On Feb. 2, the US Food and Drug Administration will hand drug makers instructions on how to supply certain pharmacogenomics data, either as components of the drug-review process, or as voluntary submissions.
When the agency released a draft of the document in early November, biopharmas began in turn to wring their hands and rub their palms: They believed that pharmacogenomics tools and applications are still relatively novel to the regulators charged with reviewing them, but they suspected that the strides they’d made performing pharmacogenomics studies in recent years would keep them ahead of competitors less hip to the new technologies.
The notion of voluntary genomic data submissions, or VGDSs, on the other hand, has been a source of consternation among drug makers.
Today, with three weeks left in the public-comment period assigned to the draft guidance, the VGDS component is dividing pharmas into two vocal, though unbalanced camps: Those who say that the submissions will ultimately help broaden the use of pharmacogenomics technologies and applications, and those who question whether they should submit their own data so freely and so soon.
“I hope to be the first person to submit” data for a VGDS, said Margot O’Toole, a senior scientist at Wyeth. “I believe they will be important if genomic technologies or pharmacogenomics data are to be used by drug makers.”
O’Toole spoke to SNPtech Pharmacogenomics Reporter last November during a meeting in Washington, DC, timed to coincide with the FDA draft guidance paper. She was the rare example of a fierce VGDS proponent. Most other sponsor representatives at the meeting and in the weeks that followed the release of the draft guidance, tended to be “cautiously optimistic,” in the words of one official. Another described himself as “optimistically cautious.”
Saying that their comments might tip-off competitors, most researchers and company officials interviewed for this article asked that their names and affiliations not be used. Many also declined to offer frank opinions even with those ground rules in place.
Haves or Have-Nots?
“I see the [draft guidance] as a clear advancement for a better discussion on what has to be submitted,” said the head of pharmacogenomics at a mid-size European biotech company who spoke on condition of anonymity. But “our concern is that it will be difficult to compare … companies that do everything to [comply with] the newest possible standards — including genomics — with those that don’t. The idea of the ‘just system’ that everybody was concerned would not exist hasn’t materialized in this guidance at all, and I was so surprised that everybody completely accepted this in the guidance,” this person said.
He gave as an example two companies submitting competing compounds. Both compounds would serve a significant medical need, and they have similar adverse-event profiles. Company A has performed extensive pharmacogenomics research, while Company B has not. However, Company B is six months ahead of Company A. As a regulator, “what would you do with the company that has [pharmacogenomics] data related to safety or efficacy?” he said.
What assurance would Company B have that its data, especially safety data, doesn’t make its way to Company A, he asked? “How will the FDA give feedback to alert other companies to do the right things at the right time without breaking any of its confidentiality issues,” he said. “I think this is a very relevant issue.” The FDA “must address this imbalance,” and “it cannot be healed by any guidance. I admit that it is difficult for the FDA … to establish this form of justice,” he explained.
Other sponsors agree, but play down any threat this may have: “This is not a major hurdle at all, but it would be helpful to make things a bit more clear,” said a director of pharmacogenomics research at a large US-based pharmaceutical company who also requested anonymity.
Moreover, this issue shouldn’t be news to the agency. “I don’t think this has escaped [the FDA’s] attention, because they have voiced this issue in our meetings,” said an official with the Pharmacogenomics Working Group who asked not to be identified. “I think they now just have also realized that this is all you can do for the time being.”
Confronting Trust Issues
For its part, the FDA stressed that the VGDSs will be for “FDA knowledge building;” will “not be used in [the] regulatory process;” and will be “kept confidential.” Clearly, the agency has sensed that trust may be a significant barrier to widescale VGDS acceptance. As Robert Rubin, a professor at MIT’s Program on the Pharmaceutical Industry, told SNPtech Reporter last spring: “Everybody is suspicious of everybody else, and the whole [regulatory] system has been an adversarial one for too long. The industry has some issues.”
To an extent, Janet Woodcock, who oversees FDA’s Center for Drug Evaluation and Research — and whose team, along with the FDA’s Center for Biologics Evaluation and Research, composed the draft guidance — has conceded that industry “is afraid we will over-interpret these data in a way that will be harmful for drug development or it will slow down their drug development.” She also said in the past that “the relationship [between the] FDA [and] the pharmaceutical industry was somewhat adversarial.”
The draft itself acknowledges this, saying that drug makers “have been reluctant to embark on programs of pharmacogenomics testing” during the drug-development process “because of uncertainties in how the data will be used by the FDA” in its review process. “We need to get this issue settled,” Woodcock said at a May pharmacogenomics conference at Yale [see 5/2/03 SNPtech Reporter].
Woodcock has reiterated at virtually every meeting since the draft was released that “no voluntarily submitted pharmacogenomics data will ever be used in the drug-review process.”
The FDA even plans to create an agency-wide Interdisciplinary Pharmacogenomic Review Group to review VGDSs and “work on ongoing policy development, and … advise review divisions dealing with pharmacogenomic data,” according to the draft guide.
But some doubts may linger even after all obvious questions have been answered. “The remaining doubt will be, ‘Well, if you give something to the agency, can they really ignore it?’” said Gregory Glover, a partner in the Washington, DC office of Boston-based Ropes & Gray LLP who deals with regulatory issues. “‘Are they really not going to use it in a way that is going to be harmful to us? Are they going to basically do what they’re going to do?’” he said.
“I think that kind of comfort level is only going to come from time, where people get experience about submitting information that isn’t quite ready for prime time, and seeing what the FDA does with it,” he said.