Beginning 5 May, pharmaceutical, biologic and generic manufacturers will have to submit to the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) all New Drug Applications (NDAs), Biologics License Application (BLAs) and Abbreviated New Drug Applications (ANDAs) using the electronic Common Technical Document (eCTD).
Drug Master Files (DMFs), Biological Product Files (BPFs) and other master files also have to meet the 5 May deadline for transitioning to the eCTD. The only exemptions that will be allowed will be for single patient compassionate use investigational new drug applications (INDs) and academic-initiated INDs.
The eCTD is designed to make regulatory submissions easier and more efficient by requiring a common global standard for companies to electronically submit the quality, safety and efficacy information required for approval to the regulatory agencies in the US, EU, Canada and Japan.
A Growing Requirement
In the US, the 2012 reauthorization and update of the Prescription Drug User Fee Act (PDUFA), within the Food and Drug Administration Safety and Innovation Act (FDASIA), elevated the eCTD format to be the new requirement, and it will also be required for commercial INDs beginning 5 May 2018.
Internationally, the eCTD has been required for Centralised Procedure applications to the European Medicines Agency (EMA) since 2010. Use of the format is also strongly encouraged in Canada, Japan and other developed markets worldwide.
Although its status as a requirement is relatively recent, the eCTD itself is not new. It was adopted by the International Council on Harmonisation (ICH) in 2003, three years after the eCTD's paper-based predecessor, the Common Technical Document (CTD), was developed by ICH.
Benefits of the eCTD
The eCTD allows regulators to use computer-based tools such as searching, copying and pasting text, making the review process more efficient. Agency staff can complete reviews online in less time than it would take using hard copies, which also benefits sponsors. For sponsors, eCTD submissions also can be less expensive to produce and ship, provided they have business processes to accommodate the change from a paper-based format to an all-electronic one. In addition, applications can be repurposed more easily for submissions to several different agencies.
Since the introduction of the eCTD, submissions to FDA using the format have continued to grow steadily. According to FDA, eCTD submissions to the agency have climbed each year since 2004. In fiscal 2007, they made up about 9% of NDAs. In fiscal 2016, eCTDs accounted for 93% of NDAs.
Increasing Use (and Increasing Challenges)
It's not hard to understand why eCTD use has rapidly increased. Submitting applications electronically benefits all parties. However, anyone who started out using paper submissions may have to unlearn some of the old ways of doing things to be successful with the eCTD format. With e-submission becoming mandatory, smaller companies, less technologically advanced companies and those with fewer resources may be particularly challenged.
Failure to pass the validation process will result in FDA refusing to receive the submission and the sponsor will be asked to correct any errors and resubmit. If a submission passes initial validation, a large number of medium-severity errors combined with a lack of navigation aids, such as a table of contents, bookmarks and hyperlinks, could still trigger a "refuse to file" during the 60-day period in which FDA evaluates the completeness of a submission before starting a review.
Learn How to Handle the eCTD
For the past several years, RAPS has hosted a series of eCTD workshops where attendees learn about agency validation criteria and how to comply. An introductory workshop covers the basics of eCTD for those who are new to regulatory submissions. An intermediate workshop is designed for those who have some experience or familiarity with the CTD already.
For more information about RAPS’ eCTD workshops or to register, visit the following pages: