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ICH Draft Guidance Seeking to Harmonize PGx Terms Aims to Abet Global Drug Development

A recently released draft guidance by the International Conference on Harmonization hopes that internationally standardized definitions of pertinent pharmacogenomic terms will help integrate the discipline into global drug development and approvals.
The guidance, called the E15 Terminology in Pharmacogenomics, was released on Jan. 8. The US Food and Drug Administration will be accepting written or electronic comments on the draft guidance until April 9.
It “is the first step necessary to talking about pharmacogenomics on a global regulatory scale,” Felix Frueh, associate director of genomics at the FDA, told Pharmacogenomics Reporter this week. “Proper definitions will facilitate clear communication and create a foundation upon which we can build further activities, such as biomarker validation.”
The draft results from an ICH steering committee meeting last year, during which representatives from US, European, and Japanese regulatory agencies and industry organizations met for the first time to discuss pharmacogenomics.
The goal of that initial meeting was to eventually incorporate uniform pharmacogenomics terminology into drug discovery and development protocols [see PGx Reporter 06-14-06].
Although harmonizing these terms will have regulatory impact, Frueh doesn’t expect the guidance to change the way business is done, or to squelch intellectual disagreements over the definitions.
The Terms
According to the draft guidance, although each of the three ICH regions has developed guidances or concept papers on pharmacogenomics and pharmacogenetics, “the lack of consistently applied definitions to commonly used terminology raises the potential for conflicting use of terms in regulatory documentation and guidances or inconsistent interpretation by regulatory authorities, ethics committees and sponsor companies.”
The draft guidance, which can be found here, defines pharmacogenomics as “the investigation of variations of DNA and RNA characteristics as related to drug response.” Pharmacogenetics, “a subset of pharmacogenomics,” is defined as “the influence of variations in DNA sequence on drug response.”
Although, some of the principles in the document “might be applicable to proteomics, metaobonomics, and other related disciplines,” the draft guidance specifically notes that “the definitions of PGx and PGt do not include other disciplines such as proteomics and metabonomics.”
The draft also defines the term “genomic biomarker,” as well as genomic data and sample coding categories.
Genomic biomarker is defined as a “measurable DNA or RNA characteristic that is an indicator of normal biologic processes, pathogenic processes, and/or response to therapeutic or other intervention.” DNA characteristics can include SNPs, variability of short sequence repeats, DNA modification, insertions, deletions, copy number variations, and cytogenetic rearrangements. RNA characteristics may include RNA sequence, expression levels, processing, and microRNA levels.
While genomic biomarkers are not limited to human samples, “the definition for a genomic biomarker does not include the measurement and characterization of proteins or low molecular weight metabolites,” the guidelines state.
According to Frueh, the terms were chosen based on what the ICH regions felt were the most important considerations for building the groundwork for future harmonization activities in this field.
“The goal of the effort overall is to harmonize the use of pharmacogenomics in drug development,” Frueh said. “At the very beginning we need to ensure that we all talk about the same thing. We cannot, for example, discuss the validation process of a genomic biomarker if we are unclear what we mean by a ‘genomic biomarker.’” 
Genomic Data Coding Categories
Another area of focus in the draft guidance includes coding categories for genomic data and samples. The standardization of genetic data coding categories in clinical studies may lead to better privacy protections for study participants.
“PGx and PGt research depends on the use of samples to generate data,” the draft guidance states. “A harmonized definition for the coding of these samples and their associated data will facilitate use in research and development of new medicines.”
The draft identified four general data categories of coding: identified, coded (single and double), anonymized, and anonymous. Each category offers varying degrees of privacy protection, with “identified” samples offering the least protections and “anonymous” data having no chance of being traced back to the subject (see side bar).
“The implications of using a specific data and sample coding category should be considered in the design of PGx and PGt research studies,” the guidelines state.
In Frueh’s view, these terms will contribute to the implementation of future policies and procedures that have a regulatory impact. 
“We do not expect that these definitions will change the way business is done nor do we expect that everybody will agree to the specific text,” he said. “What is important is that these definitions can be used for future discussions to harmonize the use of genomic biomarkers in drug development on a global scale.”

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