The specification for the eCTD is based on “Extensible Markup Language” (XML) technology and lists the criteria that make an e-submission technically valid. It focuses on “the ability to transfer the registration application electronically from industry to a regulatory authority.” The data and document files that form part of a submission are mostly provided in a portable document format (PDF) and are embedded into the XML backbone of the eCTD.
The change from paper to e-submissions bears some challenges: The implementation of suitable information and communication technology (ICT), the adaption of related business processes, as well as working practices, and particularly, the professional use of ICT play key roles for a successful e-submission project.
As brought to the point in Europe’s Digital Competitiveness Report 2010: “Investment in ICT is not sufficient if not accompanied by the reorganization of internal processes. ICT applications that help automatic business processes can be an important source of efficiency gains when accompanied by innovative working practices and the appropriate skills.
In this context, particularly in view of Europe’s digital agenda for a flourishing digital economy by 2020, it is worth exploring whether current practices can allow the efficient handling of an eCTD submission project.
“eCTD-compliant” Navigable Files
One major advantage of the eCTD is its ability to allow navigation through a complete electronic submission. However, the eCTD can only be navigated provided that each file is navigable itself and provided referenced files are hyperlinked with each other.
In order to become “navigable,” the PDF files need to fulfill specific formal requirements (e.g., document granularity, specific file names) and need specific properties which allow navigation, like bookmarks, intra- and inter-text hyperlinks (see Figure 1). The properties of a PDF file are specified in a U.S. FDA guidance and in a number of regional eCTD-related guidance documents.
If the author or writer of a document does not consider these requirements, a file needs to go through numerous time-consuming formatting steps until it is ready for a submission in eCTD format (for examples, see Figure 2). That happens mainly when the files are provided by external parties, e.g., Clinical Research Organizations (CROs) or medical writers.
The major efforts of time-consuming reformatting can be prevented by standardizing the document format. This can be achieved by either using harmonized templates and/or by setting up a style guide where aspects of document granularity, document formats, hyperlinking, etc., are specified. However, all parties/persons providing submission-relevant files need to be informed and trained, if necessary, in the document format standardization or as the U.S. FDA points out on its related website “Ask CROs in advance to provide reports in searchable PDF format compliant with the ICH M4 Granularity Annex and FDA PDF Specification.”
Even when working with standardized document format, interoperability problems may occur by using different operating systems and software standards (e.g., by using different Microsoft® Office software versions). Before exchanging any submission-relevant files with external parties, an interoperability check may help to identify and prevent the problems.
The need for “interoperability and standards” was identified as one of the seven actions in Europe’s Digital Agenda Communication initiated to make “proposals for actions that need to be taken urgently to get Europe on track for smart, sustainable and inclusive growth….”
Adapting Business Processes, Working Practices & Improving e-Skills
Working with electronic files rather than paper requires the adaption of eCTD-related business processes.
The eCTD submission project can only be efficient when the underlying business processes are accompanied by innovative e-working practices and the appropriate e-skills.
In practice, however, and as listed below, business processes and working practices sometimes run counter to an efficient eCTD submission project processing, especially in small and medium-sized enterprises (SMEs).
The following are common challenges an eCTD submission project can face, but it is certainly not an exhaustive list:
•Inadequate or even missing project management skills. There is a risk that the eCTD submission project could get out of control and be behind schedule.
•Unnecessary multiplication of documents and bytes when large and confidential files are exchanged via email (see Figure 3). A secure, web-based virtual project place (like Microsoft® SharePoint®) is needed as a document repository that is accessible for all project members and enables the collaboration on documents and data (see Figure 4 ).
•A lack of e-skills, resulting in:
– missing interdisciplinary communication with ICT specialists regarding ICT-needs (either company-internal or service provider)
– suboptimal use of software (using the computer as a “typewriter” without being aware of useful software functionalities or the information about additional software to optimize specific working practices)
– Lack of knowledge about electronic document properties and how to change them (image-based versus text-based PDFs, protected PDFs, file size reduction, inherit zoom magnification, file size reduction, etc.)
In light of these challenges, the following questions arise:
Do regulatory affairs professionals bring along the required e-skills to adapt innovative e-working practices in order to manage a complex eCTD submission project? If not, what measures will become necessary?
One answer was given in last year’s European e-Skills Conference: “Organizations need to invest not only in infrastructure but in the higher level e-skills of their workforce…. The critical factor for future success…is the capacity for the competitive application of technologies.
In conclusion and in view of Europe’s digital agenda, the time has come for Good e-Submission Practice.
About the Author
Barbara is based in Switzerland. She is the Managing Director of PhACT GmbH; a company that provides advice and service in drug regulatory affairs, with a specialty in EU regulatory submissions including biotechnology. Barbara has more than 20 years of experience in regulatory affairs and previously worked with the Federal Institute for Drugs and Medicinal Devices (BfArM)-the German Health Authorities.
No comments:
Post a Comment