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By Malorye A. Branca

December 15, 2003 | The FDA last month released its first-ever guidance for “Pharmacogenomics Data Submissions,” drawing clear distinctions between data submitted in formal support of new drug applications and data that is pertinent but not required. Although the guidance breaks little new ground, it is must reading for drug developers. 

“Pharmaceutical sponsors have been reluctant to embark on programs of pharmacogenomic testing during the FDA-regulated phases of drug development because of uncertainties in how the data will be used by the FDA in the drug application review process. This guidance is intended to help clarify FDA policy in this area,” reads the document (available at

Whether the FDA has accomplished this stated goal is unclear. The latest guidance has rekindled interest in pharmacogenomics, but also left many thinking  pharmacogenomics is starting to look like one of those things companies worry about mainly because they have to.

Many in the industry have long been concerned about how the agency might use pharmacogenomic data, because companies themselves have a hard time interpreting this data. But FDA commissioner Mark McClellan has made pharmacogenomics one of his priorities. He sees it as a major tool to “make drugs better and safer,” he said at the recent Drug Information Association (DIA) meeting.

In the guidance, the FDA tries first to clearly distinguish those genomic data that companies must submit from those that can be kept private or submitted voluntarily. The latter have no regulatory relevance. The guidance also says companies cannot be penalized later for such voluntary submissions, which the agency hopes to use for educating its staff about this emerging field.

“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,” the document states. “However, to be prepared to appropriately evaluate the anticipated future submissions, FDA scientists need to develop an understanding of relevant scientific issues.”

“Therefore, the FDA is requesting that sponsors … consider providing pharmacogenomic data to the Agency voluntarily, when such data are not otherwise required under IND and NDA or BLA regulations. Voluntary Genomic Data Submissions (VGDSs) can be used for the submission of pharmacogenomic studies that are not required to be submitted. The FDA will establish a cross-center Interdisciplinary Pharmacogenomic Review Group (IPRG) 240 to review VGDSs, to work on ongoing policy development, and to advise review divisions dealing with pharmacogenomic data.”

Remaining Questions
But many gray areas remain that are extremely troubling to companies. Standards are one of the major bones of contention. Many companies claim they can do pharmacogenomic studies reliably within their own walls, but data from two different companies rarely agrees. Companies worry about what could happen if a third party develops a putative pharmacogenomic marker for another company’s drug. How will that marker be evaluated? Will the company whose drug it is get a chance to review the marker data?

Some vendors see the guidance as an opportunity. “It is important to us because our ArrayPlate measures gene expression very accurately and reproducibly, while addressing many genes at a time,” says Bruce Seligmann, president and CEO of High Throughput Genomics. 

Others think that, ultimately, standard operating procedures will make the biggest difference. “This is the demographic data from Hell,” says Lee Evans, vice president of pharmaceuticals and biotechnology at Intrasphere Technologies, a consulting firm and application developer.  “When you abstract pharmacogenomic data with that from clinical trials, it just can’t be done without appropriate standards.”

For now, just understanding the guidance terminology is keeping many experts busy.  “I think the pharmaceutical companies will want more guidance on what are validated gene markers,” Seligmann says.

These problems really represent the tip of a massive iceberg. The FDA needs to sort out myriad other issues, such as exactly who gets to see the voluntary data, how the agency will coordinate with other international regulatory bodies, and what type of information researchers will need to put into informed consent documents in case “exploratory” data could end up going to the FDA.

Ultimately, the guidance was no big surprise. “They said what they have been saying for the last six to eight months,” says Richard Judson, vice president and chief scientific officer at Genaissance Pharmaceuticals. Everyone agreed there is a tremendous amount of work left to be done. At the DIA meeting, the FDA and industry began that work, discussing more appropriate definitions, how good the technologies really are, and what the data actually mean.

“This is the first step towards giving clear guidance on what the regulatory uses of this information will be,” says Brian Spear, director of pharmacogenomics at Abbott Laboratories. “But it’s still just a start.”


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