ANDAs: Pre-Submission

Facility Correspondence
Associated with Priority
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DRAFT GUIDANCE
This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft
guidance.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 Division of Dockets Management (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) Nikhil Thakur 301-796-5536.

U.S. Department of Health and Human Services

Food and Drug Administration
Center for Drug Evaluation and Research (CDER)

June 2017
Pharmaceutical Quality/ CMC
 ANDAs: Pre-
Submission Facility
Correspondence
Associated with Priority
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
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

U.S. Department of Health and Human Services

Food and Drug Administration
Center for Drug Evaluation and Research (CDER)

June 2017
Pharmaceutical Quality/CMC
 Contains Nonbinding Recommendations
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TABLE OF CONTENTS

I. INTRODUCTION............................................................................................................. 1
II. BACKGROUND ............................................................................................................... 2
III. SCOPE ............................................................................................................................... 4
IV. PRE-SUBMISSION FACILITY CORRESPONDENCE CONTENT .......................... 4
A. General Information ...................................................................................................................... 4
B. Statement of ANDA Eligibility for Priority Review .................................................................... 5
C. Manufacturing Process and Testing Facility Information ......................................................... 6
D. Bioequivalence Summary and Site/Organization Information.................................................. 9
V. ANDA SUBMISSION WINDOW ................................................................................. 10
VI. RECEIPT AND ASSESSMENT PROCESS (FOR PFC AND PLANNED ANDA).. 10
A. PFC Receipt and Assessment ...................................................................................................... 10
B. ANDA Submission ....................................................................................................................... 12
C. Differences in Facility Information between the PFC and the Planned ANDA ...................... 13
VII. OUTCOMES ................................................................................................................... 13
A. Eligibility of the PFC for Further FDA Assessment ................................................................. 13
B. Determining the Goal Date for the Planned ANDA .................................................................. 14
VIII. QUESTIONS AND ANSWERS ..................................................................................... 15
IX. DEFINITIONS ................................................................................................................ 16
APPENDIX – PRE-SUBMISSION FACILITY CORRESPONDENCE SUGGESTED
FORMAT ..................................................................................................................................... 19
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1 ANDAs: Pre-Submission Facility Correspondence Associated with

2 Priority Submissions
3 Guidance for Industry 1,2
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 I. INTRODUCTION
15
16 This guidance describes the process through which prospective generic drug applicants submit
17 pre-submission facility correspondence (PFC) in advance of priority 3 generic drug submissions.
18
19 In 2016-2017, the Food and Drug Administration (FDA), regulated industry, and public
20 stakeholders conducted negotiations concerning reauthorization of the Generic Drug User Fee
21 Amendments (GDUFA II). 4 A chief product of these congressionally mandated discussions is
22 the GDUFA II Commitment Letter. The GDUFA II Commitment Letter describes the FDA’s
23 performance goals under GDUFA II as well as changes and improvements to the user fee
24 program. The performance goals and program enhancements specified in the GDUFA II
25 Commitment Letter concern aspects of the generic drug review program that are important for
26 facilitating timely access to quality, affordable generic medicines.
27
28 As one of the enhancements specified in the GDUFA II Commitment Letter, the PFC is a
29 mechanism to achieve expedited review of priority abbreviated new drug applications (ANDAs),
30 prior approval supplements (PASs), and their amendments (collectively ANDAs). Using a PFC,
31 a prospective applicant submits certain information related to manufacturing and bioequivalence
32 facilities (collectively facilities) 5 that will be referenced in a planned ANDA 6 prior to submission

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.
2
When final, this guidance will represent the FDA’s current thinking on this topic. For the most recent version of a
guidance, check the FDA Drugs guidance web page at
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
3
In Section IX of this guidance, the term priority ANDA is defined.
4
See GDUFA Reauthorization Performance Goals and Program Enhancements, FYs 2018-2022. All public
documents cited in this guidance may be found on the FDA website (www.fda.gov).
5
In Section IX of this guidance, the term facilities is defined.

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33 of the ANDA itself. Pre-submission facility correspondence should also demonstrate that the
34 planned ANDA meets the criteria for a priority submission. The priority designation criteria are
35 described in the Center for Drug Evaluation and Research’s (CDER) Manual of Policies and
36 Procedures (MAPP) 5240.3, Rev. 2, Prioritization of the Review of Original ANDAs,
37 Amendments, and Supplements (Prioritization MAPP). 7 For example, if the ANDA drug product
38 is the subject of a current drug shortage, the ANDA would potentially qualify for priority
39 review. 8
40
41 The information submitted in the PFC provides the Agency with the opportunity to determine
42 whether facility inspections will be needed. When deemed necessary, the Agency will initiate
43 inspection planning earlier in the review of the ANDA. Further, it enables FDA to meet the
44 shorter review timeframe (shorter goal dates 9) for the planned ANDA as defined in the GDUFA
45 II Commitment Letter. If a PFC successfully demonstrates that the planned ANDA may be a
46 priority submission and the information is complete and accurate and is unchanged, 10 the
47 ANDA may qualify for shorter goal dates for the planned ANDA. Absent extraordinary
48 circumstances, FDA does not expect to utilize its limited resources to review a second PFC on
49 the same submission if the first one is deficient.
50
51 In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
52 Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
53 as recommendations, unless specific regulatory or statutory requirements are cited. The use of
54 the word should in Agency guidances means that something is suggested or recommended, but
55 not required.
56
57
58 II. BACKGROUND
59
60 Under the performance goals and program enhancements for GDUFA II, FDA agreed to a
61 shorter goal date for action on a priority generic drug submission if:
62

6
In Section IX of this guidance, the term planned ANDA is defined.
7
Prioritization of review is determined per the criteria established in CDER’s MAPP 5240.3, Rev. 2, entitled
Prioritization of the Review of Original ANDAs, Amendments, and Supplements.
8
This is an example of an ANDA that could qualify for priority designation under the current MAPP. The MAPP is
subject to change and should be consulted at the time of PFC submission for FDA’s then-current prioritization
criteria. To make sure you have the most recent version of a MAPP, check the CDER MAPPs web page at
https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ManualofPoliciesProc
edures/default.htm.
9
In Section IX of this guidance, the term shorter goal date is defined.
10
In Section IX of this guidance, the term change is defined to reflect the definition of “change, with respect to
facility information” as stated in the GDUFA II Commitment Letter.

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63 • A complete and accurate PFC 11 is submitted to FDA 2 months ahead of the planned
64 ANDA submission, and
65 • Facility information remains unchanged in the ANDA.
66
67 A complete and accurate PFC allows the Agency to begin the facility assessment process in
68 advance of the planned ANDA submission. This critical 2 month lead time provides the Agency
69 the opportunity to determine whether facility inspections will be needed, and when they are, to
70 initiate inspection planning earlier in the review of the ANDA, enabling FDA to meet the shorter
71 review timeframe.
72
73 Note: If the criteria above for the shorter goal date are not met at any time after PFC
74 submission, the ANDA may still be prioritized for review but the standard goal date would
75 apply.
76
77 The GDUFA II Commitment Letter states that a complete and accurate PFC lists all of the
78 following:
79
80 1. All facilities involved in manufacturing processes and testing for the ANDA and
81 corresponding Type II active pharmaceutical ingredient (API) drug master file (DMF)
82 as required by 21 CFR 314.50(d)(1)(i) and (iii). 12 For each manufacturing or testing
83 facility, the correspondence includes facility name, operation(s) performed, facility
84 contact name, address, FEI number (if a required registrant or one has been assigned),
85 DUNS number, 13 registration information (for required registrants), a confirmation
86 that the facility is ready for inspection, a description of the manufacturing process,
87 and a certification by the applicant that any Type II DMF has similarly complete and
88 accurate facility information as required by 21 CFR 314.50(d)(1)(i), including
89 complete facility information (i.e., facility name, operation, facility contact name,
90 address, FEI number, and DUNS number). Facility information that is included in a
91 corresponding Type II DMF is not required to be duplicated in the PFC for the
92 ANDA.
93
94 2. All sites or organizations involved in bioequivalence and clinical [endpoint
95 bioequivalence] studies used to support the ANDA submission as described in 21
96 CFR 314.94(a)(7) [and 21 CFR 320.24(b).] 14 This information is provided using a

11
In Section IX of this guidance, the term complete and accurate Pre-Submission Facility Correspondence (PFC) is
consistent with the definition provided in the GDUFA II Commitment Letter.
12
The GDUFA II Commitment Letter captures the term manufacturing sites under the definition of complete and
accurate PFC as, “All facilities involved in manufacturing processes, packaging and testing for the ANDA and
corresponding Type II API DMF as required by 21 CFR 314.50(d)(1)(i) and (iii).”
13
The Data Universal Numbering System (D - U - N - S) is a unique nine-digit sequence provided by Dun &
Bradstreet, which serves as a unique identifier for each physical location of a business. See the guidance for
industry Self-Identification of Generic Drug Facilities, Sites, and Organization (Sept. 2016).
14
The GDUFA II Commitment Letter captures the term bioequivalence sites under the definition of complete and
accurate PFC as, “All sites or organizations involved in bioequivalence and clinical studies used to support the

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97 standardized electronic format and includes unique identifiers that are current and
98 accurate, including site or organization name, address and website; and study
99 information including a listing of study names, dates of conduct and main
100 investigators.
101
102 For the purpose of this guidance, the term facility is inclusive of all sites that are considered to be
103 manufacturing sites AND bioequivalence sites as defined in this guidance. 15
104
105 This guidance describes PFC content and format, as well as the Agency’s approach to assessing
106 this information.
107
108 III. SCOPE
109
110 This guidance establishes FDA’s expectations for the content, timing, and assessment of the
111 PFC. Specifically, the guidance defines:
112
113 • The content and format of the information that should be submitted in the PFC to enable
114 FDA’s assessment of facilities listed in the PFC.
115 • PFC timeframes and their intersection with the subsequent ANDA submissions.
116 • The possible outcomes of the Agency’s assessment of the PFC.
117 • When and how the PFC submitter is notified by the Agency about the status of the PFC.
118
119 IV. PRE-SUBMISSION FACILITY CORRESPONDENCE CONTENT
120
121 A complete and accurate PFC, as defined by the GDUFA II Commitment Letter, provides the
122 information needed for FDA to conduct a meaningful assessment of the facilities that will be
123 used to support the planned ANDA submission. Notably, the PFC should include a thorough
124 description of the manufacturing process as outlined in Section IV.C and all study information as
125 outlined in Section IV.D.
126
127 The PFC should include the following information:
128
129 A. General Information
130
131 • Planned ANDA Pre-Assigned Number
132 • Date of PFC Submission
133 • PFC Submitter Information:
134 o Name of PFC Submitter
135  Telephone Number (include country code, if applicable, and
136 area code)

ANDA submission as described in 21 CFR 314.94(a)(7).” For purposes of this guidance, the term “clinical studies”
in this definition refers to clinical “endpoint bioequivalence” studies. PFC Submitters / Applicants should also refer
to 21 CFR 320.24(b) “Types of evidence to measure bioavailability or establish bioequivalence.”
15
In Section IX of this guidance, the terms manufacturing site and bioequivalence site are defined.

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137 Facsimile (FAX) Number (include country code, if applicable,
138 and area code)
139  Address (Street Address, City, State/Province/Region, Country,
140 Zip or Postal Code)
141  Secure Email Address
142 o Contact or U.S. Agent Name
143  Telephone Number (include country code, if applicable, and
144 area code)
145  Facsimile (FAX) Number (include country code, if applicable,
146 and area code)
147  Address (Street Address, City, State/Province/Region, Country,
148 Zip or Postal Code)
149  Secure Email Address
150 o DMF Right of Reference Letter
151 o As applicable – Statement from the DMF holder permitting FDA to
152 access the DMF information such that FDA is authorized to review
153 relevant confidential information as a part of the review of the PFC 16
154
155 • NOTE Regarding PAS or PAS Amendments:
156
157 If the PFC is associated with a PAS or PAS Amendment, 17 then a statement
158 should be provided, describing:
159 o The reason for the PAS (or Amendment) 18
160 o Whether the submission is a PAS or PAS Amendment
161 o The anticipated disciplines that would review the PAS, when it is
162 submitted to the Agency (e.g., Chemistry, Labeling, DMF,
163 Bioequivalence, Microbiology or Clinical)
164
165 This description will enable the Agency to effectively route the submission for
166 appropriate review.
167
168 If the PFC is associated with “Grouped Supplements,” 19 then it will be
169 assessed on behalf of all the supplements within the group.
170
171 B. Statement of ANDA Eligibility for Priority Review
172

16
See FDA.gov, “Drug Master Files (DMFs)” – DMF holders should submit the Letter of Authorization (LOA) to
the DMF, and a copy of that LOA to the ANDA applicant.
17
21 CFR 314.70(b) describes the types of changes that require prior approval.
18
Examples of reasons for submitting a PAS include, but are not limited to, new strength, reformulation, Rx to OTC
switch, or change in manufacturing processes.
19
“Grouped Supplements” as defined by CDER’s MAPP 5015.1, Rev. 1, entitled Review of Grouped Product
Quality Supplements.

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173 As a prerequisite for the planned ANDA to be eligible for the shorter goal date,
174 the product to be submitted in the planned ANDA should appear to meet the
175 priority designation criteria as described in the Prioritization MAPP. To aid
176 FDA’s determination regarding eligibility for priority review, the PFC should
177 include a statement explaining which of the priority designation criteria in the
178 Prioritization MAPP are met.
179
180 C. Manufacturing Process and Testing Facility Information
181
182 The PFC should contain the following information to inform the Agency’s
183 assessment of the manufacturing site associated with the planned ANDA.
184
185 1. Administrative Information about facilities (including those referenced in
186 a Type II DMF)
187
188 The PFC should include the following administrative information for each
189 manufacturing site associated with the planned ANDA, including any
190 relevant manufacturing site identified in a corresponding Type II DMF:
191
192 • Facility Name
193 • Facility Contact
194 • Facility Address
195 • Telephone Number
196 • Fax Number
197 • Email Address
198 • FEI Number
199 • DUNS Number 20
200 • Operation(s) performed at the facility
201 • Confirmation that the facility is ready for inspection
202
203 When site and manufacturing process information for a drug substance is
204 provided in a corresponding Type II DMF, the following additional
205 information should be provided in the PFC:
206
207 • Reference to the corresponding DMF Number
208 • A certification that FDA has performed its “Completeness
209 Assessment” for the referenced Type II DMF 21 and found it complete,
210 and that the Type II DMF was “active” at the time the PFC was
211 submitted 22, 23

20
Some manufacturing sites might not have a DUNS number. If a DUNS number is assigned, then it should be
provided in the PFC.
21
See the guidance for industry Completeness Assessments for Type II API DMFs Under GDUFA, Section III.
22
Ibid., Definition of “Active DMF.”

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212
213 Although manufacturing site information that is included in a
214 corresponding Type II DMF is not required to be duplicated in the PFC,
215 the PFC submitter should include all of the basic information about the
216 Type II DMF facility as described above to ensure that FDA identifies and
217 assesses the relevant sites listed in the DMF.
218
219 2. Information about the Drug Substance and Drug Product
220
221 The following information about the drug substance and drug product
222 should be provided in the PFC or incorporated by reference to a Type II
223 DMF that contains this information:
224
225 • Nomenclature (drug substance)
226 • Structure (drug substance)
227 • General Properties (drug substance)
228 • Description and Composition of Drug Product – including the drug
229 product batch formula (drug product)
230 • Specification (drug substance and product)
231 • Batch Analyses (drug product)
232
233 3. Information about the Manufacturing Process for the Drug Substance and
234 Drug Product
235
236 The following information about the manufacturing process should be
237 provided in the PFC or incorporated by reference to a Type II DMF that
238 contains this information:
239
240 • Description of Manufacturing Process and Controls – this includes a
241 description of the process and controls for the drug product
242 • Control of Materials, Critical Steps, and Intermediates
243 • Drug Product Manufacturing Process Development Information
244 • Available Process Validation Information – to demonstrate that the
245 proposed process can successfully manufacture the drug
246 product/substance
247
248 4. Manufacturing and Testing for Non-Drug Constituent Parts 24 and
249 Combination Products
250

23
See the list of DMFs that have passed the “Completeness Assessment” and are available for reference by planned
ANDAs at http://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM332875.xls.
24
The drugs, devices, and biological products included in combination products are referred to as “constituent parts”
of the combination product.

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251 If the product in the planned ANDA is a combination product defined in 21
252 CFR Part 3.2(e)(1) or (2), the PFC should also include the following
253 information regarding the facilities involved in manufacturing and testing
254 of the non-drug constituent part(s) (i.e., biologic or medical device) and
255 the finished combination product (e.g., final kit assembly for co-packaged
256 drug and device constituent parts):
257
258 • Administrative Information for Non-Drug Constituent Part and
259 Combination Product Manufacturing Sites, including the following:
260
261 o Manufacturing site information as listed above in Section
262 IV.C.1
263
264 o Indication of whether the manufacturing site follows the
265 streamlined approach to demonstrate compliance with the
266 current good manufacturing practice (CGMP) requirements
267 and, if so, identify the streamlined approach (e.g., drug
268 CGMP-based or device QS-based streamlined approach)
269 used 25, 26
270
271 • Information about the Combination Product and Non-Drug Constituent
272 Parts, including the following:
273
274 o Description of the manufacturing or assembly process at the
275 finished combination product facility and, where applicable, the
276 non-drug constituent part
277
278 o For single-entity and co-packaged combination products 27 with
279 a device constituent part, we recommend that the PFC submitter
280 provide general descriptions/summaries of basic Quality System
281 procedures, including management review procedures (21 CFR
282 820.20(c) and (e)), design controls (21 CFR 820.30), purchasing

25
21 CFR 4.4.
26
See the guidance for industry Current Good Manufacturing Practice Requirements for Combination Products,
Section 2.C “Overview of the Final Rule.” As described in this guidance, for drug-device combination products, 21
CFR part 4 identifies two ways to demonstrate compliance with CGMP requirements. Under the first option,
manufacturers demonstrate compliance with all CGMP regulations applicable to each of the constituent parts
included in the combination product. Under the second option, manufacturers implement a streamlined approach for
combination products that include both a drug and a device by demonstrating compliance with either the drug
CGMPs (21 CFR parts 210 and 211) or the device Quality System (QS) regulation (21 CFR part 820), and also
demonstrating compliance with specified provisions from the other of these two sets of CGMP requirements.
27
21 CFR Part 3.2(e)(1) and (2) – single entity and co-packaged combination products defined.

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283 controls (21 CFR 820.50), and corrective and preventive action
284 procedures (21 CFR 820.100) 28
285
286 D. Bioequivalence Summary and Site/Organization Information
287
288 The following information should be submitted in the PFC for each
289 bioequivalence site associated with the planned ANDA submission:
290
291 1. Information about Bioequivalence Sites
292
293 • Site or Organization Name
294 • Contact Name
295 • Address at which study was conducted
296 • Telephone Number
297 • Fax Number
298 • Email Address
299 • Website
300 • Confirmation that the site or organization is ready for inspection
301
302 2. Study Information
303
304 • Study Names and Numbers
305 • Dates Conducted
306 • Main Investigators
307 • Summary of Biopharmaceutic Studies and Associated Analytical
308 Methods
309 • Synopsis
310 o Study Report
311 o Protocol and Amendments
312 o List and Description of Investigators
313 o Randomization Schemes
314 o Discontinued Subjects
315 o Protocol Deviations
316 o Subjects excluded from the statistical analysis (for example,
317 adverse effects and serious adverse effects)
318 • Comparative Bioavailability and Bioequivalence Study Reports and
319 related information
320 • In-Vitro – In-Vivo Correlation Study Reports and Related Information
321 • Reports of Bioanalytical and Analytical Methods for all
322 bioequivalence studies
323

28
See the guidance for industry Current Good Manufacturing Practice Requirements for Combination Products.

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324 V. ANDA SUBMISSION WINDOW
325
326 According to the GDUFA II Commitment Letter, the PFC should be submitted 2 months ahead
327 of the submission date for the planned ANDA in order for it to be eligible to receive the shorter
328 goal date. This timing allows the Agency to initiate the assessment in advance of receiving the
329 planned ANDA. FDA believes if the time elapsed between submission of the PFC and
330 submission of the planned ANDA is too long, it is less likely that facility information will remain
331 unchanged, as defined by the GDUFA II Commitment Letter. Thus, FDA’s PFC facility
332 assessment may become out-of-date and need to be repeated after the planned ANDA is
333 submitted, eliminating the benefit of the PFC submission to both FDA and the applicant.
334 Therefore, this guidance establishes a window of time between 2 and 3 months after PFC
335 submission during which applicants should submit their planned ANDA (“ANDA Submission
336 Window”).
337
338 If the planned ANDA is submitted within 2 months of submission of the PFC, the ANDA will not
339 generally be eligible for the shorter goal date. Applicants should submit the planned ANDA no
340 more than 3 months after submission of the PFC to reduce the likelihood of changes that result in
341 the loss of eligibility for the shorter goal date.
342
343 For example, if the PFC is submitted on November 1, then the planned ANDA should be
344 submitted between January 1(i.e., 2 months after submission of the PFC) and February 1(i.e., 3
345 months after the submission of the PFC). Similarly, if the PFC is submitted on November 30,
346 then the planned ANDA should be submitted between January 31(i.e., 2 months after submission
347 of the PFC) and February 28 (i.e., 3 months after submission of the PFC).
348
349
350 VI. RECEIPT AND ASSESSMENT PROCESS (FOR PFC AND PLANNED ANDA)
351
352 The following section describes the process for the PFC submission and how it interfaces with
353 the planned ANDA:
354
355 A. PFC Receipt and Assessment
356
357 The following section summarizes the process for PFC receipt and assessment.
358
359 1. Obtaining a Pre-Assigned ANDA Number
360
361 The applicant should request a pre-assigned application number, which
362 will also be used in the planned ANDA.
363
364 2. Submitting the PFC
365
366 The PFC should be submitted as an Adobe® Portable Document Format
367 (PDF) file through the FDA electronic submissions gateway (ESG)

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368 following the Agency’s PDF Specifications. 29 The PFC submitter should
369 index the information submitted within the PDF file using the “bookmark
370 feature.” The PFC should be electronically submitted in non-electronic
371 Common Technical Document (non-eCTD) format via the Agency’s
372 Electronic Submission Gateway (ESG). When submitting the PFC
373 through the ESG, choose “CDER” when selecting the appropriate Center,
374 and should choose “PFC” when selecting the submission type.
375
376 If the PFC will be submitted via “Electronic Physical Media,” 30 it should
377 be submitted to:
378
379 U. S. Food and Drug Administration
380 Office of Generic Drugs – HFD-600
381 Center for Drug Evaluation and Research
382 Metro Park North VII
383 7620 Standish Place
384 Rockville, MD 20855-2773
385
386 The PFC should contain the necessary information to allow the Agency to
387 successfully conduct the facility assessment. Any information that is
388 missing from the PFC will be considered for its impact on our ability to
389 complete the facility assessment. If the missing information precludes the
390 Agency from completing its facility assessment, the PFC will be not be
391 eligible for further assessment, and the planned ANDA will be assigned the
392 standard goal date.
393
394 The applicant should submit the planned ANDA within the “ANDA
395 Submission Window” described above in Section V. If the applicant
396 determines that the planned ANDA will not be submitted within the
397 “ANDA Submission Window” for any reason, FDA should be notified in
398 writing before the start of the “ANDA Submission Window.” The letter
399 should reference the PFC number, and state the applicant’s intent not to
400 submit the planned ANDA within the “ANDA Submission Window.”
401 Upon receipt of this letter, the Agency will terminate the assessment of the
402 PFC.
403
404 3. FDA’s Initial Assessment of the PFC
405
406 After receiving the PFC, the Agency will preliminarily assess whether the
407 product with the planned ANDA appears to meet the priority designation

29
See Fda.gov, “Electronic Submissions Gateway,” for technical details related to submitting documents through
FDA’s Electronic Submission Gateway.
30
See Transmitting Electronic Submissions Using eCTD Specifications, Revision 1.6, March 4, 2016, for definition
of accepted Electronic Physical Media Format.

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408 criteria under the Prioritization MAPP, at the time that the PFC is
409 assessed. The preliminary assessment of priority designation is influenced
410 not only by information in the PFC, but also by other factors and
411 circumstances. For example, if the drug product associated with a PFC is
412 no longer in shortage, and not anticipated to be in future shortage, then the
413 PFC may not result in a priority designation.
414
415 Based on this preliminary assessment, the Agency will send an
416 acknowledgement letter to the PFC submitter to indicate whether or not
417 the planned ANDA appears to meet the priority designation criteria.
418
419 Note that this assessment of priority is preliminary. Priority designation
420 will be reevaluated using the Prioritization MAPP after the planned ANDA
421 is submitted. Applicants will be notified of priority status in the ANDA
422 acknowledgement letter sent by FDA.
423
424 4. FDA’s Assessment of the PFC Content
425
426 If the planned ANDA appears to meet the priority designation criteria,
427 FDA will begin the facility assessment process with the expectation that
428 the planned ANDA will be submitted within the “ANDA Submission
429 Window,” as described above in Section V.
430
431 Please note that specifically with regard to “Grouped Supplements,” each
432 of the supplements in the group should meet the priority designation
433 criteria to qualify for the shorter goal date.
434
435 If the PFC is found to be missing information that precludes the Agency
436 from completing its facility assessment, the PFC will be not be eligible for
437 further assessment and the Agency will notify the applicant that the
438 planned ANDA will not be eligible for the shorter goal date.
439
440 B. ANDA Submission
441
442 When seeking a shorter goal date through priority designation and submission of
443 a complete and accurate PFC, FDA recommends that:
444
445 • The planned ANDA be submitted within the “ANDA Submission Window”
446 described above in Section V.
447 • The planned ANDA be submitted in the appropriate format as described above
448 in Sections VI.A.1 and 2.
449 • The planned ANDA include the facility information that was originally
450 submitted as part of the PFC. The facility information should be located in the
451 appropriate eCTD section of the planned ANDA.
452 • The planned ANDA cover letter clearly reference the PFC, the date it was
453 submitted, and date of FDA’s acknowledgement letter indicating the PFC’s

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454 eligibility for further assessment. A copy of the FDA’s acknowledgement
455 letter related to the PFC should be included in the planned ANDA.
456 • A stand-alone certification letter be included stating that the facility
457 information that was initially submitted in the PFC, “has not changed” in the
458 planned ANDA. The certification letter should identify any and all differences
459 between the facility information submitted in the ANDA versus the PFC, and
460 certify that all differences between the PFC and planned ANDA have been
461 identified. If a certification letter is not submitted with the planned ANDA,
462 the submission will not be eligible for a shorter goal date.
463
464 FDA’s review of the planned ANDA will be performed in accordance with its
465 established statutes, regulations, policies and procedures for ANDA reviews. The
466 following additional elements will be included:
467
468 • Receipt of the ANDA by the Agency will result in an Acknowledgement
469 Letter to the applicant as described below in Section VII.
470 • The Agency will assess whether the product in the ANDA submission is
471 priority under the Prioritization MAPP. The priority designation is based on
472 the information submitted in the ANDA, and/or external factors and
473 circumstances, such as the likelihood of drug shortage for the drug product, its
474 designation as a President’s Emergency Plan for AIDS Relief drug, and others
475 that would impact the Agency’s assessment for priority designation based on
476 the Prioritization MAPP.
477
478 C. Differences in Facility Information between the PFC and the Planned ANDA
479
480 Under the GDUFA II Commitment Letter, in order to maintain eligibility for the
481 shorter goal date, the information in the PFC must be accurate, complete, and
482 remain unchanged. Accordingly, if there are differences between the facility
483 information in the PFC and the ANDA, an important question will be whether
484 those differences constitute a change, with respect to facility information, as
485 defined by the GDUFA II Commitment Letter. If the facility information in the
486 planned ANDA differs from the PFC in any respect, those differences should be
487 specifically identified in the certification letter to be included with the planned
488 ANDA. FDA will determine whether these differences constitute a change. If the
489 Agency determines that a difference between the PFC and the planned ANDA
490 constitutes a change, the planned ANDA will be assigned the standard goal date as
491 described in the GDUFA II Commitment Letter.
492
493
494 VII. OUTCOMES
495
496 A. Eligibility of the PFC for Further FDA Assessment
497

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498 If FDA determines that the product to be submitted in the planned ANDA
499 preliminarily appears to meet priority designation criteria as defined in the
500 Prioritization MAPP, the Agency will send a letter to:
501
502 • Acknowledge that the PFC is eligible for further assessment;
503 • Inform the submitter that a priority designation determination will be made
504 after submission of the planned ANDA; and
505 • Inform the submitter that they should calculate their “ANDA Submission
506 Window” as identified above in Section V.
507
508 If FDA determines that the drug product is not priority under the Prioritization
509 MAPP, the Agency will send a letter stating that the PFC is not eligible for further
510 assessment.
511
512 B. Determining the Goal Date for the Planned ANDA
513
514 After receiving the planned ANDA, FDA will determine the applicable goal date or
515 set of goal dates as outlined in the GDUFA II Commitment Letter. Establishing the
516 appropriate goal date for the planned ANDA is based on the Agency’s priority
517 designation assessment, assessment of the facility information submitted in the PFC,
518 and the stand-alone certification letter described in Section VI.B – bullet 5 (i.e., a
519 comparative assessment of the facility information submitted in the ANDA and the
520 PFC). The Agency will convey the outcomes of these assessments, and the resulting
521 goal date, in the acknowledgement letter associated with the application, supplement,
522 or amendment. Under the terms of the GDUFA II Commitment Letter, a shorter goal
523 date applies only to priority ANDAs. If, upon receiving the ANDA, FDA determines
524 that the application does not meet FDA’s priority designation criteria as defined in
525 the Prioritization MAPP, the ANDA will receive a goal date consistent with a
526 standard ANDA 31—even if the PFC is otherwise found to be complete, accurate, and
527 the information provided in it is unchanged.
528
529 An ANDA that is not eligible for the shorter goal date may still be treated as priority
530 if it meets the criteria in the Prioritization MAPP.
531
532 In addition, if the facility information in the PFC does not remain complete, accurate,
533 and unchanged upon submission of the ANDA, under the terms of the GDUFA II
534 Commitment Letter, the standard goal dates as outlined in the GDUFA II
535 Commitment Letter will apply.
536
537 If, during the course of ANDA review, FDA determines that there are any differences
538 between the PFC and ANDA that were not identified in the applicant’s certification
539 letter as described in Section VI.B of this guidance, the review goal will be converted
540 to the standard goal date.

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In Section IX of this guidance, the term Standard ANDA is defined.

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541
542
543 VIII. QUESTIONS AND ANSWERS
544
545 A. What types of submissions may be eligible for the PFC process?
546
547 Priority abbreviated new drug applications (ANDAs), prior approval supplements
548 (PASs), and their amendments can be eligible for the PFC process.
549
550 B. If a facility identified in the PFC closes, will FDA consider that as a change, with
551 respect to facility information?
552
553 Yes, FDA considers facility closures to be a change, with respect to facility
554 information as defined in the GDUFA II Commitment Letter because closures are
555 changes in operations performed by facilities in the PFC or planned ANDA.
556
557 C. What is the purpose of the stand-alone certification letter to which Section VI
558 refers?
559
560 The stand-alone certification letter ensures that FDA is made aware of any differences
561 between the facility information submitted in the PFC versus the planned ANDA. The
562 Agency will determine whether these differences constitute a change, with respect to
563 facility information as defined in the GDUFA II Commitment Letter. If any
564 differences are considered to meet this definition of change, then the planned ANDA
565 will not receive a shorter goal date.
566
567 D. When the planned ANDA is submitted, should it include the facility information
568 that was originally provided in the PFC?
569
570 Yes. The planned ANDA should include the facility information that was originally
571 submitted as part of the PFC. The facility information should be located in the
572 appropriate eCTD sections of the planned ANDA. The applicant should also submit a
573 certification letter in their ANDA as described above in Section VI.
574
575 E. Why should applicants submit the planned ANDA 2 to 3 months after submission
576 of the PFC?
577
578 The GDUFA II Commitment Letter states that the PFC will be submitted 2 months
579 prior to the date of the ANDA. The Agency recommends 3 months prior to
580 submission of the ANDA as the outside timeframe for a PFC to be submitted because
581 within 3 months of the PFC submission the facility information related to the planned
582 ANDA is more likely to remain factually accurate and unlikely to change prior to
583 submission of the planned ANDA.
584

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585 F. If there are differences between the facility information submitted in the PFC
586 versus the planned ANDA, how should they be reported?
587
588 As described in Section VI, the applicant’s stand-alone certification letter should
589 identify any differences between the facility information submitted in the ANDA
590 versus the PFC, and certify that all differences have been identified in the stand-alone
591 certification letter.
592
593 G. When could an applicant not receive the shorter goal date for their planned
594 ANDA?
595
596 A planned ANDA may not receive the shorter goal date if, among other reasons:
597 • Differences between the facility information submitted in the planned ANDA
598 versus the PFC constitute a change, with respect to facility information, as
599 defined in the GDUFA II Commitment Letter.
600 • A facility is not ready for inspection.
601 • The PFC is not complete, or not accurate. FDA recommends that applicants
602 include the facility-related information described in this guidance.
603 • FDA determines that the PFC or the ANDA is not a priority as defined by the
604 Prioritization MAPP.
605 • The ANDA is not submitted within the submission window as described in
606 Section V.
607
608 H. Is there a user fee payment required at the time of submitting PFC?
609
610 No. Any relevant user fees are paid at the time of the ANDA submission. 32
611
612 I. Which bioequivalence sites should be submitted in the PFC?
613
614 All sites or organizations involved in bioequivalence and clinical [endpoint
615 bioequivalence] studies used to support the ANDA submission as described in 21
616 CFR 314.94(a)(7) and 21 CFR 320.24(b).14
617
618
619 IX. DEFINITIONS
620
621 A. Planned ANDA
622 For the purposes of this guidance, the term “planned ANDA” refers to the ANDA
623 submission that is prospectively associated with the PFC, specifically including:
624 Original ANDA Submissions, Original ANDA Amendments, ANDA Prior Approval
625 Supplements (PASs), and PAS Amendments. The qualifier “planned” indicates that
626 at the time of submitting the PFC, the ANDA has not been submitted. This term also

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See Fda.gov - Generic Drug User Fee Cover Sheet and Payment Information.

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627 includes “Grouped Supplements,” as defined by CDER’s MAPP 5015.1, Rev. 1,
628 entitled Review of Grouped Product Quality Supplements.
629
630 B. Standard ANDA
631 The term “standard ANDA” refers to Original ANDA Submissions, Original ANDA
632 Amendments, PASs, and PAS Amendments not identified by FDA as eligible for the
633 priority designation pursuant to the CDER MAPP 5240.3, Prioritization of the
634 Review of Original ANDAs, Amendments, and Supplements.
635
636 C. Complete and Accurate Pre-Submission Facility Correspondence (PFC)
637 The GDUFA II Commitment Letter defines a “complete and accurate Pre-
638 Submission Facility Correspondence” as listing the following information:
639
640 1. All facilities involved in manufacturing processes and testing for the ANDA and
641 corresponding Type II API DMF as required by 21 CFR 314.50(d)(1)(i) and (iii).12
642 For each manufacturing or testing facility, the correspondence includes facility name,
643 operation(s) performed, facility contact name, address, FEI number (if a required
644 registrant or one has been assigned), DUNS number, registration information (for
645 required registrants), a confirmation that the facility is ready for inspection, a
646 description of the manufacturing process, and a certification by the applicant that any
647 Type II DMF has similarly complete and accurate facility information as required by
648 21 CFR 314.50(d)(1)(i), including complete facility information (i.e., facility name,
649 operation, facility contact name, address, FEI number and DUNS number). Facility
650 information that is included in a corresponding Type II DMF is not required to be
651 duplicated in the Pre-Submission Facility Correspondence for the ANDA.
652
653 2. All sites or organizations involved in bioequivalence and clinical [endpoint
654 bioequivalence] studies used to support the ANDA submission as described in 21
655 CFR 314.94(a)(7) [and 21 CFR 320.24(b).]14 This information is provided using a
656 standardized electronic format and includes unique identifiers that are current and
657 accurate, including site or organization name, address and website; and study
658 information including a listing of study names, dates of conduct and main
659 investigators.
660
661 D. Change, with Respect to Facility Information (also referred to as change)
662 The GDUFA II Letter defines “change, with respect to facility information” to mean a
663 change to information in the Pre-Submission Facilities Correspondence that causes
664 FDA to re-evaluate its facility assessment (i.e., assess the impact of the change on its
665 previous recommendation), such as a change in facility (as described by address, FEI
666 number, or DUNS number), change in operation(s) performed by a facility, addition
667 of a new facility, withdrawal of a facility used to generate data to meet application
668 requirements or intended for commercial production, or a change in inspection
669 readiness (i.e., a facility is no longer ready for inspection).
670

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671 FDA interprets a “change in operation(s) performed by a facility” to include closure
672 of the facility. FDA uses change and change, with respect to facility information
673 interchangeably in this guidance.
674
675 E. Bioequivalence Sites
676 All sites or organizations involved in bioequivalence and clinical [endpoint
677 bioequivalence] studies used to support the ANDA submission as described in 21
678 CFR 314.94(a)(7) [and 21 CFR 320.24(b).]14 For the purposes of this guidance, this
679 term also captures sites that conduct analytical testing in support of the planned
680 ANDA.
681
682 F. Manufacturing Sites
683 All facilities involved in manufacturing processes, packaging and testing for the
684 ANDA and corresponding Type II API DMF as required by 21 CFR 314.50(d)(1)(i)
685 and (iii).12 For the purpose of this guidance, this term refers to any manufacturing,
686 packaging or testing site associated with a planned ANDA that conducts an operation
687 to support manufacturing or testing of the drug substance and/or product. This
688 definition includes sites listed in Type II DMFs and sites that manufacture non-drug
689 constituent parts of a combination product.
690
691 G. Facility
692 For the purposes of this guidance, the term “facility(ies)” means “manufacturing site”
693 and “bioequivalence site.” The terms “manufacturing site” and “bioequivalence site”
694 are also explicitly defined in this guidance.
695
696 H. Shorter Goal Date
697 The term “shorter goal date” refers to the accelerated goal dates identified in the
698 GDUFA II Commitment Letter for ANDAs that are designated priority by FDA and
699 have submitted within the proper timeframe, a complete and accurate PFC containing
700 facility information that remains unchanged in the subsequent ANDA. 33
701
702 I. Priority
703 The term “priority” refers to FDA’s designation of priority for ANDAs as defined by
704 the Prioritization MAPP.
705
706
707

33
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708 APPENDIX – PRE-SUBMISSION FACILITY CORRESPONDENCE SUGGESTED
709 FORMAT
710
711 The PFC should be submitted as an Adobe Portable Document Format file, as described in
712 Section VI.A.1 and 2 above. Although the PFC itself is not considered to be an ANDA (or PAS
713 or Amendment), a PFC will be included as an associated record in the regulatory record of any
714 planned ANDA upon submission.
715
716 A. PFC Title
717
718 The PFC title should be prefaced with the label “Pre-Submission Facility
719 Correspondence.” This label will enable FDA to appropriately capture the PFC when
720 it is submitted to the electronic submissions gateway.
721
722 B. File Format
723
724 The PFC should be submitted in an Adobe PDF file format to ensure complete
725 processing of the correspondence by the Agency. The applicant should index the
726 information submitted within the PDF file using the “bookmark feature” to enable the
727 Agency’s expedient assessment of the PFC.
728
729 C. Layout
730
731 Section IV of this guidance establishes the information that should be provided at a
732 minimum in order for the PFC to be considered complete. Although the layout of the
733 PFC is left to the discretion of the submitter, the Agency recommends that the
734 following elements be considered for the PFC format.
735
736 1. General Recommendations
737
738 The Agency suggests using the headings in Section IV of this guidance to
739 denote the overall layout of the PFC as shown below. If a submitter
740 chooses to use another format, they should ensure that their PFC provides
741 the information requested in Section IV of this document.
742
743 A. General Information
744
745 B. Statement of ANDA Eligibility for Priority Review
746
747 C. Manufacturing Process and Testing Facility Information
748 1. Administrative Information about Facilities (including
749 those referenced in a Type II DMF)
750 2. Information about the Drug Substance and Product
751 3. Information about the Manufacturing Process for Drug
752 Substance and Drug Product

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753 4. Manufacturing and Testing Facilities for Non-Drug
754 Constituent Parts and Combination Products
755 • Administrative Information for Non-Drug
756 Constituent Part and Combination Product
757 manufacturing site
758 • Information about the Combination Product and
759 Non-Drug Constituent Parts
760
761 D. Bioequivalence Summary and Site/Organization Information
762 1. Information about Sites or Organizations
763 2. Study Information
764
765 2. Recommendations for Specific Headings under Section IV
766
767 • Statement of Why ANDA Submission Should Be Considered for
768 Priority Review
769
770 This statement and the associated justification should be stand-alone,
771 to expedite the Agency’s initial assessment of the PFC, as described in
772 Section VI.A.3 of this guidance.
773
774 • Manufacturing Site(s) Information
775
776 When describing the administrative information associated with
777 manufacturing and testing facilities (see Section IV.C.1), including
778 where appropriate, those facilities listed in a Type II DMF (relevant to
779 the planned ANDA), and facilities related to the combination product
780 and non-drug constituent parts of a combination product, the submitter
781 is encouraged to use a standardized format to list this information. See
782 the example below:
783
784 Figure 1. Example of Standardized Format for Administrative
785 Information related to Manufacturing and Testing Facilities
786
Facility #1 Facility #2 Facility #3
Facility Name
Facility Contact Name
Facility Address
Telephone Number
Fax Number
Email Address
FEI Number
DUNS Number
Operation performed at the
facility
Confirmation that the

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facility is ready for
inspection
Reference to corresponding
DMF Number (For DMF
listed facility)
A Certification that FDA
has performed its
“Completeness
Assessment” for the
referenced Type II DMF
and found it complete
CGMP Approach (For
combination product
manufacturing facilities
only, e.g., drug CGMP-
based or device QS-based
streamlined approach)
787
788 • Bioequivalence Site(s) Information
789
790 Information regarding the bioequivalence sites should be included as
791 described in Section IV.D of this document. For information related to
792 bioequivalence sites and organizations, the submitter should follow the
793 format.
794
795 Figure 2. Sample Study Summary Table (One Table for Each Study)
796
Study Number
Study Title

Study Type  In Vivo BE  In Vitro BE  Permeability  Other

Reports Included in PFC

Study Report Included in PFC?  Yes  No
Validation Report Included in PFC?  Yes  No
Bioanalytical Report Included in PFC?  Yes  No
Clinical Site
(Name, Address)

Phone #
Fax #
Principal Clinical Investigator
(Name, Email)

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Dosing Dates

Analytical Site
(Name, Address)

Phone #
Fax #
Analysis Dates
Principal Analytical
Investigator (Name, Email)
Storage Period of Biostudy
Samples
(a) Duration (no. of days from
the first day of sample
collection to the last day of
sample analysis)
(b) Temperature Range:
Long-Term Storage Stability
Coverage (no. days @ temp ºC)
797
798

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799
800
801 Figure 3. Sample Summary Table of Bioequivalence Studies
802 (One Table for Each Study)
803

804