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Roundtable participants discuss challenges and successes with early eCTD implementation.
Like all technologies, the traditional Roger's curve of technology adoption applies to the electronic Common Technical Document (eCTD) in the pharmaceutical industry. The eCTD is, as of January 2008, FDA, CDER division's specified format for submitting an electronic application for new NDA, IND, ANDA, BLA, Annual Report, and DMF submissions. That curve features the upward trend of innovators and early adopters followed by the early majority (see Figure 1).
Clarkston Consulting recently brought together a group of these eCTD innovators and early adopters of eCTD implementation for a roundtable discussion. These regulatory experts—charged with eCTD implementation at their companies—shared their specific challenges and insights to the process. Applied Clinical Trials was invited to report on the event.
There are approximately 15 eCTD vendors offering an eCTD software solution. In selecting the eCTD tool, the roundtable participants discussed what went into their tool criteria process.
As the only representative from a large, global CRO, Laurie Henricks, senior director, global regulatory affairs and medical writing for Quintiles, said that a tool that fit global requirements was key. "We could not make it a U.S.-centric thing," she said. After determining the main global requirements, Henricks involved her IT group, so they could evaluate the potential vendors and the IT resources required.
Return on eCTD Investment
Henricks added: "As a CRO, we then had to look at what kind of return on investment we would get because we don't own our projects, we basically have outsourced projects that come to us for creation." The list of requirements then went to the global regions, for consensus on criteria on the Quintiles' short list.
Carol Rutkowski, senior director, global regulatory operations for Shire Pharmaceuticals, also explained the need for a global solution. "We established a global team, which took into consideration global and regional requirements and we made sure all those parameters were met."
Albert Edwards, PharmD, RAC, director, regulatory operations for Takeda Global Research & Development Center in Lake Forest, IL, described his company as early adopters, though on the Roger's Curve, they appear more as innovators having moved to eCTD since 2000.
"Even though we were pretty U.S.-centric at the time, we needed publishing that could occur at 7:30, 8:30, 10:30 at night, and we wanted to make sure that we had that kind of coverage. We also wanted the ability to have a development copy of the software that we could bring in-house for testing and kicking the tires to see if it worked."
What comprises tire kicking? To Edwards, a pilot test and a load test of the software is key. Once criteria is set, the pilot test before the product implementation will go a long way in determining the tool's actual usability and impact on IT resources before the fact. "I've got to pilot test what I'm going to use ahead of time so that I'm reassured the needs of the organization and our user population are met," remarked Edwards.
Valerie Mackner, MS, senior manager, global regulatory operations with Wyeth Research, said the company has had its own in-house solution since 2002. As an early adopter of eCTD, she explained that at that time, they felt available off-the-shelf solutions weren't going to fit their requirements. Now they are looking for a tool with more functionality.
Said Mackner, "We need to be able to validate within the tool and we need a tool that allows us to see things the way health authorities are viewing. Right now, our tool does not mirror what FDA sees, or the EMEA, so those are the kind of requirements we're going to be looking at."
Other requirements included that the tool be Web-based and integrate well with the document software used. And selecting the tool also involves selecting the right vendor.
When it comes to selecting the tool, it seems IT should have a good sized role. Many of these early adopters say that the IT department will perform its own audits of the technology vendors. Those audits include examining information such as financial viability of the vendor and infrastructure requirements.
In addition, Edwards suggests that you ask the vendor what its history is with hitting targets on software version upgrades. "You want to be assured that upgrades will actually occur within the time frame originally promised so your organization can be appropriately prepared. Delays in software version upgrades have potential impacts on IT staffing for other projects and possible budget implications if the upgrade arrives in the next budget year."
Rutkowski noted that going into the selection, sponsors should be aware that the original vendor contact who is consulted may not be the same person who works on your implementation. Therefore, they may not be up-to-date on your original stated requirements.
The group consensus was that with the number of vendors out there, the onus falls on the sponsor to do its homework. In addition to the IT needs, the level of vendor experience, vendor's upgrade plans, vendor's hitting upgrades (as previously noted), and the financial stability of the vendor go into the tool selection process. Ideally, the number of technology vendors to bring into the selection process should be narrowed down to between three and five. Anymore than that can be time consuming and unproductive.
"Paper is still acceptable as an alternative to electronic submissions," so says the FDA Web site. And a large portion of the world—90%—still supplies submission via paper. But these early adopters praise the benefits of eCTD. Getting the rest of the curve over the hump could be more difficult based on their expert observations.
For the regulatory professional unsure of his or her eFuture, the move from the security of paper is difficult. Edwards explained this phenomenon from an experience perspective. "I totaled it up one time and in our regulatory affairs department there's easily over 200 years of experience dealing with paper applications and—at the time I did that—there was three years experience with eCTD. If you put those two on a scale, paper will win every time in terms of people's comfort level with the eCTD."
The other participants agreed that many in the regulatory, and in the FDA, still prefer paper. But they all also agreed that once employees/professionals have used eCTD and become familiar with it, they will prefer it.
Another group that appears somewhat wary of the "e" in CTD is the smaller biopharma companies. According to Janel Firestein, partner at Clarkston Consulting and the roundtable's moderator, "The small biotechs are tending to outsource to the CROs and not embarking on the eCTD solution because of what they perceive as the cost implications of that, and not wanting to slow down what they are doing. So, therefore, they are looking to depend on the CROs. Where in big pharma, they are bringing it in-house and doing it themselves and setting their standards."
Henricks noted that Quintiles offers both an eCTD solution and a paper solution for its clients, allowing them the choice based on their needs. She said a lot of companies are still doing paper, and many of them are the smaller companies. "We see companies coming to us wanting to do electronic, but then they get scared," said Henricks.
She views this hesitancy as a fear that they don't have complete control because of the outsourced paradigm. "They don't mind the outsourcing of the original submission, but they want to do their own amendments and updates."
As their CRO representative, she does encourage the sponsors to go with eCTD and assures them that Quintiles will be with them throughout the whole process.
Michael McGraw, PharmD, MS, regulatory affairs manager for Teva Neuroscience, said that some documents may need to be in the paper form, such as an orphan drug application. So relying on just eCTD software will not work. In addition, some countries will require both paper and electronic. Therefore, a need to keep dual processing—paper and electronic—is necessary. McGraw did note, however, that some applications can also be sent electronically on CD, for example.
The dual processing is inconvenient from both an IT and training perspective. Henricks explained that it is IT intensive to have a paper and electronic submission solution. The concepts between the submission process for paper and electronic are very different.
"You don't want to train new employees in the old paper way but sometimes you have to, and it's confusing because the concepts are very different," Henricks noted.
As Edwards said, however, when it comes to group review time, there is just no way around having a paper printout of the electronic submission.
"We did not originally have a paper component for our eCTD software, but in working with our IT staff, we found a way that we could produce paper," he explained. "The practical reason for this is that in any outlicensing situation you may have a request for four people to look at the regulatory dossier. So that's four computers. Then, sometimes the four people turn into 15, and it's very difficult to pull together that many computers to look at the dossier's contents. So, there is a definite need for a paper component."
With the early adoption phase over, and these experts now cruising to eCTD successes, Firestein asked what would they do differently, and more importantly, what did they do well in their eCTD process?
Edwards said that he thought they did a lot of things well. "I think we involved members of the user community, and let them know well ahead of time what the timelines were going to be with activities, so that no one was surprised as we moved along the process. And we engaged our financial department early in the process."
Other keys to successful eCTD implementation include ongoing education and training of both the regulatory affairs department and authors; establishing a go-to person in regulatory who is solely responsible for users' questions; creating an understanding within senior management that "perpetual investment" is needed to continuously fund upgrades and IT support after the new system is launched; and understanding the global regulatory agencies' role in the process, as well as global requirements.
These topics will be covered in an article scheduled to appear in our September issue. For updated information on eCTD, visit the FDA web site at http://www.fda.gov/cder/regulatory/ersr/ectd.htm.
Lisa Henderson is the Editor-in-Chief of Applied Clinical Trials, email: firstname.lastname@example.org
To listen to podcasts of members from the roundtable discuss their eCTD experiences with Applied Clinical Trials, visit http://appliedclinicaltrialsonline.com/eCTD/Podcasts.