Controlled 
Correspondence 
Related to Generic 
Drug Development 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
December 2020 
Generics 
 
 
OMB Control No. 0910-0797 
Expiration Date:  06/30/2023 
See additional PRA statement in Section VI of this guidance 
 
  Contains Nonbinding Recommendations 
 
 
Controlled 
Correspondence 
Related to Generic 
Drug Development 
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/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
 
December 2020 
Generics 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  CONTROLLED CORRESPONDENCE ........................................................................ 3 
A.  Guidance on Inquiries Within the Scope of Controlled Correspondence ................................ 3 
1. Controlled Correspondence Related to a Pending Citizen Petition, Petition for Stay of Action, or 
Petition for Administrative Reconsideration of Action ........................................................................ 3 
2. Requests Related to Matters Still Under Consideration by the Agency ........................................... 4 
B.  Guidance on Inquiries Outside the Scope of Controlled Correspondence ............................... 4 
1. Requests More Appropriately Addressed Through Other Mechanisms ........................................... 4 
2. Exceptions to the Definition of Controlled Correspondence ........................................................... 5 
3. Topics Outside the Scope of Controlled Correspondence ............................................................... 7 
4. Entities Outside the Scope of Controlled Correspondence .............................................................. 8 
C.  Application of GDUFA II Program Enhancements to Controlled Correspondence 
Submitted During GDUFA I ................................................................................................................. 8 
IV.  SUBMITTING A CONTROLLED CORRESPONDENCE ......................................... 8 
A.  How To Submit a Controlled Correspondence ........................................................................... 8 
B.  Content of a Controlled Correspondence .................................................................................... 9 
C.  Additional Recommendations on the Content of Specific Types of Controlled 
Correspondence Inquiries .................................................................................................................... 10 
1. Requests Related to Inactive Ingredients ....................................................................................... 11 
2. Requests for Q1/Q2 Formulation Assessment ............................................................................... 11 
3. Requests Related to Product Quality ............................................................................................. 13 
4. Requests Requiring Review by More Than One Discipline ........................................................... 13 
5. Requests Concerning Postapproval Submission Requirements ..................................................... 13 
6. Complex Controlled Correspondence ............................................................................................ 14 
D.  Controlled Correspondence Review Disciplines ....................................................................... 14 
1. OGDs Office of Bioequivalence ................................................................................................... 15 
2. OGDs Office of Research and Standards ..................................................................................... 15 
3. OGDs Office of Regulatory Operations, Division of Filing Review ............................................. 15 
4. OGDs Office of Regulatory Operations, Division of Labeling Review ........................................ 15 
5. OGDs Office of Generic Drug Policy ........................................................................................... 15 
6. Office of Pharmaceutical Quality, Office of Policy for Pharmaceutical Quality .......................... 15 
V.   FDAS COMMUNICATIONS TO REQUESTORS AND REQUESTS TO 
CLARIFY AMBIGUITIES IN FDAS CONTROLLED CORRESPONDENCE 
RESPONSE ................................................................................................................................. 16 
A.  Communications Related to Initial Submissions ....................................................................... 16 
B.  Clarification of the Controlled Correspondence Response ...................................................... 17 
VI.   PAPERWORK REDUCTION ACT OF 1995 .............................................................. 19  Contains Nonbinding Recommendations 
 
Controlled Correspondence Related to  
Generic Drug Development 
Guidance for Industry1 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
 
 
I.  INTRODUCTION  
 
This guidance provides information regarding the process by which generic drug manufacturers 
and related industry or their representatives can submit to FDA controlled correspondence 
requesting information related to generic drug development.  This guidance also describes the 
Agencys process for providing communications related to such correspondence.   
 
This guidance replaces the September 2015 guidance for industry Controlled Correspondence 
Related to Generic Drug Development.  The September 2015 guidance was issued as part of 
FDAs implementation of the Generic Drug User Fee Amendments of 2012 (GDUFA I).2  This 
guidance is being issued to incorporate program enhancements related to the review of controlled 
correspondence to which FDA committed, and industry agreed, as part of the reauthorization of 
GDUFA (GDUFA II).3 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required.  
 
 
                                                 
1 This guidance has been prepared by the Office of Generic Drugs in the Center for Drug Evaluation and Research at 
the Food and Drug Administration.  
2 Food and Drug Administration Safety and Innovation Act (Public Law 112-144). 
 
3 FDA Reauthorization Act of 2017 (Public Law 115-52). 
 
 
  1  Contains Nonbinding Recommendations 
 
 
 
II.  BACKGROUND 
 
GDUFA was reauthorized on August 18, 2017, to facilitate timely access to high-quality, 
affordable generic medicines.4  In accordance with the GDUFA Reauthorization Performance 
Goals and Program Enhancements Fiscal Years 2018-2022 (GDUFA II Commitment Letter or 
GDUFA II Goals Letter)5 that accompanied the legislation, FDA agreed to certain goals and 
procedures for the review of controlled correspondence received both before and on or after 
October 1, 2017.6  Specifically, the Agency agreed that: 
 
  FDA will review and respond to 90 percent of standard controlled correspondence 
within 60 calendar days of the date of submission. 
  
  FDA will review and respond to 90 percent of complex controlled correspondence 
within 120 calendar days of the date of submission.  
  
  FDA will review and respond to 90 percent of submitter requests to clarify 
ambiguities in the controlled correspondence response within 14 calendar days of 
FDAs receipt of the request.7    
 
In the case of controlled correspondence that raises an issue that relates to one or more pending 
citizen petitions, the 60- or 120-calendar day time period starts on the date FDA responds to the 
petition (if there is only one petition) or last pending petition.8 
 
The GDUFA II Commitment Letter defined standard controlled correspondence as: 
 
1.  Correspondence submitted to the Agency, by or on behalf of a generic drug 
manufacturer or related industry, requesting information on a specific element of 
generic drug product development, as described in the September 2015 guidance for 
industry Controlled Correspondence Related to Generic Drug Development9  
 
                                                 
4 Id. 
5 Available at http://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM525234.pdf.  
6 The application of GDUFA II goals to controlled correspondence that was submitted during GDUFA I will be 
discussed in section III.C. of this guidance.   
7 GDUFA II Commitment Letter at 9.   
8 Id.  As discussed in section III.A.1. of this guidance, this GDUFA II commitment also applies to controlled 
correspondence related to petitions for stay of action and petitions for administrative reconsideration of action.  
9 Since this guidance replaces the September 2015 guidance for industry Controlled Correspondence Related to 
Generic Drug Development, FDA is incorporating the definition of controlled correspondence into this guidance.   
 
  2  Contains Nonbinding Recommendations 
 
2.  Concerning postapproval submission requirements that are not covered by guidance 
on postapproval changes and are not specific to an abbreviated new drug application 
(ANDA)10  
 
The GDUFA II Commitment Letter defined complex controlled correspondence as 
correspondence involving: 
 
1.  Evaluation of clinical content 
 
2.  Review of bioequivalence (BE) protocols for drugs that reference listed drugs with 
risk evaluation and mitigation strategies (REMS) with elements to assure safe use 
(ETASU) 
 
3.  Requested evaluations of alternative BE approaches within the same study type (e.g., 
pharmacokinetic, in vitro, clinical)11 
 
This guidance provides additional detail and recommendations concerning:  
 
  What inquiries FDA considers to be controlled correspondence for the purposes of 
meeting the Agencys GDUFA II commitment 
 
  What information requestors should include in a controlled correspondence to 
facilitate FDAs consideration of and response to a controlled correspondence 
 
  What information FDA will provide in its communications to requestors that have 
submitted controlled correspondence 
 
  How requestors can submit requests to clarify ambiguities in FDAs controlled 
correspondence response and the Agencys process for responding to those requests 
 
 
III.  CONTROLLED CORRESPONDENCE 
 
Standard controlled correspondence and complex controlled correspondence are defined in the 
GDUFA II Commitment Letter and in section II of this guidance.   
 
A.  Guidance on Inquiries Within the Scope of Controlled Correspondence 
 
1.  Controlled Correspondence Related to a Pending Citizen Petition, Petition for Stay of 
Action, or Petition for Administrative Reconsideration of Action 
 
                                                 
10 GDUFA II Commitment Letter at 27-28.  
11 Id. at 25. 
 
  3  Contains Nonbinding Recommendations 
 
Consistent with GDUFA I and FDAs current practice, if a controlled correspondence is 
submitted that raises an issue that relates to one or more pending citizen petitions, petitions for 
stay of action, or petitions for administrative reconsideration of action, the 60- or 120-day time 
period starts on the date FDA responds to the petition (if there is only one petition) or the last 
pending petition.12  FDA will notify the requestor if the Agency determines that the controlled 
correspondence is related to an issue raised in a pending petition.  When the Agency issues a 
response to the petition, it will commence consideration of the controlled correspondence.  FDA 
will not notify the requestor when review of the controlled correspondence has commenced; the 
requestor can monitor the current status of the petition at https://www.regulations.gov.      
 
2.  Requests Related to Matters Still Under Consideration by the Agency 
 
FDA occasionally receives requests for information on issues that the Agency is considering, but 
for which no scientific or regulatory decision has been made or for which there is no clear 
clinical consensus.  For a request for which controlled correspondence is the appropriate pathway 
but the subject is still under consideration at the time of the response goal date, FDA will notify 
the requestor that the goal date has been missed because the request raises issues about which 
FDA has not made a decision.  In such instances, the request will remain open until FDA issues a 
response.  
 
B.  Guidance on Inquiries Outside the Scope of Controlled Correspondence 
 
1.  Requests More Appropriately Addressed Through Other Mechanisms 
 
In certain circumstances, controlled correspondence may not be the optimal mechanism to gain 
FDAs feedback on a topic.  For example, a pre-ANDA meeting13 may provide a better forum in 
which to discuss certain issues, such as methods of characterization for complex products or 
clinically critical BE considerations.  Other topics that are general in nature would be more 
appropriately considered as part of the Regulatory Science Initiative, such as the proposed use of 
in vitro data to support demonstration of BE for a class of reference listed drug (RLD) products 
for which no ANDAs have been submitted.  For such questions, the Agency will notify the 
requestor of the recommended alternative pathway and close the control.14   
                                                 
12 Id. at 9.  FDA considers a controlled correspondence to be related to one or more pending petitions if we 
determine that a decision regarding the issue raised in the petition could affect our response to the controlled 
correspondence.   
13 The pre-ANDA meetings referenced in the GDUFA II Commitment Letter only apply to meeting requests for 
complex products that may be submitted in an ANDA on or after October 1, 2017.  FDA has received, responded to, 
and granted certain pre-ANDA meeting requests for products that do not fit within the definition of a complex 
product as defined in the GDUFA II Commitment Letter.  Meeting requests for products that are not classified as 
complex products will be granted based on the workload and availability of staff and anticipated value to the ANDA 
assessment process. 
14 Controlled correspondence is intended to request information on a specific element of generic drug development, 
so it is not appropriate for requests that ask FDA to develop a new regulatory policy or change an existing policy.  
As described elsewhere in this document, however, FDA intends to monitor subjects of controlled correspondence to 
consider future topics for developing guidance documents.   
 
  4  Contains Nonbinding Recommendations 
 
 
2.  Exceptions to the Definition of Controlled Correspondence 
 
Historically, FDA has treated three types of inquiries that fall within the above definition of 
controlled correspondence differently from other inquiries on generic drug development: (1) 
requests for recommendations on the appropriate design of BE studies for a specific drug product 
(BE guidance requests); (2) requests for review of BE clinical protocols (clinical protocol 
requests); and (3) requests for meetings to discuss generic drug development before ANDA 
submission (pre-ANDA meeting requests).  FDAs process to respond to these inquiries, as 
outlined in the GDUFA II Commitment Letter, is described further below. 
 
First, FDA will continue to address BE guidance requests consistent with the public process 
described in the Agencys guidance for industry on Bioequivalence Recommendations for 
Specific Products15 and FDAs good guidance practices regulation.16  Under this approach, FDA 
publishes BE recommendations in product-specific guidances, the availability of which is 
announced in the Federal Register; public comments are requested for a designated period to 
ensure they are received before the Agency issues a final guidance, however, comments can be 
submitted on draft or final guidance documents at any time under our good guidance practices.  
The product-specific guidance process enhances transparency, provides a mechanism for public 
comment on recommended BE studies, provides for more efficient use of Agency resources, and 
follows FDAs good guidance practices regulation.   
 
With this public process, FDA can be proactive in developing and publishing guidance for new 
drug products without waiting for inquiries on BE methodologies from individual requestors.17   
FDA anticipates that this process will continue to expedite the availability of BE methodologies 
to generic drug manufacturers.  This process involves time frames that differ from the goal dates 
for controlled correspondence, however, and the Agency has determined that it would not be 
appropriate to circumvent this public process by responding to individual requestors to meet the 
GDUFA II goal dates for controlled correspondence because we believe public input is important 
                                                 
15 We update guidances periodically.  To make sure you have the most recent version of a guidance, check the FDA 
Drugs guidance web page at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
16 21 CFR 10.115.      
17 FDA has committed to issuing product-specific guidance identifying the methodology for developing drugs and 
generating evidence needed to support ANDA approval for 90 percent of new chemical entity new drug applications 
that are approved on or after October 1, 2017, at least 2 years before the earliest lawful ANDA filing date. However, 
this goal does not apply to complex products.  (GDUFA II Commitment Letter at 14.)  A complex product generally 
includes: (1) products with complex active ingredients (e.g., peptides, polymeric compounds, complex mixtures of 
active pharmaceutical ingredients, naturally sourced ingredients); complex formulations (e.g., liposomes, colloids); 
complex routes of delivery (e.g., locally acting drugs such as dermatological products and complex 
ophthalmological products and otic dosage forms that are formulated as suspensions, emulsions, or gels) or complex 
dosage forms (e.g., transdermals, metered dose inhalers, extended release injectables); (2) complex drug-device 
combination products (e.g., auto injectors, metered dose inhalers); and (3) other products where complexity or 
uncertainty concerning the approval pathway or possible alternative approach would benefit from early scientific 
engagement.  (GDUFA II Commitment Letter at 25.) 
 
  5  Contains Nonbinding Recommendations 
 
to the development of BE methodologies.  The Agency will continue to consider BE guidance 
requests in prioritizing BE guidance development.18   
 
Second, FDA will continue to exclude requests for BE clinical protocol review from controlled 
correspondence and the related goal dates if the RLD product is not subject to REMS ETASU.  
These requests include requests for review of protocols for in vivo BE studies with 
pharmacokinetic, pharmacodynamic, or comparative clinical endpoint studies conducted to 
support demonstration of BE for a proposed generic product.  Historically, FDA has not 
considered such requests as controlled correspondence because these requests are more time- and 
resource-intensive than other requests and often call for consultation with multiple disciplines 
within the Office of Generic Drugs (OGD), as well as with other offices or centers (e.g., the 
Center for Devices and Radiological Health).  Below are recommended alternatives to 
submitting a request for BE clinical protocol review: 
 
  If the request for BE clinical protocol review is intended to address a specific 
question not covered by a product-specific BE guidance, FDA recommends that in 
lieu of submitting a request for BE clinical protocol review, parties submit a 
controlled correspondence requesting FDA to comment on the specific question.  
  
  If the request for BE clinical protocol review involves the evaluation of a BE study 
design that deviates from the BE studies recommended in the available product-
specific guidance, FDA recommends that in lieu of submitting a request for BE 
clinical protocol review, parties submit a controlled correspondence requesting FDA 
evaluate the alternative approach.   
 
  If the request for BE clinical protocol review involves multiple questions or complex 
issues, FDA recommends that in lieu of submitting a request for BE clinical protocol 
review, parties submit a pre-ANDA meeting19 request or a controlled correspondence. 
 
Third, FDA will not treat pre-ANDA meeting requests as controlled correspondence because 
such requests serve a different purpose than controlled correspondence and should include 
different information from the requestor.  The purpose of the controlled correspondence process 
is to provide a mechanism for a direct inquiry on FDAs position with respect to a particular 
element of generic drug development and for the Agencys direct, brief, and timely response.  
The purpose of a pre-ANDA meeting request, by contrast, is to seek a dialogue with the Agency 
                                                 
18 Interested parties may submit requests for consideration of BE methods that modify or deviate from those 
proposed for a specific product to the public docket for product-specific BE guidances (FDA-2007-D-0369).  As an 
alternative, generic drug manufacturers and related industry or their authorized representatives can submit controlled 
correspondence through the CDER Direct NextGen Collaboration Portal (the portal) requesting the evaluation of an 
alternative BE approach within the same study type for a drug product for which a product-specific BE guidance is 
available to industry (see section IV.C.6.).  In addition, if a requestor wants clarification on a BE study 
recommended in the related product-specific guidance to support development of a generic drug product, the 
requestor can submit an inquiry as a controlled correspondence.  
19 We remind applicants to review the GDUFA II Commitment Letter to determine whether the product under 
development meets the criteria as a complex product and may, therefore, follow the pre-ANDA development 
program outlined in the GDUFA II Commitment Letter.   
  6  Contains Nonbinding Recommendations 
 
on a particular matter for which the controlled correspondence process is not suitable (e.g., 
methods of characterization for complex products or clinically critical BE considerations).  
Similarly, materials and information submitted with a controlled correspondence should provide 
the Agency with the relevant information on which to base its considerations, while the materials 
submitted in support of a meeting request should help the Agency determine whether a meeting 
is appropriate.  Accordingly, we will treat pre-ANDA meeting requests separately.   
 
We recommend that parties submit requests for recommendations on the appropriate design of 
BE studies for a specific drug product and for review of BE clinical protocols through the CDER 
Direct NextGen Collaboration Portal (the portal), which can be accessed at https://edm.fda.gov.  
For meeting requests, parties should refer to the draft guidance for industry Formal Meetings 
Between FDA and ANDA Applicants of Complex Products Under GDUFA regarding the process 
for submitting requests for meetings to discuss generic drug development before ANDA 
submission.20   
 
3.  Topics Outside the Scope of Controlled Correspondence 
 
This section provides additional guidance on the types of inquiries or topics that do not fall 
within the definition of standard or complex controlled correspondence described above.  First, 
the Agency considers any question related to a specific pending or approved ANDA to be 
outside the scope of a controlled correspondence.21  Such inquiries should be submitted only to 
the ANDA so they can be included as part of the full administrative record for that application.  
 
Second, inquiries that are submitted to FDA that are not directly related to generic drug 
development will not be considered controlled correspondence for the purposes of GDUFA II.  
For example, inquiries requesting information on the administrative practices of OGD, or on 
development of generic products for which there has never been a U.S.-approved RLD identified 
in FDAs Approved Drug Products with Therapeutic Evaluations (the Orange Book), will not be 
considered controlled correspondence.   
 
Third, as reflected in the definition of controlled correspondence, FDA expects that a controlled 
correspondence will contain inquiries on a specific element of generic drug development or 
postapproval submission requirements and not general questions related to product planning.  
Consistent with FDAs past and current practices, general or insufficiently detailed questions 
related to product development are not the appropriate subject of controlled correspondence.  For 
example, an inquiry seeking information on general approval standards for a particular product is 
                                                 
20 When final, this guidance will represent FDAs current thinking on this topic. 
21 The Agency has identified limited situations in which we will consider a request for information in a controlled 
correspondence related to a specific pending or approved ANDA.  For example, the Agency will consider a request 
for information in a controlled correspondence regarding development of a new strength for a product for which the 
submitter is an applicant of a pending or approved ANDA for other strengths.  The Agency also will consider a 
request for information in a controlled correspondence regarding development of a different package configuration 
for a product for which the submitter is an applicant of a pending or approved ANDA for other package 
configurations.  For example, if an inquiry pertaining to a gel in a metered-dose pump is submitted and there is a 
pending or approved ANDA for gel in a unit-dose package, the controlled correspondence could still be accepted for 
review.   
  7  Contains Nonbinding Recommendations 
 
not the appropriate subject of a controlled correspondence for the purposes of GDUFA II.  
Likewise, an inquiry about the acceptability of an excipient without a proposed level for a 
specific RLD (which includes a specific product strength) or a question about the general 
acceptability of a particular device provides insufficient detail for the Agency to respond.  FDA 
provides information to stakeholders on its approval standards and general submission 
recommendations through FDA regulations and guidances, and the Agency encourages generic 
drug manufacturers and related industry to review this information before submitting controlled 
correspondence to OGD.  The controlled correspondence process is intended to facilitate, not 
supplant, the generic drug development endeavor. 
 
4.  Entities Outside the Scope of Controlled Correspondence 
 
The controlled correspondence process, historically (and under the definition above), is available 
to generic drug manufacturers and related industry or their authorized representatives that have a 
question related to a potential ANDA submission to OGD, because this mechanism exists to 
facilitate generic drug development.  Other parties (e.g., private citizens, financial firms, or 
public advocacy groups that are not directly involved in developing generic drug products) 
should submit their inquiries related to generic drugs to the Division of Drug Information.22   
 
C.  Application of GDUFA II Program Enhancements to Controlled 
Correspondence Submitted During GDUFA I 
 
As stated in the GDUFA II Commitment Letter, FDA will [c]ontinue to review and act on . . .  
controlled correspondence submitted prior to October 1, 2017, that have been assigned GDUFA I 
goal dates pursuant to the GDUFA I review metrics applicable to those submissions.23  For any 
controlled correspondence submitted during GDUFA I for which FDA issued a response after 
October 1, 2017, and for which a submitter requests clarification of ambiguities in the controlled 
correspondence response (see section V.B. below), FDA will grant such a request for 
clarification, when possible, within the performance goal identified in the GDUFA II 
Commitment Letter.24  
 
 
IV.  SUBMITTING A CONTROLLED CORRESPONDENCE 
 
A.  How To Submit a Controlled Correspondence 
 
Requestors seeking FDAs response to a controlled correspondence by the goal dates articulated 
in the GDUFA II Commitment Letter (and listed above) should submit the correspondence 
                                                 
22 See contact information for the Division of Drug Information on the second title page of this guidance. 
23 GDUFA II Commitment Letter at 9-10.  To act on an application means that FDA will either issue a complete 
response letter, an approval letter, a tentative approval letter, or a refuse to receive letter. 
24 See GDUFA II Commitment Letter at 9. 
 
  8  Contains Nonbinding Recommendations 
 
electronically through the the portal, which can be accessed at https://edm.fda.gov.25   This will 
facilitate prompt consideration of and response to the controlled correspondence by the 
appropriate discipline.  Requestors should register a corporate email address with the portal.26  
We do not intend to consider portal submissions that are generated from general, personal 
accounts as controlled correspondence.  If a requestor would like to obtain a secure email 
account, a requestor (or its U.S. agent) may apply for a secure email pathway by contacting 
secureemail@fda.hhs.gov.     
 
FDA strongly discourages submitting controlled correspondence inquiries to individual 
FDA employees and submitting additional copies of a controlled correspondence in paper 
form, by courier, or by facsimile.  As described in section V.A. below, FDA intends to provide 
requestors notification via the portal on the status of a request soon after it is submitted, which 
should provide a requestor adequate assurance that the Agency has received the communication.  
The Agencys response will either state that FDA is considering the request as a controlled 
correspondence or provide the basis for not responding to it as a controlled correspondence, as 
described in this guidance.   
 
B.  Content of a Controlled Correspondence  
 
FDA recommends the cover letter to a controlled correspondence be submitted on corporate 
letterhead and include the following information: 
 
  Name, title, address, email, phone number, and entity (e.g., corporate affiliation) of the 
person submitting the controlled correspondence.  If the controlled correspondence is not 
submitted by the generic drug manufacturer or related industrys authorized 
representative, the generic drug manufacturer or related industrys authorized agent, or 
the agents authorized representative, located in the United States, then FDA will not 
treat the submission as controlled correspondence under the GDUFA II commitment 
letter.27   
 
  Please identify the company for which you are the authorized agent and include a 
copy of a letter of authorization with each controlled correspondence.28  The letter 
of authorization should be on corporate letterhead and dated within one year of 
                                                 
25 Requestors that are unable to submit a controlled correspondence through the portal may send their controlled 
correspondence, as an attachment to an email, to GenericDrugs@fda.hhs.gov.  In this situation, requestors should 
include the information specified in section IV.B. of this guidance.  GenericDrugs@fda.hhs.gov is a general OGD 
address to which certain submissions related to generic drugs may be submitted.  If requestors submit their 
controlled correspondence to GenericDrugs@fda.hhs.gov instead of the portal, all communications regarding that 
controlled correspondence will be through email and will not be captured in the portal. 
26 Requestors may register with the portal at https://edm.fda.gov.  
27 See the definition of controlled correspondence (A correspondence submitted to the Agency, by or on behalf of a 
generic drug manufacturer or related industry, requesting information on a specific element of generic drug product 
development). 
28 When possible, FDA recommends identification of the applicant of the potential ANDA, which facilitates linkage 
of the controlled correspondence to the ANDA when submitted.  
 
  9  Contains Nonbinding Recommendations 
 
the date the controlled correspondence is submitted.  FDA intends to provide a 
response to the companys U.S. authorized agent or the agents authorized 
representative, similar to FDA practice when an ANDA is submitted.   
 
  FDA-assigned control number and submission date of any previous, related controlled 
correspondence that was accepted for substantive review and response, if any, as well as 
a copy of that previous controlled correspondence and FDAs response, if any. 
 
  Relevant RLD(s) and/or reference standard(s),29 as applicable, including application 
number, proprietary (brand) name, manufacturer, active ingredient, dosage form, and 
strength(s).  
 
  Statement that the controlled correspondence is related to a potential ANDA submission 
to OGD or a request concerning postapproval submission requirements.  Include the 
ANDA number if the controlled correspondence is related to a submitted ANDA,30 
including an ANDA that FDA has refused to receive, or if the controlled correspondence 
is related to a potential and not yet submitted ANDA that has already been assigned an 
ANDA number.      
 
  Concise statement of the inquiry for which the controlled correspondence is being 
submitted. 
 
  Recommendation of the appropriate FDA review discipline to review the controlled 
correspondence.  General information regarding review disciplines is provided in section 
IV.D. below.   
 
Requestors also should include, either in the cover letter or as an attachment to the cover letter, 
relevant prior research and supporting materials on the specific element of generic drug 
development about which the requestor seeks information.   
 
If FDA determines that the inquiry does not contain the information specified in section IV.B. of 
this guidance, then FDA will not consider the inquiry to be submitted as controlled 
correspondence for purposes of GDUFA II.31   
 
C.  Additional Recommendations on the Content of Specific Types of Controlled 
Correspondence Inquiries 
 
                                                 
29 21 CFR 314.3(b) (Reference standard is the drug product selected by FDA that an applicant seeking approval of 
an ANDA must use in conducting an in vivo bioequivalence study required for approval). 
30 Although the Agency considers any question related to a specific pending or approved ANDA a review issue that 
should be submitted only to the ANDA, the Agency has identified requests for information related to a specific 
pending or approved ANDA that may be submitted in a controlled correspondence.  See section III.B.3, note 21. 
31 See section V.A. of this guidance for additional information. 
 
  10  Contains Nonbinding Recommendations 
 
This section provides additional recommendations for the content of specific types of inquiries 
submitted as controlled correspondence. 
 
1.  Requests Related to Inactive Ingredients 
 
The Agency often receives requests for information pertaining to whether particular inactive 
ingredients present at higher levels than the maximums listed in the Agencys Inactive Ingredient 
Database are permissible in a generic drug product.32  FDA recommends that a requestor submit 
for evaluation no more than three inactive ingredients and no more than three proposed levels for 
a drug product in any given controlled correspondence.  For example, in any given controlled 
correspondence, a requestor may submit (1) a request that proposes three inactive ingredients 
with one level each, or (2) a request that proposes one inactive ingredient with three levels.  If a 
requestor submits a range of levels for an inactive ingredient, the Agency only will review the 
highest proposed level in that range for that inactive ingredient.  In addition, requestors should 
only submit the inactive ingredients they wish to be evaluated and their proposed levels, not the 
whole formulation as this would include inactive ingredients that are not in question.   
 
A requestor should wait for FDAs response to the controlled correspondence before submitting 
a different request for consideration.  The Agency believes this is a reasonable limit based on 
what can be evaluated for a particular drug product within the GDUFA II goal date period.  This 
also encourages applicants to provide targeted submissions to the Agency and allows applicants 
to refine their subsequent formulation proposals based on FDAs previous responses.   
 
Such requests should identify the RLD (including the specific drug product strength(s)) to allow 
FDA to evaluate the potential acceptability of an excipient in the context of a specific proposed 
drug product.  Absent that information, there is no means for FDA to evaluate the safe use of that 
inactive ingredient, which depends on many factors, including the conditions of use (e.g., the 
indicated population including pediatrics, route of administration, and duration of use) for the 
RLD.  Although FDA may provide information regarding an inactive ingredient through a 
controlled correspondence, FDA evaluates the ultimate acceptability of an inactive ingredient in 
the context of a specific proposed drug product formulation during ANDA review, when the 
Agency has the full complement of data and information in support of ANDA approval to 
consider.  
 
2.  Requests for Q1/Q2 Formulation Assessment 
 
For certain types of products, FDAs regulations generally require that proposed products be 
qualitatively (Q1) and quantitatively (Q2) the same as the RLD with respect to inactive 
ingredients.33  In addition, FDAs guidances sometimes recommend certain BE studies for drug 
                                                 
32 Parties seeking to provide information to update FDAs Inactive Ingredient Database (e.g., to correct information 
on FDA-approved products contained in the database or to provide data for FDA-approved products not in the 
database) should send such notifications to IIDUpdate@fda.hhs.gov.  Such updates should not be submitted to 
GenericDrugs@fda.hhs.gov.  The Inactive Ingredient Database is available at the FDA web page, 
https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm.  
33 See e.g., 21 CFR 314.94(a)(9)(iii).   
  11  Contains Nonbinding Recommendations 
 
products that are Q1/Q2 with respect to the RLD.  When seeking review of proposed Q1/Q2 
formulations, we recommend the controlled correspondence include the following information 
about the RLD (which can be found in the Orange Book): 
  
  Relevant RLD application holder 
  Application number  
  Proprietary name  
  Active ingredient  
  Dosage form  
  Route of administration 
  RLD approval date  
  Market status (i.e., whether the product is prescription, over-the-counter, or in the 
Discontinued section of the Orange Book, which lists drug products that have been 
withdrawn from the market) 
   
The formulation descriptions should include adequate details, including salt and hydration forms, 
purity, grade or type, and function of the active ingredients and excipients.34  FDA recommends 
that no more than three proposed Q1/Q2 formulations of a single drug product be submitted in 
one controlled correspondence.  Limiting a single controlled correspondence to no more than 
three formulation requests allows for FDAs targeted and timely review of such requests.  In 
addition, the Agency recommends against submitting a request for a Q1/Q2 formulation 
assessment and a separate request for evaluation of a proposed inactive ingredient amount or 
concentration at the same time.   
 
If a requestor is seeking formulation assessment for multiple drug products, FDA recommends 
that each drug product request be submitted in a separate controlled correspondence.  Thus, a 
requestor should not seek Q1/Q2 formulation assessment for generic drugs with different RLDs 
in a single controlled correspondence.  This also includes separate formulation assessment 
requests for drug products with multiple strengths, because each strength is a separate drug 
product.  It should be noted that Agency policy or regulation may limit the amount or type of 
information that FDA may disclose in response to a request for Q1/Q2 formulation assessment.35 
 
Consistent with the Agencys past and current practices, FDA does not intend to review 
proposed formulations that are neither required by regulation nor recommended in guidance to 
be Q1/Q2 to the RLD.  Non-Q1/Q2 formulations are permissible for certain products so long as 
the differences do not affect the safety or effectiveness of the product.  The acceptability of such 
differences would be considered in the context of an ANDA review.  FDA also does not intend 
to provide clarification on why a formulation is not Q1/Q2 (see section V.B. below).36   
 
                                                 
34 To facilitate consideration of the request, FDA recommends that the inactive ingredient and/or the formulation 
information be presented in the format in which it would be submitted in an ANDA.  In cases in which a drug 
product is supplied as a dose pack, such as a vial containing lyophilized product and a diluent, the requestor should 
submit formulation compositions for both the lyophilized product and the diluent. 
35 See e.g., 21 CFR 20.61(a) and (b). 
36 Id. 
  12  Contains Nonbinding Recommendations 
 
3.  Requests Related to Product Quality 
 
The Agency often receives requests for information pertaining to chemistry, manufacturing, and 
controls for generic drugs and inquiries related to Type II drug master files for drug substances 
submitted in support of generic drug applications.  FDA recommends that a requestor include 
prior research and supporting product quality information in the controlled correspondence, so 
the Agency can adequately respond to the inquiry. The level of detail of the supporting product 
quality information should be commensurate with the question(s) being asked.  Typically, a 
submission related to product quality would include, as applicable, a brief description of the 
proposed formulation, manufacturing process, container-closure system, and developmental 
studies.  For example: (1) an inquiry on stability bracketing/matrixing design should include 
whether a common blend is used to make the drug product, proposed product strengths, storage 
conditions, and a description of the container-closure system, including any other necessary 
information to justify the reduced stability design; and (2) a question on size, shape, or other 
physical attributes of a drug product should be supported by comparative data of the proposed 
generic drug product and RLD with regard to product dimensions, volume, images, and other 
relevant properties.  A detailed description, with relevant prior research and supportive 
information, in a controlled correspondence will increase the likelihood that FDA will have the 
necessary information to provide a specific response to the inquiry.  
4.  Requests Requiring Review by More Than One Discipline 
 
If a requestor seeks information related to separate elements of generic drug product 
development requiring review by more than one discipline (e.g., information on a proposed 
formulation and proposed product labeling), FDA recommends that the requestor submit separate 
requests regarding the product.37  This will facilitate timely review and response.   
 
5.  Requests Concerning Postapproval Submission Requirements 
 
As indicated in the definition of standard controlled correspondence, FDA will respond to 
controlled correspondence seeking information on postapproval submission requirements.38  
FDA will only respond to correspondence requesting information on postapproval submission 
requirements that are not covered by existing guidance on postapproval changes.39  If the request 
is related to a specific ANDA, then FDA will not treat the request as controlled correspondence 
for purposes of GDUFA II.40  Postapproval controlled correspondence includes, but is not 
                                                 
37 Requests requiring review by more than one discipline may be submitted concurrently.  As discussed in section 
IV.B., FDA recommends that a controlled correspondence include the submission date of any other, related 
controlled correspondence that was accepted for substantive review and response.   
38 GDUFA II Commitment Letter at 27-28. 
39 Guidances on postapproval changes include, but are not limited to, Changes to an Approved NDA or ANDA 
Questions and Answers.  We encourage requestors to review all guidances on postapproval changes at the FDA 
Drugs guidance web page at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.   
40 GDUFA II Commitment Letter at 27-28.  As discussed in section III.B.3. of this guidance, requests related to a 
specific ANDA should be submitted to the application. 
 
  13  Contains Nonbinding Recommendations 
 
limited to, specific questions related to a product site transfer that would affect more than one 
approved ANDA and specific questions related to modernizing a manufacturing facility that is 
approved for more than one ANDA.     
 
6. Complex Controlled Correspondence 
 
Pursuant to the GDUFA II Commitment Letter, the definition of complex controlled 
correspondence includes controlled correspondence involving evaluation of clinical content, BE 
protocols for RLDs with REMS ETASU, and requested evalutions of alternative BE approaches 
within the same study type (e.g., pharmacokinetic, in vitro, clinical).41   
 
Consistent with FDAs past and current practices, FDA will continue to consider controlled 
correspondence that requires evaluation of clinical content to include requests that require input 
from the Division of Clinical Review in OGD.  FDA also will consider, on a case-by-case basis, 
whether controlled correspondence that requires input from other offices and centers (e.g., the 
Center for Devices and Radiological Health) includes the evaluation of clinical content and is 
therefore considered complex controlled correspondence by the Agency.  The evaluation of 
clinical content also includes, but is not limited to, clear, concrete questions related to the 
planning of a BE study with clinical endpoints and questions related to adverse events that occur 
during the conduct of a BE study. 
 
FDA will address requests for Covered Product Authorizations for RLDs subject to a REMS 
with ETASU as complex controlled correspondence, consistent with the timing requirements set 
forth in the law widely known as CREATES.42   
 
FDA will consider requests to evaluate alternative BE approaches within the same study type 
(e.g., pharmacokinetic, in vitro, clinical) to be complex controlled correspondence for drug 
products for which a product-specific BE guidance is available to industry.     
 
D.  Controlled Correspondence Review Disciplines 
 
This section provides additional information on the different disciplines that might review and 
respond to a controlled correspondence.  In addition, this section provides examples of the types 
of inquiries each discipline might review.  The Agency anticipates that this information will 
assist requestors in recommending the appropriate discipline to review a particular controlled 
                                                 
41 Id. at 25.  FDA may determine that a controlled correspondence is a complex controlled correspondence at any 
point during our review of the inquiry.  Please note that a complex controlled correspondence is defined by the 
content of the controlled correspondence and not whether the drug product is a complex product as defined in the 
GDUFA II Commitment Letter.   
42 21 U.S.C. 355-2.  CREATES was enacted as part of the Further Consolidated Appropriations Act of 2020, and 
establishes a pathway to obtain samples of the RLD. For those who wish to use this pathway to obtain products 
subject to a REMS with ETASU, CREATES requires that the interested developer obtain a Covered Product 
Authorization from FDA and sets forth a 120-calendar day time period for FDA to review these requests; thus, these 
requests will be treated as complex controlled correspondence.  The pathway for obtaining a Covered Product 
Authorization under CREATES replaces the process for obtaining a Safety Determination Letter described in the 
Agencys draft guidance for industry How to Obtain a Letter from FDA Stating that Bioequivalence Study Protocols 
Contain Safety Protections Comparable to Applicable REMS for RLD.    
  14  Contains Nonbinding Recommendations 
 
correspondence, as suggested above in section IV.B.  These descriptions are not intended to be 
exhaustive, and FDA has the discretion to determine which discipline should review and respond 
to a controlled correspondence. 
 
1.  OGDs Office of Bioequivalence 
 
FDA anticipates that the Office of Bioequivalence will review correspondence containing 
inquiries related to the planning of BE studies, including the review of protocols for drug 
products subject to REMS ETASU.  The Office of Bioequivalence also will review questions 
related to the maximum daily exposure of an inactive ingredient.   
 
2.  OGDs Office of Research and Standards 
 
FDA anticipates that the Office of Research and Standards will review correspondence 
containing questions on complex products43 or drug-device combination products. 
 
3.  OGDs Office of Regulatory Operations, Division of Filing Review 
 
FDA anticipates that the Division of Filing Review will review correspondence containing 
inquiries regarding FDAs Inactive Ingredient Database and drug product formulation. 
 
4.  OGDs Office of Regulatory Operations, Division of Labeling Review 
 
FDA anticipates that the Division of Labeling Review will review correspondence regarding 
submission requirements when the ANDA packaging configuration differs from the RLDs and 
appropriate labeling differences. 
   
5.  OGDs Office of Generic Drug Policy 
 
FDA anticipates that the Office of Generic Drug Policy, which includes the Orange Book staff, 
will review correspondence regarding patent listings or RLD designation or new reference 
standard selection questions. 
 
6.  Office of Pharmaceutical Quality, Office of Policy for Pharmaceutical Quality 
 
FDA anticipates that the Office of Policy for Pharmaceutical Quality will coordinate the Office 
of Pharmaceutical Qualitys (OPQ) review of correspondence among OPQs Office of Lifecycle 
Drug Products, Office of New Drug Products/Division of Lifecycle API and Division of 
Biopharmaceutics, and Office of Process and Facilities, with input from the Office of Testing 
and Research and the OPQ Science staff as appropriate.  OPQ will review correspondence 
containing inquiries regarding chemistry, manufacturing, and controls, as well as product quality 
microbiology for generic drugs.  In addition, we anticipate that OPQ will review inquiries related 
to Type II drug master files for drug substances submitted in support of generic drug 
applications. 
                                                 
43 See GDUFA II Commitment Letter at 25. 
  15  Contains Nonbinding Recommendations 
 
 
 
V.   FDAS COMMUNICATIONS TO REQUESTORS AND REQUESTS TO 
CLARIFY AMBIGUITIES IN FDAS CONTROLLED CORRESPONDENCE 
RESPONSE  
 
A.  Communications Related to Initial Submissions 
 
For inquiries submitted through the portal, FDA will provide the following information to a 
requestor through the portal regarding receipt and consideration of the inquiry.44   
 
Upon receipt of a submission, FDA will evaluate whether the submission will be considered a 
controlled correspondence for the purposes of GDUFA II.  FDA will then send the requestor one 
of two emails that can be accessed through the portal:  (1) an email confirming acceptance of the 
submission as a controlled correspondence for the purposes of GDUFA II, which will include an 
FDA-assigned control number;45 or (2) an email informing the requestor either that the Agency 
does not consider the submission a controlled correspondence and the basis for that decision or 
that FDA lacks adequate information to make this determination.  In most instances, we 
anticipate confirming acceptance of the submission within 7 calendar days,46 and the 
communication will contain a receipt date47 that the requestor can use to calculate the goal date. 
If a requestor resubmits a request for information that addresses any problem that FDA identified 
with a previous request, the Agency will consider this a new controlled correspondence and 
process it as such.   
 
If FDA determines, during substantive review of the inquiry, that the inquiry lacks sufficient 
information, it can either close the controlled correspondence at that time or contact the requestor 
for additional information through the portal.  If the Agency decides to close the controlled 
correspondence, it will notify the requestor through the portal of that decision and the basis for 
that decision.  If FDA contacts the requestor for additional information, the GDUFA II goal date 
for that controlled correspondence will be extended by the amount of time that the Agencys 
request for additional information is outstanding with the requestor.   
 
After substantive review of the request for information in the controlled correspondence, FDA 
will respond in written form via an email that can be accessed in the portal.  FDA will only send 
                                                 
44 For inquiries submitted to GenericDrugs@fda.hhs.gov, FDAs communications regarding the controlled 
correspondence will be sent to the email address from which the controlled correspondence originated. 
45 OGD recommends that the requestor refer to the controlled correspondence using the FDA-assigned control  
number in the cover letter of any related ANDA submissions and include a copy of the correspondence. 
46 If you do not receive confirmation from FDA within 7 calendar days, please contact GenericDrugs@fda.hhs.gov.   
47 Please refer to FDAs guidance for industry Providing Regulatory Submissions in Electronic Format  Receipt 
Dates for information on how FDA calculates receipt dates for regulatory submissions in electronic format, 
including controlled correspondence.  As described in that guidance, controlled correspondence will be received by 
the Agency Monday through Friday from 12:00 a.m. to 11:59 p.m. Eastern Standard Time/Eastern Daylight Time, 
excluding Federal holidays and days when the FDA office that will review the correspondence is closed.   
 
  16  Contains Nonbinding Recommendations 
 
a response to the person who originally submitted the controlled correspondence.  The length and 
content of FDAs response will depend on the nature of the inquiry submitted.  We intend that 
the comments we provide in response to a controlled correspondence will be comprehensive as 
of the date of the response.  We note that comments in the response represent our thinking on a 
topic at that time and that our thinking may evolve in the future. 
 
FDA will not respond to status requests regarding pending controlled correspondence before the 
goal date.48  If the Agency does not respond to the controlled correspondence by the goal date, 
FDA will send an acknowledgement to the requestor with notification that the request is still 
under consideration.49      
 
B.  Clarification of the Controlled Correspondence Response 
 
In general, FDA considers follow-up questions to FDAs controlled correspondence response 
and requests for additional information as new controlled correspondence.  This ensures that the 
follow-up question is tracked and that all requestors are treated equitably.  In these instances, we 
recommend that a requestor submit a new controlled correspondence and include the FDA-
assigned control number of the previous inquiry to facilitate FDAs review and response.   
 
FDA will respond to requests to clarify ambiguities in the Agencys controlled correspondence 
response, and such requests may be treated differently than follow-up questions.  As defined in 
the GDUFA II Commitment Letter, ambiguity in the controlled correspondence response means 
the controlled correspondence response or a critical portion of it, in FDAs judgment, merits 
further clarification.50  All requests for clarification of a controlled correspondence should be 
included in a single submission to FDA.  The request for clarification should be submitted within 
7 calendar days of issuance of FDAs controlled correspondence response.51  Requests for 
clarification received after 7 calendar days from issuance of the controlled correspondence 
response will be considered a new controlled correspondence.    
 
Requestors seeking clarification of ambiguities in FDAs controlled correspondence response 
should submit the request electronically through the portal, which can be accessed at 
https://edm.fda.gov.52  The cover letter for the request to clarify ambiguities in the controlled 
correspondence response should include the following information: 
                                                 
48 For pre-FY 2015 controlled correspondence, OGD will strive to respond to these controls as expeditiously as 
practicable.  
49 In circumstances in which there is a related pending petition, FDA will not notify the requestor when review of 
the controlled correspondence has commenced and it is the responsibility of the requestor to monitor the current 
status of the petition at https://www.regulations.gov (see section III.A.1. of this guidance).     
50 GDUFA II Commitment Letter at 24. 
51 The Agency believes that 7 calendar days provides a requestor sufficient time to review FDAs controlled 
correspondence response and identify any portion of the response the requestor believes is ambiguous.  It also 
ensures that requestors submit clarification requests for controlled correspondence that have recently been reviewed 
and responded to by the Agency.    
52 Requestors that are unable to submit a request for clarification through the portal may send their request, as an 
attachment to an email, to GenericDrugs@fda.hhs.gov.  In this situation, requestors should include the information 
 
  17  Contains Nonbinding Recommendations 
 
 
  Name, title, address, email, phone number, and entity (e.g., corporate affiliation) of the 
person submitting the request for clarification of the controlled correspondence response.  
If the request for clarification of FDAs controlled correspondence response is not 
submitted by the generic drug manufacturer or related industrys authorized 
representative, the generic drug manufacturer or related industrys authorized agent, or 
the agents authorized representative, located in the United States, FDA will not treat the 
request for clarification as subject to the GDUFA II Commitment Letter.53  Where 
possible, the request to clarify ambiguities in FDAs controlled correspondence response 
should be submitted by the person who originally submitted the controlled 
correspondence on which clarification is sought.  If this is not possible, FDA will accept 
the request from an alternate, authorized representative of the generic drug manufacturer 
or related industry, its authorized agent, or the agents authorized representative, located 
in the United States.   
 
  Please identify the company for which you are the authorized agent and include a 
copy of a letter of authorization.  The letter of authorization should be on 
corporate letterhead and dated within one year of the date the request for 
clarification of FDAs controlled correspondence response is submitted.  FDA 
intends to provide a response to the companys U.S. authorized agent or the 
agents authorized representative, similar to FDA practice when an ANDA is 
submitted.   
 
  FDA-assigned control number, submission date of the controlled correspondence on 
which the requestor is seeking clarification, a copy of that previous controlled 
correspondence, and FDAs response to the controlled correspondence. 
 
  Clarifying questions and the corresponding section(s) of FDAs controlled 
correspondence response on which the requestor is seeking clarification.   
 
The scope of the clarifying questions should be limited to the content of FDAs controlled 
correspondence response.  Any requests to review new or additional information will be 
considered a new controlled correspondence and should be submitted as such to the portal.   
 
As agreed to in the GDUFA II Commitment Letter, FDA will review and respond to 90 percent 
of requests to clarify ambiguities in the controlled correspondence response within 14 calendar 
days of the Agencys receipt of the request.54  If FDA determines that the request does not 
                                                 
specified in section V.B. of this guidance.  For inquiries submitted to GenericDrugs@fda.hhs.gov, FDAs 
communications regarding the request for clarification will be sent to the email address from which the request 
originated. 
53 Supra note 27. 
54 GDUFA II Commitment Letter at 9.  For the purpose of meeting this commitment, requests to clarify ambiguities 
in FDAs controlled correspondence response will be received by the Agency Monday through Friday from 12:00 
a.m. to 11:59 p. m. Eastern Standard Time/Eastern Daylight Time, excluding Federal holidays and days when the 
FDA office that will review the clarification request is closed.    
  18  Contains Nonbinding Recommendations 
 
contain the information specified in the bulleted list in this section, the request will not be 
considered to be received for purposes of GDUFA II.   
 
After reviewing the request for clarification, FDA, at its discretion, will either call the requestor 
or respond in written form via an email that can be accessed in the portal.  FDAs response will 
either clarify the ambiguity in the controlled correspondence response or state that, in FDAs 
judgment, the controlled correspondence response does not merit further clarification.  Any 
subsequent inquiries regarding FDAs response to a controlled correspondence or FDAs 
response to a request for clarification of ambiguities should be submitted in a new controlled 
correspondence.   
 
 
VI.   PAPERWORK REDUCTION ACT OF 1995 
 
This guidance contains information collection provisions that are subject to review by the Office 
of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 
3501-3520). 
 
The time required to complete this information collection is estimated to average 5 hours per 
response, including the time to review instructions, search existing data sources, gather the data 
needed, and complete and review the information collection. Send comments regarding this 
burden estimate or suggestions for reducing this burden to the Office of Generic Drugs, Center 
for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Silver Spring, MD 20993-0002. 
 
An agency may not conduct or sponsor, and a person is not required to respond to, a 
collection of information unless it displays a currently valid OMB control 
number.  The OMB control number for this information collection is 0910-0797 
(expires 06/30/2023).  
  19