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 
 
1
Guidance for Review Staff and Industry  
Good Review Management Principles  
and Practices for PDUFA Products 
 
 
 
This guidance represents the Food and Drug Administrations (FDAs) 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. 
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys 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.  
  1 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 
FDAs primary public health mission for human drug and biologic products,3 help the FDA 
continue to define processes that fulfill the Agencys PDUFA mandates, promote efficient use of 
the FDAs 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 Agencys 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 FDAs 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 FDAs 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. 
  2 Contains Nonbinding Recommendations 
 
Additional Agency documents are available to supplement the information in this guidance, 
including staff instruction documents (i.e., CDERs Manual of Policies and Procedures (MAPP), 
and CBERs 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 FDAs 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 FDAs 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.  
 
  3 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 Agencys 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 
  4 Contains Nonbinding Recommendations 
 
Agencys 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 applicants 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. 
  5 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 Agencys 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 FDAs 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 Agencys 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.  
  6 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.  
 
  7 Contains Nonbinding Recommendations 
 
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 Agencys review decision.  The official written 
regulatory approval action contains important information on the Agencys basis for its decision 
and includes conditions of approval.  Alternatively, the official written regulatory action 
documents the Agencys 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 applicants 
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. 
  8 Contains Nonbinding Recommendations 
 
 
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 
  9 Contains Nonbinding Recommendations 
 
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 FDAs 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 teams 
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 divisions 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. 
 
  10 Contains Nonbinding Recommendations 
 
Filing Determination and Review Planning Phase 
Timeline  Activity  Reference5  Responsibility 
Day 0  Application Receipt    Central Document Room (CDER) or 
Document Control Center (CBER) 
Days 0  14  Assign RPM     Chief, Project Management Staff 
(CPMS) 
Begin Regulatory Filing Review  FDA Form 356h   RPM 
(including, but not limited to):   
  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) 
  Overview of Content and Format  21 CFR 314.50 
   
By Day 14    Acknowledge application receipt in writing     
Assign Review Team, as needed     Review Discipline Team Leaders 
  Medical/Clinical    (CDER) 
  Pharmacology/Toxicology (P/T)    Review Division Management 
  Chemistry, Manufacturing, and Controls (CMC)     (CBER) 
  Biometrics/Statistical   
  Clinical Pharmacology and Biopharmaceutics   
  Clinical Microbiology   
  BioResearch Monitoring (BiMo)   
Schedule Filing Meeting    RPM 
 
 
 
 
                                                 
5 The references listed in this table are considered important to this topic, but are not all inclusive. 
  11 Contains Nonbinding Recommendations 
 
Filing Determination and Review Planning Phase 
Timeline  Activity  Reference  Responsibility 
Days 0  45 (30)6   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,    To Office of Drug Safety (ODS) 
packaging, drug delivery device (working model),  (CDER) 
package insert (PI), patient package insert (PPI),  To Division of Drug Marketing and 
MedGuide and other consumer information, as  Communication (DDMAC) (CDER) 
needed  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  To Controlled Substances Staff 
the Controlled Substance Staff on  (CDER) 
Abuse Liability, Drug Dependence, 
Risk Management, and Drug 
Scheduling 
  Pregnancy Labeling    To Pregnancy Labeling Team 
(CDER) 
To OCBQ (CBER) 
  Health-Related Quality of Life (HRQL) and Patient-   To Study Endpoints and Labeling 
Reported Outcomes (PROs)  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    ONDC or OBP (CDER)  
request inspections (for NDA)  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    To Division of Scientific 
biopharmaceutics research sites  Investigation (DSI) (CDER) 
To BiMo (CBER) 
Days 0  45 (30)  Applicant Orientation Presentation (optional)     For Review Team 
Designate Priority Review Classification/Status (Priority  CBER SOPP 8401, Administrative  Review Division Director 
or Standard)   Processing of Biologics License  Office Director 
Applications, SOPP 8405, Complete 
Review and Issuance of Action 
Letters 
CDER MAPP 6020.3, Priority 
Review Policy 
Conduct Filing Review    Review Team 
  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)   
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) 
By Day 45 (30)  Hold Filing Meeting    Review Team 
    Discuss filing review    Consultants 
  Make filing recommendations   
Make Filing Decision  CBER SOPP 8404, Refusal to File  Review Division Director 
Procedures for BLAs  Office Director (consulted for 
CDER guidance Refusal to File  RTFs) 
By Day 45 (30)  Conduct Planning Meeting (with Filing Meeting where    Review Team 
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 division director, or higher level, review    Review Team 
  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   
  Issuance of action letter by PDUFA goal date   
 
 
 
 
 
 
  14 Contains Nonbinding Recommendations 
 
Filing Determination and Review Planning Phase 
Timeline  Activity  Reference  Responsibility 
By Day 60  Inform Applicant of a Priority Designation in Writing     RPM 
  Communicate Filing Determination to Applicant, if RTF  21 CFR 314.101(a)(3)  Review Division Director (for RTF) 
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) 
By Day 74  Communicate Filing Review Issues to Applicant  CDER MAPP 6010.5, NDAs:   RPM 
Filing Review Issues, CBER SOPP 
8401.1, Issuance and Review of 
Responses to Information Requests 
and Discipline Review Letters to 
Pending Applications 
 
 
  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 
Begin at time of  Conduct Review    Review Team 
assignment     Interaction of primary and secondary reviewers    Consultants 
  Interdisciplinary interaction    Signatory Authority, as 
  Team meetings    needed 
  Issue IR Letter or other requests for information, as   
needed 
By End of Month 5  Mid-Cycle Meeting   
(3)    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   
  Brief signatory authority    
By End of Month 8  Complete Primary Review     Review Team 
(5)   
 
 
 
 
                                                 
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  Plan AC Meeting    Review Team 
for AC meeting is  Consultants, as needed 
identified  FDA Advisors and Consultants 
Variable    Formulation of questions for AC    Staff 
By 2 weeks before    Disseminate and disclose applicant and FDA   
AC meeting  background materials9 
By End of Month 8  Conduct AC Meeting  FDA guidance, Implementation of   
(5)  Section 120 of the Food and Drug 
  Administration Modernization Act of 
1997  Advisory Committees 
Variable  Follow-Up to AC     
Within 2 weeks    Internal meeting to integrate AC input into review    Review Team 
after AC meeting  outcomes and request or conduct additional analyses 
With Action    Confidential memo to AC to announce action and    Review Division Director 
interpretation of AC input 
 
                                                 
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 FDAs 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 divisions 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 applicants 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 leaders statement as part of the signatory process, or document in 
writing the basis for nonconcurrence, if necessary. 
 
  21 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 
By End of   Wrap-Up Meeting    Review Team 
Month 8 (5)    Integrate outcomes of reviews, consults, inspection    Consultants  
  reports, and AC input  Signatory Authority 
  Consider need for center level input (e.g., Regulatory   
Briefing) 
Internal Briefings for Signatory Authority, as needed   
4 Weeks Before  Preapproval Safety Conference (for NMEs in CDER)  CDER MAPP 6010.1, NDAs:   Review Team 
Approval Action  Preapproval Safety Conferences  ODS 
Initiate Compliance Check Request (BLAs)    RPM 
Begin 3 Weeks  Labeling Discussions     Review Team 
Before Division  (for Approval and Approvable Actions)  Consultants, in CDER:  
Sign-Off    Apply labeling review checklist  CBER SOPP 8412, Review of Product    ODS  
Labeling     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  Review Team 
21 CFR Part 201  Signatory Authority 
  Finalize dependent materials (PPI, MedGuide)    Review Team 
Consultants 
Negotiation of Postmarketing Commitments, if needed     
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 
By 6 (4-6)  Compile Action Package  CBER SOPP 8401, Administrative  RPM 
Weeks Before  Processing of Biologics License 
Action  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: 
Approval Actions)  21 CFR 314.105 
21 CFR 601.4(a) 
Draft Action Letter with Comprehensive List of  NDA Approvable:  RPM 
Deficiencies (for Actions Other than Approval)  21 CFR 314.110 
NDA Not Approvable: 
21 CFR 314.120 
BLA Denial of License: 
21 CFR 601.4(b) 
Circulate and Review Action Package and Letter    Review Team 
  To primary reviewers (and consultants, as needed)    Signatory Authority  
  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    To signatory authority, with revision as needed   
Before Action 
By PDUFA Goal  Action    Signatory Authority 
Date    Archive signed letter    RPM 
  Send official copy to applicant (by facsimile, secure   
e-mail, or postal service) 
  Verify and document applicant receipt   
  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 
CDERs Web Site 
 
  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 applicants 
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 
After PDUFA  Meet or Discuss with Applicant     Review Team 
Goal Date    Lessons learned     Signatory Authority 
  Clarify deficiencies and expected responses (actions  21 CFR 314.102(d)  Consultants 
other than approvals)   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 
  Dispute Resolution (when necessary, can occur  21 CFR 314.103 
throughout review process)  FDA guidance, Formal Dispute 
Resolution:  Appeals Above the 
Division Level 
 
                                                 
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 Agencys 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 
 
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 CDERs  
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 
  32