Submissions Processes with Templates for Microsoft Word®

For Pharmaceuticals:

As regulatory agencies such as the U.S. Food and Drug Administration (FDA), and parallel agencies in Europe, Japan, and Canada, move toward a completely electronic submission environment, tools like templates for Microsoft Word® become increasingly essential to submissions content development processes. Templates can be essential during the preparation of electronic common technical documents, or eCTDs. The eCTD is a standard created by the International Conference on Harmonisation (ICH), a consortium of regulators from Europe, the United States, and Japan, who developed a common standard for marketing applications for drug and biologic marketing applications in those geographic areas.

Templates can insure that a cohesive story is being told across not only the initial application but also in all accompanying sequences of an investigational drug application or a new drug or biologic marketing application.

Along with the introduction of the eCTD, the concept of granularity was also introduced. In essence, those components of eCTDs that are written in regards to the safety, quality, and efficacy of a drug or biologic product are prepared in much smaller units than earlier formats for submissions. This granularity allows such units to be updated over the course of a marketing application without having to resubmit an entire large unit for review by a regulator. As a result, guidances have been issued by the FDA and ICH instructing industries to supply PDF documents with eCTD submissions to required levels of granularity. Not only must the bulk of e-submissions be available in PDF format, but they must also be complete with tables of contents, contain bookmarks and hyperlinks, have eCTD module-specific numbering and text in page headers, be of highly-constrained page size, and be optimized for legibility in an electronic submission review tool. In this sense, templates assure compliance with eCTD granularity and PDF format specifications by their very nature if they have been designed to be compliant with FDA and ICH requirements for PDF files.

Templates can streamline submissions processes by providing a uniform appearance across all content of the dossier. Effective templates allow content to be reused throughout the submission, meaning that the same voice is used to describe the drug product and mechanism of actions. This aspect of good templates can insure that a cohesive story is being told across not only the initial application but also in all accompanying sequences.

A robust template offering will also typically include common functions in toolbars and styles, which can dramatically reduce the total number of keystrokes required for assuring the document formatting converts to compliant PDF files. This enables those individuals in an organization who are responsible for entering the technical content of a submission to focus on content rather than being concerned with standardizing format elements such as headings, table figures, table titles, and such. With an effective template offering, the consistency of appearance is already taken care of for the author.

Another helpful characteristic of a template package is that it can help a company enforce its own standards and conventions, such as:

• Confidentiality statements that may be required on documents
• Company logos that may be required on headers of documents
• A title page requiring certain language for company identification
• Signature pages that may require particular signatures on the technical aspects of the content

Other key features of effectual template packages that can help a company authoring content intended for marketing applications include:

• As new authors approach the task of writing eCTDs, they may not necessarily know which content applies to specific file granularity. With an effective template package, instructional text should be included with each template to guide authors in preparing and writing content for each particular component of the electronic submission. A good quality template package will reference ICH guidances, FDA guidances, Code of Federal Regulations (CFR), EU regulations, or similar references where they are relevant to particular components of the content. In this way, templates provide specific assistance to authors regarding well-defined information that should be included in particular components or granules of the eCTD.
• Specifically in reference to the eCTD and FDA, the concept of electronic submissions extends throughout the entire lifecycle of a product, from the initial investigational new drug (IND) application process all the way through post-marketing. In the rest of the world not subject to FDA regulations, electronic submissions are intended for marketing applications only, but the FDA has extended the concept to be used very early in the drug development lifecycle. Some agencies in Europe are accepting the Clinical Trial Authorization and Investigational Medicinal Product (CTA-IMPD) content in eCTD submissions.
• If the template package includes toolbars that support common Microsoft Word formatting functions, authors are not required to have extensive knowledge of MS Word in order to perform common functions. As previously discussed, this also reduces the number of actions necessary to execute common functions and allows authors to activate formatting functions in Word with a single keystroke. A symbol toolbar can not only reduce the amount of keystrokes required for common symbols but can also insure that symbols are drawn from the correct embedded font and are presented correctly to reviewers without font substitution when the Word file is converted to PDF.
• Since the FDA began accepting eCTDs in 2005, some of the key triggers for "refusal to file" (RTF) letters have been the poor quality of the PDFs in the eCTD. Template toolbars should enable authors to create documents that, when converted to PDFs, are compliant with PDF file requirements specified in ICH and FDA guidances. The primary purpose of a template package should be to preserve compliance and insure that authors are performing tasks correctly without being required to have excessive training and/or a deep knowledge of Word.
• A high-quality template package should support all variations of eCTD granularity. While there is a high degree of granularity recommended, that granularity does not necessarily apply to all products in all circumstances. Vendors offering template packages should provide full documents as one option and full granularity as another alternative.
• Even if you are submitting your CTD in paper format, the requirement for file granularity and the organization of the content in the paper submission must reflect the granularity and organizational concepts of the eCTD. Plus the use of templates assures the electronic files used to publish the paper CTD have required characteristics—such as bookmarks—that are used by submission publishing systems to create tabs, to insert slip sheets, and to create module tables of contents for paper CTDs.

When selecting a template package, all the topics discussed above should be taken into account, as should the following items:

• The value of the documentation included with the templates package (user guides, training manuals, installation instructions, etc.)
• Availability of support (via e-mail, toll-free hotlines, etc.)
• Availability of on-site training
• Configuration/customization assistance (including company logos, changing default fonts, etc.)
• The vendor's plans for future development

Implementing templates can drastically save a company's time and resources—not to mention accelerate submissions processes and, ultimately, a product's time to market—but purchasing a templates package is a major step for any company. Prior to selecting a template package you should have the confidence that the vendor's offering can effectively lead you through the processes of producing and managing an eCTD and that the templates possess the robustness necessary to adapt as electronic submission regulations develop and change through the years.

Antoinette Azevedo founded www.e-submissionssolutions.com to advise all sizes of biotechnology and pharmaceutical companies on the use of technology to manage regulatory documents and publish electronic submissions. Her clients range from large, international pharmaceutical companies to small, virtual biotechnology companies.Antoinette was director of West Coast Operations for Liquent from 1997 to 2000. She was principal consultant in the CSC Consulting life sciences practice as technical lead for regulatory submission publishing from 1994 to 1997, working with pharmaceutical clients in North America and Western Europe. Her entire career has been devoted to document management and electronic publishing through several generations of technologies and architectures in various industries. Antoinette has lectured internationally for RAPS and DIA, at vendor-user conferences, and for local regulatory affairs professional groups.

Read more about electronic submissions:

FDA Links:

eCTDs Providing Regulatory Submissions in Electronic Format - Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications FDA Guidance for Portable Document File Specifications Guidance for Industry — Providing Regulatory Submissions in Electronic Format – General Considerations

Additional Links:

ICH Website

Submissions Key Factors

Electronic Common Technical Documents