Manual of Standard Operating Procedures and Policies

General Information
Procedures for the Preparation, Routing and Issuance of Guidance Documents
SOPP 8002	Version #4	Date: January 15, 2004

Purpose

This document provides instruction to you, Center for Biologics Evaluation and Research (CBER) staff, on the proper development, formatting, processing, routing, and use of FDA/CBER guidance documents. This document will also help to ensure that you adhere to Good Guidance Practices (GGPs) established in "Administrative Practices and Procedures; Good Guidance Practices," 21 CFR 10.115, in the development, issuance, and use of guidance documents.

Definitions

Guidance Documents

Documents prepared for FDA staff, applicants/sponsors, and the public that:

Describe the agency's interpretation of or policy on a regulatory issue;
Relate to the processing, content, and evaluation/approval of submissions;
Relate to the design, production, manufacturing, testing, labeling, and promotion of regulated products;
Relate to inspection and enforcement policies and procedures.

Guidance documents do not include documents related to:

Internal FDA procedures;
Agency reports;
General information provided to consumers or health professionals;
Speeches;
Journal articles and editorials;
Media interviews and press materials;
Warning letters;
Memoranda of understanding;
Other communications or actions taken by individuals at FDA or directed to individual persons or firms;
Documents directed at public health emergencies.

Level 1 Guidance Documents

Guidance documents that:

Set forth initial interpretations of statutory or regulatory requirements;
Set forth major changes in interpretation of statutory or regulatory requirements, or policy;
Include novel or complex scientific issues; or,
Cover highly controversial issues.

Level 2 Guidance Documents

All guidance documents not considered to be Level 1. Level 2 documents set forth existing practices or minor changes in interpretation of statutory or regulatory requirements, or policy.

NOA

A "Notice of Availability" is a notice issued in the Federal Register that:

Notifies the public of the issuance of the guidance document;
Invites comment on the guidance document; and
Informs the public how to obtain copies of the guidance document.

RPS

This is an acronym for the Regulations and Policy Staff in the Center for Biologics and Evaluation (CBER).

NOTE: "Guideline," "Memorandum to Industry," "Blood Memo," and "Points to Consider" are terms that formerly applied to guidance documents. These terms are no longer used when drafting new or revised guidance documents.

Background

Guidance documents provide to the regulated industry and FDA assistance by clarifying requirements imposed by Congress or promulgated by FDA and by explaining how industry and FDA may comply with those statutory and regulatory requirements. Guidance documents provide industry with specific details that often are not included in the relevant statutes and regulations. These documents also provide specific review and enforcement approaches to help ensure that FDA's employees implement FDA's mandate in an effective, fair, and consistent manner. Guidance documents do not establish legally enforceable rights or responsibilities and, as such, are not binding on the agency or the public. Rather, they explain how the agency believes the statutes and regulations apply to regulated activities and reflect FDA's current thinking on the subject addressed in the document.

The "Food and Drug Administration Modernization Act of 1997" (FDAMA) amends the Federal Food, Drug, and Cosmetic Act by incorporating aspects of good guidance practices, including the provision for public participation in the development of significant guidance documents and the opportunity for public comment upon issuance of all guidance. In response to FDAMA, FDA codified its policies and procedures for the development and issuance of guidance documents in 21 CFR 10.115.

Policy

CBER staff involved in the development, issuance, and application of guidance documents must follow the GGP regulations at 21 CFR 10.115. Guidance documents are documents prepared for FDA staff, applicants/sponsors, and the public and describe FDA's interpretation of or policy on a regulatory issue. It is important that you follow the templates for formatting and write all guidance documents in "Plain Language." (See Ref.4) Guidance documents are intended to represent our current thinking on matters discussed in the documents. Furthermore, we are obligated to amend guidance documents in a timely manner to clarify any changes in our policies and procedures. Because guidance documents represent FDA's current thinking, CBER staff may depart from guidance documents only with appropriate justification and supervisory concurrence (§ 10.115(d)(3)). Any consistent deviation from a guidance document indicates that we should revise it.

Procedures and Responsibilities

General Information

FDA has adopted a two-level approach to developing guidance documents, depending on whether the guidance document is a Level 1 guidance or a Level 2 guidance (see Definitions, above). Once a year, FDA publishes in the Federal Register a comprehensive list of available guidance documents.

Level 1 Guidance Documents

For level 1 guidance, FDA publishes a notice in the Federal Register announcing the availability of the draft guidance for public comment. CBER makes the draft guidance available through a variety of methods including the CBER web site, other web sites when jointly issued with another Center, the FDA Dockets web site, and by mail (upon request). Generally, FDA offers a comment period of 60 to 90 days. CBER may recommend a shorter or longer comment period, if appropriate. After reviewing the public comments, CBER will revise the guidance, incorporating recommended changes, when appropriate, and publish another notice in the Federal Register, announcing the availability of the final guidance. The public may submit at any time comments on the final guidance.
CBER may issue a level 1 guidance for immediate implementation if prior public participation is not feasible or is not appropriate. In this case, FDA still offers an opportunity for public comment by a Federal Register notice announcing the availability of the guidance. CBER will review any public comments submitted and revise the guidance as appropriate.

Level 2 Guidance Documents

For a level 2 guidance, CBER posts the guidance on the CBER web site, other web sites when jointly issued with another Center, the FDA Dockets web site, and by mail (upon request). Unless otherwise stated when we make the guidance available, the guidance is effective immediately. The public may submit at any time comments on the guidance.
It is CBER's option to prepare a Federal Register notice announcing the availability of the level 2 guidance.

Paperwork Implications

Some guidance documents may have associated with them information collection burdens (paperwork burdens), beyond those associated with the related regulations.
The agency is required to evaluate paperwork burdens, such as information that should be sent to FDA, recordkeeping, labeling changes, or third party notifications, and apply for approval by the Office of Management and Budget (OMB) (5 CFR Part 1320), see "How to request OMB approval for information collection in a guidance document" (Ref. 6).
OMB approval is required even if the paperwork burdens result from voluntary compliance with FDA recommendations.
If you suspect that your guidance generates new paperwork burdens in addition to those associated with existing regulations, as early as possible consult with RPS.
RPS will prepare the documents needed for paperwork approval. The issuing Office should be prepared to provide to RPS information for estimating the paperwork burdens. This information may be required from more than just the issuing office, such as the Regulatory Information Management Staff.
Because of the need to evaluate these burdens and gain OMB approval, expect additional time in issuing a final guidance.

Communication with the Public During Guidance Development

When considering the development of guidance, CBER may freely discuss issues with the public.
If the issues to be addressed are particularly complex or controversial, you may consider holding a public meeting or advisory committee meeting on the issues before drafting the guidance.
Once preparation of a draft guidance document has been initiated but has yet to issue, you should not reveal the specifics of the guidance to the public. When the guidance has been issued in draft, issues related to the draft guidance may be discussed but you should not discuss our specific intentions regarding the final guidance. You must follow 21 CFR 10.80 for disseminating information to the public on guidance before issuance.
You may solicit information from the public at any time during the guidance development process.

Submission of Draft Guidance by Industry or the General Public to FDA

Anyone may recommend to FDA that a guidance document be created, revised, or withdrawn by FDA.
The recommendation should include a statement listing the reasons for the request. In addition, anyone may submit his/her own draft guidance.
The public should submit draft guidance through the Division of Dockets Management.
FDA has the discretion to pursue the use of such guidance and determines whether and how to revise a draft submitted by the public.
Only FDA can issue a guidance document.

Average Timeframe for Issuance of Guidance Document

Once the guidance document and request for publication memo are forwarded to RPS, it generally takes an average of 3 to 6 months to issue. This time varies depending on the number of reviews within the Center, whether another Center reviews it, paperwork issues, and other priorities set by the agency.
RPS will route the NOA and/or guidance document to the appropriate Office Director(s), the issuing Office chair or staff member "(champion)" responsible for development of the guidance, and other Centers or agencies for comment, as appropriate.
RPS can send review copies to others if requested by the champion or the Center Director. RPS may also send courtesy FYI copies to the remaining CBER Office Directors.
The option exists for CBER Coordinating Committees to discuss and provide comment on these documents at this time, or if significant issues arise following "Consideration of Public Comments on a Guidance Document" (see below).
The deadline for review depends on the complexity of the subject, number of reviewers who are asked to comment, and relative priorities. The review deadline will generally be 1-3 weeks for the NOA and guidance document.

Consideration of Public Comments on Draft Guidance

When a level 1 or level 2 guidance document is being revised in response to public comments received on an earlier publication, you must consider all comments (21 CFR 10.115(g)).
As comments are submitted to the docket, they are forwarded to the project manager in RPS, who then forwards it to the chair of the development committee.
You are not required to respond to these comments in the revised guidance document or NOA.
CBER may reject or accept comments without providing to the public an explanation through the NOA or in the guidance of why comments were accepted or rejected.
At the Center's discretion, the notice may discuss very significant comments or comments that caused significant revision to the guidance document.
You should work with appropriate staff members to complete the step of reviewing comments, revising the draft guidance, and issuing a final guidance without delay.

Consideration of Public Comments on Final Guidance

When a final guidance is issued, the NOA will offer an opportunity for additional public comment.
You must consider these comments but are not obligated to revise and reissue the guidance or to respond to the comments.
The public may comment on any guidance document at any time.

CBER's responsibilities for the preparation and issuance of guidance documents by other Centers and the Agency

When a CBER staff member is representing CBER in preparing guidance documents to be issued by another Center or the Agency, the representative must bring issues back to CBER for comment and resolution as they occur and not wait for final sign off.

Responsibilities for the preparation and issuance of CBER guidance documents

The Office Issuing the Guidance

Prior to Drafting a Guidance Document:

Form a committee to develop the policy, when appropriate. This committee may include staff from other appropriate CBER Offices, other Centers, Office of Chief Counsel (OCC), and any other individual within FDA that may contribute expertise in developing the guidance document.
Identify a leader or chair (champion) who is responsible:

for generating a timeline (or schedule) for each step in the development of the guidance document,
for preparing a short description of the guidance document (one or two paragraphs describing the problem and how the guidance will address it),
for identifying leads from other Centers/Agencies/Commissioner's Office as appropriate, and
for keeping track of the status and revising the document as needed.

The champion must also provide the following information to the Associate Director for Policy, CBER, and RPS as soon as possible:

the leader's name,
the timeline (identify accelerated timelines),
intent of the guidance document, and
the names of leads from other components/Centers, as appropriate.

Consider whether the document has implications for FDA staff external to CBER and, if so, coordinate preparation with the appropriate technical staff at the other Center(s), Office of Regulatory Affairs, or other appropriate organizations.
Consult with OCC early in the preparation process when there are extensive legal issues. Early coordination will help avoid delays when interested Center(s) and OCC are asked to concur with the guidance document prior to publication.
When a scientific/regulatory/policy issue is raised by a committee member during guidance development, that committee member (or that Committee member's Office) is responsible for efficiently researching, developing a position and proposing language for the guidance to facilitate publication in a timely manner. If jurisdiction of the issue raised by a committee member resides in another Office, then the committee representative of that Office is responsible for researching the issue and providing a proposed solution. If there is any jurisdiction ambiguity, then the person chairing the committee will decide which Office is charged with addressing the issue to ensure timely issuance of the guidance

Drafting of Guidance Documents

Draft all guidance documents in "Plain Language." (Also called "Plain English.") Additional information about Plain Language is available from FDA's web site (Ref. 5) and from the RPS, CBER. Guidance documents not in Plain Language may be returned for redrafting.
Use only Microsoft Word on a PC Platform to prepare guidance documents. Do not use a MacIntosh computer to prepare the document.
Avoid the use of other software, such as "Excel" or "PowerPoint" unless absolutely necessary.
Use the standardized format for guidance documents, including standardized cover pages.
Do not use a draft taken from the CBER web page, when revising guidance. You may obtain copies of the posted drafts from RPS.
Use Appendix 1 for proper formatting, for sample formats for cover pages, instructions on obtaining existing guidance in Microsoft Word format, and other standardized language.
Additional information and help is available from RPS.
Use preformatted outlines to help ensure a standardized construction of guidance documents in CBER. Appendix 2, Templates for Drafting Guidance Documents for CBER

Forwarding to RPS the Guidance Document for Issuance

Obtain agreement from your Office Director or designee following your Office procedures before forwarding to RPS the draft guidance for issuance.
Forward to RPS the draft guidance document in electronic format with a request for publication memo or email addressed to the Director, RPS, sent through or signed by the Office Director with primary responsibility for the document. This memo should contain the following information:

Request for publication of the NOA and/or posting of the guidance document on the CBER web site;
A brief description of the purpose of the document;
Any background information on the issues not covered in the draft guidance, which is important to understanding the guidance;
Whether the guidance document is level 1 or level 2 and, if level 1, whether the guidance should be issued for immediate implementation;
If you are recommending that a guidance document be issued for immediate implementation, before an opportunity for public comment, add a brief justification for that recommendation;
A proposed time frame for the announcement;
Primary contact person for the guidance;
The status of the information collection burden assessment (paperwork burden) of the guidance document, i.e., whether there is paperwork burden to be addressed in the NOA. The status should be assessed with the assistance of your office's staff member trained in information collection burden.
If the document supercedes any previous guidance.

The developer of the guidance may optionally provide a draft NOA as an attachment to the memo. A template for the preparation of an NOA is available from RPS (or Appendix 3). If a draft NOA is not provided, RPS will draft the notice.

NOTE: Omission of significant information may result in a delay of the processing of your document.

The Regulations and Policy Staff

Final Review of Guidance Documents

Prepares the NOA.
Reviews guidance document for proper format.
Assesses guidance document for information collection burden.
Coordinates the final CBER, OCC, and general agency review of the guidance document and, as applicable, the NOA.
Receives comment on the NOA and/or guidance document from FDA staff.
Addresses comments specific to the NOA, and forwards comments specific to the guidance document to the chair of the development committee for consideration.

NOTE: If significant changes are made to the guidance document based on comments received, the document may require a second (sometimes limited) CBER review. If a second review is warranted, RPS will coordinate the review.

Circulates finalized guidance document and NOA with "blue sheet" final clearance record for Center sign off in this order: RPS Project Officer, Team Leader, and Director; Director of the Office issuing the guidance document; the Associate Director for Policy; and Director, CBER.

NOTE: Once the blue sheet is signed by the Center Director, the guidance document and NOA will not be changed unless absolutely necessary.

Sends the document to OCC, if appropriate, for final review and sign off on the blue sheet.
Sends the NOA with a copy of the guidance document (for docket display purposes only) to the Regulations Policy and Management Staff, Office of Policy (OP), who is responsible for routing the NOA to the Regulations Editorial Staff, OP, for review and editing. The NOA is then sent to the Deputy Commissioner for Policy for signature on the Federal Register NOA.

NOTE: A level 1 guidance document NOA is signed by the Deputy Commissioner for Policy, FDA, and a level 2 guidance document is signed by the Center Director, CBER.

Submits to the Office of Communication, Training and Manufacturers Assistance a request to post the guidance document on the CBER web site and to make the guidance document otherwise publicly available.
Forwards to the chair of the development committee copies of comments submitted by the public to the docket on the issued guidance document. These comments are for consideration in revising the issued guidance document, whether it is a level 1 draft or final, or a level 2 guidance document.

Effective Date

January 15, 2004

Appendices

Appendix 1: Tip List on Formatting CBER Guidance Documents for Posting on the Internet

Appendix 2: Templates for Drafting Guidance Documents for CBER

Appendix 3: Template for the preparation of a Notice of Availability

References

The final rule "Administrative Practices and Procedures; Good Guidance Practices," (65 FR 56468, September 19, 2000)
The Food and Drug Administration Modernization Act of 1997
SOPP 8105, "Submitting Documents for the CBER Websites"
Presidential Memorandum on Plain Language, dated June 1, 1998.
"How to request OMB approval for information collection in a guidance document"

History

Written/Revised	Approved	Approval Date	Version Number	Comment
RPS	Robert Yetter, Ph.D.	January 15, 2003	4	Revised to include OCC change in template language; also includes technical changes.
Paula McKeever, RMCC	Robert Yetter, Ph.D.	January 15, 2003	3	Addition of updated instructions and templates.
S. Sensabaugh/ G. Hicks	Rebecca Devine, Ph.D.	June 24, 1997	2	Reissued as SOPP 8002 in August 1997. No change to Guide content.
S. Ripley	Rebecca Devine, Ph.D	December 31, 1996	1	Revisions to content pursuant to FDA Modernization Act of 1997.

Manual of Standard Operating Procedures and Policies

General Information

Procedures for the Preparation, Routing and Issuance of Guidance Documents

SOPP 8002

Version #4

Date: January 15, 2004