FDA appears to be using a multi-front strategy for designing and implementing plans to standardize electronic data formats and application filings.

It also involves industry members working together to create voluntary data standards for research of major diseases like cancer, which could create another option for widespread adoption.

The agency is pushing for applications and other filings to be sent electronically through a common format. Those submitted on paper or in different electronic formats prevent staff from performing advanced analyses and asking in-depth questions, FDA has argued.

Using Commissioner Margaret Hamburg’s Regulatory Science Initiative is one potential route for the standards, but its funding remains in limbo amid proposed federal budget cuts (Also see "With Federal Dollars Scarce, FDA May Fundraise For Regulatory Science Initiative" - Pink Sheet, 7 February, 2011.).

The agency also could use the Prescription Drug User Fee Act reauthorization to implement the standards, but industry does not appear enthusiastic about giving FDA unilateral authority in writing them.

CDER Director Janet Woodcock said in December the lack of data standards makes the effort required to review applications less predictable.

Speaking during the FDA-CMS Summit, sponsored by Elsevier Business Intelligence, publisher of "The Pink Sheet," Woodcock said standardization of data submissions, along with other changes, would make significant improvements possible.

“All the efficiency and all the consistency people are asking for, we don’t even know whether we have it or not until we get data standards and standard analyses … in place,” she said.

In fiscal year 2010, CDER received on average about 62% of NDA-related submissions in electronic common technical document format, according to agency data. During the year, the percentage ranged from as low as 58% to as high as 66% during an individual month. The electronic submission tally represents significant progress; in FY 2008, only 33% of NDA submissions used the eCTD format.

Data contained on paper or in portable document format (pdf) is not "mineable" and makes it nearly impossible for reviewers to do cross-study assessments, said Vicki Seyfert-Margolis, senior advisor for science, innovation and policy in the Office of the Commissioner.

Even data submitted in Excel spreadsheets is difficult to interpret, FDA says

By 2013, the agency hopes to have a data repository in place to integrate all its data for use by reviewers looking at product classes and other issues, she said.

“This scientific enclave will allow us to pilot out a number of analytical strategies, software, development of algorithms and a variety of other approaches that enable scientists and ultimately reviewers to search, model and analyze data and enable personalized medicine or tailored therapies and conduct better safety and efficacy analyses,” Seyfert-Margolis said Jan. 28 during a webinar sponsored by the Drug Information Association.

As part of PDUFA negotiations, the agency asked for the ability to circumvent the formal regulation writing process so it can produce new data submission standards faster. Industry was concerned about allowing standard-setting without the formal comment process (Also see "PDUFA Update: FDA Wants To Automatically Extend Complex Application Reviews" - Pink Sheet, 4 October, 2010.).

FDA has revised the proposal to implement the new electronic standards through the guidance process and allow stakeholders to give input. The agency said it would issue guidance outlining the new data standards and implementation timeline so industry could plan ahead and comment, if necessary, according to minutes of a Nov. 22, 2010, negotiating session.

The new standards would be tested prior to implementation to ensure they meet users’ needs. The agency also intends to include tools that ensure application data meets the standards prior to submission.

FDA agreed, at industry’s suggestion, to revise the proposal to allow for waivers of the standard format requirements under certain circumstances, according to minutes of a Dec. 13, 2010, negotiation.

CDER Data Standards A Priority

The electronic data standards issue has been percolating for some time. CDER issued a draft data standards plan last spring that outlined the potential approaches to developing and managing data standards.

New regulatory requirements for electronic submissions are a priority for CDER during the next two years, Woodcock said in presentation slides. A proposed rule requiring submission of electronic data also is in the works as well as enhanced guidance and reviewer resources, she said.

Hamburg also included data standards development for electronic submissions as part of the regulatory science initiative, announced last October.

That plan called for the creation of an Office of Regulatory Science to oversee the initiative, but pending budget cuts could leave the proposal without its necessary funding (Also see "FDA Has Regulatory Science Plan; Now It Needs Funding" - Pink Sheet, 6 October, 2010.).

Research Data Standards Being Designed Outside FDA

The Critical Path Institute also has partnered with the Clinical Data Interchange Standards Consortium to set clinical data standards to improve drug development for major diseases.

Critical Path President and CEO Raymond Woosley said standards for neurodegenerative diseases like Parkinson’s are upcoming. Woosley also said FDA has asked the group to work on data standards for diabetes, cancer and pain conditions because those are priorities. He said lung cancer standards are going to be the next big target.

“It’s all a voluntary standard,” Woosley said. “The companies have indicated that it’s for their best interest to use the same data and of course the FDA really likes that because they can compare data on different biomarkers and different diseases across companies.”

A common standard was used when Critical Path created its Alzheimer’s disease clinical trials database, which includes data from 4,000 patients from 11 control trials. Companies have agreed to use the standards in future trials and the database now is available to researchers to help design clinical trials for new treatments (Also see "Next Up, Parkinson's: Coalition Against Major Diseases Moves To Link Neurodegenerative Ailments In Database" - Pink Sheet, 11 June, 2010.).

Woosley said he expected major efficiencies in the application review process once the new standards are completed and embraced.

Now companies use different biomarkers in their research, leaving reviewers unsure of the data because they may not be qualified. If FDA qualifies the biomarkers, those along with the data standards will lessen the reviewers’ workload, Woosley said.

“The reviewers can say, 'OK they used methods that we already evaluated so I don’t have to worry about those,'” he said. “I can just look at the drug.”

By Derrick Gingery

NDA Data Standardization Efforts Emerging Along Public, Private Fronts

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