the full development process. This delay in the priorities stated on the agenda would content of the proposed documents. development of guidance documents not remain accurate for an extended Thus, a determination of whether a would not serve us or you. period of time. We try to maintain a document meets the criteria for a Level We determine whether a document is current (i.e., updated at least 1 designation (§ 10.115(c)(1)) would be Level 1 or Level 2 based on the criteria semiannually) guidance document premature. described in § 10.115(c). If you disagree agenda on the Internet. (Comment 7) One comment suggested with the designation of a document In efforts separate from this that we make the guidance document (e.g., if you believe that a guidance rulemaking, we are considering ways to agenda more user-friendly by separating issued as a Level 2 should have been enhance our lists of guidance guidance documents on cross-cutting issued as a Level 1), you may send us documents maintained on the Internet. issues from those that are technology- an explanation of your reasons for For example, we are trying to make the specific. disagreeing with our determination lists easier to navigate and search. These The purpose of the guidance when you comment on the guidance enhancements may allow you to more document agenda is to notify you of document. If, after issuance, you still efficiently find the information you seek guidance documents we are developing have a disagreement, you can appeal our on the comprehensive list and the so you may comment on topics for new designation using the dispute resolution agenda. documents and possible revisions to process. (Comment 4) One comment suggested existing documents. We believe the (Comment 9) One comment suggested that we include a brief statement guidance agenda is currently organized that we announce the development and describing each document on the to disseminate this information most issuance of Level 2 documents in the comprehensive list. effectively. The documents on the Federal Register. Another comment We understand that much of the value agenda are organized by the issuing recommended that we receive of the comprehensive list lies in its center or office and generally are further comments on Level 2 guidance

VerDate 112000 09:40 Sep 18, 2000 Jkt 190000 PO 00000 Frm 00007 Fmt 4700 Sfmt 4700 E:\FR\FM\19SER1.SGM pfrm08 PsN: 19SER1 56470 Federal Register / Vol. 65, No. 182 / Tuesday, September 19, 2000 / Rules and Regulations documents before we issue them as final we should respond to each suggestion (Comment 14) We received many guidance. for a revision to an existing guidance comments on early collaboration and We decline to amend our procedures document within 90 days. Other meetings to discuss guidance for announcing and receiving comment comments stated that we should explain documents as they are being developed. on Level 2 guidance documents. When to the public why we changed, or why Generally, the comments were very we issue Level 2 documents, they are we did not change, a guidance supportive of our efforts to facilitate immediately posted on the Internet. document between the draft and final early interaction with you. Some Also, their issuance is announced in the stages. Some comments recommended comments suggested that we issue a comprehensive list of guidance that we provide general responses to clear policy about the procedures for documents that is published annually in comments grouped by topic. Others collaboration and early meetings. One the Federal Register and maintained on suggested that we be required to issue suggested that we provide a means for the Internet. a written response when certain criteria industry to recommend a particular Under section 701(h)(1)(D) of the act, are met (e.g., when a majority of the collaborative approach for a guidance we must solicit public comments ‘‘upon comments on a guidance document document under development. Another implementation’’ of guidance concern the same issue). comment recommended that we provide documents that describe existing We believe that it is in the public opportunities for you to engage in ‘‘real practices or minor changes in agency interest to have an efficient process for time dialogues’’ with us before we begin policy. We believe the provisions of developing guidance documents. The to write a draft or final guidance. The § 10.115(g)(4) are consistent with the act guidance document development comment noted a number of avenues for and describe adequate provisions for process would be hampered if we were this type of collaboration, including developing and issuing Level 2 required to respond to each comment. joint task forces, public and private guidance documents. When comments received are very meetings, advisory committee meetings, (Comment 10) Under § 10.115(g)(1)(v), significant or cause us to revise a and e-mail correspondence. Other we may issue a second draft of a guidance, we often discuss those comments stated that certain agency guidance document and solicit comments in the notice of availability components had refused to meet about comment on the document after (NOA) for the final guidance or in the a guidance document before that providing an opportunity for comment final guidance document. We intend to document was issued in draft. One on the first draft. One comment stated continue this practice. However, making comment specifically requested that we that two situations usually merit this a firm commitment to provide a written use more mandatory language regarding procedure: When the first draft guidance response to all comments when issuing preproposal collaboration with you. on a medical or scientific topic is highly a final guidance would unnecessarily We agree that early collaboration (i.e., controversial and when the first draft delay the issuance of the document. input from you in the early stage of guidance is in conflict with other developing the approach we will take in widely recognized sources of scholarly (Comment 13) Two comments suggested that we be required to a new or revised guidance document) guidance (e.g., International Conference can be a very valuable tool in on Harmonization guidance, respond to your proposals for draft guidance documents. developing regulatory guidance. We pharmacopeial standards). have created several mechanisms to We agree with this comment. When We agree that it may be appropriate encourage early input, including the you have taken the time to develop a for us to issue a second draft of a following: guidance document in the two guidance document and submit it to us • We provide an opportunity to situations described in the comment. In for review, you should receive, at a suggest new or revised guidance. addition, it may also be appropriate for minimum, an acknowledgment of • We publish an agenda of the us to issue a second draft guidance in receipt of the document. Therefore, we guidance documents that we are other circumstances. For example, if we are now accepting guidance document working on and request your comments revise a document for clarification, we submissions at the Dockets Management on the agenda. may want to issue a second draft Branch. If you submit a document to us, • We notify you when we issue draft guidance document to receive comment you should designate it as a ‘‘Guidance guidance documents and request your on whether our revisions made the Document Submission,’’ include the comments on the drafts. document easier to understand. name of the center or office with • We may hold meetings or (Comment 11) One comment oversight over the subject matter workshops even before we develop a suggested that we allow the public to covered by the guidance document, and draft document. request the deletion of guidance submit the document to the Dockets We encourage your involvement in documents that are no longer useful. Management Branch (HFA–305), 5630 our development of guidance Under § 10.115(f), you can suggest Fishers Lane, rm. 1061, Rockville, MD documents. Often, we develop guidance that a document on the comprehensive 20852. documents based on your suggestions. list of guidance documents or on the The Dockets Management Branch will We solicit your comments on draft guidance document agenda be revised ensure that the document is assigned a guidance documents because our views or withdrawn if you find that the public docket number and it is sent to are not yet finalized and we want your document is no longer relevant or the appropriate office or center. All input on the contents of the final accurate. We amended the final rule to proposed guidance documents will be guidance. explicitly state that you can suggest that available through the public docket. We We understand that you would like to a guidance be withdrawn will send you a written meet with us more regarding the (§ 10.115(f)(4)). acknowledgment that we have received development of guidance documents. (Comment 12) Many comments urged your document, and to the extent Our policies on meeting with the public us to include a provision in the feasible, we also will inform you of our on guidance development are evolving. regulation requiring us to provide actions regarding the document you In efforts separate from this rulemaking, written responses to public comments have submitted. These changes to the we are exploring ways to increase this or suggestions for revising guidance final rule are included in revised interaction within the confines of documents. One comment stated that § 10.115(f)(3). applicable statutes and regulations, and

VerDate 112000 09:40 Sep 18, 2000 Jkt 190000 PO 00000 Frm 00008 Fmt 4700 Sfmt 4700 E:\FR\FM\19SER1.SGM pfrm08 PsN: 19SER1 Federal Register / Vol. 65, No. 182 / Tuesday, September 19, 2000 / Rules and Regulations 56471 are considering our need to provide all ensure that this information is made observation on Form FDA 483 (List of interested parties access to the process, available in a timely manner. Inspectional Observations). our interest in issuing documents in a 5. Legal Effect of Guidance Documents We agree with this comment. timely manner, and our resource Guidance documents are not binding. constraints. We welcome your (Comment 18) We received several An enforcement action may be taken suggestions in this area. comments on the legal effect of only when we find a violation of (Comment 15) One comment guidance documents. A number of statutory or regulatory requirements. If a proposed establishing a mechanism in comments referred to the statement in guidance document contains a reference § 10.115(g) whereby companies can the proposed regulation that we are to a regulatory or statutory requirement, fund a market research initiative that willing to discuss an alternative then enforcement action may be taken if would permit us, through approach with you to ensure that it the regulation or statutory requirement questionnaires, focus groups, and other complies with the relevant statutes and is violated. Of course, enforcement techniques, to obtain input on proposed regulations (§ 10.115(c)(3)). The action may be taken if a requirement in policies directly from patients, doctors, comments stated that if a guidance a regulation or statute is violated and other stakeholders. document is not binding, the discussion whether or not there is a reference to the We welcome input from patients, of alternative approaches should not be requirements in any guidance doctors, and other stakeholders. We required. document. We discuss this issue in the The comments misinterpreted the believe that the procedures described in GGP training we provide employees intent of the statement in § 10.115(c)(3). § 10.115, especially our increased use of under § 10.115(l)(1). If you take an alternative approach, you the Internet to disseminate information, (Comment 21) We received one provide adequate avenues for patient, are not required to discuss that comment on how we should interpret a doctor, and stakeholder involvement in approach with us. Instead, we are draft guidance document during the the development of our policies. We offering our assistance to make sure that time that it is out for comment, before decline at this time to establish a funded any alternative approach you take meets the document has been finalized. The market research initiative because the appropriate statutory or regulatory comment suggested that we maintain administering such a program would requirements. Discussing alternative three categories of guidance documents: divert personnel resources from other approaches may help you understand Draft, approvable, and approved. public health priorities. our interpretation of the applicable (Comment 16) One comment statutes and regulations and may further We believe the provisions of suggested that we consider interactive our understanding of the merits of your § 10.115(g) sufficiently describe both the techniques, such as town hall meetings, approach. process for issuing draft Level 1 that may encourage industry input on (Comment 19) Two comments guidance documents for comment and setting priorities for the development of suggested that compliance with a the process of implementing Level 1 guidance documents listed on the guidance document should provide a guidance documents without comment agenda. company with a safe harbor from FDA when prior public participation is not We welcome industry input on enforcement action. The comments feasible or appropriate. We do not prioritizing our development of recommended that we change the believe that adding more categories will guidance documents. We believe that regulation to require us to amend, or at improve the process; instead, it could the procedures described in the GGP’s least publish a proposal to amend, a confuse the users of the documents. on the guidance document agenda, guidance document before initiating an Early in the process of developing the especially our increased use of the enforcement action against a company GGP’s, comments strongly urged the Internet to disseminate the agenda and that acted in accordance with a agency to streamline and simplify the our request for comments on the agenda, guidance. The comments also noted that nomenclature for guidance documents. provide adequate avenues for industry if we do not provide a safe harbor from We have done so. If you are concerned and others to assist us in prioritizing enforcement, at a minimum, a about FDA’s thinking on an issue that is guidance documents. Furthermore, the company’s action in accordance with a reflected only in a draft guidance, you agenda is only one of several guidance document should be evidence should contact the appropriate office mechanisms we use to solicit input on of the company’s intent to comply with within FDA to discuss the issue. prioritizing the guidance documents we our regulations. While a draft Level 1 guidance are developing. For example, we may Section 701(h)(1)(B) of the act document is out for comment, you may participate in public meetings and provides that guidance documents be concerned that the guidance will public hearings and may raise guidance ‘‘shall not be binding on the Secretary.’’ change based on comments received. document issues at advisory committee Creating a ‘‘safe harbor’’ in a guidance Because a guidance document meetings. At this time, we decline to document that would preclude us from represents the agency’s current thinking change the GGP’s in the manner taking action would impermissibly bind on a subject but it is not ever binding suggested but will continue to consider us. In issuing enforcement-related on FDA or outside parties, you should avenues for encouraging input at all guidance documents, we express our not rely on any guidance document, stages of guidance development. current thinking regarding regulatory draft or final. If you have questions (Comment 17) One comment matters and believe this provides useful about compliance with statutory or suggested that any proposed guidance information. However, you always regulatory requirements, you can documents submitted to advisory remain independently responsible for discuss those issues with an FDA committees be made public in a manner complying with applicable statutes and employee. that provides sufficient time for review regulations. Whether you have complied 6. Standard Elements before the meeting. with the law is determined from the We agree that proposed guidance facts of each case. (Comment 22) We received two documents submitted to advisory (Comment 20) We received two comments suggesting that the committees should be made public as comments suggesting that we clarify to designation as Level 1 or Level 2 be a soon as practicable to allow for a review our staff that FDA may not cite failure standard element of each guidance of those materials. We are working to to follow a guidance document in any document.

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

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

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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/¢dms/orgchart.html Center for Veterinary Medicine www.fda.gov/cvm/fda/mappgs/contactcvm.html Office of Regulatory Affairs www.fda.gov/ora/inspectlref/iom/IOMORADIR.html

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

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In addition to amending the final rule development and issuance of draft As described in the preamble to the as described previously in response to documents resulting from international proposed rule, all guidelines are now comments, we are making one revision negotiations, we have modified the final treated as guidance documents (65 FR that will improve our ability to rule to state that when issuing ‘‘draft’’ 7321 at 7326). Because we no longer participate in international negotiations guidances that are the product of issue guidelines, we need not determine on guidance documents. As described in international negotiations, we need not whether they would warrant a Level 1 § 10.115(i)(1) and (i)(2), a guidance apply the provisions of § 10.115(i)(1) or Level 2 determination. If any document must: (1) Include the term and (i)(2). However, we recognize and documents previously issued as ‘‘guidance,’’ (2) identify the center(s) or the final rule provides that final guidelines are amended, we will follow office(s) issuing the document, (3) guidances that are the product of the same procedures used for amending identify the activity to which and the international negotiations must comply guidance documents (i.e., we will people to whom the document applies, with all of the provisions of § 10.115(i). determine whether modifying the (4) include a statement of the We anticipate that this amendment will document meets the criteria for a Level document’s nonbinding effect, (5) provide many advantages, including our 1 or Level 2 change). include the date of issuance, (6) note if ability to: (1) Provide more time for (Comment 44) One comment asked it is a revision to a previously issued public comment on draft guidance whether we ensure that all broadly guidance, and (7) contain the word documents that are the result of disseminated letters are posted on the ‘‘draft’’ if the document is a draft international negotiations, (2) receive Internet and whether we have guidance. Furthermore, guidance more public comments on these draft procedures in place for quality control documents must not include mandatory documents, (3) negotiate based on issues of this process. language such as ‘‘must’’ or ‘‘required’’ raised in public comments more We currently post all broadly unless we use those words to describe effectively, and (4) resume international disseminated letters on the Internet, a statutory or regulatory requirement. negotiations in a timely manner. including ‘‘Dear Doctor’’ letters, and In accordance with our mission, we letters that are broadly circulated but do actively participate in international III. Conforming Amendments not provide the agency’s current efforts to reduce the burden of We refer to guidelines issued under thinking on a regulatory issue. All regulation, harmonize regulatory former § 10.90(b) throughout our broadly disseminated letters that fall requirements, and achieve appropriate regulations. Because we are revising our under the definition of guidance reciprocal arrangements (section administrative regulations by deleting documents are issued under the 903(b)(3) of the act 21 U.S.C. 393(b)(3)). guidelines and adding guidance procedures described in this rule. Each Through these efforts, we frequently documents issued under § 10.115, we center and office has personnel who negotiate guidance documents with are making conforming amendments to determine whether a broadly representatives of other countries. For 21 CFR parts 7, 10, 14, 19, 25, 101, 107, disseminated letter meets the criteria for example, our participation in the 110, 114, 170, 310, 312, 314, 316, 500, a guidance document and should be International Conference on 514, 601, 803, 814, and 860 to reflect issued as such. Harmonisation of Technical our changes. We are also adding (Comment 45) One comment asked Requirements for Registration of § 601.29, Guidance documents, to the whether we post on the Internet letters Pharmaceuticals for Human Use (ICH) biologics regulations, to be consistent containing information about public has allowed us to work with with §§ 312.145, 314.445, and 814.20. health alerts. representatives of regulatory authorities These conforming amendments will In § 10.115(b)(3), we clarify that from Europe, Japan, and the United ensure the accuracy and consistency of guidance documents do not include States and experts from the the regulations. general information documents pharmaceutical industry in the three provided to consumers or health regions to develop numerous guidance IV. Environmental Impact professionals. Public health alerts fall documents on the regulation of human The agency has determined under 21 within this category of documents. drug and biological products. CFR 25.30 that this action is of a type While public health alerts are not When draft documents are negotiated that does not individually or guidance documents, and the comment with representatives of other countries, cumulatively have a significant effect on is beyond the scope of this rulemaking, we seek public comment on the the human environment. Therefore, we do post such information on the resulting documents. We believe it is neither an environmental assessment Internet, as appropriate. important to publish draft documents nor an environmental impact statement (Comment 46) One comment for comment at the same time as other is required statement would be required. questioned whether we have a countries so we may review the public mechanism in place for receiving and comments and resume negotiations in a V. Analysis of Impact evaluating suggestions for novel or more timely manner. However, other We have examined the impacts of the efficient procedures. The same comment countries do not follow our GGP’s; final rule under Executive Order 12866, suggested that we create a data base that therefore internationally negotiated the Regulatory Flexibility Act (5 U.S.C. contains all correspondence issued to a draft documents often do not comply 601–612), and the Unfunded Mandates company. The comment also requested with all of the provisions of Reform Act of 1995 (Public Law 104–4). that we post on the Internet all of our § 10.115(i)(1) and (i)(2). For example, Executive Order 12866 directs agencies speeches and the preamble to the documents negotiated through ICH do to assess all costs and benefits of September 29, 1978, current good not include the Center for Drug available regulatory alternatives and,

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Administrative practice and may have a significant economic impact 21 CFR Part 10 procedure, Animal drugs, Confidential on a substantial number of small business information, Reporting and entities, an agency must consider Administrative practice and recordkeeping requirements. alternatives that would minimize the procedure, News media. 21 CFR Part 601 economic impact of the rule on small 21 CFR Part 14 entities. Section 202(a) of the Unfunded Administrative practice and Mandates Reform Act requires that Administrative practice and procedure, Biologics, Confidential agencies prepare a written assessment of procedure, Advisory committees, Color business information. additives, Drugs, Radiation protection. anticipated costs and benefits before 21 CFR Part 803 proposing any rule that may result in an 21 CFR Part 19 expenditure by State, local, and tribal Imports, Medical devices, Reporting governments, in the aggregate, or by the Conflict of interests. and recordkeeping requirements. private sector, of $100 million in any 21 CFR Part 25 21 CFR Part 814 one year (adjusted annually for Administrative practice and inflation). Environmental impact statements, procedure, Confidential business We believe that this final rule is Foreign relations, Reporting and recordkeeping requirements. information, Medical devices, Medical consistent with the regulatory research, Reporting and recordkeeping philosophy and principles identified in 21 CFR Part 101 requirements. Executive Order 12866 and in these two Food labeling, Nutrition, Reporting statutes. This rule does not impose any 21 CFR Part 860 and recordkeeping requirements. mandates on State, local, or tribal Administrative practice and governments. The rule will not be 21 CFR Part 107 procedures, Medical devices. significant as defined by the Executive Food labeling, Infants and children, Therefore, under the Federal Food, Order and will not require further Nutrition, Reporting and recordkeeping Drug, and Cosmetic Act, the Public analysis under the Regulatory requirements, Signs and symbols. Health Service Act, and under authority Flexibility Act. The Unfunded Mandates delegated to the Commissioner of Food Reform Act does not require us to 21 CFR Part 110 and Drugs, 21 CFR parts 7, 10, 14, 19, prepare a statement of costs and benefits Food packaging, Foods. 25, 101, 107, 110, 114, 170, 310, 312, for the rule because the rule in any 1- 314, 316, 500, 514, 601, 803, 814, and year expenditure would not exceed 21 CFR Part 114 860 are amended as follows: $100 million adjusted for inflation. The Food packaging, Foods, Reporting and current inflation-adjusted statutory PART 7ÐENFORCEMENT POLICY threshold is $110 million. recordkeeping requirements. 21 CFR Part 170 1. The authority citation for 21 CFR VI. Paperwork Reduction Act of 1995 part 7 continues to read as follows: Administrative practice and This regulation would impose no procedure, Food additives, Reporting Authority: 21 U.S.C. 321–393; 42 U.S.C. 241, 262, 263b–263n, 264. additional reporting or recordkeeping and recordkeeping requirements. requirements. Therefore, clearance by § 7.1 [Amended] the Office of Management and Budget 21 CFR Part 310 2. In § 7.1, remove the word under the Paperwork Reduction Act of Administrative practice and 1995 is not required. ‘‘guidelines’’ and add in its place the procedure, Drugs, Labeling, Medical word ‘‘guidance’’. VII. Federalism devices, Reporting and recordkeeping requirements. Subpart C [Amended] We have analyzed this final rule in 21 CFR Part 312 3. In the heading for subpart C, accordance with the principles set forth consisting of §§ 7.40 through 7.59, in Executive Order 13132. We have Drugs, Exports, Imports, remove the word ‘‘guidelines’’ and add determined that the rule does not Investigations, Labeling, Medical in its place the word ‘‘guidance’’. contain policies that have substantial research, Reporting and recordkeeping direct effects on the States, on the requirements, Safety. § 7.40 [Amended] relationship between National 21 CFR Part 314 4. In 7.40(a), remove the word Government and the States, or on the ‘‘guidelines’’ and add in its place the distribution of power and Administrative practice and word ‘‘guidance’’. responsibilities among the various procedure, Confidential business levels of government. Accordingly, we information, Drugs, Reporting and PART 10ÐADMINISTRATIVE have concluded that the rule does not recordkeeping requirements. PRACTICES AND PROCEDURES contain policies that have federalism 21 CFR Part 316 implications as defined in the order 5. The authority citation for 21 CFR and, consequently, a federalism Administrative practice and part 10 continues to read as follows: summary impact statement is not procedure, Drugs, Reporting and Authority: 5 U.S.C. 551–558, 701–706; 15 required. recordkeeping requirements. U.S.C. 1451–1461; 21 U.S.C. 141–149, 321–

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397, 467f, 679, 821, 1034; 28 U.S.C. 2112; 42 existing practices or minor changes in guidance document should be revised or U.S.C. 201, 262, 263b, 264. interpretation or policy. Level 2 withdrawn and, if applicable, how it § 10.20 [Amended] guidance documents include all should be revised. guidance documents that are not (5) Once a year, FDA will publish, 6. In § 10.20(j)(1)(v), remove the classified as Level 1. both in the Federal Register and on the phrase ‘‘guidelines filed under (3) ‘‘You’’ refers to all affected parties Internet, a list of possible topics for § 10.90(b)’’ and add in its place the outside of FDA. future guidance document development words ‘‘guidance documents developed (d) Are you or FDA required to follow or revision during the next year. You under § 10.115’’. a guidance document? can comment on this list (e.g., by (1) No. Guidance documents do not § 10.45 [Amended] suggesting alternatives or making establish legally enforceable rights or recommendations on the topics that 7. In § 10.45(d), remove the words ‘‘on responsibilities. They do not legally FDA is considering). a guideline issued under § 10.90,’’. bind the public or FDA. (6) To participate in the development (2) You may choose to use an § 10.85 [Amended] and issuance of guidance documents approach other than the one set forth in through one of the mechanisms 8. In § 10.85, remove paragraph (d)(5). a guidance document. However, your described in paragraphs (f)(1), (f)(2), or alternative approach must comply with § 10.90 [Amended] (f)(4) of this section, you should contact the relevant statutes and regulations. the center or office that is responsible 9. In § 10.90, remove ‘‘guidelines,’’ FDA is willing to discuss an alternative for the regulatory activity covered by the from the section heading and remove approach with you to ensure that it guidance document. and reserve paragraph (b). complies with the relevant statutes and (7) If FDA agrees to draft or revise a 10. Add § 10.115 to subpart B to read regulations. guidance document, under a suggestion as follows: (3) Although guidance documents do made under paragraphs (f)(1), (f)(2), not legally bind FDA, they represent the § 10.115 Good guidance practices. (f)(3) or (f)(4) of this section, you can agency’s current thinking. Therefore, participate in the development of that (a) What are good guidance practices? FDA employees may depart from guidance document under the Good guidance practices (GGP’s) are guidance documents only with procedures described in paragraph (g) of FDA’s policies and procedures for appropriate justification and this section. developing, issuing, and using guidance supervisory concurrence. (g) What are FDA’s procedures for documents. (e) Can FDA use means other than a developing and issuing guidance (b) What is a guidance document? guidance document to communicate documents? (1) Guidance documents are new agency policy or a new regulatory (1) FDA’s procedures for the documents prepared for FDA staff, approach to a broad public audience? development and issuance of Level 1 applicants/sponsors, and the public that The agency may not use documents or guidance documents are as follows: describe the agency’s interpretation of other means of communication that are or policy on a regulatory issue. excluded from the definition of (i) Before FDA prepares a draft of a (2) Guidance documents include, but guidance document to informally Level 1 guidance document, FDA can are not limited to, documents that relate communicate new or different seek or accept early input from to: The design, production, labeling, regulatory expectations to a broad individuals or groups outside the promotion, manufacturing, and testing public audience for the first time. These agency. For example, FDA can do this of regulated products; the processing, GGP’s must be followed whenever by participating in or holding public content, and evaluation or approval of regulatory expectations that are not meetings and workshops. submissions; and inspection and readily apparent from the statute or (ii) After FDA prepares a draft of a enforcement policies. regulations are first communicated to a Level 1 guidance document, FDA will: (3) Guidance documents do not broad public audience. (A) Publish a notice in the Federal include: Documents relating to internal (f) How can you participate in the Register announcing that the draft FDA procedures, agency reports, general development and issuance of guidance guidance document is available; information documents provided to documents? (B) Post the draft guidance document consumers or health professionals, (1) You can provide input on on the Internet and make it available in speeches, journal articles and editorials, guidance documents that FDA is hard copy; and media interviews, press materials, developing under the procedures (C) Invite your comment on the draft warning letters, memoranda of described in paragraph (g) of this guidance document. Paragraph (h) of understanding, or other section. this section tells you how to submit communications directed to individual (2) You can suggest areas for guidance your comments. persons or firms. document development. Your (iii) After FDA prepares a draft of a (c) What other terms have a special suggestions should address why a Level 1 guidance document, FDA also meaning? guidance document is necessary. can: (1) ‘‘Level 1 guidance documents’’ (3) You can submit drafts of proposed (A) Hold public meetings or include guidance documents that: guidance documents for FDA to workshops; or (i) Set forth initial interpretations of consider. When you do so, you should (B) Present the draft guidance statutory or regulatory requirements; mark the document ‘‘Guidance document to an advisory committee for (ii) Set forth changes in interpretation Document Submission’’ and submit it to review. or policy that are of more than a minor Dockets Management Branch (HFA– (iv) After providing an opportunity for nature; 305), 5630 Fishers Lane, rm. 1061, public comment on a Level 1 guidance (iii) Include complex scientific issues; Rockville, MD 20852. document, FDA will: or (4) You can, at any time, suggest that (A) Review any comments received (iv) Cover highly controversial issues. FDA revise or withdraw an already and prepare the final version of the (2) ‘‘Level 2 guidance documents’’ are existing guidance document. Your guidance document that incorporates guidance documents that set forth suggestion should address why the suggested changes, when appropriate;

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(B) Publish a notice in the Federal guidance documents in response to your (2) When significant changes are Register announcing that the guidance comments when appropriate. made to the statute or regulations, the document is available; (h) How should you submit comments agency will review and, if appropriate, (C) Post the guidance document on on a guidance document? revise guidance documents relating to the Internet and make it available in (1) If you choose to submit comments that changed statute or regulation. hard copy; and on any guidance document under (3) As discussed in paragraph (f)(3) of (D) Implement the guidance paragraph (g) of this section, you must this section, you may at any time document. send them to the Dockets Management suggest that FDA revise a guidance (v) After providing an opportunity for Branch (HFA–305), 5630 Fishers Lane, document. comment, FDA may decide that it rm. 1061, Rockville, MD 20852. (l) How will FDA ensure that FDA should issue another draft of the (2) Comments should identify the staff are following GGP’s? guidance document. In this case, FDA docket number on the guidance (1) All current and new FDA will follow the steps in paragraphs document, if such a docket number employees involved in the (g)(1)(ii), (g)(1)(iii), and (g)(1)(iv) of this exists. For documents without a docket development, issuance, or application of section. number, the title of the guidance guidance documents will be trained (2) FDA will not seek your comment document should be included. regarding the agency’s GGP’s. before it implements a Level 1 guidance (3) Comments will be available to the (2) FDA centers and offices will document if the agency determines that public in accordance with FDA’s monitor the development and issuance prior public participation is not feasible regulations on submission of documents of guidance documents to ensure that or appropriate. to the Dockets Management Branch GGP’s are being followed. (3) FDA will use the following specified in § 10.20(j). (m) How can you get copies of FDA’s procedures for developing and issuing (i) What standard elements must FDA guidance documents? FDA will make Level 1 guidance documents under the include in a guidance document? copies available in hard copy and, as circumstances described in paragraph (1) A guidance document must: feasible, through the Internet. (i) Include the term ‘‘guidance,’’ (g)(2) of this section: (ii) Identify the center(s) or office(s) (n) How will FDA keep you informed (i) After FDA prepares a guidance issuing the document, of the guidance documents that are document, FDA will: (iii) Identify the activity to which and available? (A) Publish a notice in the Federal the people to whom the document (1) FDA will maintain on the Internet Register announcing that the guidance applies, a current list of all guidance documents. document is available; (iv) Prominently display a statement New documents will be added to this (B) Post the guidance document on of the document’s nonbinding effect, list within 30 days of issuance. the Internet and make it available in (v) Include the date of issuance, (2) Once a year, FDA will publish in hard copy; (vi) Note if it is a revision to a the Federal Register its comprehensive (C) Immediately implement the previously issued guidance and identify list of guidance documents. The guidance document; and the document that it replaces, and comprehensive list will identify (D) Invite your comment when it (vii) Contain the word ‘‘draft’’ if the documents that have been added to the issues or publishes the guidance document is a draft guidance. list or withdrawn from the list since the document. Paragraph (h) of this section (2) Guidance documents must not previous comprehensive list. tells you how to submit your comments. include mandatory language such as (3) FDA’s guidance document lists (ii) If FDA receives comments on the ‘‘shall,’’ ‘‘must,’’ ‘‘required,’’ or will include the name of the guidance guidance document, FDA will review ‘‘requirement,’’ unless FDA is using document, issuance and revision dates, those comments and revise the guidance these words to describe a statutory or and information on how to obtain document when appropriate. regulatory requirement. copies of the document. (4) FDA will use the following (3) When issuing draft guidance (o) What can you do if you believe procedures for developing and issuing documents that are the product of that someone at FDA is not following Level 2 guidance documents: international negotiations (e.g., these GGP’s? If you believe that (i) After it prepares a guidance guidances resulting from the someone at FDA did not follow the document, FDA will: International Conference on procedures in this section or that (A) Post the guidance document on Harmonisation), FDA need not apply someone at FDA treated a guidance the Internet and make it available in paragraphs (i)(1) and (i)(2) of this document as a binding requirement, you hard copy; section. However, any final guidance should contact that person’s supervisor (B) Immediately implement the document issued according to this in the center or office that issued the guidance document, unless FDA provision must contain the elements in guidance document. If the issue cannot indicates otherwise when the document paragraphs (i)(1) and (i)(2) of this be resolved, you should contact the next is made available; and section. highest supervisor. You can also contact (C) Invite your comment on the Level (j) Who, within FDA, can approve the center or office ombudsman for 2 guidance document. Paragraph (h) of issuance of guidance documents? Each assistance in resolving the issue. If you this section tells you how to submit center and office must have written are unable to resolve the issue at the your comments. procedures for the approval of guidance center or office level or if you feel that (ii) If FDA receives comments on the documents. Those procedures must you are not making progress by going guidance document, FDA will review ensure that issuance of all documents is through the chain of command, you may those comments and revise the approved by appropriate senior FDA ask the Office of the Chief Mediator and document when appropriate. If a officials. Ombudsman to become involved. version is revised, the new version will (k) How will FDA review and revise be placed on the Internet. existing guidance documents? PART 14ÐPUBLIC HEARING BEFORE (5) You can comment on any guidance (1) The agency will periodically A PUBLIC ADVISORY COMMITTEE document at any time. Paragraph (h) of review existing guidance documents to this section tells you how to submit determine whether they need to be 11. The authority citation for 21 CFR your comments. FDA will revise changed or withdrawn. part 14 continues to read as follows:

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Authority: 5 U.S.C. App. 2; 15 U.S.C. PART 110ÐCURRENT GOOD § 312.145 Guidance documents. 1451–1461; 21 U.S.C. 141–149, 321–394, MANUFACTURING PRACTICE IN (a) FDA has made available guidance 467f, 679, 821, 1034; 28 U.S.C. 2112; 42 MANUFACTURING, PACKING, OR U.S.C. 201, 262, 263b, 264. documents under § 10.115 of this HOLDING HUMAN FOOD chapter to help you to comply with § 14.27 [Amended] certain requirements of this part. 22. The authority citation for 21 CFR 12. In § 14.27(b)(3), remove the word part 110 continues to read as follows: (b) The Center for Drug Evaluation and Research (CDER) and the Center for ‘‘guidelines’’ and add in its place the Authority: 21 U.S.C. 342, 371, 374; 42 words ‘‘guidance documents’’. U.S.C. 264. Biologics Evaluation and Research (CBER) maintain lists of guidance § 14.33 [Amended] § 110.80 [Amended] documents that apply to the centers’ 13. In § 14.33(c), remove the word 23. In § 110.80, remove the word regulations. The lists are maintained on ‘‘guidelines’’ and add in its place the ‘‘guidelines,’’ in paragraphs (a)(3) and the Internet and are published annually words ‘‘guidance documents’’. (a)(4). in the Federal Register. A request for a copy of the CDER list should be directed PART 19ÐSTANDARDS OF CONDUCT PART 114ÐACIDIFIED FOODS to the Office of Training and AND CONFLICTS OF INTEREST Communications, Division of 24. The authority citation for 21 CFR Communications Management, Drug 14. The authority citation for 21 CFR part 114 continues to read as follows: Information Branch (HFD–210), Center part 19 continues to read as follows: Authority: 21 U.S.C. 342, 371, 374; 42 for Drug Evaluation and Research, Food U.S.C. 264. Authority: 21 U.S.C. 371. and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. A request § 114.100 [Amended] § 19.10 [Amended] for a copy of the CBER list should be 25. In § 114.100(a), remove the word directed to the Office of 15. In § 19.10(c), remove the word ‘‘guidelines’’ and add in its place the Communication, Training, and ‘‘guidelines’’ and add in its place the words ‘‘guidance documents’’. Manufacturers Assistance (HFM–40), words ‘‘guidance documents’’. Center for Biologics Evaluation and PART 170ÐFOOD ADDITIVES PART 25ÐENVIRONMENTAL IMPACT Research, Food and Drug CONSIDERATIONS 26. The authority citation for 21 CFR Administration, 1401 Rockville Pike, part 170 continues to read as follows: Rockville, MD 20852–1448. 16. The authority citation for 21 CFR Authority: 21 U.S.C. 321, 341, 342, 346a, PART 314ÐAPPLICATIONS FOR FDA part 25 continues to read as follows: 348, 371. APPROVAL TO MARKET A NEW DRUG Authority: 21 U.S.C. 321–393; 42 U.S.C. § 170.39 [Amended] 262, 263b–264; 42 U.S.C. 4321, 4332; 40 CFR 33. The authority citation for 21 CFR parts 1500–1508; E.O. 11514, 35 FR 4247, 3 27. In § 170.39(h), remove the word part 314 continues to read as follows: CFR, 1971 Comp., p. 531–533 as amended by ‘‘guidelines’’ wherever it appears and E.O. 11991, 42 FR 26967, 3 CFR, 1978 Comp., add in its place the words ‘‘guidance Authority: 21 U.S.C. 321, 331, 351, 352, p. 123–124 and E.O. 12114, 44 FR 1957, 3 documents’’. 353, 355, 371, 374, 379e. CFR, 1980 Comp., p. 356–360. § 314.50 [Amended] § 25.30 [Amended] PART 310ÐNEW DRUGS 34. In § 314.50, in the introductory 17. In § 25.30(h), remove the word 28. The authority citation for 21 CFR text remove the word ‘‘guidelines’’ and ‘‘guidelines’’ and add in its place the part 310 continues to read as follows: add in its place the words ‘‘guidance words ‘‘guidance documents’’. Authority: 21 U.S.C. 321, 331, 351, 352, documents’’. 353, 355, 360b–360f, 360j, 361(a), 371, 374, PART 101ÐFOOD LABELING 375, 379(e); 42 U.S.C. 216, 241, 242(a), 262, § 314.70 [Amended] 263b–263n. 35. In § 314.70(a), remove the words 18. The authority citation for 21 CFR § 310.500 [Amended] ‘‘guideline, notice,’’ and add in their part 101 continues to read as follows: place the word ‘‘notice’’. Authority: 15 U.S.C. 1453, 1454, 1455; 21 29. In § 310.500(e), remove the words U.S.C. 321, 331, 342, 343, 348, 371. ‘‘guidelines’’ and ‘‘guideline’’, § 314.94 [Amended] respectively, and add in their place the § 101.9 [Amended] words ‘‘guidance’’ and ‘‘guidance on’’, 36. In § 314.94, in the introductory respectively. text remove the words ‘‘guidelines’’ and 19. In § 101.9(b)(7)(vi), remove the add in its place the words ‘‘guidance word ‘‘guideline’’ wherever it appears PART 312ÐINVESTIGATIONAL NEW documents’’. and add in its place the words DRUG APPLICATION ‘‘guidance document’’. § 314.105 [Amended] 30. The authority citation for 21 CFR 37. In § 314.105(c), remove the word PART 107ÐINFANT FORMULA part 312 continues to read as follows: ‘‘guidelines’’ and add in its place the 20. The authority citation for 21 CFR Authority: 21 U.S.C. 321, 331, 351, 352, words ‘‘guidance documents’’. 353, 355, 371; 42 U.S.C. 262. part 107 continues to read as follows: § 314.420 [Amended] Authority: 21 U.S.C. 321, 343, 350a, 371. § 312.23 [Amended] 31. In § 312.23(a)(8), remove the word 38. In § 314.420(c), remove the words § 107.270 [Amended] ‘‘guidelines’’ and add in its place the ‘‘under § 10.90(b) a guideline’’ and add in their place the word ‘‘guidance’’. 21. In § 107.270, remove the word words ‘‘guidance documents.’’ ‘‘guidelines’’ and add in its place the 32. Revise § 312.145 to read as 39. Revise § 314.445 to read as word ‘‘guidance’’. follows: follows:

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§ 314.445 Guidance documents. PART 601ÐLICENSING Rockville, MD 20850, FAX 301–443– (a) FDA has made available guidance 8818. documents under § 10.115 of this 46. The authority citation for 21 CFR * * * * * chapter to help you to comply with part 601 continues to read as follows: certain requirements of this part. Authority: 15 U.S.C. 1451–1561; 21 U.S.C. PART 860ÐMEDICAL DEVICE (b) The Center for Drug Evaluation 321, 351, 352, 353, 355, 360, 360c–360f, CLASSIFICATION PROCEDURES and Research (CDER) maintains a list of 360h–360j, 371, 374, 379e, 381; 42 U.S.C. guidance documents that apply to 216, 241, 262, 263; sec. 122, Pub. L. 105–115, 52. The authority citation for 21 CFR CDER’s regulations. The list is 111 Stat. 2322 (21 U.S.C. 355 note). part 860 continues to read as follows: maintained on the Internet and is 47. Add § 601.29 to subpart C to read Authority: 21 U.S.C. 360c, 360d, 360e, published annually in the Federal as follows: 360i, 360j, 371, 374. Register. A request for a copy of the § 601.29 Guidance documents. CDER list should be directed to the § 860.3 [Amended] Office of Training and Communications, (a) FDA has made available guidance 53. In § 860.3(c)(2), remove the words Division of Communications documents under § 10.115 of this ‘‘guidelines’’ and ‘‘guidelines for’’ and Management, Drug Information Branch chapter to help you comply with certain add in their place the words ‘‘guidance (HFD–210), Center for Drug Evaluation requirements of this part. documents’’ and ‘‘guidance on’’, and Research, Food and Drug (b) The Center for Biologics respectively. Evaluation and Research (CBER) Administration, 5600 Fishers Lane, Dated: September 1, 2000. Rockville, MD 20857. maintains a list of guidance documents that apply to the center’s regulations. Margaret M. Dotzel, PART 316ÐORPHAN DRUGS The lists are maintained on the Internet Associate Commissioner for Policy. and are published annually in the [FR Doc. 00–23887 Filed 9–18–00; 8:45 am] 40. The authority citation for 21 CFR Federal Register. You may request a BILLING CODE 4160±01±F part 316 continues to read as follows: copy of the CBER list from the Office of Authority: 21 U.S.C. 360aa, 360bb, 360cc, Communication, Training, and 360dd, 371. Manufacturers Assistance (HFM–40), DEPARTMENT OF HEALTH AND HUMAN SERVICES 41. Revise § 316.50 to read as follows: Center for Biologics Evaluation and Research, Food and Drug Food and Drug Administration § 316.50 Guidance documents. Administration, 1401 Rockville Pike, FDA’s Office of Orphan Products Rockville, MD 20852–1448. Development will maintain and make 21 CFR Parts 203 and 205 publicly available a list of guidance PART 803ÐMEDICAL DEVICE [Docket No. 92N±0297] documents that apply to the regulations REPORTING in this part. The list is maintained on Prescription Drug Marketing Act of the Internet and is published annually 48. The authority citation for 21 CFR 1987; Prescription Drug Amendments in the Federal Register. A request for a part 803 continues to read as follows: of 1992; Policies, Requirements, and copy of the list should be directed to the Authority: 21 U.S.C. 352, 360, 360i, 360j, Administration Procedures; Public Office of Orphan Products Development 371, 374. Hearing (HF–35), Food and Drug § 803.14 [Amended] AGENCY: Administration, 5600 Fishers Lane, Food and Drug Administration, Rockville, MD 20857. 49. In § 803.14(b), remove the word HHS. ‘‘guidelines’’ and add in its place the ACTION: Announcement of public PART 500ÐGENERAL words ‘‘guidance documents’’. hearing; request for comments. 42. The authority citation for 21 CFR PART 814ÐPREMARKET APPROVAL SUMMARY: The Food and Drug part 500 continues to read as follows: OF MEDICAL DEVICES Administration (FDA) is announcing a Authority: 21 U.S.C. 321, 331, 342, 343, public hearing to discuss certain 348, 351, 352, 353, 360b, 371. 50. The authority citation for 21 CFR requirements of the final rule part 814 continues to read as follows: implementing the Prescription Drug § 500.80 [Amended] Authority: 21 U.S.C. 351, 352, 353, 360, Marketing Act of 1987 (PDMA), as 43. In § 500.80(a), remove the word 360c–360j, 371, 372, 373, 374, 375, 379, 379e, modified by the Prescription Drug ‘‘guidelines’’ wherever it appears and 381. Amendments of 1992 (PDA) and the add in its place the words ‘‘guidance 51. In § 814.20, revise paragraph (g) to FDA Modernization Act of 1997 documents’’. read as follows: (Modernization Act), which published in the Federal Register of December 3, PART 514ÐNEW ANIMAL DRUG § 814.20 Application. 1999 (64 FR 67720), (hereinafter referred APPLICATIONS * * * * * to as the PDMA final rule). The purpose (g) FDA has issued a PMA guidance of the hearing is to elicit comment from 44. The authority citation for 21 CFR document to assist the applicant in the interested persons, including part 514 continues to read as follows: arrangement and content of a PMA. This professional groups and associations, Authority: 21 U.S.C. 351, 352, 360b, 371, guidance document is available on the the regulated industry, health care 379e, 381. Internet at http://www.fda.gov/cdrh/ professionals, and consumers, on the dsma/pmaman/front.html. This potential impact of certain requirements § 514.1 [Amended] guidance document is also available in the PDMA final rule relating to 45. In § 514.1(d)(2), remove the word upon request from the Center for wholesale distribution of prescription ‘‘guidelines’’ wherever it appears and Devices and Radiological Health, drugs by distributors that are not add in its place the words ‘‘guidance Division of Small Manufacturers authorized distributors of record, and documents’’. Assistance (HFZ–220), 1350 Piccard Dr., distribution of blood derivatives by

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