Regulatory Focus™ > News Articles > PhRMA, BIO Express Unanimous Concerns About FDA Electronic Submission Guidance Docs

PhRMA, BIO Express Unanimous Concerns About FDA Electronic Submission Guidance Docs

Posted 13 May 2014 | By Alexander Gaffney, RAC

Two of the pharmaceutical industry's largest trade groups are weighing in on the US Food and Drug Administration's (FDA) proposal to digitize the drug application submission process, saying the agency is generally on-point, but needs to clarify a few outstanding issues.


In 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) was passed into law, and with it a provision mandating that all applications submitted under Section 505(b)/(i)/(j) or 351(a)/(k)-that is, any new drug, investigational drug, generic drug, biologic drug or biosimilar drug-be submitted electronically in a format specified by FDA.

The requirement is set to begin at least 24 months after FDA issues a final guidance indicating which electronic submission format it wishes to use.

In early February 2014, FDA released a new draft guidance document, Providing Regulatory Submissions in Electronic Format - Submissions Under Section 745A(a) of the  Federal Food, Drug, and Cosmetic Act, it says is intended to clarify the extremely technical submission process.

That document is intended to be something of a roadmap, describing which types of submissions must be submitted electronically, which submissions are exempt from the requirements, and when submissions will need to be submitted electronically.

But the guidance is also unusual among most guidance documents in that it contains binding provisions-not just non-statutorily-binding recommendations.

A second guidance document, also released in early February 2014, went into detail regarding the study data formats that sponsors must use when submitting data, with FDA indicating that if the correct formats weren't used, the agency would reject the product application.

(Note: A third guidance document, released several days later, also covers electronic submissions, but is not the focus of this article.)

Comments: More Specificity, More Advance Notice

That's all well and good, PhRMA and the Biotechnology Industry Organization (BIO) write in joint comments submitted to the agency this week and made available to Focus, but the guidance could use some additional specificity in parts.

Specifically, the duo argue that FDA needs to be clear in the guidance documents about what is required by statute versus what is recommended as a matter of good practice by FDA. "It will be important that binding guidances and the standards and formats specified therein are clearly distinguishable from other non-binding guidances and documents," they wrote.

In addition, PhRMA and BIO said the guidance document should include a "comprehensive list of the guidances that are affected or delivered as a result of the binding provisions under Section 745(a)." That proposal could make the guidance document difficult to keep updated in the future, as each new guidance document relating to electronic submissions would require an addition-a process PhRMA and BIO said should follow a "format process for public comment."

Their comments also stress the "importance of using the formal guidance process and public comment period" when issuing new standards or formats. While FDA will sometimes issue new formats in the Federal Register, other times it simply places a notice on its website. "Pharma and BIO believe that these revisions and updates are unlikely to have only minor impact on sponsors, and therefore should only be required after notice of availability of revised draft guidance and public comment period," they wrote.

The organizations also noted the challenges associated with developing drugs-a process that can regularly take more than a decade. Since FDA plans to change electronic submission standards with some regularity, PhRMA and BIO expressed concern that this might require sponsors to re-configure existing data while contributing little benefit to the development process. "Therefore, FDA must be able to accept previously required standards for decades after the standard has been deprecated," they recommended.

Minor Changes-Big Headaches

The groups also took issue with how the guidance documents treat updates to the standards. FDA has indicated that it plans to only implement changes after a period of 24 months, though minor changes may be made more quickly, and even immediately. BIO and PhRMA said they want FDA to better define the scope of those changes-what is a minor change?-and to keep in mind that even small changes in a data submission format can have major changes in regulated industry.

"Changes, even minor, in a standard may require the company's initiation of an impact assessment, development or purchase of new software (including validation of new systems and software), development of new processes, updates to data capture systems, additional training of personnel, re-work of components of submissions that had already been prepared, or all of the above," they wrote.

As a result, even minor changes should be subject to a waiting period of 24 months, they said.

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