Qualification Process for 
Drug Development 
Tools 
Guidance for Industry 
and FDA Staff 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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) 
 
November 2020 
Drug Development Tools  
Qualification Process for 
Drug Development 
Tools 
Guidance for Industry 
and FDA Staff 
 
 
Additional copies are available from: 
 
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Center for Drug Evaluation and Research 
Food and Drug Administration 
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Email: druginfo@fda.hhs.gov 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
 
and/or 
 
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Food and Drug Administration 
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Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-
guidancesk 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
and the Center for Biologics Evaluation and Research (CBER) 
 
November 2020 
Drug Development Tools 
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
A.  Cures Act ........................................................................................................................................ 2 
B.  A Taxonomy for DDTs: the BEST Glossary ............................................................................... 2 
C.  Qualification of DDTs and COUs ................................................................................................. 3 
D.  DDT Qualification Programs ........................................................................................................ 4 
E.  Cures Act: Promoting DDT Development, Collaboration, and Use .......................................... 5 
F.  General DDT Program Frequently Asked Questions ................................................................. 7 
1. How Do Requestors Determine Their Readiness to Initiate the Qualification Process? ................ 7 
2. When Does the Review Time Frame Begin? .................................................................................... 7 
3. What Are SMEs and How Are They Used in Submission Review? .................................................. 7 
4. What Does an Accept or Not Accept Determination Mean and How Is It Made? ........................... 8 
5. What Does It Mean to Withdraw from a DDT Program? ................................................................ 8 
6. How Can Biomedical Research Consortia and Partnerships Contribute to DDT Qualification? .. 8 
III.  QUALIFICATION PROCESS ........................................................................................ 9 
A.  Three Sequential Stages of Submission and Review Steps ......................................................... 9 
1. Submission Content .......................................................................................................................... 9 
2. FDA Review Process ........................................................................................................................ 9 
3. Letter of Intent (Stage 1) ................................................................................................................ 10 
4. Qualification Plan (Stage 2) .......................................................................................................... 10 
5. Full Qualification Package (Stage 3) ............................................................................................ 11 
B.  Post-Qualification Rescission and Modification ........................................................................ 11 
IV.  COMMUNICATIONS AND SUBMISSION PROCESS ............................................ 12 
A.  Communications .......................................................................................................................... 12 
B.  Submission Process ...................................................................................................................... 13 
1. Electronic Portal Account Creation and Submissions ................................................................... 13 
2. Submissions and Data Standards ................................................................................................... 13 
GLOSSARY................................................................................................................................. 14 
A.  Definitions ..................................................................................................................................... 14 
B.  Acronyms and Abbreviations ..................................................................................................... 18 
APPENDIX .................................................................................................................................. 19 
 
  Contains Nonbinding Recommendations 
Qualification Process for Drug Development Tools 
Guidance for Industry and FDA Staff1 
 
 
 
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 
 
Section 3011 of the 21st Century Cures Act (Cures Act)2 added new section 507, Qualification 
of Drug3 Development Tools (DDTs), to the Federal Food, Drug, and Cosmetic Act (FD&C 
Act).  This guidance meets the Cures Acts mandate to issue final guidance on the section 507 
qualification process.  Specifically, this guidance represents the Center for Drug Evaluation and 
Researchs (CDERs) and the Center for Biologics Evaluation and Researchs (CBERs)4 current 
thinking on implementation of section 507 of the FD&C Act with respect to describing the 
process for requestors5 interested in qualifying DDTs and on taxonomy for biomarkers and other 
DDTs. 
 
This guidance does not address evidentiary standards or performance criteria for purposes of 
DDT qualification, nor does it address qualifying medical device development tools (MDDTs) 
through the Center for Devices and Radiological Health (CDRH).  These topics will be discussed 
                                                 
1 This guidance has been prepared by the Center for Drug Evaluation and Research in cooperation with the Center 
for Biologics Evaluation and Research at the Food and Drug Administration. 
 
2 Public Law 114-255. 
 
3 The term drug refers to both human drugs and biological products unless otherwise specified. 
 
4 The recommendations in this guidance apply to CDER and CBER and do not include other FDA centers. 
 
5 Under section 507, a requestor means an entity or entities, including a drug sponsor or a biomedical research 
consortia seeking to qualify a drug development tool for a proposed context of use.  FDA recognizes the important 
contributions of academia, patient advocacy groups, and other stakeholder communities as requestors and as 
supporters of DDT development efforts. 
 
1  Contains Nonbinding Recommendations 
in other guidances and materials available on FDAs DDT programs6 and MDDT programs 
web pages, respectively.7 
 
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. 
 
 
II.  BACKGROUND 
 
A.  Cures Act 
 
Building on the qualification program that CDER proposed in Critical Path reports issued in 
2004 and 2006, the Cures Act amended the FD&C Act and added new section 507 to establish a 
statutory process for qualifying DDTs.  DDTs can be used, as appropriate, to support regulatory 
applications, including investigational new drug applications (INDs), new drug applications 
(NDAs), abbreviated new drug applications (ANDAs), and biologics license applications 
(BLAs). 
 
B.  A Taxonomy for DDTs: the BEST Glossary 
 
The Biomarkers, EndpointS, and other Tools (BEST) glossary8 is a taxonomy for classifying and 
developing biomarkers and other DDT-related scientific concepts.  The BEST glossary is 
periodically updated9 and clarifies important definitions, captures the distinction among different 
types of biomarkers and DDTs, and describes some of the hierarchical relationships, 
connections, and dependencies among DDT terms.  Unless otherwise noted, the discussion of 
biomarker classes or categories and types of DDTs in this guidance follows the BEST glossary 
                                                 
6 See https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-
programs. 
 
7 MDDT qualification is not a section 507 program and is administered by CDRH.  For more information on 
MDDTs, see https://www.fda.gov/medical-devices/science-and-research-medical-devices/medical-device-
development-tools-mddt. 
 
8 Section 3011(b)(3)(A) of the Cures Act states For purposes of informing guidance under this subsection, the 
Secretary shall, in consultation with biomedical research consortia and other interested parties through a 
collaborative public process, establish a taxonomy for the classification of biomarkers (and related scientific 
concepts) for use in drug development.  FDA has identified the BEST glossary as this taxonomy. 
 
9 See https://www.ncbi.nlm.nih.gov/books/NBK326791/. 
 
 
2  Contains Nonbinding Recommendations 
definitions.  For examples of how the BEST10 terminology is used in submissions or in qualified 
DDTs and context of use (COU) statements, see the DDT programs web pages.11 
 
C.  Qualification of DDTs and COUs 
 
DDTs are methods, materials, or measures that can aid drug development and regulatory review.  
Under the new section 507 of the FD&C Act, qualification and qualified mean FDAs 
determination that a DDT and its proposed COU can be relied upon to have a specific 
interpretation and application in drug development and regulatory review.12  A qualified DDT 
used within the COU may be applied to support or obtain approval or licensure (as applicable) of 
any drug, provided that the qualification has not been rescinded or modified.13  For more 
information on how DDTs can benefit drug development, see the FDA DDT programs web 
pages.14 
 
The COU statement identifies the specific use of the DDT in drug development.  FDA expects 
the content in DDT submissions to provide supporting evidence demonstrating the reliability and 
accuracy of the proposed DDT and its COU.  For more information on the construction of a 
COU and details on the supporting evidence needed in submissions to demonstrate that a DDT 
merits qualification, see the program-specific web pages.15  The DDT and its COU may evolve 
over the course of a qualification effort and are directly related to the information provided in 
qualification submissions. 
 
Seeking qualification of a DDT for a specified COU is voluntary.  DDTs that have not been 
qualified or that are qualified for a different COU may still be used in regulatory applications, 
when scientifically appropriate for a specific application, based on agreement with the 
appropriate review division or office.  Upon agreement with the review division, such use of a 
DDT within a regulatory application, however, is not considered qualified under section 507.  
                                                 
10 For more information on the BEST glossary, see https://www.ncbi.nlm.nih.gov/books/NBK326791/. 
 
11 For examples of biomarkers and related COU statements, see Biomarker Qualification Submissions at 
https://www.fda.gov/drugs/cder-biomarker-qualification-program/biomarker-qualification-submissions and List of 
Qualified Biomarkers at https://www.fda.gov/drugs/cder-biomarker-qualification-program/list-qualified-biomarkers. 
For examples of Clinical Outcome Assessment (COA) projects and related COU statements, see COA Submissions 
at https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/clinical-outcome-assessments-coa-
qualification-submissions and Qualified COAs at https://www.fda.gov/drugs/development-approval-process-
drugs/qualified-clinical-outcome-assessments-coa. 
 
12 FD&C Act section 507(e)(7). 
 
13 FD&C Act section 507(b)(2). 
 
14 See https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-
programs. 
 
15 See the Biomarker Qualification Program (BQP) web page at https://www.fda.gov/drugs/drug-development-tool-
ddt-qualification-programs/cder-biomarker-qualification-program; the COA Qualification Programs web page at 
https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/clinical-outcome-assessment-coa-
qualification-program; and the Animal Model Qualification Programs web page at https://www.fda.gov/drugs/drug-
development-tool-ddt-qualification-programs/animal-model-qualification-amqp-program. 
3  Contains Nonbinding Recommendations 
 
Encouraging the identification and use of reliable DDTs can significantly facilitate the 
development of new, safe, and effective drugs.  Qualified DDTs allow integration of innovative 
technology and new science and approaches to new areas of drug development as knowledge of 
disease and pathogenesis advances.  For example, using a DDT to enrich a study population with 
individuals exhibiting certain characteristics may help to reduce the size of the study population 
and shorten the duration of the study. 
 
D.  DDT Qualification Programs 
 
There are three DDT qualification programs at FDA:  biomarker, COA, and animal model.  
Other DDT qualification programs may be established based on scientific need and availability 
of resources.  Section 507(e)(5) of the FD&C Act defines DDTs as including biomarkers and 
COAs and any other method, material, or measure that FDA determines aids drug development 
and regulatory review.  FDA has determined that animal models evaluated under the Animal 
Model Qualification Program (AMQP) aid drug development and regulatory review for purposes 
of section 507. 
 
The BQP applies to biomarkers,16 which are defined in section 507(e)(1) of the FD&C Act as 
characteristics (such as a physiologic, pathologic, or anatomic characteristic or measurement) 
that are objectively measured and evaluated as an indicator of normal biologic processes, 
pathologic processes, or biological responses to a therapeutic intervention.17  Molecular, 
histologic, radiographic (imaging), and physiologic characteristics are examples of types of 
biomarkers.  A biomarker is not an assessment of how an individual feels, functions, or survives, 
as noted in the BEST glossary biomarker definition.18  FDAs BQP provides input and direction 
to stakeholders to aid in identifying a relevant public health need, ensuring a biomarker category 
is consistent with the proposed use, supporting the correct construction of the COU, and 
identifying the types of data or studies needed to support qualification. 
 
The COA Qualification Program (COAQP) applies to a COA, which includes but is not limited 
to patient-reported outcome (PRO), observer-reported outcome (ObsRO), clinician-reported 
outcome (ClinRO), and performance outcome (PerfO) measures.19  Section 507(e)(3) of the 
FD&C Act describes a COA as a measurement of a patients symptoms, a patients overall 
                                                 
16 The term biomarker includes those used as surrogate endpoints; FD&C Act section 507(e)(1). 
 
17 Qualifying a biomarker does not result in the qualification or endorsement of an exclusive technology or 
measurement method.  If an alternative measurement method is used in drug development, equivalence may be 
demonstrated to the relevant review division or office such that the alternative method has the same or similar 
performance characteristics to the method used for the qualification.  A sponsor interested in pursuing the 
development of a specific biomarker test for marketing as a device should consult the appropriate center at FDA 
(CDRH or CBER) that is responsible for review of the test. 
 
18 For the BEST glossary definition of a biomarker, see https://www.ncbi.nlm.nih.gov/books/NBK338448/. 
 
19 For the BEST glossary definition of a COA, see https://www.ncbi.nlm.nih.gov/books/NBK326791/. 
 
 
4  Contains Nonbinding Recommendations 
mental state, or the effects of a disease or condition on how the patient functions.  A COA may 
be used to determine whether a drug has demonstrated a clinical benefit.  Generally, FDA will 
qualify a COA if it is well defined and reliably assesses a targeted concept for a specified COU 
when used in adequate and well-controlled investigations.20,21 
 
The AMQP applies only to animal models intended for use in the adequate and well-controlled 
animal efficacy studies that serve as substantial evidence of effectiveness for drugs developed 
under the regulations commonly referred to as the Animal Rule.22,23  Other types of animal 
models, such as those used in general drug development for proof-of-concept testing or for safety 
testing, are not eligible for qualification through the AMQP.  Section III. D of the guidance for 
industry Product Development Under the Animal Rule (October 2015) discusses the AMQP, 
provides helpful information on animal model development, and describes the qualification of an 
animal model as follows: 
 
Qualification of an animal model through the AMQP indicates that (1) FDA has 
concluded that a specific animal species, given a specific challenge agent by a 
specific route, produces a disease process or condition that in multiple important 
aspects corresponds to the human disease or condition of interest, and (2) FDA 
has accepted the description of the models appropriate use in regulatory 
applications, including the definition of the parameters of the disease or condition 
that will be used as measures of quality control and quality assurance when the 
model is used. 24 
 
E.  Cures Act: Promoting DDT Development, Collaboration, and Use 
 
The Cures Act contains transparency provisions that includes information in the qualification 
submissions and FDAs Determination Letters in response to such submissions.  The Cures Act 
codified a statutory process for DDT qualification and added transparency provisions that help 
promote an understanding of how to develop DDTs for qualification, support a shared learning 
                                                 
20 See 21 CFR 314.126. 
 
21 Resources for information on types of COAs and appropriate COA selection are available on the programs web 
pages at https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/clinical-outcome-
assessment-coa-qualification-program and in the BEST glossary.  For information and methodologic guidance on 
patient-reported outcome measures and other clinical outcome assessments, see 
https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-
series-enhancing-incorporation-patients-voice-medical. 
 
22 For additional information, see the AMQP web page at https://www.fda.gov/drugs/drug-development-tool-ddt-
qualification-programs/animal-model-qualification-amqp-program. 
 
23 FDA supports the principles of the 3Rs, to reduce, refine, and replace animal testing when feasible; however, 
adequate and well-controlled efficacy studies conducted in animal models of the human disease or condition of 
interest are required for approval under the Animal Rule. 
 
24 We update guidances periodically.  To make sure you have the most recent version of a guidance, check the FDA 
guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
 
5  Contains Nonbinding Recommendations 
environment for developing best practices, provide information about the availability of qualified 
DDTs, and provide opportunities for information sharing and collaborative DDT development.  
These transparency provisions apply to qualification submissions sent to FDA under section 507 
of the FD&C Act after December 13, 2016.  Consistent with section 507, FDA posts information 
on the qualification programs web pages that includes the following:25 
 
  Requestor name 
 
  DDT qualification program (biomarker, COA, or animal model) 
 
  DDT name or description 
 
  COU 
 
  Start date of the comprehensive review,26 status (e.g., accept or not accept or qualified or 
not qualified), and stage (letter of intent (LOI), qualification plan (QP), or full 
qualification package (FQP)) 
 
  Information central to the submission, as described in the qualification submission 
content element outlines (for more information, see III. A. 1., Submission Content) 
 
  For LOI or QP, the Determination Letter (accept or not accept) 
 
  For FQP, the qualification Determination Letter and the FDA reviews 
 
  Rescission Letter or Modification Letter, if applicable 
 
FDA also intends to publicly post updates to submissions that significantly impact a DDTs 
development, which may include refinements to a DDT or COU (e.g., for a COA there may be 
interim submissions between the LOI and QP to ensure that the development of the COA is 
progressing).  FDAs posting of information, in compliance with the Cures Act, that is contained 
in LOI, QP, and FQP submissions does not constitute an endorsement, representation, or 
guarantee about the accuracy, completeness, currency, or suitability of the information contained 
in materials submitted by external parties. 
 
If FDA receives a Freedom of Information Act request for information that it has not posted on 
its web pages as part of the Cures Act transparency provisions described above, the Agency will 
                                                 
 
25 For more information on FDAs transparency provisions for qualification submissions, see 
https://www.fda.gov/drugs/drug-development-tool-qualification-programs/drug-development-tool-qualification-
process-transparency-provisions. 
 
26 For more information, see sections II. F. 2, When Does the Review Time Frame Begin? and III. A. 2, FDA 
Review Process. 
 
 
6  Contains Nonbinding Recommendations 
respond in accordance with applicable law.  Consistent with the Freedom of Information Act and 
other applicable law, the Agency will not publicly disclose information that constitutes trade 
secret or privileged, confidential commercial or financial information obtained from a person or 
an organization, nor will the Agency publicly disclose information in covered files that 
constitutes a clearly unwarranted invasion of personal privacy.27 
 
F.  General DDT Program Frequently Asked Questions 
 
Drug developers or other interested parties should consult the DDT programs web pages to learn 
about program considerations and recommendations related to a specific qualification project or 
to learn more about program resources available to DDT developers. 
 
1.  How Do Requestors Determine Their Readiness to Initiate the Qualification 
Process? 
 
Requestors may ask for a meeting with the relevant DDT qualification program at any time to 
discuss the qualification pathway for their specific DDT and COU.  Early interaction with FDA 
before formal submission provides advantages, including identification of a drug development 
need, alignment on an appropriate drug development COU, and identification of a pathway for 
the development of the supporting evidence for qualification.  FDA recommends prospective 
requestors provide a draft LOI or other supporting materials to focus the requested discussion 
with the relevant DDT program (see section IV, Communications and Submission Process). 
 
2.  When Does the Review Time Frame Begin? 
 
Once an LOI, a QP, or an FQP submission is deemed complete and understandable in an initial 
assessment, FDA will issue the requestor a reviewable memorandum marking the date that the 
comprehensive review starts and the review time frame begins.  FDA aims to complete its 
comprehensive reviews of complete LOIs, QPs, and FQPs within 3, 6, and 10 months, 
respectively.  During the comprehensive review, FDA may ask for additional information from 
the requestor.  The end of the review time frame is marked by issuance of a Determination 
Letter, which informs the requestor of the LOI or QP accept or not accept determination and, for 
an FQP, the qualified or not qualified DDT Committee determination. 
 
3.  What Are SMEs and How Are They Used in Submission Review? 
 
Subject Matter Experts (SMEs) include FDA staff and can include external SMEs who have 
demonstrated knowledge relevant to a proposed DDT project and its COU.  SMEs review 
submissions at each stage to identify the scientific and regulatory considerations important to a 
specific DDT and COU and send these scientific considerations with a recommendation to the 
DDT Committee. 
 
 
 
                                                 
27 See, for example, 5 U.S.C. 552(b)(4), (b)(6); 18 U.S.C. 1905. 
 
7  Contains Nonbinding Recommendations 
4.  What Does an Accept or Not Accept Determination Mean and How Is It Made? 
 
The DDT Committee, composed of CDER and CBER SMEs, scientists, and senior level medical 
officers and their designees, makes the determination to accept or not accept a submission into 
the relevant program based on several factors, including the scientific merit of the submission, 
the ability of the DDT and COU to address a specified drug development need, the availability of 
information and resources that support the proposed qualification effort, and, if appropriate, 
demonstration that the DDT is feasible and practical in a clinical trial context.28 
 
A determination to accept an LOI or QP submission indicates that the requestor may proceed to 
the next stage, the QP or FQP, respectively, provided the requestor addresses the 
recommendations and comments in the Determination Letter.29  A determination not to accept an 
LOI or QP submission is not a final determination, as a requestor may address information 
requests or recommendations from a prior Determination Letter and resubmit an updated LOI or 
QP submission.  Requestors may not proceed from the LOI or QP stage to the next stage unless 
they receive an accept determination at these stages.30 
 
5.  What Does It Mean to Withdraw from a DDT Program? 
 
Withdrawal is generally an action taken at the requestors discretion, at any point in the process, 
to remove a project from further consideration by a DDT program.  Requestors may ask for a 
meeting with the relevant program to discuss their intention to withdraw.  A project is considered 
withdrawn upon a programs receipt of the requestors withdrawal memorandum, when there is a 
lack of progress or the requestor has been unresponsive to FDAs request for an update for a 
prolonged period of time.  Although a project may be withdrawn, information related to that 
project remains publicly posted.  A project that is withdrawn may be reinitiated by submitting a 
new LOI. 
 
6.  How Can Biomedical Research Consortia and Partnerships Contribute to DDT 
Qualification? 
 
The cost, complexity, and multidisciplinary nature of many DDT qualification projects may 
create challenges for individual stakeholders engaging in the qualification process.  FDA 
encourages the adoption of best practices for DDT development, which may include a 
collaborative setting to enhance data sharing, cooperative data generation, and application of 
joint expert knowledge and resources to accelerate qualification.  DDT programs may refer 
requestors to specific consortia when the program considers that a qualification effort would 
benefit from a consultation or collaboration. 
 
 
 
                                                 
28 See FD&C Act section 507(a)(2)(B). 
 
29 See FD&C Act section 507(a)(1). 
 
30 Ibid. 
8  Contains Nonbinding Recommendations 
III.  QUALIFICATION PROCESS 
 
A.  Three Sequential Stages of Submission and Review Steps 
 
Each DDT qualification project advances through three sequential stages of submission (LOI, 
QP, and then FQP) with LOI and QP progressing to the next stage (QP and FQP, respectively) 
upon receipt of an accept Determination Letter for the previous stage.  At the LOI and QP stages 
a not accept determination does not allow progression to the next stage (QP or FQP, 
respectively) until issues have been addressed, ensuring that the requestor is well prepared to 
proceed to the next stage.31  The qualification process for a project ends with FDA issuing an 
FQP Determination Letter for a submission with a qualified or not qualified determination.  The 
qualification process stages and review process are described in greater detail below. 
 
1.  Submission Content 
 
At each stage of submission, requestors should provide sufficient information to demonstrate the 
submission merits acceptance by FDA.  The type and amount of supporting information that 
should be included will depend on the stage of submission.  For more detailed information about 
the content included in each stage of submission, see the content element outlines on the DDT 
programs web pages.32 
 
2.  FDA Review Process 
 
For each of the three sequential stages of the qualification process (i.e., LOI, QP, and then FQP), 
FDA initiates a three-step review process upon receipt of each submission.  First, FDA performs 
an initial assessment (Step 1) to ensure the submission is complete and understandable (e.g., 
containing all relevant content elements).33  If the initial assessment indicates the submission is 
                                                 
31 See FD&C Act section 507(a)(1). 
 
32 For program-specific qualification submission content element outlines, see the BQP at 
https://www.fda.gov/drugs/cder-biomarker-qualification-program/resources-biomarker-requestors (Qualification 
Stages & Submissions), the COAQP at https://www.fda.gov/drugs/drug-development-tool-qualification-
programs/clinical-outcome-assessments-qualification-program-resources-stage (COA Qualification Program Stages 
and Submissions), and the AMQP at https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-
programs/animal-model-qualification-amqp-program. 
 
33 In sufficient detail specific to the stage of submission and relevant content element outline, the initial assessment 
evaluates the submission for clarity, consistency, and adequacy of the DDT description and its measurement 
approach, the description of the drug development need, the COU, relevance and strength of supporting data, and 
project priority in terms of the public health need.  A submission deemed reviewable includes the content elements 
outlined (see footnote 32) by the specific program for the particular stage (i.e., LOI, QP, or FQP) and, where 
relevant, includes clearly identified responses to the DDT programs prior recommendations or data requests.  
Characteristics of a reviewable submission include that it is clearly and concisely written, is well organized, is 
adequately supported throughout by in-text citations to the scientific literature, and contains the appropriate 
supportive information.  Discussion of extraneous qualities of a DDT or extraneous measurements, inclusion of 
additional COUs, or other content that is outside the specific qualification effort, even when positive, will detract 
from the quality of a qualification submission. 
 
9  Contains Nonbinding Recommendations 
not reviewable, FDA will inform the requestor of deficiencies and recommend that it is revised 
and resubmitted to facilitate the review process and increase the likelihood of acceptance.  The 
advantage of getting feedback early is to allow FDA to work with the requestor in the 
development of a high-quality submission.  Given the variation in submission content, quality, 
and complexity, it is not feasible to provide a review timeline for the initial assessment. 
 
If the submission is complete, FDA issues a memorandum indicating the submission is 
reviewable, and it undergoes a comprehensive review (Step 2).  The comprehensive review 
results in a list of considerations, which may include information requests, and makes a 
determination recommendation to the DDT Committee. 
 
The DDT Committee (Step 3) evaluates the SMEs project considerations and recommendation 
and makes a determination, and then the requestor is issued a Determination Letter containing 
the submissions status (e.g., for LOI or QP an accept or not accept status, and for the FQP a 
qualified or not qualified status) with considerations to help the requestor address deficiencies in 
its next submission. 
 
For more information, requestors may consult the DDT programs respective web pages and 
communicate with the appropriate program to ensure that their submissions contain the 
appropriate content elements, are complete, and adequately address the scientific considerations 
associated with the DDT and COU.  Timelines between the end of one stage and the beginning 
of the next in any given project are largely under the requestors control and will vary. 
 
3.  Letter of Intent (Stage 1) 
 
Submitting an LOI initiates the qualification process.34  The LOI is a concise document that 
describes the DDT, a relevant drug development need, and a proposed COU.  The LOI should 
provide a scientific rationale to support the DDT and its COU. 
 
FDA aims to complete the LOI review within 3 months of issuing the reviewable memorandum.  
The LOI review concludes when FDA issues the requestor an LOI Determination Letter.  An 
LOI Determination Letter indicates whether the project is accepted into the relevant DDT 
qualification program and includes recommendations, considerations, and requests for 
information to advise the requestor about achieving next steps. 
 
4.  Qualification Plan (Stage 2) 
 
The QP submission describes available relevant data, knowledge gaps, proposed data collection 
plans, and analysis plans.  It addresses prior recommendations expressed in the LOI 
Determination Letter as well as any subsequent advice provided by reviewers.  Full study 
protocols and analytic plans should be included as needed and appropriate, with an estimated 
time frame for completing data collection, data analysis, and reporting. 
 
FDA aims to complete the QP review within 6 months of issuing the reviewable memorandum.  
The QP review concludes when FDA issues the requestor a QP Determination Letter.  The QP 
                                                 
34 See FD&C Act section 507(a)(1)(A)(i). 
10  Contains Nonbinding Recommendations 
Determination Letter will include requests for data and recommendations about data needs for 
the FQP.  Upon receipt of an accept determination for the QP, and taking into consideration the 
listed recommendations provided in the QP Determination Letter, requestors can construct a 
specific actionable plan that includes the types of supporting data, studies, and FQP content that 
they need to execute to prepare for the FQP submission.  If a QP is not accepted, the project has 
not successfully completed the second stage of the qualification process.  In this case, a requestor 
may revise and resubmit, withdraw, or redirect the project focus with a new DDT and LOI. 
 
5.  Full Qualification Package (Stage 3) 
 
The FQP is the comprehensive, third, and final stage of submission in the qualification process, 
ending with a qualification determination.  The FQP includes detailed descriptions of all studies, 
analyses, and results related to the DDT and its COU as described in FDAs response to a 
requestors QP.  Evidence supporting qualification should include full study protocols and 
reports, statistical or quantitative analysis plans, summary data, statistical program files for the 
main analyses, and subject-level data, unless summary-level data have been deemed sufficient.  
FDA conducts a comprehensive review of the FQP, which concludes with determining whether 
the evidentiary standards appropriate for that DDT have been met to qualify the DDT for its 
proposed COU or, based upon the data submitted, to qualify a DDT for a modified COU.  When 
a not-qualified determination is made, a requestor may take into account the input from the 
Agency and subsequently resubmit the FQP with modifications or submit a new LOI. 
 
FDA aims to complete the FQP review within 10 months of issuing the reviewable 
memorandum.  The FQP review concludes when FDA issues the requestor a qualification 
Determination Letter indicating qualified or not qualified status.  As described in section 507 of 
the FD&C Act, FQP review may be prioritized based on factors that include, as applicable, the 
following:  (1) the severity, rarity, or prevalence of the disease or condition targeted by the DDT 
and the availability or lack of alternative treatments for such disease or condition and (2) the 
identification, by FDA or biomedical research consortia or other expert stakeholders, of a DDT 
and its proposed COU as a public health priority.35  Additionally, FDA may prioritize FQP 
review based on other factors,36 including the potential impact of the DDT on drug development.  
Based upon these factors, an FQP that is determined to be a high or low priority may shorten or 
lengthen, respectively, the time frame needed for FDAs completion of an initial or 
comprehensive review. 
 
B.  Post-Qualification Rescission and Modification 
 
The original requestor who obtained qualification for a DDT and COU as the project owner or 
primary point of contact may modify the qualified DDT by submitting a QP (not an LOI) except 
where prohibited by law.  Modification applies only to the qualified DDT, without changes to the 
                                                 
35 See FD&C Act section 507(a)(2)(C). 
 
36 Ibid. 
 
 
11  Contains Nonbinding Recommendations 
COU.37  Examples include changing a panel or multicomponent biomarker and submitting 
longitudinal data for a COA.  Early communications, before submission of a QP, may help guide 
the requestors modification effort. 
 
A person, or organization, who is not the original requestor may propose modification to a 
qualified DDT or its COU by submitting a new LOI.  The new LOI should provide the rationale 
for the change and supporting data for the proposed modification.  The original qualification 
effort may remain qualified with the modification represented as an additional qualification, or it 
may be determined that the original qualified DDT and COU may be subsumed into one 
modified DDT and COU.  Such a determination will be indicated in the Determination Letter.  
Alternatively, the original requestor may transfer his or her ownership or interest in a project to 
another individual for modification of a qualified DDT or for the use of intellectual property 
applied in a prior DDT program submission for a new qualification effort with a formal letter 
transferring rights or ownership to the new requestor.  The written notification is similar to the 
process used for drug applications.38   
 
FDA DDT programs may decide to modify or rescind a qualified DDT and/or COU based on 
new information that calls into question the basis for such qualification or other regulatory and 
scientific considerations indicating that the DDT is not appropriate for its COU.39  When a DDT 
program initiates a rescission or modification, the DDT program intends to provide a written 
summary of the basis for making such a rescission or modification, and the requestor or 
requestors affected may request a meeting to discuss the basis for the rescission or modification 
before its effective date.  The DDT Committee intends to make determinations about whether to 
modify or rescind a qualified DDT based on the new information.  FDA intends to maintain 
information on modified and rescinded DDTs and COUs and the respective Determination 
Letters on the DDT programs web pages.  Should a rescission or modification affect a study that 
is part of an IND, NDA, ANDA, or BLA, the sponsor or applicant would be notified and should 
request a discussion with the appropriate office or review division and the DDT program to 
determine what actions, if any, are needed. 
 
 
IV.  COMMUNICATIONS AND SUBMISSION PROCESS 
 
A.  Communications 
 
Before and throughout the qualification process, there are opportunities for interactions between 
the DDT requestor and FDA.  The purpose of these communications may be to identify 
challenges and opportunities, guide the collection of data, request input on a proposed DDT or 
COU, identify the level of detail appropriate for a given stage of submission, or obtain 
clarification on considerations and recommendations.  Requestors should contact the appropriate 
qualification program for additional information on meeting types and scheduling and 
                                                 
37 Changes to a qualified COU are accomplished through submission of a new LOI. 
 
38 See 21 CFR 314.72. 
 
39 See FD&C Act section 507(b)(3). 
12  Contains Nonbinding Recommendations 
submission of premeeting materials, if applicable.  See the Appendix for contact information for 
each DDT program. 
 
A requestor may submit a request for a teleconference or other meeting type at any time.  Upon 
FDA notifying the requestor of receipt of a reviewable submission, an FDA project lead is 
identified, and all communications and exchanges of information related to the project should be 
directed to the project lead during the review process. 
 
B.  Submission Process 
 
1.  Electronic Portal Account Creation and Submissions 
 
The NextGen Portal is an integrated electronic gateway for the official submission of 
information to FDA, project tracking, and communications to and from FDA.  Requestors should 
create an account on the web page to initiate a DDT project.40  Submissions are received and 
recorded via the requestors account in the NextGen Portal.  Consortia or other groups should be 
aware that within the NextGen Portal, access to an account is not generally transferrable to 
another individual from within the portal.  Changes to account access can be made by submitting 
a request to the relevant DDT qualification program, which will work with the portal team to 
transfer access to the new account holder.  Account access through the portal is limited to the 
individual making the initial project submission.  Therefore, when projects having group 
sponsorship need team access, or when access by an alternate project representative is needed, 
advance planning on the part of the requestor can ensure such group or alternative account access 
is available.  A requestor who needs to use an alternative approach for submissions or 
communications may contact the relevant program at the email address listed in the Appendix. 
 
2.  Submissions and Data Standards 
 
Requestors may submit primary data (e.g., subject-level datasets) from studies as appropriate to 
their project account in the FDA portal.  The DDT programs strongly encourage requestors to 
use data standards, starting as early as possible in the conduct of studies in support of drug 
development, so that they are incorporated into the design, conduct, and analysis of studies.  
Requestors are strongly encouraged to use relevant data standards (e.g., Clinical Data 
Interchange Standards Consortium standards41) when submitting these data for review.42  Study 
data standards for submissions to FDA can be found at FDAs Study Data Standards web page.43 
                                                 
40 The FDA NextGen Portal can be accessed at https://edm.fda.gov.  Additional information at this URL describes 
processes such as account creation, account access, and how to communicate with the program via the portal. 
 
41 For more information on Clinical Data Interchange Standards Consortium standards, see 
https://www.fda.gov/industry/fda-resources-data-standards/study-data-standards-resources. 
 
42 For submission and review purposes, please refer to the Study Data Standards Resources, available at 
https://www.fda.gov/industry/fda-resources-data-standards/study-data-standards-resources. 
 
43 For more information on FDA study data submission, see 
https://www.fda.gov/industry/study-data-standards-resources/study-data-submission-cder-and-cber. 
 
13  Contains Nonbinding Recommendations 
GLOSSARY 
 
A.  Definitions 
 
Accept or not accept:  These terms are used at two points in the submission-review process, for 
both the LOI and QP stages and describe: (1) the recommendation made by the SMEs in 
coordination with the relevant qualification program, based upon factors that include scientific 
merit, in conjunction with listing any considerations relevant to the qualification effort; and (2) 
the determination made by the DDT Committee in response to such recommendation as it relates 
to a qualification submission. 
 
Animal model:  A specific combination of an animal species, challenge agent, and route of 
exposure that produces a disease process or pathological condition that, in multiple important 
aspects, corresponds to the human disease or condition of interest. 
 
Biomarker:  A characteristic (e.g., a physiologic, pathologic, or anatomic characteristic or 
measurement) that is objectively measured and evaluated as an indicator of normal biologic 
processes, pathologic processes, or biological responses to a therapeutic intervention, and 
includes a surrogate endpoint (FD&C Act section 507(e)(1)). 
 
Biomedical research consortia:  Collaborative groups that may take the form of public-private 
partnerships and may include government agencies, institutions of higher education (as defined 
in section 101(a) of the Higher Education Act of 1965), patient advocacy groups, industry 
representatives, clinical and scientific experts, and other relevant entities and individuals (FD&C 
Act, section 507(e)(2)). 
 
Clinical outcome:  An outcome that describes or reflects how an individual feels, functions, or 
survives (Biomarkers, EndpointS and other Tools (BEST) Glossary Resource). Assessment of a 
clinical outcome can be made through report by a clinician, patient, non-clinician observer, a 
performance-based assessment, or through other methods. 
 
Clinical outcome assessment (COA):  A measurement of a patients symptoms, overall mental 
state, or the effects of a disease or condition on how the patient functions.  These measurements 
include a patient-reported outcome (FD&C Act, section 507(e)(3)). 
 
Comprehensive review:  The detailed review of a submission, the start of which is the issuance 
of the reviewable memorandum that begins the review time frame.  The product of the 
comprehensive review is a thorough evaluation of the submission, a set of considerations and 
requests for data, and a recommendation to the DDT Committee (LOI and QP: accept or not 
accept; FQP: qualify or not qualify). 
 
Content elements:  The content elements relevant to a programs DDT type, specific stage 
(LOI, QP, or FQP), and other supporting information are available upon request to the program 
or on the specific DDT programs web page. 
 
14  Contains Nonbinding Recommendations 
Context of use (COU):  The circumstances under which the DDT is to be used in drug 
development and regulatory review (FD&C Act, section 507(e)(4)).  See the specific programs 
web page for more information on the content and structure of a COU. 
 
Determination:  A decision made at the conclusion of the review of a submission about whether 
to accept or not accept an LOI or a QP or to qualify or not qualify a DDT for a COU in an FQP. 
 
Drug development tool (DDT):  A biomarker, COA, or any other method, material, or measure 
determined to aid drug development and regulatory review (FD&C Act, section 507(e)(5)).  
Animal models developed to be used for product development under the Animal Rule have been 
determined by FDA to be DDTs under section 507 of the FD&C Act. 
 
Drug Development Tool Committee:  The DDT Committee is composed of CDER and CBER 
subject matter experts, scientists, senior-level medical officers and their designees.  The DDT 
Committee evaluates the SME and program considerations and recommendation and decides to 
accept or not accept (LOI and QP stages) or to qualify or not to qualify (FQP stage) a DDT 
qualification submission. 
 
Full qualification package (FQP):  The final stage in the series of three sequential qualification 
submissions.  The FQP describes in detail all studies, analyses, and results related to the DDT 
and its COU.  Evidence in support of qualification should include full study protocols and 
reports, summary data, statistical program files for the main analyses, and subject-level data 
unless FDA deems summary-level data to be sufficient.  Content elements are FQP-specific and 
are available upon request to the program or available on a specific DDT programs (BQP, 
COAQP, or AMQP) web pages. 
 
Initial assessment:  An administrative evaluation of a submissions completeness, scientific 
content, and overall quality that determines whether the submission is reviewable and eligible for 
a comprehensive review. 
 
Letter of Intent (LOI):  The first stage in the series of three sequential qualification 
submissions.  Submission of the LOI initiates the qualification process for a DDT and its 
proposed COU.  Content elements are LOI-specific and are available upon request to the 
program or posted on the specific DDT programs web pages.  An accept determination at this 
stage accepts a project into the relevant DDT program. 
 
Patient-reported outcome (PRO):  A measurement based on a report from a patient regarding 
the state of the patients health condition without amendment or interpretation of the patients 
report by a clinician or any other person (FD&C Act, section 507(e)(6)). 
 
Qualification (and qualified):  An FDA determination made after review of an FQP that a DDT 
and its proposed COU can be relied upon to have a specific interpretation and application in drug 
development and regulatory review (FD&C Act, section 507(e)(7)). 
 
Qualification Plan (QP):  The second stage in the series of three sequential qualification 
submissions.  It describes available data, knowledge gaps, and the data collection plan and 
15  Contains Nonbinding Recommendations 
summarizes available evidence to support qualification.  Content elements are QP-specific and 
are available upon request to the program or posted on the specific programs web page.  
Acceptance at the QP stage, including taking into consideration the listed recommendations 
provided in the QP Determination Letter, gives requestors the information needed to construct a 
specific actionable plan that includes the types of supporting data, studies, and FQP content that 
they need to execute to prepare for the FQP submission. 
 
Requestor:  An entity or entities, including a drug sponsor or a biomedical research consortia, 
seeking to qualify a DDT for a proposed context of use (FD&C Act, section 507(e)(8)). 
 
Review time frames:  The time taken to review a submission once FDA has deemed it 
reviewable and a memorandum notifying the requestor of receipt of a reviewable submission has 
been sent to the requestor.  For LOI, QP, and FQP submissions, the time frames are targeted to 
be completed within 3, 6, and 10 months, respectively, from the date on the reviewable 
memorandum. 
 
Reviewable:  A term used to denote that a submission is ready for FDA to begin the 
comprehensive review.  A submission FDA deems reviewable includes the content elements 
outlined by the specific program for the particular stage (i.e., LOI, QP, or FQP) and, where 
relevant, includes clearly identified responses to the DDT programs prior recommendations or 
data requests.  Characteristics of a reviewable submission include that it is clearly and concisely 
written, is well-organized, is adequately supported throughout by in-text citations to scientific 
literature, and contains the appropriate supportive information.  Discussion of extraneous 
qualities of a DDT, inclusion of additional COUs or other content that is outside the specific 
qualification effort, even when positive, will detract from the quality of a qualification 
submission.  Upon a determination that a submission is not reviewable, FDA communicates 
this to the requestor in a memorandum with advice intended to improve the quality of the 
submission. 
 
Reviewable memorandum:  A memorandum issued to the requestor indicating that the 
submission is reviewable and the date the memorandum is issued is the Reviewable Date (i.e., 
the date that the comprehensive review and time frame begins). 
 
Status:  Refers to, for example, the accept or not accept determination by the DDT Committee 
for an LOI or QP submission or the qualified or not qualified determination for an FQP. 
 
Subject matter expert (SME):  A member of FDA staff or an external expert who has 
demonstrated knowledge in clinical, scientific, pharmacologic, statistical, engineering, and/or 
other technical disciplines relevant to a projects proposed DDT and COU.  SMEs are used in the 
review of submissions to identify the scientific and regulatory considerations important to a 
specific DDT and COU. 
 
Surrogate endpoint:  A marker, such as a laboratory measurement, radiographic image, 
physical sign, or other measure, that is not itself a direct measurement of clinical benefit but is 
known to predict clinical benefit and could be used to support traditional approval of a drug or 
16  Contains Nonbinding Recommendations 
biological product or is reasonably likely to predict clinical benefit and could be used to support 
the accelerated approval (FD&C Act, section 507(e)(9)). 
 
Time frame(s):  See Review time frame above. 
 
Withdrawal:  An action taken at the requestors discretion during the qualification process and 
before qualification to remove the DDT from further consideration by a DDT program. 
 
17  Contains Nonbinding Recommendations 
1  B.  Acronyms and Abbreviations 
2   
3  AMQP   Animal Model Qualification Program 
4  ANDA   Abbreviated New Drug Application 
5  BEST    Biomarkers, EndpointS and other Tools (glossary) 
6  BLA    Biologics License Application 
7  BQP    Biomarker Qualification Program 
8  CBER   Center for Biologics Evaluation and Research 
9  CDER   Center for Drug Evaluation and Research 
10  CDRH   Center for Devices and Radiological Health 
11  CFR    Code of Federal Regulations 
12  COA    Clinical Outcome Assessment 
13  COAQP  COA Qualification Program 
14  COU     Context of Use 
15  ClinRO  Clinician-Reported Outcome 
16  DDT     Drug Development Tool 
17  FDA     U.S. Food and Drug Administration  
18  FD&C Act   Federal Food, Drug, and Cosmetic Act  
19  FQP    Full Qualification Package 
20  IND    Investigational New Drug Application 
21  LOI    Letter of Intent 
22  MDDT   Medical device development tool 
23  NDA     New Drug Application 
24  ObsRO  Observer-Reported Outcome 
25  PerfO    Performance Outcome 
26  PRO    Patient-Reported Outcome 
27  QP    Qualification Plan 
28  SME    Subject Matter Expert 
29  U.S.C.    United States Code  
30     
18  Contains Nonbinding Recommendations 
31  APPENDIX 
32   
33   
34  CONTACT INFORMATION FOR EACH DDT PROGRAM 
35  All submissions to any of the qualification programs must be made through the NextGen Portal 
36  for project tracking purposes and acknowledgement of receipt of a submission.  Inquiries or 
37  meeting requests may be made via email to individual programs as noted below: 
38   
39  CDER Biomarker Qualification Program 
40  Email: CDER-BiomarkerQualificationProgram@fda.hhs.gov 
41   
42  CDER Clinical Outcome Assessment Qualification Program 
43  Email: COADDTQualification@fda.hhs.gov 
44   
45  CDER and CBER Animal Model Qualification Program 
46  Email: CDERAnimalModelQualification@fda.hhs.gov  
47   
48  CBER DDT Qualification Programs (includes Biologics Biomarkers and Clinical 
49  Outcome Assessments) 
50  Email: CBER-DDTQualificationProgram@fda.hhs.gov 
19