Guidance for Industry 
Pharmacogenomic Data 
Submissions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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) 
Center for Devices and Radiological Health (CDRH) 
 
March 2005 
Procedural 
 
OMB Control Number 0910-0557 
Expiration Date: 9/30/20 
See additional PRA statement in section VIII of this guidance 
(Note: Expiration date updated 03/11/2019) 
   
Guidance for Industry 
Pharmacogenomic Data 
Submissions
  
 
 
Additional copies are available from: 
 
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Food and Drug Administration 
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 http://www.fda.gov/cder/guidance/index.htm 
 
 Office of Communication, Training and  
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 Food and Drug Administration 
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Office of Health and Industry Programs 
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Email: dsma@cdrh.fda.gov 
Fax: 301.443.8818 
(Tel) Manufacturers Assistance: 800.638.2041 or 301.443.6597 
(Tel) International Staff Phone: 301.827.3993 
 
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) 
Center for Devices and Radiological Health (CDRH) 
 
March 2005 
Procedural 
   
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  SUBMISSION POLICY ................................................................................................... 3 
A.   General Principles .......................................................................................................................... 3 
B.   Specific Uses of Pharmacogenomic Data in Drug Development and Labeling ........................ 5 
C.  Benefits of Voluntary Submissions to Sponsors and FDA ......................................................... 7 
IV.  SUBMISSION OF PHARMACOGENOMIC DATA.................................................... 8 
A.  Submission of Pharmacogenomic Data During the IND Phase ................................................. 8 
B.  Submission of Pharmacogenomic Data to a New NDA, BLA, or Supplement ....................... 10 
C.  Submission to a Previously Approved NDA or BLA ................................................................ 11 
D.  Compliance with 21 CFR Part 58 ............................................................................................... 11 
E.  Submission of Voluntary Genomic Data from Application-Independent Research .............. 12 
V.  FORMAT AND CONTENT OF A VGDS .................................................................... 12 
VI.  PROCESS FOR SUBMITTING PHARMACOGENOMIC DATA .......................... 14 
VII.  AGENCY REVIEW OF VOLUNTARY GENOMIC DATA SUBMISSIONS......... 14 
VIII.  PAPERWORK REDUCTION ACT OF 1995 .............................................................. 16 
GLOSSARY................................................................................................................................. 18 
APPENDIX A:  SUBMISSION OF PHARMACOGENOMIC (PG) DATA TO AN IND... 20 
APPENDIX B:  SUBMISSION OF PHARMACOGENOMIC (PG) DATA TO A NEW 
NDA, BLA, OR SUPPLEMENT ............................................................................................... 22 
APPENDIX C:  SUBMISSION OF PHARMACOGENOMIC (PG) DATA TO AN 
APPROVED NDA, BLA, OR SUPPLEMENT ........................................................................ 24 
APPENDIX D:  QUICK REFERENCE ON PHARMACOGENOMIC SUBMISSIONS ... 25 
APPENDIX E: VOLUNTARY SUBMISSION COVER SHEET .......................................... 26 
  Contains Nonbinding Recommendations 
 
Guidance for Industry1 
Pharmacogenomic Data Submissions 
 
 
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic.  It 
does not create or confer any rights for or on any person and does not operate to bind FDA or the public.  
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 
and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for 
implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate 
number listed on the title page of this guidance.  
 
 
 
I.  INTRODUCTION  
 
This guidance is intended to facilitate scientific progress in the field of pharmacogenomics and to 
facilitate the use of pharmacogenomic data in drug development.  The guidance provides 
recommendations to sponsors holding investigational new drug applications (INDs), new drug 
applications (NDAs), and biologics license applications (BLAs) on (1) when to submit 
pharmacogenomic data to the Agency during the drug or biological drug product2 development 
and review processes, (2) what format and content to provide for submissions, and (3) how and 
when the data will be used in regulatory decision making.  Key information, including examples 
of when pharmacogenomic data submissions would be required and when voluntary genomic 
data submissions (VGDSs) would be welcome are provided in a separate companion document 
(Pharmacogenomic Data Submissions, Attachment:  Examples of Voluntary Submissions or 
Submissions Required Under 21 CFR 312, 314, or 601). 
 
For the purposes of this guidance, the term pharmacogenomics is defined as the use of a 
pharmacogenomic or pharmacogenetic test (see glossary for definitions) in conjunction with 
drug therapy.  Pharmacogenomics does not include the use of genetic or genomic techniques for 
the purposes of biological product characterization or quality control (e.g., cell bank 
characterization, bioassays).  The FDA plans to provide guidance on those uses at a future time. 
Pharmacogenomics also does not refer to data resulting from proteomic or metabolomic 
                                                 
1 This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) and the Center for 
Biologics Evaluation and Research (CBER), in cooperation with the Center for Devices and Radiological Health 
(CDRH) at the Food and Drug Administration.  
 
2 For the purposes of this guidance, the term drug or drug product includes human drug and biological products. 
 
Paperwork Reduction Act Public Burden Statement:  According to the Paperwork Reduction Act of 1995, a 
collection of information should display a valid OMB control number.  The valid OMB control number for this 
information collection is 0910-0557 (expires 12/31/2007).  The time required to complete this information collection 
is estimated to average 10 hours per response, including the time to review instructions, search existing data 
resources, gather the data needed and complete and review the information collection. 
 
  1  Contains Nonbinding Recommendations 
 
techniques.  This document is not meant to provide guidance on pharmacoproteomics or 
multiplexed protein analyte based technologies.  However, the voluntary submission process 
described in this guidance may be used to submit such data if so desired. 
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agency's 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 
 
The promise of pharmacogenomics lies in its potential to help identify sources of inter-individual 
variability in drug response (both effectiveness and toxicity); this information will make it 
possible to individualize therapy with the intent of maximizing effectiveness and minimizing risk.  
However, the field of pharmacogenomics is currently in early developmental stages, and such 
promise has not yet been realized. The Agency has heard that pharmaceutical sponsors have been 
reluctant to embark on programs of pharmacogenomic testing during FDA-regulated phases of 
drug development because of uncertainties in how the data will be used by FDA in the drug 
application review process.  This guidance is intended to help clarify FDA policy in this area.  
 
Sponsors submitting or holding INDs, NDAs, or BLAs are subject to FDA requirements for 
submitting to the Agency data relevant to drug safety and effectiveness (including 21 CFR 
312.22, 312.23, 312.31, 312.33, 314.50, 314.81, 601.2, and 601.12).  Because these regulations 
were developed before the advent of widespread animal or human genetic or gene expression 
testing, they do not specifically address when such data must be submitted.  The FDA has 
received numerous inquiries about what these regulations require of sponsors who are 
conducting such testing. 
 
From a public policy perspective, a number of factors should be considered when interpreting 
how these regulations apply to the developing field of pharmacogenomics.  Because the field of 
pharmacogenomics is rapidly evolving, in many circumstances, the experimental results may not 
be well enough established scientifically to be suitable for regulatory decision making.  For 
example: 
 
  Laboratory techniques and test procedures may not be well validated.  In addition, test 
systems may vary so that results may not be consistent or generalizable across different 
platforms.  A move to standardize assays is underway, and much more information 
should be available within the next several years. 
 
  The scientific framework for interpreting the physiologic, toxicologic, pharmacologic, or 
clinical significance of certain experimental results may not yet be well understood. 
 
  2  Contains Nonbinding Recommendations 
 
  The findings from a specific study often cannot be extrapolated across species or to 
different study populations (e.g., various human subpopulations with different genetic 
backgrounds). 
  The standards for transmission, processing, and storage of the large amounts of highly 
dimensional data generated from microarray technology have neither been well defined 
nor widely tested.  
 
Despite these concerns, some pharmacogenetic tests  primarily those related to drug 
metabolism  have well-accepted mechanistic and clinical significance and are currently being 
integrated into drug development decision making and clinical practice. 
 
It is important for FDA to have a role in the evaluation of pharmacogenomic tests, both to ensure 
that evolving FDA policies are based on the best science and to provide public confidence in the 
field.  The FDA developed this guidance to facilitate the use of pharmacogenomic tests during 
drug development and encourage open and public sharing of data and information on 
pharmacogenomic test results. 
 
To this end, the Agency has undertaken a process for obtaining input from the scientific 
community and the public. On May 16 and 17, 2002, the Agency held a workshop, cosponsored 
by pharmaceutical industry groups, to identify key issues associated with the application of 
pharmacogenetics and pharmacogenomics to drug development.   Subsequently, on April 8, 2003, 
a public presentation was made to the FDA Science Board.  This presentation contained a 
proposal for developing guidance on the submission of information on pharmacogenomic tests 
and a potential algorithm for deciding whether submission of such data is voluntary or required.  
The Science Board endorsed moving forward with both of these proposals. In November 2003, 
FDA published a draft version of this guidance and received public comment on the draft 
guidance. The Agency also has developed internal policy related to pharmacogenomics and 
voluntary submissions.3  
 
The policies and processes outlined in this final guidance are intended to take the above factors 
into account and to assist in advancing the field in a manner that will benefit both drug 
development programs and the public health. 
 
 
III.  SUBMISSION POLICY 
 
A.   General Principles 
 
The FDA recognizes that its pharmacogenomic data submission policies must be consistent with the 
relevant codified regulatory submission requirements for investigational and marketing application 
submitters and holders.  At present, many pharmacogenomic results are not well enough established 
                                                 
3 A charter has been developed outlining the organization, principles, and function of the inter-center 
Interdisciplinary Pharmacogenomics Review Group (IPRG) (MaPP 4180.2).  In addition, policy has been developed 
for Agency staff, explaining how voluntary genomic data submissions (VGDSs) will be received and reviewed in 
the Agency (MaPP 4180.3; SOPP 8114).  
  3  Contains Nonbinding Recommendations 
 
scientifically to be appropriate for regulatory decision making.4  This guidance interprets FDA's 
regulations for investigational and marketing submissions, with the goal of clarifying FDA's current 
thinking about when the regulations require pharmacogenomic data to be submitted and when the 
submission of such data would be welcome on a voluntary basis.  In some cases, complete reports of 
pharmacogenomic studies suffice, while in others, an abbreviated report or synopsis should or must 
be submitted.5   
 
Because FDA regulations establish different requirements for investigational applications, 
unapproved marketing applications, and approved marketing applications, this guidance sets out 
different submission algorithms for each of these categories.  The guidance also clarifies how the 
Agency currently intends to use such data in regulatory decision making  that is, when the data will 
be considered sufficiently reliable to serve as the basis for regulatory decision making; when it will 
be considered only supportive to a decision; and when the data will not be used in regulatory decision 
making.   
 
This guidance also makes a distinction between pharmacogenomic tests that may be considered either 
probable or known valid biomarkers, which may be appropriate for regulatory decision making, and 
other less well-developed tests that are either observational or exploratory biomarkers that, alone, are 
insufficient for making regulatory decisions.  Although, currently, most pharmacogenomic 
measurements are not considered valid biomarkers, certain markers (e.g., for drug metabolism) are 
well established biomarkers with clear clinical significance.  Undoubtedly, the distinction between 
what tests are appropriate for regulatory decision making and those that are not will change over time 
as the science evolves. Throughout the development of these tests, as appropriate, FDA will continue 
to seek public comment as we evaluate whether a biomarker is a valid biomarker (e.g., via 
discussions at Advisory Committee meetings). 
 
For the purposes of this guidance, a pharmacogenomic test result may be considered a valid 
biomarker if (1) it is measured in an analytical test system with well-established performance 
characteristics and (2) there is an established scientific framework or body of evidence that 
elucidates the physiologic, pharmacologic, toxicologic, or clinical significance of the test results.  
For example, the consequences for drug metabolism of genetic variation in the human enzymes 
CYP2D6 and thiopurine methyltransferase are well understood in the scientific community and 
are reflected in certain approved drug labels.  The results of genetic tests that distinguish allelic 
variants of these enzymes are considered to be well established and, therefore, valid biomarkers.   
 
This guidance makes an additional distinction between known valid biomarkers that have been 
accepted in the broad scientific community and probable valid biomarkers that appear to have 
predictive value for clinical outcomes, but may not yet be widely accepted or independently 
verified by other investigators or institutions (see Glossary).  When a sponsor generates, or 
                                                 
4 For purposes of this document, the term regulatory decision making, as defined here, applies to decisions that FDA 
may make in the evaluation of pharmacogenomic information used to establish the dosing, safety, or effectiveness of 
a drug or biological product. FDA regulatory decisions occur throughout the investigational stages of product 
development, during premarket review, and during postmarket regulation. 
 
5 For further information on when abbreviated study reports can be submitted in NDAs and BLAs, see the guidance 
for industry Submission of Abbreviated Reports and Synopses in Support of Marketing Applications, developed 
under section 118 of the Food and Drug Administration Modernization Act. 
  4  Contains Nonbinding Recommendations 
 
possesses, data sufficient to establish a significant association between a pharmacogenomic test 
result and clinical outcomes, the test result represents a probable valid biomarker.  It would be 
expected that this biomarker would meet criteria (1) and (2) above, and its association with a 
meaningful outcome would have been demonstrated in more than one experiment. 
 
The algorithms described below for investigational and marketing application holders describe 
when to submit to FDA data on known valid biomarkers.  Data on probable valid biomarkers 
need not be submitted to the IND unless they are used by a sponsor to make decisions regarding 
specific animal safety studies or clinical trials (e.g., using biomarker data as inclusion or 
exclusion criteria, assessment of treatment-related prognosis, or stratifying patients by dose) or 
are a probable valid biomarker in human safety studies (see section IV.A).6  However, we 
recommend that sponsors or applicants submit reports on all probable valid biomarkers to new 
(i.e., unapproved) NDAs or BLAs according to the algorithm in section IV.B. 
 
Many pharmacogenomic testing programs implemented by pharmaceutical sponsors or by 
scientific organizations are intended to develop the knowledge base necessary to establish the 
validity of new genomic biomarkers.  During such a period of scientific exploration, test results 
are not useful in making regulatory judgments pertaining to the safety or effectiveness of a drug 
and are not considered known or probable valid biomarkers.  However, scientific development of 
this sort is highly desirable for advancing the understanding of relationships between genotype or 
gene expression and responses to drugs and, therefore, should be encouraged and facilitated.  For 
these reasons, although submission of exploratory pharmacogenomic data is not required under 
the regulations, FDA is encouraging voluntary submission of such data, as described below.  
  
B.   Specific Uses of Pharmacogenomic Data in Drug Development and Labeling  
 
As the field of pharmacogenomics advances, it is likely (and desirable) that sponsors will begin 
to use pharmacogenomic tests to support drug development and/or to guide therapy.  Sponsors 
may choose to submit pharmacogenomic data that have not achieved the status of a valid 
biomarker to an investigational or marketing application to support scientific contentions related 
to dosing and dosing schedule, safety, or effectiveness.  For example, a sponsor may wish to 
provide supportive data demonstrating that changes in drug-induced gene expression differ 
between species that have different toxicologic responses to a drug, thus correlating changes in 
certain gene expression patterns with a specific toxicity.  Or, a pharmacogenomic test result 
might also be used to stratify patients in a clinical trial or to identify patients at higher risk for an 
adverse event to correlate test results with clinical outcome.   
 
When pharmacogenomic results affect the design of a specific animal safety trial, or human 
safety or efficacy trial, the submission algorithms described below suggest that full information 
on the test system must be submitted to the IND ( 312.30(b) and 312.31).  In contrast, results 
from earlier feasibility studies done under the same IND (or outside the IND) to establish the 
potential usefulness of the pharmacogenomic test (e.g., from samples taken during a dose-
response study) are not a required submission, but would be encouraged as a voluntary 
                                                 
6 For the purposes of this guidance, the phrase decision making by the sponsor, as defined here, refers to study- or 
trial-specific decisions that a sponsor might make in the development of a drug, but not to overall strategies related 
to drug development or portfolio management. 
  5  Contains Nonbinding Recommendations 
 
submission.  However, a plan to perform any invasive test, including phlebotomy, with the 
possible intent to conduct pharmacogenomic testing on a sample, must be noted both in the 
protocol and the informed consent document ( 312.23(a)(6), 312.30(b), and 50.25). 
 
If a pharmacogenomic test shows promise for enhancing the dose selection, safety, or 
effectiveness of a drug, a sponsor may wish to fully integrate pharmacogenomic data into the 
drug development program.  This integration could occur in two ways: 
 
1.  The pharmacogenomic data may be intended to be included in the drug labeling in an 
informational manner.  
 
For example, such data might be used to describe the potential for dose adjustment by 
drug metabolism genotype (e.g., CYP2D6*5) or to mention the possibility of a side effect 
of greater severity or frequency in individuals of a certain genotype or gene expression 
profile.  In such cases, the pharmacogenomic test result would be considered a known 
valid biomarker.  However, an FDA-approved pharmacogenomic test may not be 
available or required to be available, or a commercial pharmacogenomic test may not be 
widely available.  Given this level of complexity, at the current time, sponsors should 
consult the relevant FDA review division for advice on how to proceed in a specific case.  
However, whenever a sponsor intends to include pharmacogenomic data in the drug label, 
complete information on the test and results must be submitted to the Agency as 
described under  314.50 and 601.2. 
 
2.  The pharmacogenomic data and resulting test or tests may be intended to be included in 
the drug labeling to choose a dose and dose schedule, to identify patients at risk, or to 
identify patient responders.   Inclusion of a pharmacogenomic test in the labeling would 
be contingent upon its performance characteristics.  For example: 
 
  Patients will be tested for drug metabolism genotype and dosed according to the test 
results. 
  Patients will be selected as potential responders for an efficacy trial (or deselected 
because of a high risk) based on genotype (e.g., of either the patient or the patients 
tumor) or gene expression profile. 
  Patients will be excluded from a clinical trial based on genotype or gene expression 
profile (e.g., biomarker for risk of an adverse event). 
In all of these cases, FDA recommends co-development of the drug and the 
pharmacogenomic tests, if they are not currently available, and submission of complete 
information on the test/drug combination to the Agency.  The FDA plans to issue further 
guidance on co-development of pharmacogenomic tests and drugs. 
 
The Office of In Vitro Diagnostics in CDRH, appropriate review divisions in CBER, and 
the Clinical and Clinical Pharmacology Review divisions in CBER or CDER are willing 
to meet jointly with sponsors to discuss both scientific and regulatory issues with regard 
to new pharmacogenomic tests.  The CDRH has both formal (IDE) and informal (pre-
IDE) processes to evaluate protocols for pharmacogenomic test development. 
  6  Contains Nonbinding Recommendations 
 
 
C.  Benefits of Voluntary Submissions to Sponsors and FDA 
 
At the current time, most pharmacogenomic data are of an exploratory or research nature, and 
FDA regulations do not require that these data be submitted to an IND, or that complete reports 
be submitted to an NDA or BLA.  However, voluntary submissions can benefit both the industry 
and FDA in a general way by providing a means for sponsors to ensure that regulatory scientists 
are familiar with and prepared to appropriately evaluate future genomic submissions.  The FDA 
and industry scientists alike would benefit from an enhanced understanding of relevant scientific 
issues, such as the following:  
 
  The types of genetic loci or gene expression profiles being explored by the 
pharmaceutical industry for pharmacogenomic testing 
  The test systems and techniques being employed 
  The problems encountered in applying pharmacogenomic tests to drug development 
  The ability to transmit, store, and process large amounts of complex pharmacogenomic 
data streams with retention of fidelity 
  The scientific rationale for standardizing naming and characterization of the genes used 
on different genomic analysis platforms and for developing bioinformatics software 
programs used to evaluate pharmacogenomic data 
  Facilitate identification of predictors of safety, effectiveness, or toxicity 
A greater understanding of the issues surrounding the use of pharmacogenomic data may prevent 
delays in reviews of future submissions where genomics are an integral part of specific studies in 
a drug development program. 
Therefore, FDA is requesting that sponsors conducting such programs consider providing 
pharmacogenomic data to the Agency voluntarily, when such data are not otherwise required 
under the regulations.  To facilitate VGDSs, FDA has established a cross-center Interdisciplinary 
Pharmacogenomic Review Group (IPRG) to review VGDSs, to work on policy development, 
and, upon request, to advise review divisions on interpretation and evaluation of 
pharmacogenomic data.   
 
For sponsors, voluntary submission of genomic data offers a number of specific potential 
benefits: 
   
  Meet informally with FDA and receive peer review assessments of scientific data from 
pharmacogenomic experts at the Agency 
  Obtain insight into the evolving regulatory decision making process as it relates to 
genetic and genomic information 
  Familiarize FDA scientists with novel pharmacogenomic experiments, data analysis, and 
interpretation approaches at an early stage 
  7  Contains Nonbinding Recommendations 
 
  Conserve time and resources by obtaining feedback from FDA on a VGDS that might 
highlight unaddressed issues that could prove time consuming or costly later during 
product development 
  Identify new opportunities for drug development (e.g., feedback from FDA might help 
reach new strategic decisions).  For example, a shelved product may be continued when 
new tools such as genotyping assays become available to demonstrate effectiveness in a 
subpopulation. 
  Make a contribution to the VGDS data repository to facilitate advancement of 
pharmacogenomics and development of rational, data-based policies and guidances 
 
IV.  SUBMISSION OF PHARMACOGENOMIC DATA 
 
The FDA's regulations establish different requirements for INDs, new (i.e., unapproved) NDAs 
and BLAs, and approved NDAs and BLAs.  For this reason, there are different submission 
algorithms for the submission of pharmacogenomic data. 
 
A.  Submission of Pharmacogenomic Data During the IND Phase 
 
Section 312.23 describes information submission requirements for an IND, including data 
generated or available during the IND phase.  Section 312.23(a)(8) contains the requirements for 
pharmacology and toxicology information:  Adequate information about pharmacologic and 
toxicological studies of the drug involving laboratory animals or in vitro, on the basis of which 
the sponsor has concluded that it is reasonably safe to conduct the proposed clinical 
investigations (emphasis added).  The in vitro and animal studies needed to establish a basis for 
proceeding with human trials of various types are well established internationally.  Therefore, 
pharmacogenomic data relevant to, or derived from, animal or in vitro studies must ordinarily be 
submitted according to  312.23(a)(8) when the sponsor wishes to use these data to make a 
scientific case, or when the pharmacogenomic test is a known valid biomarker.   
 
Section 312.23(a)(9) sets forth the requirements for submitting previous human experience with 
an investigational drug.  The application must include a summary of trials or human experience 
relevant to an evaluation of the safety or effectiveness of a drug.  Therefore, sponsors must 
submit human data of known relevance (e.g., known valid pharmacogenomic biomarkers).  In 
addition, sponsors or applicants must submit "any other information that would aid evaluation of 
the proposed clinical investigations with respect to their safety or their design and potential as 
controlled clinical trials to support the marketing of the drug" ( 312.23(a)(10)(iv)).  Sponsors 
may possess human data that suggest that a particular biomarker is a probable valid biomarker 
for evaluating the safety of the drug being evaluated.  In these cases, information on the 
biomarker must be submitted to the IND because it could potentially aid in evaluation of the 
safety of the investigations per the regulations.   
 
In addition, section 312.23(a)(11) states that a sponsor must submit "if requested by FDA, any 
other relevant information needed for review of the application."  Therefore, during the IND 
review, FDA may request pharmacogenomic information the Agency considers relevant (e.g., 
information related to the mechanism of action of the drug).  
  8  Contains Nonbinding Recommendations 
 
 
Sponsors holding INDs who generate or possess pharmacogenomic data related to an 
investigational drug can comply with FDA requirements using the following algorithm: 
 
Pharmacogenomic data must be submitted to the IND under  312.23 if ANY of the following 
apply: 
 
1.  The test results are used for making decisions pertaining to a specific clinical trial, or in 
an animal trial used to support safety (e.g., the results will affect dose and dose schedule 
selection, entry criteria into a clinical trial safety monitoring, or subject stratification).  
2.  A sponsor is using the test results to support scientific arguments pertaining to, for 
example, the pharmacologic mechanism of action, the selection of drug dosing and 
dosing schedule, or the safety and effectiveness of a drug. 
3.  Test results constitute a known valid biomarker for physiologic, pathophysiologic, 
pharmacologic, toxicologic, or clinical states or outcomes in humans, or the test is a 
known valid biomarker for a safety outcome in animal studies.  If the information on the 
biomarker (example, human CYP2D6 status) is not being used for purposes 1 or 2 above, 
the information can be submitted to the IND as an abbreviated report.  
 
Submission to an IND is NOT required, but voluntary submission is encouraged (i.e., 
information does not meet the criteria of  312.23) if 
 
4.  Information is from exploratory studies or is research data, such as from general gene 
expression analyses in cells/animals/humans, or single-nucleotide polymorphism (SNP) 
analysis of trial participants. 
5.  Information consists of results from test systems where the validity of the biomarker is 
not established. 
Although submission of such data in cases 4 and 5 is not required under the regulations, FDA 
would welcome voluntary submission of the data in a VGDS.  See Appendix A for additional 
guidance on assessing whether to submit pharmacogenomic data to an IND.  
 
Note:  Regardless of requirements for submission, the fact that samples will be collected for 
potential analysis must be noted in any clinical protocol ( 312.23(a)(6)) and informed consent 
documents ( 50.25). 
 
Data from a VGDS submission concerning a product under an IND will not be used for 
regulatory decision making.  However, after the sponsor submits a VGDS, if additional 
information becomes available that triggers the requirements for submission under  312, 314, 
or 601, the sponsor must submit the data to the relevant application and should follow the 
appropriate algorithm.  
 
  9  Contains Nonbinding Recommendations 
 
B.  Submission of Pharmacogenomic Data to a New NDA, BLA, or Supplement 
 
Section 314.50 outlines the NDA submission requirements; section 601.2 generally outlines 
BLA submission requirements.  As the introduction to  314.50 states, the [NDA] application is 
required to contain reports of all investigations of the drug product sponsored by the applicant, 
and all other information about the drug product pertinent to an evaluation of the application that 
is received or otherwise obtained by the applicant from any source.  Therefore, to comply with 
these regulations, sponsors must provide reports of certain pharmacogenomic investigations in 
their NDAs, and to permit a thorough analysis of a biologics application, a sponsor must submit 
such a report in its BLA.  However, the extent and format of such reports will depend on the 
relevance and application of the information.  
 
Subsequent paragraphs of  314.50 outline the submission requirements in specific disciplines. 
Nonclinical pharmacology and toxicology submission requirements are described in  314.50(d)(2); 
human pharmacokinetics and bioavailability requirements in  314.50(d)(3); and clinical data 
requirements in  314.50(d)(5). 
 
Section 601.2 generally outlines the BLA submission requirements. Section 601.2 states that the 
BLA manufacturer shall submit data derived from nonclinical laboratory and clinical studies that 
demonstrate that the manufactured product meets prescribed requirements of safety.  Like NDA 
sponsors, BLA sponsors must provide reports of certain pharmacogenomic investigations in their 
BLAs.  However, the extent and format of such reports will depend on the relevance and 
application of the information.  
 
Sponsors who have generated or possess pharmacogenomic data related to a drug can comply 
with the regulations' requirements using the algorithm below describing what kind of report to 
submit: 
 
1.  Provide full (complete) reports on pharmacogenomic investigations intended by the 
sponsor to be used in the drug label or as part of the scientific database being used to 
support approval as complete submissions (not in the form of an abbreviated report, 
synopsis, or VGDS), including information about test procedures and complete data, in 
the relevant sections of the NDA or BLA.  If the pharmacogenomic test is already 
approved by FDA or is the subject of an application submitted to the Agency, 
information on the test itself can be provided by cross reference.   
The following examples would fit this category.   
  Pharmacogenomic test results from clinical trials used to support scientific 
arguments made by the sponsor about selecting drug doses, assessing safety, 
selecting patients for treatment, or monitoring the beneficial responses   
  Pharmacogenomic test results that the sponsor proposes to describe in the drug 
labeling 
  Pharmacogenomic tests that are essential to achieving the dosing, safety, or 
effectiveness described in the drug labeling 
   
  10  Contains Nonbinding Recommendations 
 
2.  Submit reports of pharmacogenomic test results that constitute known valid biomarkers 
for physiologic, pathophysiologic, pharmacologic, toxicologic, or clinical states or 
outcomes in the relevant species, but that the sponsor is not relying on or mentioning in 
the label, to the Agency as an abbreviated report (not in the form of a synopsis or VGDS).  
(If a pharmacogenomic test of this type was conducted as part of a larger overall study, 
the reporting of the pharmacogenomic test results can be incorporated into the larger 
study report.) 
3.  Submit reports of pharmacogenomic tests that represent probable valid biomarkers for 
physiologic, pathophysiologic, pharmacologic, toxicologic, or clinical states or outcomes 
in the relevant species to the NDA or BLA as an abbreviated report.  (If the 
pharmacogenomic testing of this type was conducted as part of a larger study, the 
abbreviated report can be appended to the report of the overall study.) 
4. There is no need to submit detailed reports of general exploratory or research information, 
such as broad gene expression screening, collection of sera or tissue samples, or results of 
pharmacogenomic tests that are not known, or probable valid biomarkers to the NDA or 
BLA.  Because the Agency does not view such studies as germane in determining the 
safety or effectiveness of a product, the submission requirements in  314.50 or 601.2 
will be satisfied by the submission of a synopsis of the study.  However, the Agency 
encourages the voluntary submission of the data from such a study in a VGDS.    
See Appendix B for additional guidance on how to assess whether to submit pharmacogenomic 
data to an unapproved NDA or BLA.  
 
C.  Submission to a Previously Approved NDA or BLA  
 
The requirements for submitting new scientific information to a previously approved NDA or 
BLA are outlined in  314.81(b)(2) and 601.12.  Results of nonclinical or clinical 
pharmacogenomic investigations on known or probable valid biomarkers must be submitted in 
the annual report as synopses or abbreviated reports ( 314.81(b)(2)). 
 
Pharmacogenomic study results of other types do not meet the submission requirements outlined 
in the regulations ( 314.81(b)(2)).  However, such reports can be voluntarily submitted to the 
NDA or BLA as a VGDS. 
 
Pharmacogenomic data collected in pharmacoepidemiologic and observational studies can be 
submitted as a VGDS by the applicant in accordance with the recommendations in this guidance 
(see Section VI).  
 
D.  Compliance with 21 CFR Part 58 
 
Questions have been raised about the need for pharmacogenomic studies to comply with the 
requirements of 21 CFR part 58, which describes good laboratory practices (GLPs) for 
nonclinical laboratory studies that support INDs and NDAs.  Section 58.3(d) (21 CFR 58.3(d)) 
defines nonclinical laboratory studies as in vivo or in vitro experiments in which test articles 
are studied prospectively in test systems under laboratory conditions to determine their safety.  
The term does not include studies using human subjects or clinical studies or field trials in 
  11  Contains Nonbinding Recommendations 
 
animals.  The term does not include basic exploratory studies carried out to determine whether a 
test article has any potential utility.... 
 
The requirements of part 58 apply to nonclinical studies submitted to support safety findings, 
including nonclinical pharmacogenomic studies intended to support regulatory decision making.  
If full compliance with 21 CFR Part 58 cannot be met, a sponsor must clearly indicate in the 
study report the areas in which such data do not comply with Part 58 ( 312.23(a)(8)(iii) and 
314.50(d)(2)(v)).  Any studies eligible to be submitted in an abbreviated report, synopsis, or 
VGDS under the algorithms discussed above do not fall under part 58.   
 
The FDA recognizes that it may not be feasible to conduct separate, long-term, non-GLP 
preclinical studies.  For this reason, FDA encourages sampling of tissues from GLP studies for 
investigational purposes.  Removal of tissue samples and the reason for removal (e.g., 
exploratory, mechanistic study, tissue banking) should be specified in the protocol.  Removal of 
specimens for investigational purposes from a study does not invalidate the GLP status of the 
main toxicology study, if otherwise acceptable.  If the tissue samples are subsequently analyzed, 
the results should be reported to the NDA as a synopsis.  The FDA would also be interested in 
receiving these data in a VGDS.  If findings from these studies are considered by the sponsor to 
be relevant to the safety of the compound under study (e.g., related to a known valid biomarker), 
the findings must be reported to the application, as is necessary for any other relevant nonclinical 
study findings 312.23(a)(8), 312.32(c)(1)(i)(B), 314.50(d)(2)). 
 
E.  Submission of Voluntary Genomic Data from Application-Independent 
Research  
 
The FDA will also accept pharmacogenomic data from investigators who may not have an active 
IND, NDA, or BLA , but who wish to provide the information voluntarily to FDA, according to 
the process described in Section VI of this guidance. 
 
We recommend that all VGDSs be prominently marked as VGDS, or VOLUNTARY 
SUBMISSIONS, on the cover letter that accompanies the submission (see Appendix E). 
 
 
V.  FORMAT AND CONTENT OF A VGDS 
 
The FDA invites submission of exploratory pharmacogenomic data on drugs or candidate drugs 
whether or not the molecules are currently the subject of an active IND, NDA, or BLA.  
Exploratory genomic data may result from, for example, microarray expression profiling 
experiments, genotyping or single-nucleotide polymorphism (SNP) profiling experiments, or 
from other studies using evolving methodologies that are intended to facilitate global analysis of 
gene functions, but not specific claims pertaining to drug dosing, safety assessments, or 
effectiveness evaluations.  Currently, consensus standards do not exist for presenting and 
exchanging genomic data, although such standards are evolving.  Therefore, this guidance does 
not recommend a specific data format for the VGDS.   
 
  12  Contains Nonbinding Recommendations 
 
We recommend that, to achieve the goals of the VGDS process as delineated in Section III(C), 
the content of a VGDS, and the level of detail, be sufficient for the Agency to interpret the 
information and independently analyze the data, verify results, and explore possible genotype-
phenotype correlations across studies.  We do not, however, want the submission of a VGDS to 
be overly burdensome and time-consuming for sponsors.  Therefore, VGDS could be submitted 
in a number of forms: 
 
  As an article submitted to a peer-reviewed scientific journal with raw or processed data 
submitted electronically  
  As an evolving public standard for specific types of experiments, such as the Minimum 
Information About a Microarray Experiment (MIAME) standard for microarray expression 
data.7  Using an approach similar in content to MIAME one can format a VGDS containing 
genotyping or other genomic data derived from technology platforms other than nucleic acid 
hybridization arrays. 
  As a full report on a gene expression microarray experiment, the content could contain the 
following analytical, preclinical and/or clinical information, for example:  
 Title page 
 Table of contents 
 Background and scientific rationale 
 Primary and secondary study goals 
 Synopses and summary of findings 
 Study design and sample collection 
 Array design and description 
- Sample processing and preparation 
- Demonstration of quality of RNA or DNA 
- Hybridization procedures and parameters 
- Measures of performance of hybridization such as spike-in control 
- Measurements and quantification 
- Normalization controls 
- Number of repeats (array hybridized), number of biological assays performed 
 Data Analysis 
- Statistical analysis 
- Bioinformatics tools and software used.  Source of gene annotation 
 Results and conclusions, including, for example, data visualization (e.g., scatter plots, 
principle component analysis (PCA), hierarchical clustering (heat maps)), correlation 
between expression profiles and outcomes, and appropriate information about 
relevant co-factors  
 References 
 
  Additional Study Information related to mircroarray studies might include the following:  
 Confirmation of SNP analysis by sequencing or other assays 
                                                 
7 Brazma, A., et al., Nature Genetics, 29, 365-371, 2001 and http://www.mged.org/workgroups/miame.html. 
  13  Contains Nonbinding Recommendations 
 
- Confirmation of gene expression by other conventional assays (e.g., Northern blot, 
RT-PCR (real time polymerase chain reaction)).  As much as possible, all genes of 
importance should be confirmed with secondary assays.  However, if the genomic 
profile is of importance, it may be appropriate to sample a selected subpopulation of 
affected genes   
- Alternative approaches that examine endpoints other than gene expression changes 
may also be appropriate under certain circumstances (e.g., immunohistochemistry 
or Western blot, if reagents available). 
 
 
VI.  PROCESS FOR SUBMITTING PHARMACOGENOMIC DATA 
 
Using the decision trees (see Appendices A-C), sponsors should submit genomic data according 
to the following recommendations. 
 
  For required submissions, complete reports, abbreviated reports, or synopses of 
pharmacogenomic studies should be submitted to INDs, NDAs, or BLAs in the usual 
manner. 
  For candidate drugs or stand alone voluntary submissions (submissions not related to any 
application), sponsors should submit the package clearly labeled as VOLUNTARY 
GENOMIC DATA SUBMISSION (VGDS).  A voluntary submission cover sheet that 
can be used is included in Appendix E. For VGDSs related to an existing IND, NDA, or 
BLA, please include the reference number on the voluntary submission cover sheet.   
 
 
VII.  AGENCY REVIEW OF VOLUNTARY GENOMIC DATA SUBMISSIONS 
 
The FDA has received many questions about the use of pharmacogenomic data in the application 
review process.  Questions reflect the concern that the Agency will raise new questions and 
require additional data based on findings from exploratory pharmacogenomic studies, that new 
studies will be required or suggested based on preliminary human pharmacogenomic data, that 
indicated populations will be narrowed or restricted based on the pharmacogenomic results in 
subpopulations, or that new studies in subpopulations will be required after retrospective analysis 
suggests differential responses based on pharmacogenomic subgrouping.  There is also concern 
about the availability of staff who are experts in interpretation of such data.  
 
The FDA will not use genomic information submitted through the voluntary process for 
regulatory decision making on INDs, BLAs, or NDAs.    
 
VGDSs will be reviewed by the Interdisciplinary Pharmacogenomic Review Group (IPRG).  The 
review process is intended to ensure that scientific staff experienced in the evaluation of 
genomics studies participate first-hand in analysis and review of the data.  Any data evaluation 
will be conducted for scientific and informational purposes  not for regulatory decision 
making.  If additional information becomes available after a sponsor submits a VGDS that 
triggers the submission requirements under  312, 314, or 601, the sponsor must resubmit the 
  14  Contains Nonbinding Recommendations 
 
data to the investigational or marketing application and should follow the appropriate algorithm 
described in this guidance for a required submission.  Also, a review division may consult the 
IPRG when pharmacogenomic data are submitted as part of an IND, NDA, or BLA.  
 
The animal and in vitro toxicology database needed to support human trials at various stages of 
the IND process and to support marketing of short- or long-term use drugs is well established.  
Any proposals for the substitution or addition of new animal genomic safety tests will ordinarily 
be the product of a public process involving the international scientific and drug development 
communities.  If FDA becomes aware that a particular pharmacogenomic test has taken on great 
significance based upon cumulative experience (e.g., from evaluating results across submissions, 
and/or obtaining input from Advisory Committees), the Agency will notify sponsors about its 
findings.  
 
Currently, as discussed above, only a few pharmacogenetic tests for certain drug metabolizing 
enzymes are considered known valid biomarkers in humans.  Considerable concern has been 
expressed about how FDA will evaluate newer types of pharmacogenomic data (e.g., results that 
may predict increased risk of adverse events, or point to an enhanced probability of effectiveness 
response). The FDA has considerable experience dealing with these issues in other contexts.  
Examples of how pharmacogenomic studies fit into this experience include the following.  
 
  Descriptions of drug metabolizing phenotypes and discussion of their effects on dosing 
are common in drug labels.  Extrapolation of this information to pharmacogenetic testing 
is straightforward. 
  There are many conditions or co-factors that may increase an individuals susceptibility 
to an adverse event (e.g., co-morbid conditions, metabolic susceptibilities such as hepatic 
failure, or concomitant drug therapies) or the probability of a beneficial response.  
The FDAs usual approach in such cases has been to request that information be added to the 
drug labeling that describes the possible interaction and relevant co-factors and advises on 
precautions.  If a sponsor discovers a new pharmacogenomic test that could possibly distinguish 
patients at greater risk for a serious adverse event, it is likely that both the sponsor and the 
Agency would have great interest in exploring the correlation in the appropriate populations.  
However, if the sponsor also moved forward on developing the drug in the overall indicated 
population, FDA would evaluate the safety database on its merits.  If the sponsor decided to 
develop the drug solely in populations from which certain patients were excluded based on 
pharmacogenomic testing, FDA would recommend co-development of the pharmacogenomic 
test (as a diagnostic) and the drug because FDA would be unable to approve a drug for which the 
risk or benefit was predicated on a pharmacogenomic test that was unavailable.   
 
It is most likely that, in the near future, pharmacogenomic biomarkers that predict drug toxicity 
will be identified and developed on a path parallel with overall drug development.  In other 
words, a drug would be developed in a conventional manner with a parallel effort to identify 
appropriate predictors of toxicity.  If the drugs risk-benefit profile were acceptable in the entire 
target population, the drug could be approved prior to the completion of efforts to refine and 
develop the relevant pharmacogenomic tests.  When and if a test's predictive values were to be 
  15  Contains Nonbinding Recommendations 
 
established and the test were to become commercially available (either as an approved device or 
as a service), the drug label could be changed to reflect the data.  
 
  The FDA has similar experience with tests used to target populations likely to respond to 
therapy.  
 
Several decades ago, broad indications for use were described in labels.  Over time, as more 
exact diagnoses were developed, narrower indications were sought by sponsors, based on the 
clinical trials conducted.  A similar evolution occurred in the field of anti-HIV therapies as drug 
resistance testing became available.  We encourage sponsors to continue to develop 
pharmacogenomic tests that are predictive of subpopulations with enhanced response to therapy.  
However, if overall drug development is pursued in the larger population, the effectiveness and 
risk-benefit will be evaluated in that population, and approval decisions will be based on the 
overall database. 
 
Much of the concern about FDA actions in this area is based on the perception that 
pharmacogenomic testing is likely to give definitive answers about the probability of safety and 
effectiveness in subpopulations.  Such specificity may occur occasionally (e.g., where a product 
is designed to inhibit a specific molecular target), and in such cases, rapid development of a 
diagnostic test is highly encouraged.  However, this is unlikely to be the ordinary case.  In most 
instances, a genotype or particular gene expression profile is likely to be one of a number of 
factors that affects the probability of an adverse event or a favorable response.  For this reason, 
pharmacogenomic biomarkers can ordinarily be handled like other non-genomic predictive 
markers in the clinical arena. 
 
 
VIII.  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 50 hours to 
prepare and submit voluntary pharmacogenomic data, including the time to review instructions, 
search existing data resources, gather the data needed, and complete and review the information 
collection.  Send comments regarding this burden estimate or suggestions for reducing this 
burden estimate to:  Office of Regulatory Policy, Center for Drug Evaluation and Research, Food 
and Drug Administration, 10903 New Hampshire Ave., Silver Spring, M 20993-0002. 
 
This guidance also refers to previously approved collection of information found in FDA 
regulations.  The collections of information for pharmacogenomic data required to be submitted 
to an IND, NDA, BLA, or annual report are approved under OMB Control numbers 0910-0014, 
(INDs), 0910-0001 (NDAs and annual reports), and 0910-0338 (BLAs).  
  16  Contains Nonbinding Recommendations 
 
 
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 0910-0557 (expires 9/30/20 (Note:  Expiration date updated 
03/11/2019)). 
 
 
 
  17  Contains Nonbinding Recommendations 
 
 
GLOSSARY 
 
The following definitions are for use in the processes outlined in this guidance and are not 
intended to be broadly applicable to the entire field. 
 
Biological marker (biomarker):  A characteristic that is objectively measured and evaluated as 
an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a 
therapeutic intervention.8 
 
Pharmacogenetic test:  An assay intended to study interindividual variations in DNA sequence 
related to drug absorption and disposition (pharmacokinetics) or drug action 
(pharmacodynamics), including polymorphic variation in the genes that encode the functions of 
transporters, metabolizing enzymes, receptors, and other proteins 
 
Pharmacogenomic test:  An assay intended to study interindividual variations in whole-genome 
or candidate gene, single-nucleotide polymorphism (SNP) maps, haplotype markers, or  
alterations in gene expression or inactivation that may be correlated with pharmacological 
function and therapeutic response.  In some cases, the pattern or profile of change is the relevant 
biomarker, rather than changes in individual markers. 
 
Valid biomarker:  A biomarker that is measured in an analytical test system with well-
established performance characteristics and for which there is an established scientific 
framework or body of evidence that elucidates the physiologic, toxicologic, pharmacologic, or 
clinical significance of the test results.  The classification of biomarkers is context specific.  
Likewise, validation of a biomarker is context-specific and the criteria for validation will vary 
with the intended use of the biomarker.  The clinical utility (e.g., predict toxicity, effectiveness or 
dosing) and use of epidemiology/population data (e.g., strength of genotype-phenotype 
associations) are examples of approaches that can be used to determine the specific context and 
the necessary criteria for validation. 
 
  Known valid biomarker:  A biomarker that is measured in an analytical test system 
with well-established performance characteristics and for which there is widespread 
agreement in the medical or scientific community about the physiologic, toxicologic, 
pharmacologic, or clinical significance of the results 
 
  Probable valid biomarker:  A biomarker that is measured in an analytical test 
system with well-established performance characteristics and for which there is a 
scientific framework or body of evidence that appears to elucidate the physiologic, 
toxicologic, pharmacologic, or clinical significance of the test results.  A probable 
valid biomarker may not have reached the status of a known valid marker because, 
for example, of any one of the following reasons: 
  The data elucidating its significance may have been generated within a single 
company and may not be available for public scientific scrutiny. 
                                                 
8 Biomarkers Definitions Working Group, "Biomarkers and Surrogate Endpoints:  Preferred Definitions and 
Conceptual Framework," Clinical Pharm. & Therapeutics, vol. 69, N. 3, March 2001.  
  18  Contains Nonbinding Recommendations 
 
 The data elucidating its significance, although highly suggestive, may not be 
conclusive. 
 Independent verification of the results may not have occurred.  
 
Voluntary genomic data submission (VGDS):  The designation for pharmacogenomic data 
submitted voluntarily to FDA.
  19  Contains Nonbinding Recommendations 
 
 
APPENDIX A:  SUBMISSION OF PHARMACOGENOMIC (PG) DATA TO AN IND  
 
Reports of pharmacogenomic investigations should be submitted to the IND in accordance with the decision tree below and in the formats indicated here or in the 
body of the guidance: 
 
 
  Animal or human PG Study Results 
 
 
 
 
  Y 
 
 
  Meets   Full report to IND 
  1 or 2, below? 
 
 
 
 
  N 
 
 
    Y  Abbreviated report to IND 
  Meets  
  3, below? 
 
 
 
 
N 
 
 
No required submission needed; VGDS encouraged 
 
 
 
 
Pharmacogenomic data must be submitted to the IND under  312.23 if ANY of the following apply: 
 
  20  Contains Nonbinding Recommendations 
 
1.  The test results are used for making decisions pertaining to a specific clinical trial, or in an animal trial used to support safety (e.g., the results will 
affect dose selection, entry criteria into a clinical trial safety monitoring, or subject stratification).  
2.  A sponsor is using the test results to support scientific arguments pertaining to, for example, the pharmacologic mechanism of action, the selection 
of drug dosing or the safety and effectiveness of a drug. 
3.  The test results constitute a known, valid biomarker for physiologic, pathophysiologic, pharmacologic, toxicologic, or clinical states or outcomes in 
humans, or is a known valid biomarker for a safety outcome in animal studies or a probable valid biomarker in human safety studies.  If the 
information on the biomarker (example, human CYP2D6 status) is not being used for purposes 1 or 2 above, the information can be submitted to 
the IND as an abbreviated report.  
 
Submission to an IND is NOT required, but voluntary submission is encouraged (i.e., information does not meet the criteria of  312.23) if 
 
4.  Information is from exploratory studies or is research data, such as from general gene expression analyses in cells/animals/humans, or single-
nucleotide polymorphism (SNP) analysis of trial participants.  
5.  Information consists of results from test systems where the validity of the biomarker is not established.
  21  Contains Nonbinding Recommendations 
 
 
APPENDIX B:  SUBMISSION OF PHARMACOGENOMIC (PG) DATA TO A NEW NDA, BLA, OR SUPPLEMENT 
 
Reports of pharmacogenomic investigations should be submitted to the NDA in accordance with the decision tree below and in the formats indicated here or in 
the body of the guidance: 
 
 
 
 
Animal or human PG study results 
 
 
 
 
 
Y 
 
  Meets  
  1, below?  Full report in NDA/BLA 
 
 
 
 
 
N 
 
 
  Y 
  Meets 2, or 
  3, below?  Abbreviated report to NDA/BLA 
 
 
 
 
  N 
 
  Synopsis to NDA/BLA; VGDS encouraged 
 
 
 
 
1.  The sponsor will use the test results in the drug labeling or as part of the scientific database being used to support approval as complete submissions (not 
in the form of an abbreviated report, synopsis, or VGDS), including information about test procedures and complete data, in the relevant sections of the 
  22  Contains Nonbinding Recommendations 
 
NDA or BLA.  If the pharmacogenomic test is already approved by FDA or is the subject of an application filed with the Agency, information on the 
test itself can be provided by cross reference.   
The following examples would fit this category.   
 Pharmacogenomic test results that are being used to support scientific arguments made by the sponsor about drug dosing, safety, patient selection, 
or effectiveness  
 Pharmacogenomic test results that the sponsor proposes to describe in the drug label 
 Pharmacogenomic tests that are essential to achieving the dosing, safety, or effectiveness described in the drug label 
2.  The test results are known valid biomarkers for physiologic, pathophysiologic, pharmacologic, toxicologic, or clinical states or outcomes in the relevant 
species, but the sponsor is not relying on or mentioning this in the label.  Submit to the Agency as an abbreviated report (not as a synopsis or VGDS).  If 
a pharmacogenomic test of this type was conducted as part of a larger overall study, the reporting of the pharmacogenomic test results can be 
incorporated into the larger study report. 
3.  The test results represent probable valid biomarkers for physiologic, pathophysiologic, pharmacologic, toxicologic, or clinical states or outcomes in the 
relevant species.  Submit to the Agency as an abbreviated report.  If the pharmacogenomic testing of this type was conducted as part of a larger study, 
the abbreviated report can be appended to the report of the overall study. 
4.  Information from general exploratory or research studies, such as broad gene expression screening, collection of sera or tissue samples, or results of 
pharmacogenomic tests that are not known or probable valid biomarkers to the NDA or BLA are not required to be submitted.  Because the Agency 
does not view these studies as germane in determining the safety or effectiveness of a drug, the submission requirements in  314.50 or 601.2 will be 
satisfied by the submission of a synopsis of the study.  However, the Agency encourages the voluntary submission of the data from the study in a VGDS 
submitted to the NDA or BLA.
  23  Contains Nonbinding Recommendations 
 
APPENDIX C:  SUBMISSION OF PHARMACOGENOMIC (PG) DATA TO AN 
APPROVED NDA, BLA, OR SUPPLEMENT 
 
 
 
 
Animal or human PG study results 
 
 
 
 
 
Y 
 
Known or 
 
  probable valid  Abbreviated report or synopsis 
  biomarkers? 
 
 
 
 
N 
 
 
  No required submission needed; VGDS encouraged 
 
 
  24  Contains Nonbinding Recommendations 
 
APPENDIX D:  QUICK REFERENCE ON PHARMACOGENOMIC SUBMISSIONS 
 
 
 
Submitting    New (Unapproved)   
data to an:  IND  NDA, BLA, or  Previously Approved NDA 
  Supplement  or BLA 
       
Known  Must be submitted,  Must be submitted,  Must be submitted pursuant 
Valid  pursuant to   pursuant to   to 21 CFR 314.81 in annual 
Biomarker  21 CFR  312.23 (a)  21 CFR 314.50 and  report and should be 
(8), (9), (10) (iv) or  601.2.  See section IV.B.  submitted pursuant to  
(11).  of the guidance.   601.12 as synopses or 
abbreviated reports. 
 
       
Does not need to be  The FDA recommends  Must be submitted pursuant 
 
submitted.9   submission, using  to 21 CFR 314.81 in annual 
Probable 
  algorithm in section  report and should be 
Valid 
The FDA welcomes  IV.B. of the guidance.  submitted pursuant to  
Biomarker 
voluntary submission     601.12 as synopses or 
of such data in a    abbreviated reports.  
VGDS. 
 
       
Exploratory or  The FDA welcomes  The FDA recommends  The FDA welcomes 
Research  voluntary submission  submission, using  voluntary submission of 
Pharmaco- of such data in a  algorithm in section  such data in a VGDS. 
genomic Data  VGDS.  IV.B. of the guidance. 
 
The FDA welcomes 
voluntary submission of 
such data in a VGDS. 
 
 
 
                                                 
9 Except if used in human safety studies. 
  25  Contains Nonbinding Recommendations 
 
APPENDIX E: VOLUNTARY SUBMISSION COVER SHEET 
 
Send all CDER voluntary genomic data submissions to the following address accompanied by this 
coversheet: 
FDA/CDER 
Central Document Room (CDR) 
5901-B Ammendale Road 
Beltswille, MD 20705-1266 
Attention! 
 
This is a  
 
Voluntary 
Genomic Data Submission 
 
 
Application number ________ (leave blank if this is the first submission for a stand-alone VGDS) 
 
 
_______Initial Submission 
 
_______Subsequent Submission 
 
 
 
 
 
 
Please route directly to the IPRG (HFD-850) 
After processing in the CDR! 
 
  26