Guidance for Review Staff and Industry Good Review Management Principles and Practices for PDUFA Products

Administrative draft guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Guidance for Review
Staff and Industry
Good Review Management
Principles and Practices for
PDUFA Products
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
April 2005
Procedural
J:\!GUIDANC\5812fnlcln5.doc
3/15/2005

Guidance for Review
Staff and Industry
Good Review Management
Principles and Practices for
PDUFA Products
Additional copies are available from:
Office of Training and Communications
Division of Drug Information, HFD-240
Center for Drug Evaluation and Research
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
(Tel) 301-827-4573
http://www.fda.gov/cder/guidance/index.htm
or
Office of Communication, Training, and
Manufacturers Assistance, HFM-40
Center for Biologics Evaluation and Research
Food and Drug Administration
1401 Rockville Pike, Rockville, MD 20852-1448
(Tel) 800-835-4709 or 301-827-1800
http://www.fda.gov/cber/guidelines.htm
For questions regarding the content of this document contact
(CDER) John Jenkins (301-594-3937) or (CBER) Robert A. Yetter (301-827-0373)
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
April 2005
Procedural

TABLE OF CONTENTS
I. 	INTRODUCTION............................................................................................................. 1
II. 	BACKGROUND ............................................................................................................... 1
III. 	FUNDAMENTALS OF GOOD REVIEW MANAGEMENT ...................................... 3
A. 	Fundamental Values ...................................................................................................................... 3
B. 	Operational Principles................................................................................................................... 4
IV. 	NDA/BLA REVIEW PROCESS ..................................................................................... 9
A. 	Filing Determination and Review Planning Phase...................................................................... 9
1. Filing Determination ....................................................................................................................... 9
2. Review Planning ............................................................................................................................ 10
B. 	Review Phase ................................................................................................................................ 16
C. 	Advisory Committee Meeting Phase .......................................................................................... 19
D. 	Action Phase ................................................................................................................................. 21
1. Wrap-Up ........................................................................................................................................ 21
2. Labeling ......................................................................................................................................... 21
3. Signatory Review Documentation.................................................................................................. 21
4. Regulatory Action .......................................................................................................................... 22
E. 	Post-Action Phase......................................................................................................................... 25
V. 	IMPLEMENTATION AND EVALUATION............................................................... 27
APPENDIX A: GLOSSARY OF ACRONYMS...................................................................... 28
APPENDIX B: REFERENCED GUIDANCES, MAPPS, AND SOPPS .............................. 30

Contains Nonbinding Recommendations
Guidance for Review Staff and Industry1
Good Review Management Principles
and Practices for PDUFA Products
This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It
does not create or confer any rights for or on any person and does not operate to bind FDA or the public.
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes
and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for
implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate
number listed on the title page of this guidance.
I. 	INTRODUCTION
This document provides guidance to industry and the review staff in the Center for Drug
Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER)
on good review management principles and practices (GRMPs) for the conduct of the first cycle
review of a new drug application (NDA), a biologics license application (BLA), or an efficacy
supplement under the Prescription Drug User Fee Act of 1992 (PDUFA). The GRMPs in this
guidance are based on the collective experience of CDER and CBER with review of applications
for PDUFA products and are intended to promote the practice of good review management based
on sound fundamental values and principles. This guidance also clarifies the roles and
responsibilities of review staff in managing the review process and identifies ways in which
NDA and BLA applicants may further the effectiveness and efficiency of the review process.
FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should
be viewed only as recommendations, unless specific regulatory or statutory requirements are
cited. The use of the word should in Agency guidances means that something is suggested or
recommended, but not required.
II. 	BACKGROUND
On June 12, 2002, the President signed the Public Health Security and Bioterrorism Preparedness
and Response Act of 2002, which includes the Prescription Drug User Fee Amendments of 2002
(PDUFA III). In conjunction with the reauthorization of PDUFA, the FDA agreed to meet
specific performance goals (PDUFA goals). These PDUFA goals are described in PDUFA
1 This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) and the Center for
Biologics Evaluation and Research (CBER) at the Food and Drug Administration.
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Contains Nonbinding Recommendations
Reauthorization Performance Goals and Procedures, an enclosure to a letter dated June 4, 2002,
from the Secretary of Health and Human Services to Congress.2 Under the PDUFA goals,
CDER and CBER agreed to create this joint guidance for review staff and industry on good
review management principles and practices as they apply to the first cycle review of NDAs,
BLAs, and efficacy supplements. The emphasis of GRMPs is on first cycle reviews of NDAs
and BLAs for PDUFA products in CDER and CBER. The principles of this guidance also
pertain, in general, to all preapproval reviews of NDAs, BLAs, and efficacy supplements.
The fundamental values and principles described in this guidance are intended to support the
FDA’s primary public health mission for human drug and biologic products,3 help the FDA
continue to define processes that fulfill the Agency’s PDUFA mandates, promote efficient use of
the FDA’s resources, and define ways in which both FDA review staff and applicants can further
the effectiveness and efficiency of the review process. This guidance is expected to lead to
greater consistency and efficiency of the review process within individual review divisions (also
called divisions in this guidance), across review divisions, and between CDER and CBER.
The GRMPs include the Agency’s current best practices, as well as goals for review
management improvements. The best practices have evolved from more than a decade of review
process innovations that began with the implementation of PDUFA in 1992, and many of the
GRMPs are already in use. Under the PDUFA program, CDER and CBER have continuously
improved review management for marketing applications to meet tightening review goals while
maintaining the FDA’s traditionally high standards for evaluation of safety, effectiveness, and
product quality. Management and review capability enhancements have improved the planning
and coordination of review team activities and engaged applicants in productive communications
during product development (the investigational new drug application (IND) phase) and
marketing application review.
The ability of review staff and managers to adhere to and consistently achieve these review
management principles depends on the availability of adequate resources (e.g., staffing,
information technology support). The FDA also needs the full cooperation and participation of
applicants for effective implementation of the GRMPs. This guidance, therefore, describes best
practices for both applicants and FDA review staff to facilitate efficient application review. The
GRMPs outline the FDA’s procedures and objectives for communicating with applicants during
each phase of the review cycle. The GRMPs do not address the specific conduct or content of
scientific reviews and do not alter existing Agency processes or standards for scientific and
regulatory decision making. Applicants interacting with the Agency are strongly encouraged to
be fully knowledgeable about the GRMPs.
2 The letter was sent to Congress with identical copies addressed to the Chairman and Ranking Minority Members
of the Committee on Health, Education, Labor, and Pensions, United States Senate; and the Committee on Energy
and Commerce, House of Representatives. The PDUFA goals can be found at
http://www.fda.gov/oc/pdufa/PDUFAIIIGoals.html.
3 The FDA mission statement can be found at http://www.fda.gov/opacom/morechoices/mission.html.
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Contains Nonbinding Recommendations
Additional Agency documents are available to supplement the information in this guidance,
including staff instruction documents (i.e., CDER’s Manual of Policies and Procedures (MAPP),
and CBER’s Manual of Standard Operating Procedures and Policies (SOPP)) and guidances for
industry and review staff. The documents referenced in this guidance provide more detail on
specific CDER and CBER processes, expectations for review staff performance, and
recommendations for industry.
The GRMPs are an important foundation for implementing a quality systems approach for the
new drugs and biologics review and approval process. This guidance serves as initial
documentation of what has been, and continues to be, a work in progress.
III. 	FUNDAMENTALS OF GOOD REVIEW MANAGEMENT
The FDA’s goal is to ensure that its review and approval process is managed in a consistent and
efficient manner. The GRMPs described in this guidance, when applied consistently by review
staff and applicants, are expected to improve the efficiency and effectiveness of the first cycle
review process and decrease the number of review cycles necessary for approval, ensuring that
patients have timely access to new drugs and biologics.
A. 	Fundamental Values
The fundamental values on which the GRMPs are based include quality, efficiency, clarity,
transparency, and consistency.
Quality: The FDA seeks the highest levels of quality in our reviews, our review processes,
management, and outcomes. Consistent implementation of the GRMPs by review staff and
applicants will enhance the quality of the review process and the resultant regulatory action. As
the FDA continues to implement a quality systems approach to the new drugs and biologics
review and approval process, internal assessment and public scrutiny will focus on defining
additional ways to measure the quality of FDA review activity. We will work to establish better
metrics of quality and identify more conclusive links among the numerous factors that influence
the review process.
Efficiency: Efficiency is critical to the review process. Process efficiency, however, must not be
achieved at the expense of quality. The FDA believes that the GRMPs will improve both the
efficiency of the review process and the quality of the review product and outcomes.
Clarity: The clarity of the FDA’s findings, expectations, and bases for decisions supports review
efficiency and requires accurate review and effective communication. The GRMPs describe
processes that support clarity throughout the review process, including critical review and
decision activities that must be completed before the FDA can fully explain its views.
Communications during the ongoing review, within CDER and CBER or with external groups
such as the applicant or advisory committees (AC), are expected to consistently achieve the
highest possible degree of clarity.
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Contains Nonbinding Recommendations
Transparency: Transparency ensures that review staff and applicants are kept informed of how
the review is progressing. Both parties can then anticipate and plan the next steps and respond to
potential problems as they are identified. The need for transparency, however, must not interfere
with efficiency. The GRMPs describe an appropriate balance between transparency and the
efficiency of the review process.
Consistency: Achieving consistent processes across review divisions and offices, and between
CDER and CBER, is an important goal of good review management. Consistency can help
prevent misunderstandings and confusion that can occur when review divisions adopt different
procedures to accomplish the same fundamental review activity. Consistent practices for
interaction with all applicants also preclude the need for FDA staff to develop new procedures
with each applicant. Consistent application of the GRMPs by review staff, and applicant support
of GRMPs, is critical to the overall success of good review management. The FDA recognizes
that it may be appropriate to occasionally deviate from the processes and procedures described in
the GRMPs to meet other goals. FDA staff are expected to deviate from the GRMP process only
when the thorough assessment of an individual situation justifies doing so. Changes that become
generally accepted as new best practices under GRMPs should be documented and shared across
divisions and, if possible, across centers for broader implementation.
B. 	Operational Principles
The following principles form the Agency’s current perspective on the essential elements of
good review management. This section provides definitions for each element. The subsequent
sections, detailing model review management practices, describe how these principles are
implemented.
The principles of good review management are expected to remain stable despite changes in
other factors (e.g., regulatory, economic, scientific), but the processes that stem from them may
change to adapt and respond to individual application review circumstances and to further
develop new best practices.
• 	The foundation for good review management is created during product development.
Effective interaction between the FDA and applicants during product development, prior to
NDA/BLA submission, is critical to maximize first cycle approvals for marketing applications.
We recognize that the product development phase is under the primary management of the
applicant, but there are important reasons for applicants to discuss development plans with the
Agency. First, the review staff can provide valuable scientific and regulatory advice to the
applicant during the product development phase, resulting in more efficient and robust
development programs. Second, FDA staff can interpret the general requirements of the Federal
Food, Drug, and Cosmetic Act (FD&C Act), the Public Health Services Act, and other applicable
statutes to help applicants define adequate evidence of effectiveness (e.g., endpoints, study
design, patient populations), safety (e.g., sample size, dose response, assessment of drug-drug
interactions, demographic differences), and quality (e.g., manufacturing procedures, facility
compliance with good manufacturing practices). It is critical for applicants to ascertain the
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Contains Nonbinding Recommendations
Agency’s views on the applicable statutory requirements well in advance of submission of a
marketing application.
It is preferred that open communication of advice, guidance, and notification of deficiencies
occur at pivotal points during product development. This communication can lead to
identification of potential filing and review issues that the applicant can, and should, address
before the marketing application is submitted for review. We recommend that the milestones of
development be marked with meetings to exchange ideas on program status and planning. These
meetings include, but are not limited to, pre-IND, end-of-phase 1, end-of-phase 2, and pre-
NDA/BLA meetings. The FDA guidance for industry Formal Meetings with Sponsors and
Applicants for PDUFA Products4 provides information on meeting procedures.
Another FDA guidance for industry, Special Protocol Assessment (SPA), explains that the SPA
process can be used for clinical trials that will form the basis of an efficacy claim in an NDA or
BLA. Applicants are particularly encouraged to use the SPA process for trials in which the
proposed study design or endpoints are unusual, or for studies that involve an indication or
disease for which the FDA has not previously approved a drug or biologic product.
New initiatives affecting product development are being pursued under the PDUFA goals,
including enhanced preapproval attention to risk management by the FDA and the applicant. In
addition, two pilot programs exploring the continuous marketing application (CMA) concept for
fast track designated products are underway and are the subject of separate FDA guidances,
Continuous Marketing Applications: Pilot 1 — Reviewable Units for Fast Track Products Under
PDUFA, and Continuous Marketing Applications: Pilot 2 — Scientific Feedback and
Interactions During Development of Fast Track Products Under PDUFA.
An applicant’s effective management of the period before NDA/BLA submission is essential to
create an application that is likely to satisfy the regulatory requirements and that can be readily
reviewed. We encourage applicants to inform the review division of circumstances that arise
during development that may affect product approval (e.g., inability to carry out agreed-upon
protocols, new preclinical or clinical safety concerns, important manufacturing problems). This
information can also help prevent deficiencies that could cause the FDA to refuse to file the
application or that could result in unnecessary multiple review cycles. In addition, identifying
the anticipated application submission date helps the review division manage its overall
workload, including allocation of review staff and consultant time.
• 	The applicant is responsible for submission of a complete marketing application to maximize
the efficiency of the review process and reduce the need for multiple cycle reviews.
Central to PDUFA is the agreement that industry will submit a complete application that will
receive a comprehensive and complete review within a specified time. A complete application
contains all required and expected information to support approval of the proposed claims,
labeling, and dosage forms. A complete application is also in a readable, well-organized,
4 All guidances referenced in this guidance are available on the Internet at
http://www.fda.gov/cder/guidance/index.htm.
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Contains Nonbinding Recommendations
preferably electronic, format. Numerous FDA guidances are available to provide information on
the format and content of high-quality submissions, including those in electronic formats. It is
important for the applicant to provide a complete application at the time of initial submission to
limit the need for unsolicited or unexpected amendments during the review process. Significant
omissions lead to requests for amendments or more data (i.e., not a first cycle approval). An
application is not considered complete if it meets the regulatory criteria for filing, but lacks
important information needed for approval. The focus on initial submission of a complete
application does not preclude agreements between an applicant and a division on a
postsubmission planned amendment, but it is expected that such agreements will be needed only
in exceptional situations.
• 	Effective and efficient management of the review process is primarily an FDA responsibility.
During the product development phase, the applicant retains the primary management role, and
the Agency’s regulatory role is to ensure public safety and to provide guidance on the
development program. However, the submission of a marketing application shifts the primary
management responsibility to the FDA. The FDA’s obligation is to manage the review process
and determine whether a submitted application meets the legal and scientific requirements for
approval of the product.
• 	Active applicant involvement is important during the review process.
Although the responsibility for review management lies primarily with the FDA, applicant
involvement during the review is essential. The role of the applicant, a role that changes during
the various stages of the review process, is summarized in later sections of this guidance.
• 	FDA staff adherence to internal review timelines is critical for optimal review performance.
FDA staff should establish and observe internal review timelines to help ensure efficiency and
consistency in the review process. As described in Section II, Background, FDA practices
review management mindful of both the Agency’s primary public health responsibility and
review efficiency standards set by PDUFA. The timelines for many of the elements of first cycle
review are in part established by PDUFA. A well-managed review process helps FDA staff to
allocate the time and resources necessary to complete reviews soon enough to accommodate and
adequately consider unanticipated events or findings that may develop during the course of the
review. Adherence to these timelines with key internal milestones helps avoid the potential
errors associated with crisis-style management dealing with unresolved issues at the end of the
review cycle.
Review divisions are expected to inform applicants about major elements of the internal review
timeline for each application, anticipating some flexibility for resolution of unanticipated review
findings that require adaptation of the review plan. Changes to the review plan can stem from
additional team interactions, interactions with senior management, need for consult input,
problems identified during facilities inspections, and requests for additional data or analyses
from the applicant. Staff should communicate any significant changes in the review timeline to
the applicant.
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Contains Nonbinding Recommendations
• 	Good review management requires targeted input from the entire review team.
An effective review team maintains a strong interdependence and communication among its
members and engages in frequent interactions with supervisory reviewers. In addition, the core
review team, comprised of individuals representing the primary review disciplines and project
management, should seek and consider appropriate consultative input. Given the multilevel
nature of the review and decision-making process, it is important that the review team,
supervisory staff, and consultants adhere to the agreed-upon timelines.
• 	Good review management increases first cycle approvals.
A complete and well-formatted marketing application that meets the standards for approval will
be approved on the first cycle. Good review management allows sufficient time for careful
regulatory decision making and, if needed, time to work with the applicant to resolve minor and
readily correctable deficiencies in the application. For applications that otherwise meet the
standards for approval, good review management allows for finalization of labeling and other
regulatory issues (e.g., negotiation of postmarketing commitments) and issuance of an approval
letter on or before the PDUFA goal date. While this document focuses primarily on the first
review cycle, good review management principles and practices also pertain to subsequent
review cycles.
• 	Effective and timely communication between the FDA and applicants enhances the review
process.
Communication within the Agency and with applicants promotes understanding of multiple
perspectives, and is invaluable when appropriately tailored to each phase of the review process.
Communication between applicant representatives and the review division regulatory project
manager (RPM) is generally the most effective and timely mechanism for interaction.
Applicants are encouraged to work with RPMs, particularly at the time of application
submission, to create a clear communication strategy. RPMs should promptly bring issues that
arise during communication with the applicant to the attention of other review staff. In some
cases, direct communication between the applicant and the reviewers may be appropriate and
may contribute to review efficiency. Emerging review issues should be communicated to all
review team members, and substantive issues (e.g., when agreements or understandings are
reached, deficiencies are conveyed, or additional information is requested) should be
documented in the file by RPMs or reviewers.
For applications found to have significant deficiencies that may affect approval, the review team
should obtain appropriate input from the signatory authority and communicate the deficiencies
promptly to the applicant. Timely notification of correctable deficiencies allows the applicant to
begin corrective actions, maximizes the chance for a first cycle approval, and shortens the overall
time to approval when one or more review cycles are necessary. Timely notification of
significant and potentially uncorrectable deficiencies in the marketing application may also
influence product development decisions.
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In general, few meetings with the applicant to provide feedback on the status of the review are
warranted during the review process. However, meetings that offer productive communication
opportunities for the FDA and applicants are described in subsequent sections of this guidance.
Good review management is facilitated by applicants’ submission of clear, concise background
packages for such meetings.
Applicants are encouraged to use expeditious means of communication such as secure e-mail and
teleconferencing, when appropriate.
• 	The FDA will provide an official written regulatory action for each marketing application.
The FDA will process and review all applications with the goal of issuing an official written
regulatory action (e.g., refuse to file (RTF), approval, approvable, nonapproval, complete
response letter) by the designated signatory authority for the Agency. The written regulatory
action provides an official record of the Agency’s review decision. The official written
regulatory approval action contains important information on the Agency’s basis for its decision
and includes conditions of approval. Alternatively, the official written regulatory action
documents the Agency’s basis for a decision to refuse to file or not approve an application, as
well as the information needed from the applicant to correct the identified deficiencies.
Although an applicant may voluntarily withdraw a marketing application at any time after it is
submitted, it is generally preferred that the applicant not withdraw an application, so the Agency
can issue an official written regulatory action documenting its review. FDA staff should not
request or suggest that an applicant withdraw a pending marketing application except in the most
unusual circumstances (e.g., the marketing application was submitted to the wrong center). In
cases where an applicant voluntarily withdraws a marketing application in advance of an adverse
regulatory action (e.g., RTF, nonapproval), the Agency will acknowledge the applicant’s
withdrawal of the application in writing. The withdrawal acknowledgment letter will generally
include any deficiencies identified by the review division at the time the application was
withdrawn.
• 	FDA staff should not communicate to applicants the proposed or planned regulatory action
before issuance of the official written regulatory action.
A decision on the official regulatory action for an application can be made only after the
signatory authority has completed review of the available information (e.g., from the action
package and consultation with appropriate members of the review team and FDA management).
Therefore, it is important that communication with the applicant during the review of an
application be generally limited to requests for additional information (e.g., information request
letters), conveyance of identified deficiencies that need to be corrected before the application can
be approved (e.g., discipline review letters), and preliminary comments on draft labeling. FDA
staff should make clear to the applicant that such communications are preliminary and that the
official regulatory action for the application has not yet been taken. We discourage applicants
from requesting that Agency staff speculate about the eventual official regulatory action. Such
requests are premature and can lead to unnecessary tension in the communications between the
applicant and the members of the review team.
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Once the person responsible for making a decision on this application has made a decision on the
official regulatory action, it is important to communicate this decision in writing to the applicant
in the form of an official written regulatory action (e.g., RTF, approval, nonapproval, complete
response). The review division should confirm by telephone that the applicant has received the
official written regulatory action and document the call in the application file. This approach
provides a clear record of the timing of communication of the official action to the applicant and
provides the applicant with the full text of the official regulatory action. This assists the
applicant in understanding the terms of an approval or the deficiencies identified, and what
additional information is required to support approval.
IV. 	NDA/BLA REVIEW PROCESS
The NDA/BLA review process is divided into five phases: (1) filing determination and review
planning; (2) review; (3) advisory committee meeting preparation and conduct; (4) action; and
(5) post-action. The goals of each review phase are outlined below, with information on how
applicants can best assist with review activities and the most useful type of communication
between the FDA and applicants during each phase. A table accompanying the text for each
review phase outlines each FDA review activity. Each table refers to procedural documents,
including regulations, guidances, MAPPs, and SOPPs. A full understanding of each review
phase requires integration of the content of both the appropriate text and table, as neither is a
stand-alone descriptor of FDA review practice.
Adhering to prespecified internal timelines allows sufficient time to complete each review
activity. The table associated with each review phase provides general timelines for important
milestones. These timelines may require modification by the review division based on factors
such as staffing, competing workload, and complexity of the application. Such deviations should
be carefully considered, however, and any new internal timelines should be clearly
communicated to the review team and applicant.
The standard processes described below are subject to change as the FDA continues to identify
and implement new best practices as part of developing a quality systems approach to the new
drugs and biologics review and approval process.
A. 	Filing Determination and Review Planning Phase
1. 	Filing Determination
The primary goals of the filing process are to: (1) determine whether the submitted application
meets the regulatory requirements for filing; (2) define the scope of review activity needed; and
(3) identify major elements of the application that may pose concerns during the review.
Reviewers of the INDs under which development of the product took place are assigned to
review the NDA/BLA whenever possible. A review team is comprised of the assigned RPM and
primary reviewers. Consultant input is sought when particular expertise not represented on the
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review team is needed. In some cases, outside experts (e.g., special government employees) may
participate in reviews.
The review division should convey to the applicant any significant deficiencies identified during
the filing determination and ask the applicant to clarify or complete the application. In
particular, it is important that potential RTF deficiencies be conveyed to the applicant as early in
the review cycle as possible with a clear explanation of their potential impact on the review
outcome. Based on the FDA’s judgment at the filing meeting, substantive application
deficiencies not corrected by the applicant may warrant an RTF action or may be conveyed to the
applicant in the filing review issues letter. Applicants can facilitate the filing determination by
promptly responding to FDA inquiries during the filing review.
2. 	Review Planning
Review planning also occurs during this phase to organize the associated review tasks, minimize
review overlap among review disciplines, and establish an internal review timeline. Review
planning activity can occur at the filing meeting to take advantage of the review team’s
collective input and obtain consensus on the review plan. Adherence to the review plan is
critical to the efficiency and effectiveness of the review process and reduces the need for
resource-intensive problem solving at the end of the review cycle.
Major review milestone timelines should be conveyed to applicants following review planning.
It is important that applicants be aware that these timelines are flexible and subject to change
based on division workload and other potential review issues (e.g., the need for submission of
amendments). Significant changes to the review plan should also be conveyed to applicants as
they arise. Often, changes in the review division’s planned review timeline and review team
activity can be made to optimize first cycle outcomes. Review planning is facilitated by
applicants’ provision of accurate timelines for the submission of planned amendments and safety
updates.
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Filing Determination and Review Planning Phase
Timeline 	Activity 	Reference5 	Responsibility
Day 0 	Application Receipt 	Central Document Room (CDER) or
Document Control Center (CBER)
Assign RPM 	Chief, Project Management Staff
(CPMS)
Begin Regulatory Filing Review
(including, but not limited to):
FDA Form 356h
User Fee Payment Status 	PDUFA, FDA Form 3397
Application Provision 	FD&C Act 505(b)(1) and (2)
21 CFR 314.3
Pediatric Development 	Pediatric Research Equity Act
(PREA)
Financial Disclosure 	21 CFR 54.5,
FDA Forms 3454 and 3455
Orphan Drug Status 	21 CFR 316
Patent Information/Certification (NDA) 	21 CFR 314.53, FDA Form 3542a
21 CFR 314.50(i)
Debarment Statement 	FD&C Act 306(k)(1)
Days 0 – 14
Overview of Content and Format 	21 CFR 314.50
RPM
Acknowledge application receipt in writing
Assign Review Team, as needed
Medical/Clinical
Pharmacology/Toxicology (P/T)
Chemistry, Manufacturing, and Controls (CMC)
Biometrics/Statistical
Clinical Pharmacology and Biopharmaceutics
Clinical Microbiology
BioResearch Monitoring (BiMo)
Review Discipline Team Leaders
(CDER)
Review Division Management
(CBER)
By Day 14
Schedule Filing Meeting 	RPM
5 The references listed in this table are considered important to this topic, but are not all inclusive.
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Filing Determination and Review Planning Phase
Timeline 	Activity 	Reference 	Responsibility
Request Consults (most frequently used) 	From Review Team
Claims of Categorical Exclusion 	To Office of New Drug Chemistry
(ONDC) or Office of Biotechnology
Products (OBP) (CDER)
To Division of Manufacturing and
Product Quality (DMPQ) (CBER)
Environmental Assessments (EAs) 	To OPS Environmental Scientist
(CDER)
To DMPQ (CBER)
Trade name, carton/container labels, labeling,
packaging, drug delivery device (working model),
package insert (PI), patient package insert (PPI),
MedGuide and other consumer information, as
needed
To Office of Drug Safety (ODS)
(CDER)
To Division of Drug Marketing and
Communication (DDMAC) (CDER)
To Advertising and Promotional
Labeling Branch (APLB) (CBER)
To Office of Compliance and
Biologics Quality (OCBQ) (CBER)
Postmarketing Risk Management Plan (RMP) 	To ODS (CDER)
To Division of Epidemiology (DE)
(CBER)
Abuse Potential 	CDER MAPP 4200.3, Consulting
the Controlled Substance Staff on
Abuse Liability, Drug Dependence,
Risk Management, and Drug
Scheduling
To Controlled Substances Staff
(CDER)
Pregnancy Labeling 	To Pregnancy Labeling Team
(CDER)
To OCBQ (CBER)
Days 0 – 45 (30)6
Health-Related Quality of Life (HRQL) and Patient-
Reported Outcomes (PROs)
To Study Endpoints and Labeling
Development Team (CDER)
Review Team (CBER)
6 The number in parentheses indicates modification of timeline for priority status reviews.
12

Contains Nonbinding Recommendations
Filing Determination and Review Planning Phase
Timeline 	Activity 	Reference 	Responsibility
Identify Inspection Actions 	From Review Team
Submit Establishment Evaluation Request (EER) and
request inspections (for NDA)
ONDC or OBP (CDER)
DMPQ (CBER)
Coordinate Preapproval Inspections (PAI) for BLAs 	21 CFR 601.20(d) 	DMPQ (CDER)
DMPQ or Product Reviewer
(CBER)
Request investigation of clinical, nonclinical, and
biopharmaceutics research sites
To Division of Scientific
Investigation (DSI) (CDER)
To BiMo (CBER)
Applicant Orientation Presentation (optional) 	For Review Team
Designate Priority Review Classification/Status (Priority
or Standard)
CBER SOPP 8401, Administrative
Processing of Biologics License
Applications, SOPP 8405, Complete
Review and Issuance of Action
Letters
CDER MAPP 6020.3, Priority
Review Policy
Review Division Director
Office Director
Conduct Filing Review
Review completeness and adequacy of submission 	21 CFR 314.101
21 CFR 601.2(a)
Identify any RTF issues 	21 CFR 314.101(d) and (e)
Identify any filing review issues 	CBER SOPP 8401.3, Filing Action:
Communication Options
CDER MAPP 6010.5, NDAs: Filing
Review Issues
Identify any special development or approval issues 	21 CFR 314 Subpart H or I
21 CFR 601 Subpart E or H
Identify omissions from the submission
Identify need for AC input
Identify potential for postmarketing commitments 	FDA Modernization Act of 1997
(Section 130)
Review Team
Days 0 – 45 (30)
Convey Potential RTF Issues to Applicant 	RPM
13

Contains Nonbinding Recommendations
Filing Determination and Review Planning Phase
Timeline 	Activity 	Reference 	Responsibility
Identify Signatory Authority
NME NDA and BLA 	Office Director/Deputy
Non-NME NDA 	Review Division Director/Deputy
Office Director (in special
circumstances)
Hold Filing Meeting
Discuss filing review
Make filing recommendations
Review Team
Consultants
By Day 45 (30)
Make Filing Decision 	CBER SOPP 8404, Refusal to File
Procedures for BLAs
CDER guidance Refusal to File
Review Division Director
Office Director (consulted for
RTFs)
Conduct Planning Meeting (with Filing Meeting where
possible) to Plan for and Schedule:
Periodic team progress check-ins
Mid-cycle review meeting
Team or subgroup interaction on particular issues
Primary review completion
Secondary (team leader or branch chief) review
Review Team
Review division director, or higher level, review
Consult review input
Advisory committee meetings
Internal briefings for signatory authority
Wrap-up (integration of review, consult, and
inspection input)
Preapproval safety conference (CDER) 	CDER MAPP 6010.1, NDAs:
Preapproval Safety Conferences
Preapproval facility inspections (BLAs)
Labeling negotiation
By Day 45 (30)
Issuance of action letter by PDUFA goal date
Review Team
14

Contains Nonbinding Recommendations
Filing Determination and Review Planning Phase
Timeline 	Activity 	Reference 	Responsibility
Inform Applicant of a Priority Designation in Writing 	RPM	By Day 60
Communicate Filing Determination to Applicant, if RTF 	21 CFR 314.101(a)(3)
CBER SOPP 8404, Refusal to File
Procedures for Biologic License
Applications; SOPP 8404.1,
Procedures for Filing an
Application When the Applicant
Protests an RTF Action (File Over
Protest)
Review Division Director (for RTF)
By Day 74 	Communicate Filing Review Issues to Applicant 	CDER MAPP 6010.5, NDAs:
Filing Review Issues, CBER SOPP
8401.1, Issuance and Review of
Responses to Information Requests
and Discipline Review Letters to
Pending Applications
RPM
15

Contains Nonbinding Recommendations
B. 	Review Phase
During this phase, primary reviewers conduct a review of the application, sharing findings on a
regular basis with secondary and other supervisory reviewers, reviewers of other disciplines, and
consultants. In some instances, joint reviews are conducted between reviewers of the same or
different disciplines.
Reviews are finalized with sequential signatory steps that document the action on an application.
While primary reviewers are expected to seek and consider input from secondary reviewers, the
primary review conclusions and recommendations represent the opinion of the primary reviewer.
A primary review is considered final only after it has been reviewed and signed by the secondary
reviewer. In CDER, secondary reviewers write their own brief reviews to summarize the
discipline review and note their own recommendations for the application. These written
secondary reviews are optional in CBER, except when the secondary reviewer does not agree
with the findings or conclusions of the primary reviewer.
Applicants may receive additional information requests as a result of ongoing reviews and are
encouraged to respond promptly and completely to such requests. During the first cycle, the
division ordinarily reviews all amendments solicited by the Agency during the review, and any
amendments to the application previously agreed upon (e.g., during the pre-NDA/BLA meeting).
Substantial amendments submitted late in the review cycle may, however, be reviewed in a
subsequent cycle, depending, in part, on other identified application deficiencies. The review
division attempts to review all other amendments during the first review cycle, but may not be
able to, or may decide not to do so in some instances (e.g., when the content of such an
amendment does not address a known deficiency in the application). We strongly encourage
applicants to submit complete applications, making later amendments unnecessary unless
requested by the review division.
Under the PDUFA provisions, submission of a major amendment during the last 3 months of a
review may trigger a 3-month extension of the review clock. The Agency decides whether to
extend the review clock in response to such amendments. This decision is based on a variety of
factors (e.g., content of the amendments, FDA workload and resources, existence of other known
deficiencies that may affect approval and have not been addressed by the amendment), but the
underlying principle is to consider the most efficient path toward completion of a comprehensive
review that addresses application deficiencies and leads toward a first cycle approval when
possible.
16

Contains Nonbinding Recommendations
Review Phase
Timeline 	Activity 	Reference7 	Responsibility
Conduct Review
Interaction of primary and secondary reviewers
Interdisciplinary interaction
Team meetings
Begin at time of
assignment
Issue IR Letter or other requests for information, as
needed
Mid-Cycle Meeting
Update on progress and findings of all reviews,
consults, and inspections
Define need for additional interaction with applicant
related to labeling, risk management, postmarketing
commitments
Revise review plan, if needed
By End of Month 5
(3)
Brief signatory authority
Review Team
Consultants
Signatory Authority, as
needed
By End of Month 8
(5)
Complete Primary Review 	Review Team
7 The references listed in this table are considered important to this topic, but are not all inclusive.
17

Contains Nonbinding Recommendations
Review Phase
Timeline 	Activity 	Reference 	Responsibility
Variable 	Secondary Sign-Off 	CBER SOPP 8006, Resolution of
Differences in Scientific Judgment in the
Review Process
CDER MAPP 4151.1, Resolution of
Disputes: Roles of Reviewers,
Supervisors, and Management —
Documenting Views and Findings and
Resolving Differences
CDER MAPP 6020.8, Action Packages for
NDAs and Efficacy Supplements
Variable 	Issue DR Letters, as appropriate 	FDA guidance, Information Request and
Discipline Review Letters Under the
Prescription Drug User Fee Act
18

Contains Nonbinding Recommendations
C. 	Advisory Committee Meeting Phase
The review division, in consultation with the office director, may decide to convene an advisory
committee (AC) meeting. A review division may seek AC input, for example, when: (1) the
application is for a new molecular entity (NME), especially if it is the first member of a new
class of drug; (2) the clinical study design used novel clinical or surrogate endpoints; (3) the
application raises significant issues on the safety and/or effectiveness of the drug or biologic; or
(4) the application raises significant public health questions on the role of the drug or biologic in
the diagnosis, cure, mitigation, treatment, or prevention of a disease. The decision to hold an AC
meeting should be made and communicated to the applicant early in the first cycle review
process.
The FDA and the applicant should work together during AC meeting planning to share issues
and avoid redundant presentations. Applicants are strongly discouraged from submitting
amendments that contain significant new data after the review division has sent the FDA
background package to the AC members and the applicant, because this does not allow the
review division sufficient opportunity to review and consider the new data before the meeting.
There are also strict timelines for clearance of background packages for public dissemination
before the meeting, so the FDA is not able to accommodate applicant requests for changes in
FDA background materials, other than to correct factual errors (e.g., issuance of an errata sheet).
Based on the discussions at the AC meeting and committee recommendations, the FDA may ask
an applicant to submit additional data or analyses for review. We encourage applicants to
provide these amendments in a timely manner.
19

Contains Nonbinding Recommendations
Advisory Committee Meeting Phase (if needed)
Timeline 	Activity 	Reference8 	Responsibility
Begin when need
for AC meeting is
identified
Plan AC Meeting
Variable 	Formulation of questions for AC
By 2 weeks before
AC meeting
Disseminate and disclose applicant and FDA
background materials 9
Review Team
Consultants, as needed
FDA Advisors and Consultants
Staff
By End of Month 8
(5)
Conduct AC Meeting 	FDA guidance, Implementation of
Section 120 of the Food and Drug
Administration Modernization Act of
1997 — Advisory Committees
Variable 	Follow-Up to AC
Within 2 weeks
after AC meeting
Internal meeting to integrate AC input into review
outcomes and request or conduct additional analyses
Review Team
With Action 	Confidential memo to AC to announce action and
interpretation of AC input
Review Division Director
8 The references listed in this table are considered important to this topic, but are not all inclusive.
9 The following draft guidances are references for this activity: CDER draft guidance Disclosing Information Provided to Advisory Committees in Connection
with Open Advisory Committee Meetings Related to the Testing or Approval of New Drugs and Convened by the Center for Drug Evaluation and Research
Beginning on January 1, 2000; and CBER draft guidance Disclosing Information Provided to Advisory Committees in Connection with Open Advisory
Committee Meetings Related to the Testing or Approval of Biologic Products and Convened by the Center for Biologics Evaluation and Research Beginning on
June 1, 2001. Once finalized, these draft guidances will represent the FDA’s current thinking regarding these topics.
20

Contains Nonbinding Recommendations
D. 	Action Phase
1. 	Wrap-Up
The outcomes of all review activity are integrated during wrap-up, the first part of the action
phase. An internal meeting facilitates the development of a comprehensive understanding of the
safety, efficacy, and quality of the proposed product and a preliminary decision on the regulatory
action. Consideration should be given to critical elements such as risk management, major
labeling issues, and postmarketing commitments.
2. 	Labeling
Review wrap-up determinations help form the basis for labeling discussions with the applicant to
complete the labeling for products whose approval can be anticipated (i.e., approval and most
approvable actions). Since essential labeling discussions by necessity occur toward the end of
the review cycle when available time is limited, it is important that communication between the
FDA and applicants be clear and efficient. Adherence to the review timeline, including
completion of primary and secondary reviews well in advance of the PDUFA goal date, allows
time to resolve labeling content issues and avoids crisis management of these issues near the
PDUFA goal date.
Applicants can support labeling discussions by not submitting large amounts of new data in
support of proposed labeling text, and by clearly explaining their basis for changes from the
review division’s recommended labeling language. Applicants are discouraged from printing
labels for commercial distribution before receipt of an approval letter, because the label can
change until it is approved. Labels printed in advance of the actual receipt of an approval letter
are done so at the applicant’s risk.
3. 	Signatory Review Documentation
When the review division director in CDER has signature authority for an application, the team
leader from each review discipline should write a summary of the basis for the recommended
action from that discipline. In CBER, the review discipline branch chief will write a summary of
the basis for the recommended action from that discipline only if he or she disagrees with the
findings or conclusions of the primary reviewer (see Section IV.B., Review Phase). The division
director of the responsible office should also write a summary to document the basis for the
regulatory action, taking into account the input from the entire review team. The division
director summary should describe the resolution of difficulties or disagreements and clarify any
issues that need attention during the postapproval period. In some instances, particularly when
there has been little disagreement during the review process, the medical team leader in CDER,
or the review team leader in CBER, may write the summary of the basis of the recommended
action from the multidisciplinary perspective. The division director should document
concurrence with the team leader’s statement as part of the signatory process, or document in
writing the basis for nonconcurrence, if necessary.
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Contains Nonbinding Recommendations
When the office director has signature authority, the previously described documentation is
warranted as well as an additional written summary review by the office director.
4. 	Regulatory Action
The goals of the regulatory action and FDA policy on communicating regulatory actions are
described in Section III.B., Operational Principles. The FDA processes and reviews marketing
applications with the goal of completing the review and issuing an official written regulatory
action by the PDUFA goal date. It is important that any communication with the applicant
before the official regulatory action makes it clear that a decision has not yet been made, and
there should be no speculation on the nature of the final action.
22

Contains Nonbinding Recommendations
Action Phase
Timeline 	Activity 	Reference10 	Responsibility
Wrap-Up Meeting
Integrate outcomes of reviews, consults, inspection
reports, and AC input
Consider need for center level input (e.g., Regulatory
Briefing)
By End of
Month 8 (5)
Internal Briefings for Signatory Authority, as needed
Review Team
Consultants
Signatory Authority
Preapproval Safety Conference (for NMEs in CDER) 	CDER MAPP 6010.1, NDAs:
Preapproval Safety Conferences
Review Team
ODS
4 Weeks Before
Approval Action
Initiate Compliance Check Request (BLAs) 	RPM
Labeling Discussions
(for Approval and Approvable Actions)
Apply labeling review checklist 	CBER SOPP 8412, Review of Product
Labeling
Review Team
Consultants, in CDER:
ODS
DDMAC
Study and Endpoints
Labeling Team
Consultants, in CBER:
OBE
APLB
OCBQ
Meeting/teleconference with applicant and/or secure
e-mail exchange of proposed labeling
Finalize labeling based on data 	FD&C Act, section 502
21 CFR Part 201
Review Team
Signatory Authority
Finalize dependent materials (PPI, MedGuide) 	Review Team
Consultants
Negotiation of Postmarketing Commitments, if needed
Begin 3 Weeks
Before Division
Sign-Off
Negotiation of Risk Management Program, if needed
10 The references listed in this table are considered important to this topic, but are not all inclusive.
23

Contains Nonbinding Recommendations
Action Phase
Timeline 	Activity 	Reference 	Responsibility
Compile Action Package 	CBER SOPP 8401, Administrative
Processing of Biologics License
Application (BLA); SOPP 8405, Complete
Review and Issuance of Action Letters
CDER MAPP 6020.8, Action Packages for
NDAs and Efficacy Supplements
Draft Action Letter with Conditions of Approval (for
Approval Actions)
Approval:
21 CFR 314.105
21 CFR 601.4(a)
RPM
Draft Action Letter with Comprehensive List of
Deficiencies (for Actions Other than Approval)
NDA Approvable:
21 CFR 314.110
NDA Not Approvable:
21 CFR 314.120
BLA Denial of License:
21 CFR 601.4(b)
RPM
Circulate and Review Action Package and Letter
To primary reviewers (and consultants, as needed)
By 6 (4-6)
Weeks Before
Action
To secondary reviewers (when signatory authority is
the Division Director) OR
To Division Director (when signatory authority is the
Office Director)
By 3 (2-3)Weeks
Before Action
To signatory authority, with revision as needed
Review Team
Signatory Authority
Action 	Signatory Authority
Archive signed letter
Send official copy to applicant (by facsimile, secure
e-mail, or postal service)
Verify and document applicant receipt
By PDUFA Goal
Date
Distribute approval information (for approval action) 	CBER SOPP 8106, Submission of Product
Approval Information for Dissemination to
the Public
CDER MAPP 4520.1, Communicating
Drug Approval Information
CDER MAPP 4520.2, Providing General
Consumer Information on NMEs on
CDER’s Web Site
RPM
24

Contains Nonbinding Recommendations
E. 	Post-Action Phase
During the post-action phase, the Agency and applicants should focus on learning from the
successful aspects of the review process and identifying other aspects of the review process that
could benefit from future improvement.
For actions other than approvals, it is optimal to direct activities toward improving outcomes for
subsequent review cycles by creating a clear understanding on the part of both the FDA and the
applicant of deficiencies and the expected responses. This can be accomplished by scheduling a
post-action teleconference or meeting to discuss the deficiencies. A presubmission meeting
between the review division and the applicant can also be scheduled to discuss the applicant’s
planned response to the action letter and help avoid incomplete responses. Applicants can help
optimize the outcome of subsequent review cycles by responding clearly and completely to
issues identified in the action letter.
25

Contains Nonbinding Recommendations
Post-Action Phase
Timeline 	Activity 	Reference11 	Responsibility
Meet or Discuss with Applicant
Lessons learned
Clarify deficiencies and expected responses (actions
other than approvals)
21 CFR 314.102(d)
CBER SOPP 8405.1, Procedures for
the Classification of Resubmissions
of an Application for a Product
Covered by PDUFA
CDER MAPP 6020.4, Classifying
Resubmissions of Original NDAs in
Response to Action Letters
FDA guidance, Formal Dispute
Resolution: Appeals Above the
Division Level
After PDUFA
Goal Date
Dispute Resolution (when necessary, can occur
throughout review process)
21 CFR 314.103
FDA guidance, Formal Dispute
Resolution: Appeals Above the
Division Level
Review Team
Signatory Authority
Consultants
11 The references listed in this table are considered important to this topic, but are not all inclusive.
26

Contains Nonbinding Recommendations
V. 	IMPLEMENTATION AND EVALUATION
The GRMPs are based in part on the Agency’s current best practices. Implementation activity,
including reviewer training and performance evaluation, began in October 2003 and will
continue with additional training on this guidance.
In accordance with commitments under the reauthorization of PDUFA, an independent expert
consultant under contract with the FDA will carry out the performance evaluation. The
consultant, with input from the FDA and the public, will be responsible for developing an
evaluation study design that identifies key questions, data requirements, data collection plans,
and planned analyses in accordance with the PDUFA goals.
27

Contains Nonbinding Recommendations
APPENDIX A: GLOSSARY OF ACRONYMS
AC 	Advisory Committee
APLB 	Advertising and Promotional Labeling Branch (CBER)
BiMo 	Bioresearch Monitoring Branch (CBER)
BLA 	Biologics License Application
BLS 	Biologics License Supplement
CBER 	Center for Biologics Evaluation and Research
CDER 	Center for Drug Evaluation and Research
CFR 	Code of Federal Regulations
CMA 	Continuous Marketing Application
CMC 	Chemistry, Manufacturing, and Controls
CPMS 	Chief, Project Management Staff
DDMAC 	Division of Drug Marketing, Advertising, and Communications (CDER)
DE 	Division of Epidemiology (CBER)
DMPQ 	Division of Manufacturing and Product Quality
DR 	Discipline Review
DSI 	Division of Scientific Investigations (CDER)
EA 	Environmental Assessment
EER 	Establishment Evaluation Request
EOP2 	End-of-Phase 2
FDA 	U.S. Food and Drug Administration
FD&C Act 	Federal Food, Drug, and Cosmetic Act
GRMP 	Good Review Management Principles and Practices
HRQL 	Health-Related Quality of Life
IND 	Investigational New Drug Application
IR 	Information Request
MAPP 	Manual of Policies and Procedures (CDER)
NDA 	New Drug Application
NME 	New Molecular Entity
OBE 	Office of Biostatistics and Epidemiology (CBER)
OBP 	Office of Biotechnology Products (CDER)
OCBQ 	Office of Compliance and Biologics Quality (CBER)
OCPB 	Office of Clinical Pharmacology and Biopharmaceutics (CDER)
ODS 	Office of Drug Safety (CDER)
ONDC 	Office of New Drug Chemistry (CDER)
PDUFA 	Prescription Drug User Fee Act
PI 	Package Insert
PPI 	Patient Package Insert
PREA 	Pediatric Research Equity Act
PRO 	Patient-Reported Outcome
P/T 	Pharmacology/Toxicology
RMP 	Risk Management Plan
RPM 	Regulatory Project Manager
RTF 	Refusal to File
SOPP 	Standard Operating Policies and Procedures (CBER)
28

Contains Nonbinding Recommendations
SPA 	Special Protocol Assessment
U.S.C. 	U.S. Code
29

Contains Nonbinding Recommendations
APPENDIX B: REFERENCED GUIDANCES, MAPPS, AND SOPPS
The guidances for industry, MAPPs, and SOPPs for FDA staff referenced in this document are
listed below. This is not a comprehensive list of available information from CDER and CBER.
Consult the following CDER and CBER Web pages for additional information:
http://www.fda.gov/cder/guidance/index.htm
http://www.fda.gov/cber/guidelines.htm
Presubmission
FDA Guidances
• 	Formal Meetings with Sponsors and Applicants for PDUFA Products
• 	Special Protocol Assessment
• 	Continuous Marketing Application: Pilot 1
• 	Continuous Marketing Application: Pilot 2
Filing Determination and Review Planning Phase
FDA Guidance
• 	Refusal to File
CBER SOPPs
• 	8401 	Administrative Processing of Biologics Licensing Application
(BLA)
• 	8401.1 	Issuance and Review of Responses to Information Requests and
Discipline Review Letters to Pending Applications
• 	8401.2 	Administrative Processing of Biologics License Application
Supplement (BLSs) [Except Blood, Blood Components, and Source
Plasma]
• 	8401.3 	Filing Action: Communication Options
• 	8110 	Submission of Regulatory Documents to CBER
• 	8406 	Verification of User Fee Data Sheet and Payment
• 	8405 	Complete Review and Issuance of Action Letters
• 	8404 	Refusal to File Procedures for Biologic Licensing Applications
• 	8404.1 	Procedures for Filing an Application When the Applicant Protests
a Refusal to File Action (File Over Protest)
CDER MAPPs
• 	7600.7 	Processing an Electronic New Drug Application
• 	6050.1 	Refusal to Accept Application for Filing from Applicants in
Arrears
• 	6020.3 	Priority Review Policy
• 	6010.5 	NDAs: Filing Review Issues
30

Contains Nonbinding Recommendations
• 	4200.3 	Consulting the Controlled Substance Staff on Abuse Liability,
Drug Dependence, Risk Management, and Drug Scheduling
Review Phase
FDA Guidance
• 	Information Request and Discipline Review Letters Under the Prescription
Drug User Fee Act
CBER SOPPs
• 	8006 	Resolution of Differences in Scientific Judgment in the Review
Process
• 	8401.1 	Issuance and Review of Responses to Information Requests and
Discipline Review Letters to Pending Applications
CDER MAPP
• 	4151.1 	Resolution of Disputes: Roles of Reviewers, Supervisors, and
Management — Documenting Views and Findings and Resolving
Differences
Advisory Committee Meeting Phase
FDA Guidance
• 	Implementation of Section 120 of the Food and Drug Administration
Modernization Act of 1997 — Advisory Committees
CBER Draft Guidance
• 	Disclosing Information Provided to Advisory Committees in Connection with
Open Advisory Committee Meetings Related to the Testing or Approval of
Biologic Products and Convened by the Center for Biologics Evaluation and
Research Beginning on June 1, 2001
CDER Draft Guidance
• 	Disclosing Information Provided to Advisory Committees in Connection with
Open Advisory Committee Meetings Related to the Testing or Approval of
New Drugs and Convened by the Center for Drug Evaluation and Research
Beginning on January 1, 2000
Action Phase
CBER SOPPs
• 	8405 	Complete Review and Issuance of Action Letters
• 	8106 	Submission of Product Approval Information for Dissemination to
the Public
• 	8412 	Review of Product Labeling
31

Contains Nonbinding Recommendations
32
CDER MAPPs
• 	6010.1 	NDAs: Preapproval Safety Conferences
• 	6020.8 	Action Packages for NDAs and Efficacy Supplements
• 	4520.1 	Communicating Drug Approval Information
• 	4520.2 	Providing General Consumer Information on NMEs on CDER’s
Web Site
Post-Action Phase
FDA Guidance
• 	Formal Dispute Resolution: Appeals Above the Division Level
CBER SOPP
• 	8405.1 	Procedures for the Classification of Resubmissions of an
Application for a Product Covered by the Prescription Drug User
Fee Act (PDUFA III)
CDER MAPP
• 	6020.4 	Classifying Resubmissions of Original NDAs in Response to
Action Letters