Alternative Tools:  Assessing 
Drug Manufacturing Facilities 
Identified in Pending 
Applications 
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DRAFT GUIDANCE 
 
  This guidance document is being distributed for comment purposes only.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 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance.  Submit electronic comments to https://www.regulations.gov.  Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD  20852.  All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact (CDER) Jessica Dunn at 240-402-8985 or 
Jessica.Dunn@fda.hhs.gov, or (CBER) Office of Communication, Outreach and Development, 
800-835-4709 or 240-402-8010. 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
September 2023 
Pharmaceutical Quality/Manufacturing Standards (CGMP) 
 
   
Alternative Tools:  Assessing 
Drug Manufacturing Facilities 
Identified in Pending 
Applications 
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  
and/or 
Office of Communication, Outreach and Development  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances  
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
September 2023 
Pharmaceutical Quality/Manufacturing Standards (CGMP) 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  RISK-BASED USE OF ALTERNATIVE TOOLS ........................................................ 3 
IV.  CONSIDERATIONS FOR ALTERNATIVE TOOLS.................................................. 5 
A.  Remote Regulatory Assessments .................................................................................................. 5 
B.  Inspections Conducted by Trusted Foreign Regulatory Partners ............................................. 7 
1. Information Sharing by Trusted Foreign Regulatory Partners ....................................................... 8 
2. Foreign Regulatory Inspections With FDA Remote Participants .................................................... 8 
C.  PAIs and PLIs With FDA Remote Subject Matter Experts ...................................................... 8 
V.  THE EFFECTS OF USING ALTERNATIVE TOOLS .............................................. 10 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  Alternative Tools:  Assessing Drug Manufacturing Facilities 
2  Identified in Pending Applications 
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 purpose of this guidance is to provide information to applicants on how FDA intends to use 
18  alternative tools2 to assess manufacturing facilities3 identified in a marketing application (i.e., a 
19  new drug application (NDA), an abbreviated new drug application (ANDA), a biologics license 
20  application (BLA), or a supplement to any of these types of applications).  As part of the 
21  negotiations relating to the reauthorization of the Prescription Drug User Fee Act (PDUFA) and 
22  the Biosimilar User Fee Act (BsUFA), as described in PDUFA Reauthorization Performance 
23  Goals and Procedures Fiscal Years 2023 Through 2027 (PDUFA VII commitment letter)4 and 
24  Biosimilar Biological Product Reauthorization Performance Goals and Procedures for Fiscal 
25  Years 2023 Through 2027 (BsUFA III commitment letter),5 FDA agreed to issue guidance on 
26  the use of alternative tools to assess manufacturing facilities named in pending applications and 
27  to incorporate best practices from the use of such tools during the Coronavirus Disease 2019 
28  (COVID-19) pandemic. 
29   
30  This guidance, within the context of approval and licensure decisions by FDA, describes the use 
31  of alternative tools to assess manufacturing facilities identified in an NDA, an ANDA, or a BLA6 
32  to establish that these facilities meet the applicable requirements, including under section 
33  501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 351(a)(2)(B)) 
 
1 This guidance has been prepared by the Office of Pharmaceutical Quality in the Center for Drug Evaluation and 
Research in cooperation with the Center for Biologics Evaluation and Research and the Office of Regulatory Affairs 
at the Food and Drug Administration. 
2 In this guidance, the term alternative tools, as described further within, refers to methods used by FDA in advance 
or in lieu of an inspection or to support an inspection of a drug manufacturing facility and assess compliance with 
applicable laws and regulations. 
3 In this guidance, the terms facility and establishment are synonymous (see the definitions for establishment in 21 
CFR 207.1 and 600.3(w)). 
4 See Section II.N.3 of the PDUFA VII commitment letter available at 
https://www.fda.gov/media/151712/download. 
5 See Section II.B.2. of the BsUFA III commitment letter available at https://www.fda.gov/media/152279/download. 
6 This guidance fulfills PDUFA VII and BsUFA III commitments applicable to NDAs and BLAs.  However, FDA 
also continues to use alternative tools to support the assessment of all drug application types, including ANDAs. 
  1  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
34  and either 505 of the FD&C Act (21 U.S.C. 355) or section 351 of the Public Health Service Act 
35  (PHS Act) (42 U.S.C. 262). 
36   
37  This guidance does not apply to other drug7 inspection programs including: 
38   
39    Postapproval inspections 
40    Surveillance inspections 
41    Follow-up and compliance inspections (e.g., for-cause inspections) 
42    Bioresearch monitoring inspections8 
43   
44  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
45  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
46  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
47  the word should in Agency guidances means that something is suggested or recommended, but 
48  not required. 
49   
50   
51  II.  BACKGROUND 
52   
53  The Prescription Drug User Fee Act of 1992 (PDUFA)9 amended the FD&C Act to authorize 
54  FDA to assess and collect user fees10 from companies who produce certain human drugs.  Since 
55  the passage of PDUFA, user fees have played an important role in supporting the drug approval 
56  process, and user fee programs have been established by Congress to support certain FDA 
57  activities related to several other types of medical products, including medical devices, generic 
58  drugs, and biosimilar biological products.11  These fees have helped FDA fulfill its mission of 
59  protecting the public health and promoting timely market availability of FDA-regulated products 
60  without compromising the Agencys commitment to scientific integrity, public health, regulatory 
61  standards, and patient safety.  Reauthorization of FDAs medical product user fee programs 
62  continues FDAs authority to assess and collect these user fees.  Most recently, the FDA User 
63  Fee Reauthorization Act of 2022 reauthorized FDAs human drug and device user fee 
64  programs.12  The PDUFA VII and BsUFA III commitment letters applicable to this latest 
65  reauthorization build upon previous FDA performance goals and program enhancements to 
66  facilitate timely access to safe, effective, high quality, and innovative new medicines for patients. 
 
7 In this guidance, the term drug includes biological products. 
8 Section 3612 of the Food and Drug Omnibus Reform Act of 2022 amended the Federal Food, Drug, and Cosmetic 
Act (FD&C Act) to add section 704(a)(5)(C) clarifying FDAs authority to conduct bioresearch monitoring 
inspections; however, in this guidance, bioresearch monitoring inspections are considered out of scope. 
9 Title I, the Prescription Drug User Fee Act of 1992, of Public Law 102-571. 
10 User fees are available for obligation in accordance with appropriations acts. 
11 See sections 738, 744B, and 744H of the FD&C Act (21 U.S.C. 379j, 21 U.S.C. 379j42, and 21 U.S.C. 379j52), 
respectively. 
12 See titles I through IV of Division F (the FDA User Fee Reauthorization Act of 2022) of the Continuing 
Appropriations and Ukraine Supplemental Appropriations Act, 2023. 
  2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
67  During the COVID-19 pandemic, FDA expanded its use of alternative tools to evaluate drug 
68  manufacturing facilities to support regulatory decision-making when facility inspections were 
69  not feasible.  In the PDUFA VII and BsUFA III commitment letters, FDA agreed to issue 
70  guidance on the use of alternative tools, incorporating best practices from the use of such tools 
71  during the COVID-19 pandemic, to assess manufacturing facilities named in pending 
72  applications as part of FDAs normal operations beyond the COVID-19 public health 
73  emergency.13,14 
74   
75  The following alternative tools were used during the public health emergency: 
76   
77    Requesting records and other information, pursuant to section 704(a)(4) of the FD&C Act 
78  (21 U.S.C. 374(a)(4)), directly from facilities and other entities subject to inspection 15 
79   
80    Performing remote interactive evaluations (RIEs) (e.g., remote livestreaming video of 
81  operations, teleconferences, screen sharing) 
82   
83    Requesting existing inspection reports and other information from trusted foreign 
84  regulatory partners through mutual recognition agreements and other agreements  
85   
86  FDA has strategically used these tools within the context of decisions related to preapproval 
87  inspections (PAIs) or prelicense inspections (PLIs) to maximize facility evaluation efficiency as 
88  part of appropriate, risk-based assessments.  Given the success of these innovative approaches, 
89  the Agency intends to continue risk-based use of these alternative tools and to apply certain 
90  virtual technological capabilities within a specific inspectional context defined within this 
91  guidance.  When used in advance or in lieu of PAIs and PLIs or to support PAIs and PLIs, the 
92  appropriate use of these approaches will help FDA maintain operational flexibility to support 
93  timely facility evaluations and application decisions. 
94   
95   
96  III.  RISK-BASED USE OF ALTERNATIVE TOOLS  
97   
98  FDA generally conducts a PAI or a PLI to ensure that any facility named or referenced in an 
99  application can perform the proposed manufacturing operations in conformance to the current 
100  good manufacturing practice (CGMP) requirements,16 to confirm that data submitted in the 
 
13 In this guidance, FDA refers to normal operations as the circumstances in which the COVID-19 public health 
emergency under section 319 of the Public Health Service Act (PHS Act) (42 U.S.C. 347d) has expired.  The tools 
and discretion available to FDA in response to a public health emergency are beyond the scope of this guidance. 
14 See Section II.B.2. of the BsUFA III commitment letter and Section I.N.3. of the PDUFA VII commitment letter. 
15 Section 704(a)(4) of the FD&C Act gives FDA the authority to request from a drug or device establishment or a 
site or facility subject to bioresearch monitoring inspectionsand requires a person who owns or operates such an 
establishment, site, or facility to provideany records or other information that FDA may inspect under section 704 
in advance of or in lieu of an inspection. 
16 In this guidance, current good manufacturing practice (CGMP) refers to the requirements in section 501(a)(2)(B) 
of the FD&C Act and in 21 CFR parts 4, 210, 211, and 600 through 680, as applicable. 
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
101  application are accurate and complete,17 to verify conformance to the application, and to assess a 
102  facilitys ability to develop and manufacture drugs of consistent quality.18  In some instances, 
103  FDA may determine that a PAI or a PLI may not be needed if sufficient information is otherwise 
104  available to FDA demonstrating the facilitys ability, with respect to a drugs manufacturing, to 
105  ensure and preserve the drugs identity, strength, quality, and purity19 (for an application subject 
106  to section 505 of the FD&C Act) or to ensure product safety, purity, and potency20 (for an 
107  application subject to section 351 of the PHS Act). 
108   
109  During an application assessment, FDA conducts a product quality assessment to identify 
110  potential risks to product quality, including any product-specific risks; manufacturing process 
111  and control risks; or facility risks, that would be cause for an inspection.  Potential sources of 
112  product quality or facility-related risks can include the following:  (1) gaps in the current 
113  scientific knowledge or manufacturing process understanding, (2) new technologies or dosage 
114  forms, (3) manufacturing process complexities, (4) limited commercial manufacturing 
115  experience, and (5) issues identified from previous FDA inspections or from information 
116  provided by trusted foreign regulatory partners.  FDA uses a risk-based approach to determine 
117  when an inspection in support of an application is necessary. 
118   
119  FDA intends to evaluate all risks or urgencies on a case-by-case basis and consider factors, 
120  including any or a combination of the following, to discern when the use of alternative tools may 
121  be appropriate in advance or in lieu of an inspection or to support a PAI or a PLI: 
122   
123    The facility has a drug inspection history (FDA and/or a trusted foreign regulatory 
124  partner under a mutual recognition agreement or other agreement), and the proposed 
125  operations in the application are the same as or sufficiently related to existing operations 
126  covered in previous inspections. 
127   
128    The application-specific risks or applicable facility operations can be adequately assessed 
129  through alternative tools. 
130   
131    The product addresses an urgent need (e.g., a critical public health need, a pervasive drug 
132  shortage, or other unforeseen situations). 
133   
 
17 See the guidance for industry Data Integrity and Compliance With Drug CGMP Questions and Answers 
(December 2018).  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. 
18 FDA uses drug and biologics compliance programs to guide the conduct of preapproval and prelicense 
inspections.  Drug compliance programs are available at https://www.fda.gov/drugs/guidance-compliance-
regulatory-information/drug-compliance-programs.  Biologics compliance programs are available at 
https://www.fda.gov/vaccines-blood-biologics/enforcement-actions-cber/compliance-programs-cber. 
19 See sections 505(d)(3) and 505(j)(4)(A) of the FD&C Act. 
20 See section 351(a)(2)(C)(i) of the PHS Act. 
  4  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
134    An inspection is not feasible as a result of travel limitations (e.g., pandemics, natural 
135  disasters, other unstable situations preventing travel). 
136   
137  This is not a comprehensive list, given the constantly evolving unique considerations that may 
138  arise during a particular application assessment. 
139   
140  IV.  CONSIDERATIONS FOR ALTERNATIVE TOOLS 
141   
142  FDA will consider using alternative tools for an applications facility evaluation, as appropriate 
143  and on a case-by-case basis, in advance or in lieu of an inspection or to support a PAI or a PLI.  
144  Because FDA may choose to inspect and/or to use an alternative tool at any point in the 
145  application assessment cycle,21 FDA expects all manufacturing, packaging, and control sites for 
146  drug substance and drug product facilities to be ready for inspection at the time of application 
147  submission.22  FDA does not intend to grant requests from applicants or facilities for FDA to use 
148  alternative tools.  Such decisions depend on many factors and may include information bearing 
149  on internal Agency practices, and it would not be feasible to establish a request-based program. 
150   
151  Based on any or a combination of specific risks or urgencies described above, FDA may choose 
152  to use one or more alternative tools to aid in its application facility evaluation of whether the 
153  methods used in and the facilities and controls used for the manufacturing, processing, packing, 
154  and testing of a drug are adequate to ensure and preserve the drugs identity, strength, quality, 
155  and purity23 or to ensure and preserve the drugs safety, purity, and potency.24  FDA may use 
156  alternative tools to assess whether facilities named in the application can perform the proposed 
157  manufacturing operations in conformance to the application and in compliance with applicable 
158  requirements, including the CGMP requirements for drug manufacturing. 
159   
160  A.  Remote Regulatory Assessments 
161   
162  To examine an application product, a facility, or a manufacturing process and its controls, FDA 
163  may choose to initiate a remote regulatory assessment (RRA).  An RRA is an examination of an 
164  FDA-regulated establishment and/or its records, conducted entirely remotely, to evaluate 
165  compliance with applicable FDA requirements.  An RRA complements FDAs authority to 
166  conduct inspections under section 704(a)(1) of the FD&C;25 however, in certain circumstances, 
167  records or other information obtained through an RRA (for example, under section 704(a)(4) of 
 
21 FDA does not intend to simultaneously conduct a remote regulatory assessment (RRA) and an inspection of a 
facility.  See Section III.A.6. of the draft guidance for industry Conducting Remote Regulatory Assessments 
Questions and Answers (July 2022).  When final, this guidance will represent the FDAs current thinking on this 
topic. 
22 For more information regarding which facilities should be listed in Field 28 of the Establishment Information 
section of Form FDA 356h, titled Application to Market a New or Abbreviated New Drug or Biologic for Human 
Use (available at https://www.fda.gov/media/72649/download), see the guidance for industry Identification of 
Manufacturing Establishments in Applications Submitted to CBER and CDER Questions and Answers (October 
2019). 
23 See sections 505(d)(3) and 505(j)(4)(A) of the FD&C Act.  See also 21 CFR 314.105. 
24 See section 351(a)(2)(C)(i) of the PHS Act and 21 CFR 601.2(d).  
25 FDA generally considers an inspection, such as described in section 704(a)(1) of the FD&C Act, to involve duly 
designated officers or employees of FDA physically entering (at reasonable times and in a reasonable manner) an 
establishment subject to regulation under the FD&C Act. 
  5  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
168  the FD&C Act)26 may provide information similar to what would generally be evaluated on a 
169  PAI or a PLI or used to resolve application-specific deficiencies identified during a PAI or a PLI, 
170  as further described below.  For example, FDA may use an RRA to assess an application-specific 
171  risk or to gather information sought relative to a facility evaluation. 
172   
173  An RRA may be conducted by employing the following alternative tools individually or in 
174  combination, as appropriate, to meet the needs of the assessment: 
175   
176    Pursuant to section 704(a)(4) of the FD&C Act, requesting from the owner or operator of 
177  a drug facility, records or other information that are subject to inspection under section 
178  70427 
179   
180    Conducting an RIE during application assessment28 
181   
182  For an RRA conducted under section 704(a)(4) of the FD&C Act, a response from the facility is 
183  mandatory.29  Upon receipt of a section 704(a)(4) request from FDA, each facility should 
184  carefully consider FDAs specific request and provide a response in the specified time frame 
185  with sufficient information to adequately satisfy the request.  The types of records and 
186  information requested can vary based on the product, the facility, and manufacturing process and 
187  its controls, but may include, as applicable, equipment records, process validation records and 
188  reports, test results, deviations and associated reports, complaints, or other information related to 
189  compliance with the CGMP requirements and other applicable FDA requirements.  The Agency 
190  may seek a teleconference or a virtual meeting for clarification of the records and other 
191  information sought by the Agency pursuant to section 704(a)(4) if the response does not 
192  sufficiently address FDAs request.  Refusing to permit access to records as required by section 
193  704(a), including section 704(a)(4), is a prohibited act,30 and supplying insufficient information 
194  may:  (1) delay application action if FDA does not have enough information to make a regulatory 
195  determination; (2) result in FDA sending a complete response letter31 to the applicant if FDA 
 
26 As indicated in footnote 15, section 704(a)(4) of the FD&C Act gives FDA the authority to request from a drug or 
device establishment or a site or facility subject to bioresearch monitoring inspectionsand requires a person who 
owns or operates such an establishment, site, or facility to provideany records or other information that FDA may 
inspect under section 704 in advance of or in lieu of an inspection.  Section 704(a)(4), as amended by the Food and 
Drug Omnibus Reform Act of 2022, clarifies that FDA may rely on any records or other information that [FDA] 
may inspect under [that] section to satisfy requirements that may pertain to a preapproval or risk-based surveillance 
inspection, or to resolve deficiencies identified during such inspections, if applicable and appropriate (section 
704(a)(4)(C)). 
27 FDA uses Form FDA 4003, titled FDA Inspection Records Request, to request records or other information from 
drug establishments pursuant to section 704(a)(4) of the FD&C Act.  A request under section 704(a)(4) may be used 
to support products named in multiple applications manufactured at one establishment.  In this situation, one Form 
FDA 4003 will generally be issued to the establishment to cover requests for records or other information for all the 
products in the applications being assessed. 
28 FDA will not issue a Form FDA 482, titled Notice of Inspection, to announce or open a remote interactive 
evaluation. 
29 See section 704(a)(4)(A) of the FD&C Act. 
30 See section 301(e) of the FD&C Act (21 U.S.C. 331(e)). 
31 See the definition for complete response letter in 21 CFR 314.3(b) and 21 CFR 600.3(ll).  See also 21 CFR 
314.110 and 21 CFR 601.3. 
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Draft  Not for Implementation 
196  cannot confirm that application deficiencies have been satisfactorily addressed; or (3) carry other 
197  potential regulatory or legal consequences.32 
198   
199  In contrast, a facilitys participation in an RIE is voluntary.  FDA generally may seek to conduct 
200  an RIE when visual observation (e.g., product, facility, manufacturing operations, records, and 
201  other documents) and virtual engagement with facility staff may help the Agency make an 
202  application decision.  Each facility should assess its capability to interact with FDA using 
203  technologies such as remote livestreaming, teleconferences, and screen sharing and determine 
204  whether the facility can meet FDAs request.  If a facility is unable to support a virtual 
205  interaction or if FDA determines that virtual interaction during an RIE does not permit a 
206  sufficient examination of the facility or of a corrective action, FDA may terminate the RIE and 
207  instead conduct an inspection or use other available tools.33  A facility may decline participation 
208  in an RIE (or a particular RIE request) before or during the RIE; however, FDA may not be able 
209  to complete its facility evaluation until it uses other oversight tools.  An RIE may be the quickest 
210  means for FDA to assess a facilitys activities, especially when factors prevent FDA from 
211  conducting a timely facility inspection.  As such, declining to participate in an RIE may prolong 
212  a decision on an application. 
213   
214  For additional recommendations on how to prepare for an RRA and for communication 
215  expectations after FDA requests, initiates, or conducts an RRA, applicants and facilities should 
216  refer to the draft guidance for industry Conducting Remote Regulatory Assessments Questions 
217  and Answers (July 2022) or any successor guidance. 
218   
219  B.  Inspections Conducted by Trusted Foreign Regulatory Partners 
220   
221  Section 809 of the FD&C Act (21 U.S.C. 384e) authorizes FDA to enter into arrangements and 
222  agreements with a foreign government or an agency of a foreign government to recognize the 
223  inspection of foreign establishments registered under section 510(i) of the FD&C Act (21 U.S.C. 
224  360(i)) if FDA determines that those authorities are capable of conducting inspections that meet 
225  U.S. requirements.34  Although FDA has not to date recognized PAIs or PLIs conducted by a 
226  foreign regulatory authority in the context of a section 809 mutual recognition agreement, FDA 
227  does collaborate with regulatory authorities and assesses shared inspection information to 
228  support application decisions. 
 
32 See section 501(j) of the FD&C Act, relating to adulterated drugs, and section 801(a) of the FD&C Act (21 U.S.C. 
381(a)), relating to imports.  Imported drugs from an establishment may be subject to refusal (for example, if they 
appear to be adulterated). 
33 The guidance for industry Remote Interactive Evaluations of Drug and Manufacturing and Bioresearch 
Monitoring Facilities During the COVID-19 Public Health Emergency (April 2021) includes additional information 
on how to plan and prepare for an RIE.  As described in the Federal Register of March 13, 2023 (88 FR 15417), 
FDA issued this guidance to address the circumstances of the public health emergency and revised it to continue in 
effect for 180 days after the COVID-19 public health emergency declaration expired on May 11, 2023.  As further 
described in the document, FDA intends to revise this guidance with any appropriate changes based on comments 
received and the Agencys experience with implementation. 
34 FDAs mutual recognition agreements with the European Union, Switzerland, and the United Kingdom provide 
for the acceptance of official inspection reports issued by a regulatory partner for manufacturing facilities located 
inside and outside of the partners territory.  For more information, see https://www.fda.gov/international-
programs/international-arrangements/mutual-recognition-agreement-mra and 
https://www.fda.gov/media/103391/download. 
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229  1.  Information Sharing by Trusted Foreign Regulatory Partners 
230   
231  FDA may request an existing drug inspection report and other information from a foreign partner 
232  through mutual recognition and other arrangements or agreements to assess a facilitys previous 
233  inspection history, to describe a facilitys current state of CGMP control, and to determine 
234  whether the inspection covered the proposed manufacturing operations described in an 
235  application.35  When a facility does not have an FDA inspection history or if prior FDA 
236  inspection coverage was limited, these reports help inform the Agencys determination of:  (1) 
237  whether a PAI or a PLI may not be needed in certain circumstances, or (2) if additional 
238  information is needed to adequately assess the facility through an inspection or an RRA.  FDA 
239  may request additional records and information through a section 704(a)(4) records request if the 
240  inspection report does not adequately address the application product, facility, or process-related 
241  risks. 
242   
243  2.  Foreign Regulatory Inspections With FDA Remote Participants 
244   
245  The widespread use of innovative regulatory approaches and virtual interactive tools by foreign 
246  regulators may provide an opportunity for increased inspection collaboration between regulatory 
247  authorities and for harmonized marketing authorization decisions for drug products.  FDA is 
248  evaluating the utility of collaborative assessments with regulatory partners for PAIs and PLIs 
249  when regulatory agencies have a mutual interest in a facility and/or a drug(s).  A collaborative 
250  assessment may include a combination of an on-site lead inspectorate and one or more 
251  participating remote regulatory authorities connecting through virtual interactive technologies. 
252   
253  Implementation of these collaborative assessments may help FDA streamline operations and 
254  overcome logistical travel challenges by leveraging local inspection teams and virtual interactive 
255  technologies to obtain information to support regulatory decisions.  In addition, regulator 
256  collaboration may facilitate timely availability of critical drugs in multiple markets globally and 
257  reduce inspection redundancy for the same product and facility.  At the time of issuance of this 
258  guidance, FDA is conducting a pilot project36 in this area and intends to use information and 
259  experience gained from ongoing collaborative assessment activities to inform FDAs future 
260  decision-making on this topic. 
261   
262  C.  PAIs and PLIs With FDA Remote Subject Matter Experts 
263   
264  As the Agency has gained experience with virtual interactive technologies, FDA sees the 
265  potential benefit of using these technologies to meet technical and logistical needs in certain 
266  circumstances by supplementing an inspection with remote resources.  As a result, FDA intends 
267  to make the expertise of remote personnel available to on-site FDA inspection teams to support 
 
35 Section 809 of the FD&C Act authorizes FDA to rely on inspections performed by capable foreign regulatory 
partners.  In the absence of FDAs capability determination, FDA intends to use inspection reports of other foreign 
regulatory partners as a source of information in evaluating an application. 
36 FDA is a participating member of the International Coalition of Medicines Regulatory Authorities that is piloting 
a program for collaborative hybrid inspections by multiple regulatory authorities.  For more information, see 
https://icmra.info/drupal/en/strategicinitatives/pqkms. 
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Draft  Not for Implementation 
268  PAIs and PLIs and to facilitate regulatory decision-making and timely application decisions.37  
269  This enhancement will help FDA maintain operational flexibility through enhanced efficiency 
270  and transparency. 
271   
272  For the purpose of the Agencys application decision, FDA may consider supplementing a PAI 
273  or a PLI with remote resources when:  (1) the expertise and input of a subject matter expert 
274  (SME) is determined by the on-site inspection team lead to be necessary to adequately assess an 
275  application product, a manufacturing process and its controls, or a facility, and to verify 
276  conformance to the application and compliance with the CGMP requirements; and (2) the 
277  physical, on-site participation of such an individual is not feasible.  To support a PAI or a PLI 
278  with remote resources, FDA will request confirmation of a facilitys willingness to accept 
279  involvement of remote Agency personnel as well as confirmation of the facilitys willingness 
280  and ability to adequately employ virtual interactive technologies to remotely connect an SME to 
281  an FDA inspection, when appropriate.  FDA does not intend to grant requests from facilities for 
282  the use of remote personnel to support any PAI or PLI.  Although facility agreement to the 
283  involvement of remote Agency personnel is voluntary, FDAs use of remote resources would 
284  provide for real-time, virtual engagement of an off-site expert directly with the on-site inspection 
285  team and facility staff, as the inspection team lead determines necessary, to address specific 
286  issues bearing on the inspection (e.g., aspects of product manufacturing, facility conditions). 
287   
288  When FDA anticipates using remote resources during an inspection, the Agency intends to notify 
289  the facility by electronic correspondence or by telephone call and include a written request for 
290  the facility to confirm its willingness and ability to interact with remote FDA personnel using 
291  virtual technology (to be provided by the facility or by the FDA on-site inspection team using 
292  FDA technology), including the use of a livestreaming video, screen sharing, and teleconference.  
293  The request would indicate:  (1) the name, address, and FDA Establishment Identifier or unique 
294  identifier of the facility to be inspected; (2) the application or supplement number; (3) the 
295  reasoning for FDAs use of remote resources; and (4) the names and positions of the remote 
296  personnel, if known in advance. 
297   
298  Upon the facilitys agreement to Agency use of remote resources, FDA will facilitate the 
299  planning and coordination of the inspection and involvement of a remote SME.  The on-site 
300  inspection team lead will schedule a virtual meeting with the facility to discuss logistics and 
301  expectations.  When a facility agrees to the involvement of a remote SME during an inspection, 
302  FDA expects the same level of cooperation and transparency with remote FDA personnel as 
303  expected with the on-site inspection team. 
304   
305  When the facility provides equipment enabling the involvement of a remote SME, the quality of 
306  the virtual connection (e.g., connectivity, image quality, cameras used) should be adequate for 
307  FDA to remotely review, observe, examine, and evaluate the information requested.  To the 
308  extent practicable, technologies employed also should allow access for remotely viewing and 
309  evaluating operations at the facility, as appropriate (e.g., aseptic practices, equipment cleaning 
310  and setup, material weighing and dispensing, instrument setup, sampling, testing).  Any 
 
37 FDA considers the remote subject matter expert to be a resource for use by FDA inspection teams and such use of 
a remote subject matter expert does not constitute an RRA. 
  9  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
311  challenges encountered by the facility in furnishing or operating such equipment or technologies 
312  should be communicated to the inspection team lead as soon as possible. 
313   
314  The FDA inspection team will initiate the inspection on-site before connecting the remote SME.  
315  Each virtual interaction with a remote SME will be made with the knowledge and agreement of 
316  the inspection team lead who is physically present on-site38 and will include a participating 
317  inspection team member on-site and who is participating in that interaction at the time that 
318  interaction occurs.  To ensure transparency, facilitate information collection, and provide for 
319  adequate on-site follow-up, any pertinent information or considerations noted by the remote 
320  SME will be communicated to the inspection team for confirmation while the team is physically 
321  on-site with facility staff.  The on-site inspection team will maintain responsibility for verifying, 
322  documenting, and determining which observations are listed on Form FDA 483, titled 
323  Inspectional Observations.  FDA will continually evaluate the utility of this alternative tool and 
324  the appropriate conditions for which a remote SME can best be used to support a PAI or PLI. 
325   
326   
327  V.  THE EFFECTS OF USING ALTERNATIVE TOOLS 
328   
329  In general, the use of alternative tools will help FDA fulfill its commitments to meet user fee 
330  goal dates and to make timely application decisions. 
331   
332  If observations are identified by FDA through the use of alternative tools, a written list of 
333  observations may be presented by FDA to the facility.39  A facility should submit any responses 
334  or corrective actions to FDA within 15 U.S. business days for consideration in the application 
335  assessment.  Responses received after 15 U.S. business days may be deferred for further 
336  assessment in the next application assessment cycle.  If FDA determines that there is insufficient 
337  information available to make a determination on the acceptability of a facility and an inspection 
338  is needed to address concerns, FDA will communicate this determination in application 
339  milestone meetings, action letters, postaction letters, and/or communications regarding 
340  scheduling of the inspection, as appropriate. 
 
38 The on-site presence of the inspection team lead and other inspection team members is consistent with section 
704(a)(1) of the FD&C Act, which authorizes inspections by physically present investigators.  Use of remote SMEs 
can support inspections as described above. 
39 FDA issues a Form FDA 483, titled Inspectional Observations, at the conclusion of an inspection when FDA 
observes objectionable conditions or practices. 
  10