It’s been coming for a long time. Now it’s here. The FDA and the pharmaceutical industry adopt new processes imperceptibly. Deliberately. But as the new year begins, 2008 has at least one stark shift. As of now, electronic regulatory submissions to the U.S. authorities must use the electronic common technical document (eCTD) format.

Officially, technically, waivers of the new rule are possible. Paper is acceptable. We exagerrate a bit, but you can legally turn in your scientific homework on paper towels, as the FDA states in this web page. Unofficially, the situation may be a bit less forgiving. But we’re getting ahead of ourselves.

The vendors involved in assembling and publishing eCTDs are bracing for more business. One of them is Qumas, a Jersey City, New Jersey, firm specializing in regulatory software and services for the life sciences and financial services industries.

FDA ‘Line In Sand’

Warren Perry is senior compliance advisor at Qumas. He believes the 2008 requirement for eCTDs to be used in electronic submissions is not as well understood as you might expect, given that it’s hardly a surprise. That’s true even among the folks you might expect would be best versed in the topic. “I don’t even think it is a well understood change within regulatory affairs,” Perry says. “They are not going to be able to ignore it. The FDA has really drawn a line in the sand on this one. That seems pretty clear.”

Selected parts of the sponsor community, he says, are not prepared for the firmness of the resolve on the issue at the FDA, and are likely to be unpleasantly surprised when proposing to bring the agency a semi-tractor trailer full of regulatory documents. Says Perry: “At least half of them are in denial. They believe there will be a crack in the wall, or they’re going to submit on paper.”

In practice, informally, he says the agency has been discouraging sponsors from traditional filing formats. That’s forcing some regulatory folks in the sponsor world to return from Maryland with bowed heads and bruised egos. It may be natural to assume that your organization can plead and cajole the agency to win exemptions. But based on what Perry’s heard, that would not be wise.

Your Assumptions

In an industry where sunny statements are the norm, Perry sounds a more somber, rueful tone about paper: “When they have to call Beacons and have a moving van show up, there is something dramatically wrong with that picture. It hasn’t been done by the tier one pharma for years,” says Perry. He’s been able to gather a bit of intelligence on such FDA-sponsor encounters, and it seems the agency has been taking a very hard line.

“People have been going in smugly and assuming not only that they would get an exception but doing an investigational new drug [IND] application. They are hearing, ‘If you give us paper, it is going to come back to bite you.’ What they are being told is that if they are opting for the paper submission, that that is not going to get a lot of traction.”

As for the FDA? Perry is sympathetic to the chronically underfunded agency. “They are just flat out of space to store paper,” says Perry. “The FDA is the biggest archiver of paper in the federal government. They are in the business of building warehouses at the FDA. They have not gotten more money to do that. Their budget isn’t growing. They just are not going to store paper any more.”

Warehouse Budget

Politicians, Perry says, have telegraphed the fiscal realities to the FDA, even if the new policies have not been codified in black and white. Says Perry of the message from politicians to the FDA: “The status quo is broken, and they cannot keep doing it. It’s been very clear that they better not take in any more paper. The submitters need to do everything in their power to not submit paper any more.”

Perry is quick to say that the major pharmas made the transition to electronic submissions years ago—in some cases, as early as the 1990s. They quickly earned a return on investments in better regulatory document systems, even though the technology was far more expensive then.

The situation is different for small pharmas and biotechs today, Perry says. They typically lack the manpower to attend to both routine regulatory work and manage the transition to a new system. He adds: “The purchase price of the system is not the obstacle. It is implementing. The smaller you are, the more desperately you need one of these, but the less people you have to implement them.”

Surprise Ahead

There may be cultural reasons that explain why so much paper still being used in the life sciences, Perry says. The smaller firms are usually controlled by a scientific visionary who is insulted by the mere suggestion that his firm might not send the complete and unvarnished truth to the FDA.

As Perry explains: “They are honest and ethical people. They rankle under things like audit trails and [21 CFR] Part 11 compliance. ‘Why do I need all these layers of cost and compliance? It makes no sense.’ It’s almost a personal affront to them.”

But he’s under the impression, he says, that of late such dynamics have begun to shift, partly because venture capitalists and alliance partners will not allow such companies to grow beyond a certain size without the appropriate regulatory technology in place.

What Financiers Think

Says Perry: “Less and less of those companies make it very far. Less and less of the venture capitalists fund those guys. If your intellectual property is scattered all over the place on a bunch of scientists’ laptops and filing cabinets, that value is very different than if it is on a series of servers that have audit trials and are compliant.”

Still, Perry thinks the eCTD will reduce the time needed for the FDA to review regulatory data. “There is clearly a huge advantage to their review. They no longer have to figure out where you put your efficacy and safety study. They know exactly where. If it isn’t there, they don’t take your submission.”

Some small companies may be disheartened at the delay of implementing a system. Or worried about the risk of alienating the FDA with paper. That’s the definition of being between a rock and a hard place.

But Perry relates that at least one unidentified customer, in Austria, had a very rapid switchover to his company’s system. They had a runway, believe it or not, of 90 days until an important filing was due. Says Perry: “They bought it, we installed it, we validated it. We trained them and migrated the content. We only get a certain amount of credit. They devoted a massive team to this like we’ve never seen before.”

In the end, the project was done in 86 days. Perry says that the acceptance of the system without extensive customization was a key factor in hitting the date. And, of course, the resolve to make the decision in the first place. “The sooner they get it done, the more they reap the beneifts,” he says.