Guidance for Industry 

E15 Definitions for 

Genomic Biomarkers, 

Pharmacogenomics, 

Pharmacogenetics, Genomic 

Data and Sample Coding 

Categories 

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) 

April 2008 

ICH 
Guidance for Industry 

E15 Definitions for 

Genomic Biomarkers, 

Pharmacogenomics, 

Pharmacogenetics, Genomic 

Data and Sample Coding 

Categories 

Additional copies are available from: 

Office of Training and Communication 

Division of Drug Information 

Center for Drug Evaluation and Research 

Food and Drug Administration 

10903 New Hampshire Ave.,Bldg. 51, Room 2201 

Silver Spring, MD 20993-0002 

(Tel) 301-796-3400 

 http://www.fda.gov/cder/guidance/index.htm 

Office of Communication, Training and 

Manufacturers Assistance, HFM-40 

Center for Biologics Evaluation and Research 

 Food and Drug Administration 

1401 Rockville Pike, Rockville, MD 20852-1448 

(Tel) 1-800-835-4709 or 301-827-1800 

 http://www.fda.gov/cber/guidelines.htm. 

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) 

April 2008 

ICH 
TABLE OF CONTENTS 

I. INTRODUCTION (1, 1.1, 1.3)......................................................................................... 1

II. BACKGROUND (1.2)....................................................................................................... 2

III. GUIDANCE (2) ................................................................................................................. 2

A. Genomic Biomarker (2.1)..............................................................................................................2

1. Definition (2.1.1)..............................................................................................................................2

2. Additional Information (2.1.2).........................................................................................................2

B. Pharmacogenomics and Pharmacogenetics (2.2) ........................................................................3

1. Definitions (2.2.1) ............................................................................................................................3

2. Additional Information (2.2.2).........................................................................................................4

C. Categories for Genomic Data and Samples Coding (2.3) ...........................................................4

1. Identified Data and Samples (2.3.1) ................................................................................................4

2. Coded Data and Samples (2.3.2) .....................................................................................................4

3. Anonymized Data and Samples (2.3.3) ............................................................................................5

4. Anonymous Data and Samples (2.3.4).............................................................................................6

5. Additional Information (2.3.5).........................................................................................................6

Table 1: Summary of Genomic Data and Sample Coding Categories..............................................7

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Guidance for Industry1

E15 Definitions for Genomic Biomarkers, Pharmacogenomics, 

Pharmacogenetics, Genomic Data and Sample Coding Categories 

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 (1, 1.1, 1.3)2

This guidance contains definitions of key terms in the discipline of pharmacogenomics and 

pharmacogenetics, namely genomic biomarkers, pharmacogenomics, pharmacogenetics, and 

genomic data and sample coding categories. In the effort to develop harmonized approaches to 

drug regulation, it is important to ensure that consistent definitions of terminology are being 

applied across all constituents of the International Conference on Harmonisation (ICH). This 

guidance on definitions is intended to facilitate the integration of the discipline of 

pharmacogenomics and pharmacogenetics into global drug development and approval processes. 

As new scientific knowledge in the discipline of pharmacogenomics and pharmacogenetics 

emerges, the current guidance will be reviewed and expanded if appropriate. 

The validation and qualification processes for genomic biomarkers, evidence for their intended 

use, and acceptance criteria across ICH regions are outside of the scope of this guidance. 

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 

 

1 This guidance was developed within the Expert Working Group (Efficacy) of the International Conference on 

Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and has been 

subject to consultation by the regulatory parties, in accordance with the ICH process. This document has been 

endorsed by the ICH Steering Committee at Step 4 of the ICH process, November 2007. At Step 4 of the process, 

the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan, and the United 

States. 

2

 Arabic numbers reflect the organizational breakdown of the document endorsed by the ICH Steering Committee at 

Step 4 of the ICH process, November 2007. 

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Contains Nonbinding Recommendations

cited. The use of the word should in Agency guidances means that something is suggested or 

recommended, but not required.

II. BACKGROUND (1.2) 

Pharmacogenomics and pharmacogenetics have the potential to improve the discovery, 

development, and use of medicines. Each of the ICH regions has published specific 

pharmacogenomic and pharmacogenetic guidelines, or concept papers, and is in the process of 

developing others. However, the lack of consistently applied definitions for commonly used 

terminology raises the potential for either conflicting use of terms in regulatory documentation 

and guidelines or inconsistent interpretation by regulatory authorities, ethics committees, and 

sponsor companies. 

III. GUIDANCE (2) 

Definitions of a genomic biomarker, pharmacogenomics, pharmacogenetics, and genomic data 

and sample coding categories are detailed below. The definition of what constitutes a genomic 

biomarker is key to understanding the definitions of pharmacogenomics and pharmacogenetics 

and is therefore introduced in this guidance first. Additional information useful to an 

understanding of aspects covered by each of the definitions is also provided. Some of the 

principles described in this guidance might be applicable to proteomics, metabolomics, and other 

related disciplines. 

A. Genomic Biomarker (2.1) 

1. Definition (2.1.1) 

A genomic biomarker is defined as follows: 

A measurable DNA and/or RNA characteristic that is an indicator of normal 

biologic processes, pathogenic processes, and/or response to therapeutic or other 

interventions. 

2. Additional Information (2.1.2) 

a. A genomic biomarker could, for example, be a measurement of: 

• The expression of a gene 

• The function of a gene 

• The regulation of a gene 

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Contains Nonbinding Recommendations

b. A genomic biomarker can consist of one or more deoxyribonucleic acid (DNA) 

and/or ribonucleic acid (RNA) characteristics. 

c. DNA characteristics include, but are not limited to: 

• Single nucleotide polymorphisms (SNPs) 

• Variability of short sequence repeats 

• Haplotypes 

• DNA modifications, e.g., methylation 

• Deletions or insertions of (a) single nucleotide(s) 

• Copy number variations 

• Cytogenetic rearrangements, e.g., translocations, duplications, deletions, or 

inversions 

d. RNA characteristics include, but are not limited to: 

• RNA sequences 

• RNA expression levels 

• RNA processing, e.g., splicing and editing 

• microRNA levels 

e. The definition of a genomic biomarker is not limited to human samples, but 

includes samples from viruses and infectious agents as well as animal samples, 

i.e., for the application of genomic biomarkers to nonclinical and/or toxicological 

studies. 

f. The definition of a genomic biomarker does not include the measurement and 

characterization of proteins or low molecular weight metabolites. 

B. Pharmacogenomics and Pharmacogenetics (2.2) 

1. Definitions (2.2.1) 

a. Pharmacogenomics (2.2.1.1) 

Pharmacogenomics (PGx) is defined as: 

The study of variations of DNA and RNA characteristics as related to drug 

response. 

b. Pharmacogenetics (2.2.1.2) 

Pharmacogenetics (PGt) is a subset of pharmacogenomics (PGx) and is defined 

as: 

The study of variations in DNA sequence as related to drug response. 

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2. Additional Information (2.2.2) 

a. The term drug should be considered synonymous with investigational (medicinal) 

product, medicinal product, medicine, and pharmaceutical product (including 

vaccines and other biological products). 

b. PGx and PGt are applicable to activities such as drug discovery, drug 

development, and clinical practice. 

c. Drug response includes the processes of drug absorption and disposition (e.g., 

pharmacokinetics (PK)), and drug effects (e.g., pharmacodynamics (PD), drug 

efficacy, and adverse effects of drugs). 

d. The definitions of PGx and PGt do not include other disciplines such as 

proteomics and metabolomics. 

C. Categories for Genomic Data and Samples Coding (2.3) 

PGx and PGt research depends on the use of biological samples to generate data. A harmonized 

definition for the coding of these samples and their associated data will facilitate use in research 

and development of new medicines. 

There are four general categories of coding: identified, coded, anonymized, and anonymous. 

Coded data or samples can be single or double coded. 

The implications of using a specific data and sample coding category should be considered in the 

design of PGx and PGt research studies. 

Some implications are highlighted in this section and summarized in Table 1. 

1. Identified Data and Samples (2.3.1) 

Identified data and samples are labeled with personal identifiers such as name or identification 

numbers (e.g., social security or national insurance number). As the samples and associated data 

are directly traceable back to the subject, it is possible to undertake actions such as sample 

withdrawal or the return of individual results in accordance with the subject’s request. The use 

of identified data and samples allows for clinical monitoring, subject follow-up, and the addition 

of new data from the subject. Identified data and samples offer privacy protection comparable to 

that of general health care confidentiality in everyday medical practice. Identified data and 

samples are generally not considered appropriate for purposes of clinical trials in drug 

development. 

2. Coded Data and Samples (2.3.2) 

Coded data and samples are labeled with at least one specific code and do not carry any personal 

identifiers. 

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a. Single-Coded Data and Samples (2.3.2.1) 

Single-coded data and samples are usually labeled with a single specific code and do not 

carry any personal identifiers. It is possible to trace the data or samples back to a given 

individual with the use of a single coding key. In general, the clinical investigator is 

responsible for maintaining the coding key. As the samples and associated data are indirectly 

traceable back to the subject via the coding key, it is possible to undertake actions such as 

sample withdrawal or the return of individual results in accordance with the subject’s request. 

The use of single-coded data and samples allows for clinical monitoring, subject follow-up, 

or the addition of new data from the subject. Single coding is the current standard used in 

clinical research and offers additional safeguards to the subject’s identifiers compared to the 

general health care confidentiality and privacy protection in everyday medical practice. 

b. Double-Coded Data and Samples (2.3.2.2) 

Double-coded data and samples are initially labeled with a single specific code and do not 

carry any personal identifiers. The data and samples are then relabeled with a second code, 

which is linked to the first code via a second coding key. It is possible to trace the data or 

samples back to the individual by the use of both coding keys. In general, the clinical 

investigator is responsible for maintaining the first coding key and does not have access to 

the second coding key. As the samples and associated data can very indirectly be traced back 

to the subject via the use of both coding keys, it may be possible to undertake actions such as 

sample withdrawal, or the return of individual results in accordance with the subject’s 

request. However, additional electronic or technical processes may be added to further limit 

the ability to trace back from a genotype result to an individual subject (for example, a 

specific computer process that allows new subject data to be added but prevents the 

reconnection of the genotype data back to the individual subject identifier). The use of 

double-coded data and samples allows for clinical monitoring, subject follow-up, or the 

addition of new data from the subject. The use of the second code provides additional 

confidentiality and privacy protection for subjects over the use of a single code. Access to 

both coding keys is needed to link any data or samples back to a subject identifier. 

3. Anonymized Data and Samples (2.3.3) 

Anonymized data and samples are initially single or double coded but where the link between the 

subjects’ identifiers and the unique code(s) is subsequently deleted. Once the link has been 

deleted, it is no longer possible to trace the data and samples back to individual subjects through 

the coding key(s). Anonymization is intended to prevent subject re-identification. As 

anonymized samples and associated data are not traceable back to the subject, it is not possible to 

undertake actions such as sample withdrawal, or the return of individual results, even at the 

subject’s request. The use of anonymized data and samples does not allow for clinical 

monitoring, subject follow-up, or the addition of new data from the subject. The deletion of the 

coding key(s) linking the data and samples to a given subject’s identifiers provides additional 

confidentiality and privacy protection over coded data and samples, as it prevents subject reidentification through the use of the coding key(s). 

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6

4. Anonymous Data and Samples (2.3.4) 

Anonymous data and samples are never labeled with personal identifiers when originally 

collected, neither is a coding key generated. Therefore, there is no potential to trace back 

genomic data and samples to individual subjects. In some instances, only limited clinical data 

can be associated with anonymous samples (e.g., samples from subjects with diabetes, male, age 

50-55, cholesterol>240 mg/dl). As anonymous samples and associated data are not traceable 

back to subjects, it is not possible to undertake actions such as sample withdrawal, or the return 

of individual results, even at the subject’s request. The use of anonymous data and samples does 

not allow for clinical monitoring, subject follow-up, or the addition of new data. 

5. Additional Information (2.3.5) 

The use of a specific coding category in relation to obtaining informed consent from subjects is 

not within the focus of this guidance and is not addressed in this guidance. 

The conditions under which the genomic data can be linked back to a subject’s personal 

identifiers for any purpose, including the return of genomic data to the subject, should be 

described in research related documents, e.g., the informed consent document. 
Contains Nonbinding Recommendations

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Table 1: Summary of Genomic Data and Sample Coding Categories 

Sample Coding 

Category 

Link Between Subject’s 

Personal Identifiers And 

Genomic Biomarker Data 

Traceability Back to the 

Subject 

 (Actions possible, including 

e.g., sample withdrawal or 

return of individual genomic 

results at subject’s request) 

Ability to Perform 

Clinical Monitoring, 

Subject Follow-up, or 

Addition of New Data 

Identified Yes (direct) 

Allows for subjects to be identified 

Yes Yes S

c

Single Yes (indirectly) 

Allows for subjects to be identified (via single, specific coding key) 

Coded Yes Yes S

Double Yes (very indirectly) 

Allows for subjects to be identified (via the two specific coding keys) 

Yes Yes A

cs

Anonymized No 

Does not allow for subjects to be re-identified as coding key(s) have been deleted 

No No G

lc

Anonymous No 

Identifiers never collected and coding keys never applied 

No No G

n

Does not allow for subjects to be identified