Collaboration Ensures Electronic CTD Program Success

Success in moving investigational new drug (IND) projects toward adopting the electronic common technical document (eCTD) is more about collaboration than technology, experts said at a recent industry gathering.

"Don't work in a vacuum," stressed Leah Kleylein, manager of regulatory operations submissions at Centocor Research & Development. She advised firms to engage in dialogue early and often with the FDA, vendors and internal company contributors. "You need to create team comfort with eCTD tools," Kleylein told attendees at a Drug Industry Association meeting February 10.

"Managing the team is key," agreed Nancy Smerkanich, vice president of regulatory affairs at Octagon Research Solutions. As an outside vendor and consultant, she stressed the importance of bringing participants together at the outset to address issues such as: differing interpretations of guidances and regulations; project expectations; and cultural or language barriers.

Smerkanich advocates establishing regular project and submission team meetings and monthly or weekly status reports. For INDs she typically recommends a monthly review of routine submissions, which should include representatives from all disciplines: chemistry, manufacturing and controls (CMC), and clinical and nonclinical departments.

Centocor was committed to moving its INDs towards eCTD, Kleylein said, but the company first needed to address:

Lack of knowledge about eCTD; Lack of document granularity -- ability to change one cell rather than the entire document; Lack of eCTD publishing software; and Existing INDs that were in both paper and electronic formats.

To overcome those obstacles, Centocor launched a four-step plan consisting of: demos, planning, conversion and maintenance.

Demos: The company decided to demo INDs in eCTD format for both the FDA and Centocor's internal contributors. The company created a demo team to spearhead this. That team should "ideally be the same as the IND submission team," Kleylein said. Disciplines represented on the team should include representatives from regulatory, CMC, nonclinical and medical writing departments, she said.

After submitting the demo to the FDA, be sure to follow up with the agency to get feedback and offer to present the demo in person, Kleylein said. That personal contact can help establish useful relationships, she added.

Planning: Centocor established and tasked a CMC granularity team with continuing the work started by the demo team. That team was responsible for planning a strategy to address future regulatory amendments and other changes that could require procedural or structural changes in the company's eCTD approach. "Think about the future" during the present, Kleylein said. And don't neglect "little things like formatting" along the way. For example, have all members agree in advance on consistent headers.

Conversion: Assess the impact of old formats on publishing deadlines. Some companies have three current formats for INDs, which can be a drain on resources if you choose to convert everything, Kleylein said. Take a long, hard look at what is worth converting, she advised. Establishing naming conventions is critical before undertaking major conversion work (for example, "firstnamelastname.pdf"). Getting it right at the outset helps avoid time-consuming searches through submissions later, she added.

Maintenance: It is "unglamorous, ignored, tedious [and] extremely important," Kleylein said. Separate PDFs are required for each section of documents, including annual reports, because you'll need that granularity to revise individual data cells. You should also place a high priority on fast turnaround of safety reporting, she stressed.

Managing your vendors and other contributors is critical during this process, Smerkanich said. Companies should have open lines of communication with other vendors regarding deliverables. Otherwise, you risk slowing down your esubmission timetable. Sponsors need to help their vendors act as partners throughout the process. "Realistic submission planning will result in [fewer] headaches and anxiety later in the process," she added.

Bringing your vendor in early on in the process has several advantages. For starters, you can quickly evaluate their capabilities in a real-case scenario. It can also allow you to tap their earlier eCTD experiences, Smerkanich said. -- Michael Causey