ANDAs:  Pre-Submission 
Facility Correspondence 
Related to Prioritized Generic 
Drug Submissions 
 
Guidance for Industry 
 
 
DRAFT GUIDANCE 
 
  This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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 Ranjani Prabhakara, (240) 402-4652.  
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
 
December 2022 
Pharmaceutical Quality/CMC 
 
Revision 2 
 
   
ANDAs:  Pre-Submission 
Facility Correspondence 
Related to Prioritized Generic 
Drug Submissions 
 
 
Guidance for Industry 
 
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/guidance-compliance-regulatory-information/guidances-drugs  
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
 December 2022 
Pharmaceutical Quality/CMC 
 
Revision 2 
 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  SCOPE ............................................................................................................................... 2 
IV.  PRE-SUBMISSION FACILITY CORRESPONDENCE  CONTENTS ................... 3 
A.  Drug Substance and Drug Product Manufacturing and Testing Facilities .............................. 4 
B.  Clinical Bioequivalence Study Sites and Organizations ............................................................. 5 
C.  Analytical Bioequivalence Sites and Organizations .................................................................... 5 
V.  RECEIPT AND ASSESSMENT PROCESS FOR PRE-SUBMISSION FACILITY 
CORRESPONDENCE ................................................................................................................. 9 
A.  Submitting the PFC through FDAs Electronic Submissions Gateway (ESG) ........................ 9 
B.  ANDA Submission Timing .......................................................................................................... 10 
VI.  NOTIFICATIONS TO THE APPLICANT ................................................................. 11 
A.  Pre-Submission Facility Correspondence Acknowledgement Letter ...................................... 11 
B.  Determining Whether an ANDA Qualifies for the Priority Review Goal .............................. 11 
VII.  QUESTIONS AND ANSWERS ..................................................................................... 12 
A.  What types of submissions are addressed by this guidance? ................................................... 12 
B.  What is the rationale for the manufacturing records listed in Table 1? ................................. 12 
C.  What is the purpose of the certification statement to which Section V refers? ...................... 12 
D.  What is considered a significant change? .................................................................................. 13 
E.  Can a final bioequivalence study report in an ANDA impact a priority goal date? .............. 13 
F.  Should an ANDA include facility information already provided in a PFC? .......................... 13 
G.  Should an applicant submit more of its ANDA in the PFC than is recommended in this 
guidance? ............................................................................................................................................... 14 
H.  Should the facilities be ready for inspection at the time of PFC submission? ........................ 14 
I.  Is there a user fee payment required when submitting the PFC for an original ANDA? ..... 14 
VIII.  GLOSSARY..................................................................................................................... 16 
A.  Complete and Accurate PFC ...................................................................................................... 16 
B.  Facility ........................................................................................................................................... 16 
C.  PFC ................................................................................................................................................ 16 
D.  Priority .......................................................................................................................................... 16 
E.  Priority Review ............................................................................................................................ 17 
F.  Priority Review Goal ................................................................................................................... 17 
G.  Significant Changes ..................................................................................................................... 17 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  ANDAs:  Pre-Submission Facility Correspondence Related to 
2  Prioritized Generic Drug Submissions 
3  Guidance for Industry1 
4   
5   
6  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
7  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
8  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
9  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
10  for this guidance as listed on the title page.   
11   
12   
13   
14   
15  I.  INTRODUCTION  
16   
17  The Food and Drug Administration (FDA) is issuing this revised draft guidance to incorporate 
18  program enhancements related to the content, timing, and assessment of a pre-submission facility 
19  correspondence (PFC)2 within the abbreviated new drug application (ANDA) assessment 
20  program3 agreed upon by the Agency and industry as part of the reauthorization of the Generic 
21  Drug User Fee Amendments (GDUFA III), as described in GDUFA Reauthorization 
22  Performance Goals and Program Enhancements, Fiscal Years 2023 through 2027 (GDUFA III 
23  commitment letter).4 This guidance replaces the November 2017 draft guidance for industry on 
24  ANDAs:  Pre-Submission of Facility Information Related to Prioritized Generic Drug 
25  Applications (Pre-Submission Facility Correspondence).5  
26   
27  In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
28  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
29  as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
30  the word should in Agency guidances means that something is suggested or recommended, but 
31  not required.  
32   
33   
34     
 
1 This guidance has been prepared by a multidisciplinary workgroup including members from the Office of 
Pharmaceutical Quality, the Office of Translational Sciences, the Office of Generic Drugs, and the Office of 
Business Informatics in the Center for Drug Evaluation and Research at the Food and Drug Administration, and in 
consultation with the Office of Regulatory Affairs, the Office of Combination Products, and the Center for Devices 
and Radiological Health. 
2 In this guidance, terms that are found in Section VIII, the Glossary, are bolded at first use. 
3 In this guidance, the terms review and assessment are used interchangeably. 
4 The GDUFA III commitment letter is available at https://www.fda.gov/media/153631/download.  
5 FDA issued the previous revised draft pursuant to 21 CFR 10.115 in November 2017. See Federal Register notice 
at 82 FR 51421. 
  1  Contains Nonbinding Recommendations 
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35  II.  BACKGROUND 
36   
37  The Generic Drug User Fee Amendments of 2012 (GDUFA I)6 amended the FD&C Act to 
38  authorize FDA to assess and collect user fees to provide FDA with resources7 to help ensure 
39  patients have access to quality, affordable, safe, and effective generic drugs. GDUFA fee 
40  resources bring greater predictability and timeliness to the review of generic drug applications. 
41  GDUFA has been reauthorized every 5 years to continue FDAs ability to assess and collect 
42  GDUFA fees, and this user fee program has been reauthorized two times since GDUFA I, most 
43  recently in the Generic Drug User Fee Amendments of 2022.8 As described in the GDUFA III 
44  commitment letter applicable to this latest reauthorization, FDA has agreed to performance goals 
45  and program enhancements regarding aspects of the generic drug assessment program that build 
46  on previous authorizations of GDUFA. New enhancements to the program are designed to 
47  maximize the efficiency and utility of each assessment cycle, with the intent of reducing the 
48  number of assessment cycles for ANDAs and facilitating timely access to generic medicines for 
49  American patients. 
50   
51   
52  III.  SCOPE 
53   
54  This revised draft guidance generally references the terms of the GDUFA III commitment letter 
55  and describes and provides recommendations on the content, timing, and assessment of a PFC 
56  for a priority ANDA, such that the ANDA will be eligible for priority review under the 
57  provisions of the GDUFA III commitment letter.9,10 This guidance also provides information 
58  regarding FDAs assessment process for a PFC. Specifically, the guidance describes: 
59   
60    the content and format of the facility information that should be submitted to enable 
61  FDAs assessment of facilities listed in the PFC; 
 
6 Title III of the Food and Drug Administration Safety and Innovation Act, Public Law 112-144. 
7 User fees are available for obligation in accordance with appropriations acts. 
8 Title III of Division F (the FDA User Fee Reauthorization Act of 2022) of the Continuing Appropriations and 
Ukraine Supplemental Appropriations Act, 2023. 
9 On August 18, 2017, the FDA Reauthorization Act (FDARA) (Public Law 115-52), which reauthorized GDUFA 
(Title III) and added other provisions related to generic drugs (Title VIII), was signed into law. FDARA added 
section 505(j)(11) to the FD&C Act, which provides for priority review of certain original ANDAs, while permitting 
FDA to otherwise prioritize applications, as done under the GDUFA III commitment letter (which defines priority 
submissions to include those submissions affirmatively identified as eligible for expedited assessment pursuant to 
CDERs MAPP 5240.3 Prioritization of the Review of Original ANDAs, Amendments, and Supplements 
(Prioritization MAPP)). Accordingly, as described in the glossary to this revised draft guidance, FDA intends to 
consider an ANDA to be a priority ANDA if it meets the criteria listed in section 505(j)(11) of the FD&C Act, with 
respect to an original ANDA, or if it meets the criteria in the Prioritization MAPP. The criteria for affording an 
original ANDA priority status under the Prioritization MAPP and the terms of the GDUFA III commitment letter are 
generally broader than under section 505(j)(11), and certain prior approval supplements (PASs), PAS amendments, 
and ANDA amendments are also eligible for prioritization under the MAPP and the commitment letter; see also the 
GDUFA III commitment letter, sections I.A.2, I.B, and I.A.5. The applications granted priority review under section 
505(j)(11) generally represent a subset of the applications eligible for priority review under the GDUFA III 
commitment letter.  
10 ANDAs that are not eligible for priority review under section 505(j)(11) or the GDUFA III commitment letter 
because of failure to follow the applicable PFC process and/or criteria might still receive an expedited review under 
the Prioritization MAPP, but the standard review goal will apply. 
  2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
62   
63    timeframes for the PFC, and the intersection of these timeframes with submission of an 
64  ANDA; 
65   
66    the possible outcomes of the Agencys assessment of a PFC; and, 
67   
68    when and how the Agency communicates with an applicant about receipt of the PFC and 
69  assignment of a goal date for the ANDA.  
70   
71   
72  IV.  PRE-SUBMISSION FACILITY CORRESPONDENCE  CONTENTS 
73   
74  A complete and accurate PFC should contain all information needed to inform FDAs decision 
75  regarding the need for facility inspections that support the assessment of an ANDA.11 The PFC 
76  provides the information FDA needs to assess the facilities involved in manufacturing processes 
77  and testing of the drug product, including facilities in corresponding Type II active 
78  pharmaceutical ingredient drug master files (API DMFs) referenced in an ANDA,12 and all sites 
79  or organizations involved in bioavailability/bioequivalence analytical and clinical studies used to 
80  support an ANDA.13  
81   
82  FDA assesses facility information submitted in a PFC14 to determine earlier in the review cycle 
83  for the subsequent application submission whether an inspection is necessary. In order to qualify 
84  for a priority review goal, an applicant should submit a PFC no later than 60 days prior to the 
85  date of ANDA submission. In general, under the terms of the GDUFA III commitment letter, if 
86  the PFC is found to be incomplete or inaccurate, or there are significant changes to information 
87  contained in a PFC when submitted in the ANDA, or if information received in a final 
88  bioequivalence study report included in the ANDA leads FDA to a decision that an inspection is 
 
11 See compliance programs 7348.003:  In Vivo Bioavailability-Bioequivalence Studies  Clinical, 7348.004:  In 
Vivo Bioavailability  Analytical, and 7346.832:  Preapproval Inspections. 
12 Section II.F.1.b of the GDUFA III commitment letter clarifies that information needed to inform FDAs decision 
regarding the need for a preapproval inspection, such as a description of the drug substance manufacturing process, 
is not required to be duplicated in the PFC if it is included in a corresponding Type II DMF. If an ANDA does not 
reference a Type II DMF, all information needed to inform FDAs decision regarding the need for a preapproval 
inspection should be provided in the PFC by the ANDA applicant. 
13 An applicant is responsible for identifying all the facilities that impact its ANDA, including the name and address 
of each API and drug product manufacturer (i.e., facility). In addition, an applicant must also submit a complete 
bioequivalence study report in their ANDA; see 21 CFR 314.70, 314.94, and 314.96 for requirements related to 
content of ANDAs.  
14 See the GDUFA III commitment letter, section II.F.1. 
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
89  necessary,15 the 10-month standard review goal will generally apply instead of the priority 
90  review goal.16  
91   
92  The complete and accurate PFC17 must be submitted in the electronic common technical 
93  document (eCTD) format.18 
94   
95  A.  Drug Substance and Drug Product Manufacturing and Testing Facilities 
96   
97  Preapproval evaluations and inspections support the assessment of an ANDA by ensuring that 
98  any facility named or referenced in support of an ANDA can perform a proposed manufacturing 
99  operation as described in the application, in conformance with current good manufacturing 
100  practice requirements, and that manufacturing data submitted in the ANDA are accurate and 
101  complete. FDA utilizes a risk-based approach to assess whether a preapproval inspection (PAI) is 
102  needed before an ANDA can be approved from a quality perspective. This approach focuses on 
103  understanding risks to critical quality attributes19 associated with a facility, process, or product.20  
104   
105  A complete and accurate PFC should provide the information necessary for FDA to determine 
106  each facilitys manufacturing operation capabilities for drug product21 or API,22 and to identify 
107  the need for a PAI. This information should include a description of the manufacturing process, 
108  controls of critical steps, and anticipated differences between pilot/exhibit scale and commercial 
 
15 To note, in implementing section 505(j)(11) of the FD&C Act for priority review of certain original ANDAs, 
FDA determined (per authority to identify necessary information in that context) that a final bioequivalence study 
report is required to make a determination under that provision regarding whether an inspection of a facility is 
necessary. Thus, a PFC submission under section 505(j)(11) without the final study report would not qualify the 
ANDA for priority review under that provision. However, for purposes of priority review under the GDUFA III 
commitment letter, FDA agreed that a prospective applicant can submit a PFC without the final bioequivalence 
study report and qualify for a priority review goal, if certain conditions are met. Notably, if the data and information 
contained in that report as submitted in the ANDA do not raise issues that provide a basis for inspection of the 
facility, the ANDA will receive a priority goal date under the GDUFA III commitment letter. If that data and 
information do raise issues that provide a basis for inspection, the ANDA will not receive a priority goal date under 
the GDUFA III commitment letter.  
16 See the GDUFA III commitment letter, sections I.A.2.b, I.A.6, I.B.2.c, and I.B.4.c. Of note, FDA will only review 
the original PFC submitted by an applicant. If FDA determines a PFC is not complete and accurate, as described in 
the GDUFA III commitment letter, the PFC may not be revised, and no additional review of the PFC will be 
undertaken. In such cases, FDA intends to assess and act on the ANDA within 10 months of the date of ANDA 
submission.  
17 See the GDUFA III commitment letter, section II.F.1. 
18 The electronic submission requirements of Section 745A(a) of the FD&C Act are implemented in the FDA 
guidance for industry Providing Regulatory Submissions in Electronic Format  Certain Human Pharmaceutical 
Product Applications and Related Submissions Using the eCTD Specifications, Revision 7 (February 2020). We 
update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents. See also eCTD Technical 
Conformance Guide, at https://www.fda.gov/drugs/electronic-regulatory-submission-and-review/ectd-resources.  
19 See FDA guidances for industry Q8(R2) Pharmaceutical Development (November 2009) and Q11 Development 
and Manufacture of Drug Substances (November 2012).  
20 See compliance program 7346.832:  Preapproval Inspections. 
21 See 21 CFR 210.3(b)(12) which states Manufacture, processing, packing, or holding of a drug product includes 
packaging and labeling operations, testing, and quality control of drug products.  
22 See FDA guidance for industry Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical 
Ingredients (September 2016).  
  4  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
109  scale processes.23 Information regarding the conformance of exhibit batches to specifications 
110  should be provided.24  
111   
112  For each manufacturing facility, an applicant should also provide the following: facility name, 
113  operation(s) performed, facility contact name, address, FDA Establishment Identifier (FEI) 
114  number (if a required registrant or one has been assigned), DUNS number, registration 
115  information (for required registrants), confirmation that the facility is ready for inspection,25 and 
116  certification that any Type II DMF has similarly complete and accurate facility information.26 
117   
118  A summary of facility information that should be submitted in a complete and accurate PFC, 
119  including corresponding eCTD sections and eCTD Module Numbers27 is provided in Table 1.  
120   
121  B.  Clinical Bioequivalence Study Sites and Organizations  
122   
123  Sites or organizations that perform the clinical portions of BE studies used to support an ANDA 
124  are subject to inspection to evaluate the overall quality of subject safety and data integrity at the 
125  site.28 A complete and accurate PFC should contain the information needed to inform FDAs 
126  decision regarding the need for a bioresearch monitoring inspection of these sites, including the 
127  site name, address, and website; study numbers; a list and description of all study investigators 
128  consistent with section 16.1.4 of the guidance ICH E3 Structure and Content of Clinical Study 
129  Reports (July 1996);29 study conduct dates; and study protocols and any available amendments.30  
130   
131  A summary of clinical site or organization information that should be submitted in a complete 
132  and accurate PFC, including corresponding eCTD sections and eCTD Module Numbers, 31 is 
133  included in Table 1. 
134   
135  C.  Analytical Bioequivalence Sites and Organizations  
136   
137  Sites or organizations that perform the analytical portions of clinical bioequivalence studies or in 
138  vitro bioequivalence studies (collectively referred to as analytical sites), are subject to inspection 
139  to ensure that these studies are conducted using the highest laboratory standards and in 
140  accordance with applicable regulations.32 A complete and accurate PFC should contain the 
141  information needed to inform FDAs decision regarding the need for a bioresearch monitoring 
142  inspection of analytical sites, including the site name, address, and website.  
143   
 
23 See the GDUFA III Commitment letter section II.F.1.a.ii.  
24 See FDA guidance for industry ANDA Submissions  Content and Format (June 2019). 
25 See the GDUFA III commitment letter, section II.F.1.a.i.  
26 See the GDUFA III commitment letter, section II.F.1.a.iii.  
27 Per normal submission practices, information for some subsections in eCTD section 3.2.S may be incorporated 
through reference to a type II DMF, where a letter of authorization (LOA) has been submitted to the DMF by the 
DMF holder, and the Statement of Right of Reference is included by the Applicant in eCTD section 1.4.2 of the 
ANDA. 
28 See FDA compliance program 7348.003:  Bioresearch Monitoring  Clinical. 
29 See ICH guidance for industry E3 Structure and Content of Clinical Study Reports (July 1996). 
30 See the GDUFA III commitment letter, section II.F.1.c; see also See 21 CFR 314.94(a)(7). 
31 See footnote 18. 
32 See FDA compliance program 7348.004:  Bioresearch Monitoring  Analytical.  
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Draft  Not for Implementation 
144  For those analytical studies that were initiated no later than 60 days prior to the ANDA 
145  submission, additional recommendations are: a list of investigator name(s); study conduct dates; 
146  and the analytical method validation, if completed before dosing.33  
147   
148  A summary of analytical site or organization information that should be submitted in a complete 
149  and accurate PFC, including corresponding eCTD sections and eCTD Module Numbers34 is 
150  provided in Table 1. 
 
33 See the GDUFA III commitment letter, section II.F.1.d. 
34 See footnote 18.  
  6  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
Table 1.  List of Facility Information that should be submitted in the PFC for a Priority ANDAa  
eCTD Module 
Description 
Number 
Form FDA 356hb,c  the Form FDA 356h should be submitted with the 
PFC. Submitting the Form FDA 356h will enable the Agency to expedite 
processing of the PFC. Consider the following when submitting a Form 
FDA 356h associated with a PFC: 
  Submission Field this field accommodates selection of all the 
choices that apply. For a PFC related to a priority ANDA, select 
1.1   Product Correspondence and Other. In the Other field, 
specify that this is a Pre-Submission of Facility Information 
Related to a Priority ANDA. This option should be selected for 
PASs, PAS amendments, and ANDA amendments, as well as for 
original ANDAs. 
  Submission Sub-Type Field  for this field, select Pre-
submission. 
Cover Letter  the Cover Letter accompanying the PFC should include: 
  Statement of inspection readiness 
1.2    Statement identifying the Reference Listed Drug 
  Anticipated date of original ANDA, PAS, PAS amendment, or 
ANDA amendment submission  
1.3.1.2  U.S. Agent Appointment Letter (if applicable) 
Statement of Right of Reference  this includes the DMF Right of 
1.4.2 
Reference Letter, if applicable 
Summary of Biopharmaceutic Studies and Associated Analytical 
2.7 
Methods (Tables 2 and 10)d  
3.2.S.1.1  Nomenclaturee 
3.2.S.1.2  Structuree 
3.2.S.1.3  General Propertiese 
3.2.S.2.1  Manufacturer(s)f 
3.2.S.2.2  Drug Substance Manufacturing Process Descriptiong 
3.2.S.2.4  Control of Critical Steps and Intermediatesg 
3.2.S.2.6  Manufacturing Process Developmentg 
3.2.S.4.1  Drug Substance Specifications 
3.2.S.4.4  Batch Analyses  
3.2.P.1  Description and Composition of the Drug Product 
3.2.P.2  Pharmaceutical Development  Manufacturing Process Development  
3.2.P.3.1  Manufacturer(s)  
3.2.P.3.2  Batch Formula  
3.2.P.3.3  Description of Manufacturing Process and Process Controls  
3.2.P.3.4  Control of Critical Steps and Intermediates  
3.2.P.3.5  Sterilization Validation Documentation and Datah 
3.2.P.5.1  Drug Product Specifications 
3.2.P.5.4  Batch Analyses 
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Facility Information for Non-Drug Constituent Parts of a Combination 
3.2.P.7 
Product  
Information related to bioequivalence and clinical studies. Specifically: 
  Site names, addresses, and websites  
  Study Titles 
  Study Numbers 
5.3.1.2 
  Study Conduct Dates 
  Study Protocol and Available Amendments  ICH E3 (16.1.1)i 
  List and Description of all Study Investigators  ICH E3 (16.1.4)i 
  Study Report if available at the time of the PFC 
Information related to analytical studies. Specifically: 
  Site names, addresses, and websites 
  Study Titles 
  Study Numbers 
5.3.1.4    Study Conduct Dates 
  A list of investigator name(s) 
  Analytical Method Validation Report(s) if the analytical method 
validation was completed before dosing 
  Study Report if available at the time of the PFC 
151   
152  a. See 21 CFR 314.70, 314.94, 314.96 and 314.97 for requirements related to ANDA content. 
153  b See FDAs guidance for industry, Identification of Manufacturing Establishments in Applications Submitted to 
154  CBER and CDER Questions and Answers (October 2019).  
155  c See draft guidance for industry Facility Readiness: Goal Date Decisions Under GDUFA (October 2022). When 
156  final, this guidance will represent the FDAs current thinking on this topic. 
157  d See Model Bioequivalence Data Summary Tables:  Technical Specifications Document, at 
158  https://www.fda.gov/media/75081/download. 
159  e See section III.C.1, Topic 3.2.S.1 in FDAs guidance for industry ANDA Submissions  Content and Format of 
160  Abbreviated New Drug Applications (June 2019), which states that 3.2.S.1 should not include any references to the 
161  DMF. 
162  f See section III.C.1, Topic 3.2.S.2.1 in FDAs guidance for industry ANDA Submissions  Content and Format of 
163  Abbreviated New Drug Applications (June 2019), which states that 3.2.S.2.1 Contains information about each drug 
164  substance manufacturer, including...Type II DMF number for the API or any critical or final intermediates, if 
165  applicable. 
166  g See section III.C.1, Topics 3.2.S.2.2 through 3.2.S.2.6 in FDAs guidance for industry ANDA Submissions  
167  Content and Format (June 2019), which states that that Subsections 3.2.S.2.2 through 3.2.S.2.6 may refer to the 
168  DMF. If there is no DMF referenced in the application, detailed information should be provided in these 
169  subsections.  
170  h For further information on sterilization validation documentation expectations in a marketing application, see 
171  FDAs guidance for industry for the Submission Documentation for Sterilization Process Validation in Applications 
172  for Human and Veterinary Drug Products (November 1994).  
173  i See ICH guidance for industry E3 Structure and Content of Clinical Study Reports (July 1996). 
174   
175  NOTE  For PASs, PAS amendments, and ANDA amendments, only the modules applicable to 
176  these types of submissions should be submitted.35 
177   
 
35 See 21 CFR 314.70, 314.96, and 314.97. 
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178  With regard to combination products (as defined in 21 CFR 3.2(e))36 and the facility information 
179  related to the manufacturing and testing of non-drug constituent parts,37 refer to both the eCTD 
180  Technical Conformance Guide38 and guidance for industry: Identification of Manufacturing 
181  Establishments in Applications Submitted to CBER and CDER  Questions and Answers 
182  (October 2019).39 
183   
184   
185  V.  RECEIPT AND ASSESSMENT PROCESS FOR PRE-SUBMISSION FACILITY 
186  CORRESPONDENCE 
187   
188  The following section describes the process for the receipt and assessment of the PFC related to a 
189  priority ANDA. 
190   
191  A.  Submitting the PFC through FDAs Electronic Submissions Gateway (ESG)  
192   
193  1.  Obtaining a Pre-Assigned ANDA Number (if applicable) 
194   
195  For original ANDAs, the applicant should request a pre-assigned ANDA number before 
196  submitting the PFC. For PASs, PAS amendments, and ANDA amendments, the applicant should 
197  use the relevant ANDA application number on the Form FDA 356h. 
198   
199  2.  Transmitting the PFC through FDAs ESG 
200   
201  The PFC must be submitted electronically in eCTD format40 through the FDA ESG following 
202  the Agencys instructions.41 When transmitting the PFC through the ESG, choose CDER when 
203  selecting the appropriate Center, and choose eCTD when selecting the submission type. 
204   
205  The applicant should submit the priority ANDA consistent with the ANDA Submission 
206  Timing described in section V.B. (below). If the applicant decides not to submit the ANDA 
207  after submitting the PFC, FDA should be notified in writing. The notice of decision not to submit 
 
36 A combination product is a product composed of two or more different types of medical products (i.e., a 
combination of a drug, device, and/or biological product with one another). The drugs, devices, and biological 
products included in combination products are referred to as constituent parts of the combination product. See 
section 503(g) of the FD&C Act and 21 CFR part 3. 
37 See 21 CFR part 4. See also guidance for industry Current Good Manufacturing Practice Requirements for 
Combination Products (January 2017), section II.C Overview of the final rule. 
38 For additional information on how to incorporate information regarding non-drug constituent parts into the eCTD 
Sequence, please refer to the eCTD Technical Conformance Guide at 
https://www.fda.gov/drugs/developmentapprovalprocess/formssubmissionrequirements/electronicsubmissions/ucm5
35180.htm.  
39 For additional information on how to incorporate information regarding non-drug constituent parts into the eCTD 
Sequence, please refer to the guidance for industry Identification of Manufacturing Establishments in Applications 
Submitted to CBER and CDER  Questions and Answers (October 2019). 
40 See footnote 18. 
41 See the Electronic Submissions Gateway web page at 
https://www.fda.gov/forIndustry/ElectronicSubmissionsGateway/default.htm for technical details related to 
submitting documents through FDAs Electronic Submission Gateway. 
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208  the ANDA should reference the submission number and be submitted to eCTD section 1.2, 
209  Cover Letter. 
210   
211  3.  FDAs Assessment of the PFC 
212   
213  The Agency will begin assessment of the PFC upon receipt. FDA will send a letter to the 
214  applicant to acknowledge receipt of the PFC. FDA will assess priority status and assign the 
215  appropriate review goal date after the ANDA is submitted42 as further explained in Section VI.B 
216  (below). 
217   
218  B.  ANDA Submission Timing 
219   
220  In order for an ANDA to be eligible to receive priority review, the PFC should be submitted not 
221  later than 60 days prior to the submission of the ANDA itself.43 This timing allows the Agency 
222  to begin assessing the facility information before receiving the ANDA.  
223   
224  Additionally, an ANDA should not contain any significant changes to the information submitted 
225  in the PFC.44 To minimize the possibility of significant changes to facility information between 
226  submission of the PFC and the ANDA (and consequently loss of the priority review goal), FDA 
227  recommends applicants submit the PFC not earlier than 90 days before submission of the ANDA 
228  and refer to guidance for industry Providing Regulatory Submissions in Electronic Format  
229  Receipt Dates (February 2014)45 for further details. 
230   
231  For example:  
232   
233  1.  If an original ANDA was submitted on Monday, February 12, 2024, then the PFC would 
234  have to have been submitted not later than Thursday, December 14, 2023, to be consistent with 
235  the criterion that the PFC be submitted not later than 60 days prior to the submission of the 
236  ANDA. 
237  2.  If an original ANDA was submitted on Thursday, November 16, 2023, then the PFC 
238  would have to have been submitted not later than Friday, September 15, 2023. This scenario 
239  accounts for the not later than 60 days period ending on a weekend. 
240  3.  If an original ANDA was submitted on Thursday, July 4, 2024, then the PFC would have 
241  to have been submitted not later than Monday, May 6, 2024. This scenario accounts for a Federal 
242  Holiday. 
243   
244  The applicant should submit a signed certification statement during ANDA submission (in eCTD 
245  section 1.2) stating that the applicant has 1) made no significant changes (as described in the 
 
42 See Section III (Scope) and footnotes 9 and 10.  
43 The GDUFA III commitment letter sections I.A.2.a, I.A.5.b, I.B.2.b, and I.B.4.b refer to the submission of the 
PFC not later than 60 days prior to the date of ANDA submission in order to be eligible for the 8-month priority 
review goal. See also section 505(j)(11)(B) of the FD&C Act. 
44 See the GDUFA III commitment letter sections I.A.2.b.iii, I.A.6.c, I.B.2.c.iii and I.B.4.c.iii. 
45 See footnote 18. 
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246  GDUFA III commitment letter)46 to the information contained in the PFC or 2) has made no 
247  changes except to exclude a facility not involved in generating data for the application as 
248  described in section 505(j)(11)(B) of the FD&C Act. 
249   
250  Significant changes between PFC and ANDA submission will result in assignment of the 
251  standard review goal.47 Such significant changes should be made by including information 
252  regarding the significant changes in the appropriate eCTD module with the ANDA submission. 
253  Such significant changes should be identified in the cover letter. 
254   
255  FDAs review of the ANDA, which will include an assessment and determination of whether the 
256  ANDA meets the priority designation criteria, will be performed in accordance with its 
257  applicable statutory and regulatory authorities and policies, and procedures for ANDA reviews. 
258  At the time of receipt, FDA will notify the applicant in the ANDA acknowledgement letter 
259  whether the ANDA or PAS is subject to priority review.  
260   
261   
262  VI.  NOTIFICATIONS TO THE APPLICANT 
263   
264  A.  Pre-Submission Facility Correspondence Acknowledgement Letter 
265   
266  As part of its assessment of the PFC, the Agency will send a letter to: 
267   
268    Inform the applicant that a goal date incorporating any priority designation 
269  determination will be provided after submission and receipt for assessment of the 
270  ANDA; and 
271   
272    Remind the applicant that they must not submit their ANDA earlier than 60 days 
273  after the date of submission of the PFC date to be eligible for the priority review 
274  goal.48  
275   
276  The Pre-Submission Facility Correspondence Acknowledgement Letter simply acknowledges 
277  receipt of the PFC by the Agency. Eligibility for the priority review goal based on the PFC is 
278  determined by FDA when an ANDA is submitted. 
279   
280  B.  Determining Whether an ANDA Qualifies for the Priority Review Goal  
281   
282  After receiving the ANDA, FDA will determine the applicable goal date for the submission. 
283  Establishing the applicable goal date for the ANDA is based on the Agencys priority 
284  designation determination at the time of ANDA submission; assessment of whether the applicant 
285  submitted a complete and accurate PFC, including confirmation that all facilities are ready for 
 
46 The GDUFA III commitment letter, section II.F.2 states that: Changes to information contained in a PFC when 
submitted in an ANDA that are considered a significant change include changes in the identified facilities for 
manufacture of the drug substance or drug product, the proposed manufacturing operations or operating principles, 
and the order of manufacturing unit operations. 
47 See footnote 44. 
48 See footnote 43.  
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286  inspection; and determination that the information submitted in the ANDA does not differ 
287  significantly from what was submitted in the PFC.49 The Agency will convey the outcome and 
288  resulting goal date in the ANDA acknowledgement letter.  
289   
290   
291  VII.  QUESTIONS AND ANSWERS 
292   
293  A.  What types of submissions are addressed by this guidance? 
294   
295  This revised draft guidance includes recommendations for, and applies to, priority original 
296  ANDAs, PASs, PAS amendments, and ANDA amendments. 
297   
298  B.  What is the rationale for the manufacturing records listed in Table 1? 
299   
300  A complete and accurate PFC supports GDUFA III performance goals and program 
301  enhancements designed to maximize the efficiency and utility of each ANDA assessment cycle. 
302  To this end, FDA evaluated the records and information required for an ANDA submission to 
303  determine which specific records would allow FDA to determine, earlier in the ANDA 
304  assessment cycle, if an inspection is necessary to support the assessment of an ANDA.  
305   
306  As described in FDA compliance program 7346.832: Preapproval Inspections, FDA determines 
307  the need for PAIs based on the cumulative assessment of process, product, and facility risks 
308  related to the pending application. Manufacturing information contained in the PFC provides 
309  FDA the ability to perform this assessment and determine the need for a PAI earlier in the 
310  ANDA assessment process. For example, information contained in a PFC related to 
311  manufacturing process development, description of the manufacturing process and controls, 
312  controls for critical steps, sterilization validation, specifications, and batch analyses allows FDA 
313  to assess whether manufacturing operations were designed and implemented accounting for 
314  knowledge gained during development, were executed as intended in support of the application, 
315  and that such operations reflect the intended commercial operations. The list of manufacturing 
316  sites, proposed manufacturing operations, and description of manufacturing process and controls 
317  allows FDA to assess the comparability of proposed operations to the known capabilities of 
318  manufacturers in the context of their current compliance status. If there are significant 
319  differences between the process used for the development/exhibit batches and the proposed 
320  commercial manufacturing process, or if FDA has concerns about knowledge transfer, this could 
321  indicate the need for an inspection. 
322   
323  C.  What is the purpose of the certification statement to which Section V refers? 
324   
325  The certification statement is the applicants signed statement that the PFC information is 
326  complete and accurate, and the information submitted in the ANDA does not differ significantly 
327  from what was submitted in the PFC, as is a condition for priority review goal eligibility under 
328  the terms of the GDUFA III commitment letter.50  
329   
 
49 See the GDUFA III commitment letter, section II.F. 
50 See footnote 44. 
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330  Applicants that include significant changes to the PFC information in their submitted ANDA 
331  should omit the certification statement and identify such significant changes in the cover letter. 
332  Such changes will generally result in assignment of the standard review goal.51 
333   
334  D.  What is considered a significant change? 
335   
336  Significant changes represent any changes to the facility information as submitted in an ANDA, 
337  relative to information submitted in the PFC, that have the potential to introduce or increase 
338  risk(s) to critical quality attributes associated with the facility or the process.52 A priority 
339  ANDA53 is eligible for a priority review goal only when there are no significant changes 
340  between information contained in the PFC and that submitted in the ANDA. Significant changes 
341  include, but are not limited to, changes in the identified facilities for manufacture of the drug 
342  substance or drug product, the proposed manufacturing operations or operating principles, or the 
343  order of manufacturing unit operations.54 Significant changes may alter FDAs initial decision 
344  regarding the need for a PAI, resulting in the decision to conduct an inspection that was not 
345  deemed necessary at the time of PFC assessment. In the case of significant changes, the standard 
346  review goal would apply. 
347   
348  Certain revisions of information contained in the PFC when submitted in the ANDA may not be 
349  considered a significant change, in that a decision on the need for an inspection would not 
350  require reconsideration based on such changes. For example, finalization of the development 
351  report without changes to the manufacturing process or control strategy, finalization of process 
352  parameters, or the final designation of commercial equipment without changes in design or 
353  operating principle are changes that may not be considered significant. 
354   
355  E.  Can a final bioequivalence study report in an ANDA impact a priority goal 
356  date? 
357   
358  Although an ANDA applicant may submit the final bioequivalence study report (clinical and/or 
359  analytical) at the same time as a PFC, a final bioequivalence study report is not a condition for a 
360  complete and accurate PFC under the terms of the GDUFA III commitment letter. If an applicant 
361  submits the final bioequivalence study report with a complete and accurate PFC and FDA 
362  determines that an inspection is needed, the priority goal date may still apply. However, if an 
363  applicant instead submits their final bioequivalence study report at the time of ANDA 
364  submission and FDA determines, upon assessment of the final bioequivalence study report, that 
365  an inspection of the relevant site or sites is necessary, the standard 10-month goal date will apply 
366  under the terms of the GDUFA III commitment letter.55  
367   
368  F.  Should an ANDA include facility information already provided in a PFC? 
369   
 
51 Ibid. 
52 See footnote 1919. 
53 FDA intends to consider an ANDA to be a priority ANDA per the GDUFA III commitment letter if it is 
prioritized under the Prioritization MAPP. 
54 See footnote 46.  
55 See the GDUFA III commitment letter, section I.A.2.b.iv. 
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370  No. The applicant should not re-submit the facility information contained in the PFC. However, 
371  if there have been any significant changes since submission of the PFC, the new information 
372  must be included in the ANDA56 and should be identified in the cover letter. 
373   
374  G.  Should an applicant submit more of its ANDA in the PFC than is 
375  recommended in this guidance? 
376   
377  Only the information listed in section IV of this revised draft guidance should be submitted in the 
378  PFC. A PFC including this information will be considered a complete and accurate PFC under 
379  the terms of the GDUFA III commitment letter.57  
380   
381  H.  Should the facilities be ready for inspection at the time of PFC submission? 
382   
383  The PFC should include confirmation that all facilities involved in manufacturing processes for 
384  the ANDA and corresponding Type II API DMF are ready for inspection.58 The PFC does not 
385  need to include confirmation that sites or organizations involved in bioequivalence and clinical 
386  studies, or analytical studies used to support the ANDA submission are ready for inspection, as 
387  FDA will make inspection determinations for these sites or organizations during assessment of 
388  the ANDA.59  
389   
390  Under the terms of the GDUFA III commitment letter, for original ANDAs only, if at the time of 
391  ANDA submission, any facilities involved in manufacturing processes and testing for the ANDA 
392  and corresponding Type II API DMFs are no longer ready for inspection, as indicated in the 
393  Form FDA 356h, FDA will set a goal date that is 15 months from the date of original ANDA 
394  submission.60 If the applicant previously submitted an otherwise complete and accurate PFC 
395  prior to original ANDA submission, and an amendment stating that all facilities are ready for 
396  inspection is submitted at least 30 days prior to the 15-month goal date expiration, FDA will 
397  reassign a priority goal date from the date of amendment submission.61, 62 This 15-month goal 
398  date extension for an original ANDA with a facility that is not ready for inspection is not 
399  applicable to sites or organizations involved in bioequivalence and clinical studies, or analytical 
400  studies used to support an ANDA.  
401   
402  I.  Is there a user fee payment required when submitting the PFC for an 
403  original ANDA? 
404   
 
56 See 21 CFR 314.70, 314.94, 314.96, and 314.97. 
57 See the GDUFA III commitment letter, section II.F.1. As described in Question E, an applicant may submit a final 
bioequivalence study report (clinical and/or analytical), if available, at the same time an applicant submits a PFC. A 
determination of priority review will still occur at the time of ANDA submission. 
58 See the GDUFA III commitment letter, section II.F.1.a.i.  
59 See the GDUFA III commitment letter, sections II.F.1.c and II.F.1.d.  
60 See the GDUFA III commitment letter, section I.A.3. 
61 See the GDUFA III commitment letter, section I.A.3.a. 
62 See draft guidance for industry Facility Readiness: Goal Date Decisions Under GDUFA (October 2022). 
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405  No. There are no user fees associated with the PFC. Under GDUFA, an ANDA filing fee is paid 
406  at the time of the original ANDA submission.63  
407     
 
63 Section 744B(a)(3) of the FD&C Act. See also the Generic Drug User Fee Cover Sheet and Payment Information  
https://www.fda.gov/industry/fda-user-fee-programs for further details. 
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408  VIII.  GLOSSARY  
409   
410  A.  Complete and Accurate PFC  
411   
412  A complete and accurate PFC includes: information for facilities involved in manufacturing 
413  processes, including testing, for the drug that is the subject of the application (including facilities 
414  in corresponding Type II API DMFs referenced in an application); sites or organizations 
415  involved in bioequivalence and clinical studies used to support the application;64 and includes 
416  confirmation that all facilities are ready for inspection.65 For manufacturing facilities, this 
417  includes information needed to inform FDAs decision for a PAI. 
418   
419  B.  Facility  
420   
421  For the purposes of this guidance, the term facility(-ies) means manufacturing site and 
422  bioequivalence site.  
423   
424  Manufacturing site means all sites involved in manufacturing processes, packaging, and testing 
425  for the ANDA and corresponding Type II API DMF.66,67 For the purpose of this guidance, this 
426  term refers to any manufacturing, packaging, or testing site associated with an ANDA that 
427  conducts an operation to support manufacturing or testing of the API or drug product. This 
428  includes sites listed in Type II DMFs and sites that manufacture non-drug constituent parts of a 
429  combination product. For additional information including guidance regarding those facilities 
430  that should be listed on the Form FDA 356h in support of the PFC, please refer to the FDA 
431  guidance for industry Identification of Manufacturing Establishments in Applications Submitted 
432  to CBER and CDER Questions and Answers (October 2019). 
433   
434  Bioequivalence site means all sites or organizations involved in clinical bioequivalence studies 
435  with pharmacokinetic, pharmacodynamic or clinical endpoints, and in vitro bioequivalence 
436  studies used to support the ANDA submission.68 For the purposes of this guidance, this term also 
437  captures sites that conduct analytical testing in support of the ANDA. 
438   
439  C.  PFC  
440   
441  The term PFC refers to a submission of facility information prior to ANDA submission that 
442  enables a shorter review goal (priority review goal) for certain priority original ANDAs, PASs, 
443  PAS amendments, and ANDA amendments, if the PFC meets applicable conditions. 
444   
445  D.  Priority  
446   
447  The term priority refers to ANDAs that meet the relevant criteria listed in section 505(j)(11) of 
448  the FD&C Act, in order to qualify for priority review under that provision, or submissions 
 
64 See footnote 14. 
65 See footnote 17. 
66 See footnote 2121. 
67 See footnote 22. 
68 See 21 CFR 314.94(a)(7) and 320.24(b). 
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449  identified as eligible for expedited assessment pursuant to CDERs Manual of Policies and 
450  Procedures (MAPP) 5240.3, Prioritization of the Review of Original ANDAs, Amendments, and 
451  Supplements (Prioritization MAPP). 
452   
453  E.  Priority Review 
454   
455  The term priority review refers to the 8-month review provided for under section 505(j)(11) of 
456  the FD&C Act, with respect to original ANDAs subject to that provision, or the 8-month priority 
457  review goal provided for under the terms of the GDUFA III commitment letter. 
458   
459  F.  Priority Review Goal  
460   
461  The term priority review goal refers to the shorter 8-month goal dates identified in the GDUFA 
462  III commitment letter for priority original ANDAs, PASs, PAS amendments, and ANDA 
463  amendments that are designated priority by FDA and have submitted within the proper 
464  timeframe a complete and accurate PFC that is not significantly changed relative to the date of 
465  subsequent ANDA submission.69  
466   
467  G.  Significant Changes 
468   
469  As set forth in the GDUFA III commitment letter, the term significant changes includes 
470  changes to the identified facilities for manufacture of the drug substance or drug product, to the 
471  proposed manufacturing operations or operating principles, and to the order of manufacturing 
472  unit operations, when such changes are made between the time of PFC receipt and ANDA 
473  submission.70 
474   
475    
 
69 See footnote 16. 
70 See footnote 46. 
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