Good Review Management 
Principles and Practices for 
New Drug Applications and 
Biologics License Applications 
Guidance for Industry and  
Review Staff 
 
Good Review Practice 
 
 
DRAFT GUIDANCE
 
 
  This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 90 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance.  Submit electronic comments to https://www.regulations.gov.  Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD  20852.  All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact (CDER) the Office of New Drugs at 301-
796-0700 or (CBER) the Office of Communication, Outreach, and Development at 800-835-
4709 or 240-402-8010.  
 
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) 
 
September 2018 
Procedural  
 
Revision 1 
18513915dft.docx 
09/10/18   
Good Review Management 
Principles and Practices for 
New Drug Applications and 
Biologics License Applications 
Guidance for Industry and  
Review Staff 
 
Good Review Practice 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD  20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: druginfo@fda.hhs.gov 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
and/or 
 
Office of Communication, Outreach, and Development  
Center for Biologics Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, rm. 3128 
Silver Spring, MD  20993-0002 
Phone: 800-835-4709 or 240-402-8010; Email: ocod@fda.hhs.gov 
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
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) 
 
September 2018 
Procedural  
 
Revision 1 
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  FUNDAMENTAL VALUES ............................................................................................ 2 
IV.  OPERATIONAL PRINCIPLES...................................................................................... 4 
V.  NEW PRODUCT REVIEW PROCESS ......................................................................... 8 
A.  CDERs New Product Review Process ......................................................................................... 8 
B.  CBERs New Product Review Process ......................................................................................... 8 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  Good Review Management Principles and Practices  
2  for New Drug Applications and Biologics License Applications 
3  Guidance for Industry and Review Staff1 
4   
5  Good Review Practice 
6   
7   
8   
9   
10  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
11  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
12  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
13  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
14  for this guidance as listed on the title page. 
15   
16   
17   
18   
19  I.  INTRODUCTION  
20   
21  The purpose of this guidance is to provide recommendations to industry and review staff on good 
22  review management principles and practices (GRMPs) for the review of new drug applications 
23  (NDAs), biologics license applications (BLAs), or efficacy supplements/supplements with 
24  clinical data.2  This guidance applies to human drug applications (as defined in section 735(1) of 
25  the Federal Food, Drug, and Cosmetic Act (FD&C Act)) and biosimilar biological product 
26  applications (section 744G(4) of the Public Health Service Act (PHS Act)).  The goal of GRMPs 
27  is to ensure that the review process is managed in a consistent and efficient manner, thereby 
28  decreasing the number of review cycles necessary for approval and enhancing patients timely 
29  access to important therapies.  This guidance also clarifies the roles and responsibilities of 
30  review staff in managing the review process and identifies ways in which applicants may support 
31  an efficient and robust review process.  Successful implementation of the GRMPs is crucial to 
32  FDAs mission of protecting and promoting the public health.3 
33   
34  This guidance revises the guidance for review staff and industry Good Review Management 
35  Principles and Practices for PDUFA Products issued in April 2005.  After it has been finalized, 
36  this guidance will replace the April 2005 guidance.  Significant changes in this revision reflect:   
37   
                                                 
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.  
 
2 Going forward, the Office of Pharmaceutical Quality generally will use the term assessment in place of review.  
Assessment means the process of both evaluating and analyzing submitted data and information to determine 
whether the application meets the requirements for approval and documenting that determination.  
 
3 The FDA mission statement can be found at https://www.fda.gov/opacom/morechoices/mission.html.   
  1  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
38    Advances in the Prescription Drug User Fee Act (PDUFA) program and the 
39  implementation of the Biosimilar User Fee Act (BsUFA)  
40   
41    Evolution of GRMPs to support additional regulatory programs such as breakthrough 
42  therapy, the Program for Enhanced Review Transparency and Communication for NME 
43  (New Molecular Entity) NDAs and Original 351(a) and 351(k) BLAs (the Program), and 
44  risk evaluation and mitigation strategies (REMS)   
45   
46    A consolidated focus on the fundamental values and operational principles that serve as 
47  the foundation for the GRMPs  
48   
49  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
50  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
51  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
52  the word should in Agency guidances means that something is suggested or recommended, but 
53  not required.  Although guidance documents do not legally bind the FDA, review staff may 
54  depart from guidance documents only with appropriate justification and supervisory 
55  concurrence. 
56   
57   
58  II.  BACKGROUND 
59   
60  The GRMPs are comprised of the fundamental values and operational principles described in this 
61  guidance.  Originally established under PDUFA III in 2002, FDAs implementation of GRMPs is 
62  periodically updated to reflect the ongoing evolution of statutory and regulatory requirements as 
63  well as innovations that become part of FDAs review process for marketing applications.  FDA 
64  continues to work to improve management of marketing applications to meet challenging review 
65  goals, while maintaining the highest standards for the evaluation of product safety, effectiveness, 
66  and quality.  
67   
68   
69  III.  FUNDAMENTAL VALUES 
70   
71  FDA seeks the highest levels of quality in submitted applications, Agency reviews and 
72  processes, and final regulatory decisions.  Quality can be achieved by applying the fundamental 
73  values of accountability, communication, and consistency, which serve as the foundation for the 
74  GRMPs.  Successful implementation of the GRMPs is dependent on the fulfillment of these 
75  values in the execution of policies and processes to ensure that high-quality regulatory decisions 
76  are made in a consistent and timely manner.  FDA staff must apply the appropriate statutes and 
77  regulations in their review of specific applications.  FDA staff are also expected to be current on 
78  the latest scientific advances and patient perspectives and apply this knowledge in their work.  
79  Critical thinking that is grounded in current scientific knowledge is an irreplaceable component 
80  of marketing application review and supports successful implementation of the GRMPs.  
81   
  2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
82    Accountability  
83   
84  FDA is accountable to the American public for helping to ensure the safety, efficacy, and quality 
85  of new drug and biological products.  FDA is also accountable for a high-quality and efficient 
86  review process that produces timely and informed decisions.  In addition, review staff are 
87  responsible for implementing the GRMPs and associated policies and processes.  Applicants are 
88  accountable for the quality and completeness of their applications, including optimal use of 
89  product development resources.  The quality of submitted applications is vital to achieving 
90  timely and science-based regulatory decisions.  This shared accountability to the public, 
91  including patients who participate in clinical trials, is critical to the implementation of the 
92  GRMPs by review staff and applicants.  
93   
94  Although FDAs accountability generally has been measured as compliance with targeted goal 
95  dates, with emphasis on the efficiency of first cycle reviews, FDA strives to establish better 
96  metrics for evaluating the timely analysis and critical thinking on which regulatory decisions are 
97  based.  For example, FDA also holds itself accountable for the timely completion of critical 
98  review work not included in FDAs annual performance reports, such as notification to 
99  applicants regarding issues identified during FDAs initial review of applications, notification to 
100  applicants of planned review timelines early in the review process, and internal timelines that 
101  govern other important aspects of FDAs regulatory work (e.g., labeling supplement review).4   
102   
103    Communication  
104   
105  Communication that is clear, complete, and concise is key to ensuring transparency and clarity 
106  during marketing application review.  Transparency ensures that all stakeholders understand 
107  FDAs regulatory processes and policies.  Transparency also ensures that applicants are informed 
108  of review progress and allows for both applicants and review staff to anticipate and respond to 
109  potential issues and plan for next steps.  Clarity allows FDA to understand the applicants 
110  assessment of the benefits and risks of a product as described in the marketing application.  
111  Clarity also allows the applicant to understand the reasoning behind a given regulatory action.  
112  Communications necessary to achieve transparency during an ongoing review are expected to 
113  contain the highest possible degree of clarity.  
114   
115    Consistency  
116   
117  Consistent application and support of the GRMPs by review staff and applicants are critical to 
118  the overall success of the marketing application review process.  FDA staff can exercise 
119  flexibility within the process when a thorough assessment of an individual situation justifies 
120  doing so.  Process changes that become generally accepted as new best practices will be 
121  documented and shared for broader implementation.  
122   
123   
                                                 
4 BsUFA includes annual performance goals regarding notification to applicants of issues identified during FDAs 
initial review of applications and notification to applicants of planned review timelines early in the review process 
for first cycle review of supplements with clinical data.  More information on BsUFA performance goals can be 
found at https://www.fda.gov/forindustry/userfees/biosimilaruserfeeactbsufa/default.htm.   
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
124  IV.  OPERATIONAL PRINCIPLES 
125   
126  FDAs goal is to execute an effective, efficient, and thorough review process that ensures high-
127  quality regulatory decisions.  The following operational principles are essential elements that 
128  serve to achieve that goal.  They are expected to remain stable despite changes in other factors 
129  (e.g., regulatory, economic, scientific), but the processes that stem from them may need to adapt 
130  and respond to scientific advances and evolving public health needs.  
131   
132    A well-designed and executed product development phase facilitates submission and 
133  efficient review of a high-quality marketing application  
134   
135  Effective interaction between FDA and applicants during product development is critical to 
136  maximizing first cycle marketing application review efficiency.5  Execution of a high-quality 
137  development program is the applicants responsibility.  However, there are important reasons for 
138  applicants to discuss development plans with FDA and consider the review teams feedback.  
139  Review staff can provide valuable scientific and regulatory advice to the applicant, including 
140  helping advise applicants on the level of evidence needed to demonstrate the products safety, 
141  efficacy, and quality.  Applicants should seek such feedback from FDA well in advance of the 
142  submission of a marketing application to help ensure a more efficient and robust development 
143  program.   
144   
145  Open communication between FDA and applicants should occur at pivotal points during product 
146  development.  This communication can lead to identification of potential filing and review issues 
147  that the applicant should address before submission of a marketing application.  Development 
148  milestones should be marked with meetings between FDA and applicants to exchange ideas on 
149  development program status and planning.6  Applicants should also promptly inform review 
150  divisions of circumstances that arise during development that may affect product approval (e.g., 
151  inability to carry out agreed-upon protocols, new nonclinical or clinical safety concerns, 
152  manufacturing problems).  Taking timely and appropriate action on this information can help 
153  prevent deficiencies that could cause FDA to refuse to file an application or result in additional 
154  review cycles.  
155   
156  Several regulatory approaches exist to facilitate product development and interactions with FDA 
157  to address important public health needs.  Examples include breakthrough therapy designation, 
158  regenerative medicine advanced therapy designation, and fast track designation for products that 
                                                 
5 For the purposes of this guidance, the term applicant includes any sponsor of an investigational new drug 
application or applicant for an NDA or BLA under section 505 of the FD&C Act or section 351(a)/351(k) of the 
PHS Act. 
 
6 These meetings include, but are not limited to, pre-investigational new drug application, end-of-phase 1, end-of-
phase 2, and pre-NDA/BLA meetings for PDUFA, and biosimilar biological product development Type 2, 3, and 4 
meetings for BsUFA.  The following draft guidances for industry provide information on meeting procedures:  
Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products and Formal Meetings Between 
the FDA and Sponsors or Applicants of BsUFA Products.  When final, these guidances will represent the FDAs 
current thinking on these topics.  For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/RegulatoryInformation/Guidances/default.htm. 
 
  4  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
159  address an unmet medical need in the treatment of a serious condition.7  Special protocol 
160  assessments can be used to reach agreement with FDA about the design of certain types of 
161  protocols.8  Applicants are encouraged to review the relevant regulatory approaches and discuss 
162  their potential use with FDA early in development to support a high-quality and efficient product 
163  development phase. 
164   
165  Consistent with the PDUFA and BsUFA agreements,9 which are fundamental to the success of 
166  FDAs regulatory programs, when a complete application is submitted to FDA, FDAs goal is to 
167  conduct a complete review of the application within a specified time frame.  A complete 
168  application contains all information needed to support the claims in the final labeling, and is 
169  submitted in a readable, well-organized, electronic format.  Omission of important or relevant 
170  information can lead to a refusal to file action or requests for additional information.  Applicants 
171  are strongly encouraged to respond promptly and completely to FDAs requests for additional 
172  information.  During the first review cycle, FDA ordinarily reviews all amendments to an 
173  application solicited by FDA and any amendments that were previously agreed upon (e.g., during 
174  the presubmission meeting).  FDA attempts to review all other amendments during the first 
175  review cycle, but may not be able to, or may decide not to do so in some instances (e.g., when 
176  the content of such an amendment does not address a known deficiency in the application).  
177  FDAs decision to review an amendment, and whether the amendment should extend the review 
178  clock, is based on identifying the most efficient path to completing a comprehensive review that 
179  addresses application deficiencies and leads toward a first cycle approval when possible.  
180   
181  Finally, as FDAs overall regulatory workload has increased over time, advance notice from 
182  sponsors regarding an expected marketing application submission allows review teams to plan 
183  ahead and helps ensure that adequate resources are available for a timely and rigorous review of 
184  the application.  FDA strongly recommends that sponsors provide review teams with early notice 
185  of anticipated marketing application submissions. 
186   
187    Planning is crucial to good review management 
188   
189  The submission of a marketing application shifts the primary responsibility in the review process 
190  to FDA, whose obligation is to determine whether a submitted application meets the statutory 
191  and regulatory requirements for approval.  Review planning should be grounded in the teams 
192  knowledge of the development program, with the goal of identifying key focus points for the 
193  upcoming review.  The team should also establish review timelines specific to the application 
194  under review.  This helps to ensure efficiency and consistency during the review cycle.  
195   
196  Review planning also promotes identification of potential safety issues, so their optimal 
197  management can be adequately discussed during the review cycle.  This is particularly important 
                                                 
7 More information on these programs can be found in the guidance for industry Expedited Programs for Serious 
Conditions  Drugs and Biologics. 
 
8 As discussed in the guidance for industry Special Protocol Assessment. 
 
9 More information on PDUFA and BsUFA, including the commitment letters, is available at 
https://www.fda.gov/forindustry/userfees/prescriptiondruguserfee/ and 
https://www.fda.gov/forindustry/userfees/biosimilaruserfeeactbsufa/default.htm, respectively. 
  5  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
198  in the case of safety issues that might require a REMS.  REMS can be complex programs that 
199  take time to design and implement.  Therefore, such work should begin as soon as a serious 
200  safety issue that may require a REMS is identified.  Ideally, this occurs during product 
201  development, giving the review team and applicant ample time to plan for managing the safety 
202  issue.  When major safety signals warranting discussion are identified by FDA during the 
203  application review, the review team should notify the applicant promptly.  
204   
205  Review teams should also inform applicants about major elements of the internal review timeline 
206  and promptly communicate any significant changes in the review timeline to applicants to ensure 
207  a transparent review process.  Applicants should note that some flexibility in the review of the 
208  application is needed and changes to the review plan are possible.  A well-managed review 
209  process helps FDA staff to accommodate and adequately consider unanticipated events and 
210  findings.  It also takes into account ongoing workload and other public health priorities.  
211   
212    Timely and frequent review team collaboration is critical to good review 
213  management 
214   
215  The review teams scientific assessment of an application and regulatory decision-making is a 
216  collaborative process.  Open lines of communication among reviewers are critical to an efficient 
217  and thorough review.  Review team members should communicate frequently to ensure that 
218  issues affecting multiple disciplines are shared early and that their implications are fully 
219  understood.  The team should also engage with supervisory personnel early and often to ensure 
220  alignment on the approach to review and to maintain awareness of issues identified during the 
221  review cycle.  
222   
223  An effective review team maintains a strong interdependence among its members to support a 
224  collaborative and rigorous review.  Review teams consist of members from many different 
225  disciplines.  They may also consult representatives from other intra- or inter-center disciplines or 
226  review divisions.  This underscores the need for efficient communication and teamwork during 
227  the review. 
228   
229    Effective communication between the review team and applicant is imperative 
230   
231  Applicant involvement in the review process is important to good review management and helps 
232  to ensure transparency and clarity.  During the review, the team should promptly communicate 
233  significant review issues to the applicant.  Timely notification of issues allows the applicant to 
234  begin corrective actions, maximizes the chance for a first cycle approval, and may shorten the 
235  overall time to approval when additional review cycles are necessary.  Applicants can also serve 
236  as a resource to the review team in understanding the contents of a marketing application.  
237  Communication between applicant representatives and the review division regulatory project 
238  manager (RPM) is the most effective and timely mechanism for interaction.  Applicants are 
239  encouraged to work with RPMs to establish a clear communication strategy.10  
                                                 
10 More information on best practices for communication with FDA during drug development can be found in the 
guidance for industry and review staff Best Practices for Communication Between IND Sponsors and FDA During 
Drug Development.  
 
 
  6  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
240   
241  For new molecular entity NDAs and original 351(a) and 351(k) BLAs, FDA and industry have 
242  formalized effective communication practices using the review model known as the Program.  
243  This communication strategy is described in the PDUFA and BsUFA commitment letters.11  The 
244  goals of the Program align with those of the GRMPs:  to promote the efficiency and 
245  effectiveness of the first review cycle and minimize the number of review cycles necessary for 
246  approval so that patients have timely access to safe, effective, and high-quality therapies.  To 
247  accomplish this, the Program includes meetings at key points during the review cycle.  
248  Applicants and the review team can also choose to agree on a formal communication plan that 
249  can be customized to best meet the specific needs of an application.  The Program reflects FDAs 
250  commitment to maximize transparency, flexibility, and communication for the most innovative 
251  and complex products reviewed by FDA. 
252   
253  It is important that communication with the applicant during the review of an application be 
254  generally limited to questions about the contents of an application, requests for additional 
255  information, conveyance of identified review deficiencies that need to be corrected, and 
256  preliminary comments on draft labeling.12  FDA staff should not communicate to applicants the 
257  proposed or planned regulatory action before issuance of the official written action.  Applicants 
258  should not request that FDA staff speculate on the eventual official regulatory action.  
259   
260    Clear and concise documentation of the scientific review and regulatory decision 
261  ensures a thorough and informative record of FDAs regulatory actions 
262   
263  FDA issues an official written regulatory action for each marketing application.  This document 
264  represents the official record of FDAs decision.  FDAs written review documentation of an 
265  approval action contains important information on FDAs basis for its regulatory decision and 
266  includes other requirements of the applicant such as postmarketing requirements.  In the case of a 
267  refuse-to-file or complete response action, FDAs official communication to the applicant 
268  contains the information needed to correct the identified deficiencies.  The review division 
269  should confirm that the applicant has received the official written regulatory action.  
270   
271  Although an applicant may voluntarily withdraw a marketing application at any time for various 
272  reasons, it is generally preferred that this not occur following the applications filing so that FDA 
273  can complete its review and issue a regulatory action.13  If an applicant voluntarily withdraws a 
274  marketing application in advance of an adverse regulatory action, the withdrawal 
275  acknowledgment letter generally includes any deficiencies identified by the review division at 
276  the time the application was withdrawn.  
277   
                                                 
11 More information on PDUFA and BsUFA, including the commitment letters, is available at  
https://www.fda.gov/forindustry/userfees/prescriptiondruguserfee/ and 
https://www.fda.gov/forindustry/userfees/biosimilaruserfeeactbsufa/default.htm, respectively. 
 
12 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. 
13 FDA staff should not request or suggest that an applicant withdraw a pending NDA/BLA except in the most 
unusual circumstances (e.g., the NDA/BLA was submitted to the wrong center). 
  7  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
278  An additional goal of documentation is to reflect FDAs scientific evaluation of an application.  
279  Documentation should not summarize the work that occurred over the course of a review, nor 
280  should it reiterate content that is found in the submission.  Documentation should describe 
281  FDAs scientific assessment of the submission and highlight the most important issues that led to 
282  the regulatory action.  Because these documents serve as the official record of FDAs review, it 
283  is crucial that documentation is clear, concise, and comprehensive.    
284   
285   
286  V.  NEW PRODUCT REVIEW PROCESS 
287   
288  The fundamental values and operational principles described above serve as the foundation for 
289  application review and are expected to remain relatively constant over time.  However, the 
290  review process must be able to nimbly adapt to scientific advances in product development, 
291  evolving patient perspectives, and other factors that cannot always be anticipated.  More 
292  resources concerning FDAs review process are listed below; these resources reflect FDAs goal 
293  of building in flexibility to allow the review process to evolve over time while also preserving 
294  the values and principles of the GRMPs.  It should be noted that review processes in the Center 
295  for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and 
296  Research (CBER) may diverge slightly at times; however, both processes are fully aligned with 
297  to the fundamental values and operational principles described above. 
298   
299  A.  CDERs New Product Review Process 
300   
301  CDERs review process is described in the CDER 21st Century Review Process Desk Reference 
302  Guide, available at 
303  https://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ManualofPoliciesProcedures/
304  UCM218757.pdf.  Additional detail on specific processes (e.g., meetings, advisory committees) 
305  can be found on the Good Review Practices (GRP) website, available at 
306  https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApprove
307  d/ucm092893.htm.  
308   
309  B.  CBERs New Product Review Process 
310   
311  CBERs review process is described on the Industry (Biologics) web page available at 
312  www.fda.gov/biologicsbloodvaccines/resourcesforyou/industry/default.htm. 
  8