Brief Summary: E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories

Name of Guidance

E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories

Status of Guidance

Final Guidance

Date of Guidance

April 2008

Released by

Center for Drugs and Biologics, Federal Drug Administration, Department of Health and Human Services

Link to Guidance

Target audience

Developers of drugs/biologics

Laws and Regulations

This guidance does not refer to any laws or regulations.

Definitions

Biomarker: Any substance used to detect and identify a type of cell, organelle, sub-component, biological state, or biological process

Deoxyribonucleic acid (DNA): genetic material that comprises an organism

Genome: the ordering of an organism’s full DNA sequence (or genetic code)

Genomics: the branch of genetics that focuses on organisms in terms of their genomes (or DNA sequences)

International Conference on Harmonisation (ICH): With the full name of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, the ICH is a global organization with the mission of creating a single procedural platform for regulatory and pharmaceutical entities worldwide, specifically in Europe, Japan and the US, to follow to “harmonize” the steps involved in drug development and registration.

Pharmacodynamics (PD): the study of the biochemical and physiological effects of drugs, and the mechanisms of their actions, including the relationship of their actions and effects with their chemical structure

Pharmacokinetics (PK): the area of pharmacology focusing the effect of body processes on drugs, including absorption, distribution, metabolism, and elimination

Ribonucleic acid (RNA): a nucleic acid composed of repeating nucleotide units of ribose sugar, phosphate group, and nitrogenous base that is involved in protein synthesis. RNA is different from DNA in that it includes the sugar ribose and the base uracil while DNA includes the sugar deoxyribose and the base thymine.

Single nucleotide polymorphisms (SNPs): a deviation in a sequence of DNA that involves the switch of a single nucleotide base for its alternate, as in replacing the cytosine base with the thymine base. These variations occur at an increasing rate in the population.

Background

The International Conference on Harmonisation (ICH) formed to promote the use of the same procedures and documents in the development and registration of drugs by regulatory and pharmaceutical entities worldwide. Formerly, each region of the world followed its own procedures. Part of the problem with having different procedures around the world is the accompanying discrepancy on the meanings of vocabulary used in these processes. In an effort to clarify and consolidate the vocabulary and to streamline communication, the ICH advocated for the adoption of specific vocabulary to be used with agreed-upon definitions.

Another area in drug development that needed consolidation and clarification is the labeling of biological samples that are used for research in the fields of pharmacogenomics and pharmacogenetics. Different countries use different systems for identifying and tracking these samples and the data collected on these samples. Accordingly, the ICH called for a single system for coding for these samples and data that would simplify research and the development of new drugs.

Summary

This guidance is endorsed by the ICH and provides agreed-upon definitions for commonly used words in the fields of pharmacogenetics and pharmacogenomics, and in genomic data and sample coding.

Rationale

Lack of consistency of definitions for commonly used terms in drug development around the world creates great confusion, creates work, and wastes money. Creating a system in which all parties involved in drug development and registration around the world can communicate clearly would address and end this confusion and waste, and ensure proper interpretation and communication while making drug discovery more efficient.

Resulting Recommendations

This guidance provides the following definitions to clarify meanings of terms and to ensure consistent understanding.

· Genomic biomarker: a measurable DNA and/or RNA characteristic that is an indicator of normal biologic processes, development of disease, and/or response to therapy (eg, the expression, function, or regulation of a gene)

· Pharmacogenomics (PGx): the study of variations in the characteristics of DNA and RNA as related to drug response in terms of drug discovery, drug development, and clinical practice

· Pharmacogenetics (PGt): a subset of pharmacogenomics, focusing on the study of variations in DNA sequence as related to drug response drug discovery, drug development, and clinical practice

· Drug: refers to investigational (medicinal) product, medicinal product, medicine, and pharmaceutical product (including vaccines and other biological products)

· Drug response: the processes of drug absorption and disposition (meaning pharmacokinetics), and drug effects (meaning pharmacodynamics, drug efficacy, and adverse effects of drugs).

Samples, and the data generated by them, can be labeled with one or two codes during research. This guidance recommends using a system including the following 4 specific categories for coding biological samples (and the generated genomic data).

· Identified: the samples and/or data are identified with personal information to allow tracing back to the subject from whom the sample/data was derived. Samples/data with this code can be withdrawn or returned, permitting clinical monitoring, subject follow-up, and future addition of new data from the identified subject. Clinical trials in drug development typically do not use identified samples/data.

· Coded: these samples/data do not include any personal information and are tagged with one (single-coded) or two (double-coded) codes. Single- and double-coded samples/data can be traced back to the subject, so sample withdrawal and return of results are possible. It also enables clinical monitoring, subject follow-up, and future addition of new data from the identified subject. Single-coding is the most commonly used method in clinical research today. Double-coding allows an extra layer of security on samples/data.

· Anonymized: these data/samples are single- or double-coded and increase the level of confidentiality and privacy because they do not include personal information on the subject from whom the sample came. The samples/data are not traceable back to the subject so it is not possible to withdraw the sample, return the results, conduct clinical monitoring or subject follow-up, or add new data from the subject at a future date.

· Anonymous: these samples/data are completely anonymous, with no personal information included, voiding any possibility to trace data back to the subject. The samples/data are not traceable back to the subject so it is not possible to withdraw the sample, return the results, conduct clinical monitoring or subject follow-up, or add new data from the subject at a future date.

Impact

Using an agreed-upon set of vocabulary and coding categories for biological samples (and their genomic data) will improve communication and streamline drug research worldwide.