Purpose and context

The European Medicines Regulatory Network ePI Implementation Guide describes how the HL7 FHIR standard is used to generate ePI according to the EU ePI Common Standard. Publication of the Guide is intended to provide transparency to stakeholders, including the pharmaceutical industry, on future requirements for ePI to be submitted to EU regulators.

Content of the Implementation Guide

The Implementation Guide presents the FHIR resources used to create an ePI according the EU ePI Common Standard, which has been adopted by the European Medicines Regulatory Network to enable provision of harmonised ePI across the EU.

The Guide contains information on the following resources:

• Profiles for Bundle, List, Composition and Regulated Authorization

• Details of extensions Authorization type, Image reference and Version number 

Important Note: The Guide is intended as a preview only, and does not yet constitute a formal version. On the go-live implementation of ePI for regulatory procedures, a formal version will be published with versioning in place. The guide is subject to change as development of core functionality of ePI creation and management tooling is ongoing.

European Medicines Regulatory Network ePI Implementation Guide: link

Purpose and Context

Styling information in the context of ePI refers to the way content can be displayed in a document or on a webpage. It considers aspects such as font styles (family, size, color), layout (margins, padding, positioning), and other visual properties.

Styling information is important for compliance with regulator requirements (e.g., the QRD [Quality Review of Documents] template and convention), to convey the correct meaning (e.g., italics superscript) and to provide the best user experience. 

This style guide aims to:

• instruct applicants how to incorporate styling information when importing FHIR ePI files into the PLM portal

• instruct applicants how to incorporate styling information when creating ePI using the editor at the PLM portal

• outline how and when QRD styles, as outlined in the QRD templates and QRD convention, are applied at the PLM portal

• inform consumers of ePI data about what style information to expect in data accessed from the application programming interface of the EMA-HMA-EC FHIR repository

The guide is accompanied (see Related attachments, below) by:

• the ePI QRD Cascading Style Sheet (CSS), which is used to apply QRD styles to ePI after transformation

• an Extensible Stylesheet Language Transformation (XSLT), which can be used to transform ePI to HTML format with QRD styles

1 - ePI creation

1.1 - Creating ePI by importing FHIR

Applicants can generate FHIR ePI with their own systems/providers and subsequently import FHIR into the PLM portal and submit to the regulator. In this case, applicants must follow the guidelines outlined in ‘How to style ePI’ to ensure correct styling information in the imported FHIR files. 

1.2 - Creating ePI using the editor

Applicants can create ePI in the PLM portal using the editor and subsequently submit to the regulator. 

When content is pasted from Word into the editor, styling/formatting will be automatically removed. 

In the editor, the applicant should (re)apply the following styling to the section content:

• Centre or right alignment of text (all text is left aligned by default)

• Grey shading

• Any other formatting, only where it is required for the correct meaning of the content and/or required by the regulator

In the editor, the applicant should remove: 

• Blank lines between paragraphs

• Borders on tables where invisible borders are required (e.g., for the list of local representatives of the Marketing Authorisation Holder) by selecting Cell properties>Border style: hidden

QRD styles (such as font type, size, colour and weight of section headings and body text, margins and spacing, and list style) will be automatically applied by the QRD style sheet and must not be added by the applicant in the editor.

2 - Viewing and accessing ePI

2.1 - Preview ePI

Users can preview their ePIs using the ‘Preview’ button on the ‘Manage ePI’ page, which opens a new tab displaying the ePI.

The QRD style sheet is applied, and the preview displays the ePI with QRD styles.

2.2 - Export ePI to Word

Users can export ePI as Word file(s) using the ‘Export’ button on the ‘Manage ePI’ page.

The QRD style sheet is applied, and the exported Word file(s) contain the PI with QRD styles.

2.3 - Export ePI to FHIR

Users can export ePI as a FHIR XML file using the ‘Export’ button on the ‘Manage ePI’ page.

The exported FHIR XML file does not contain QRD styles. If desired, users can convert the FHIR XML file to HTML containing QRD styles using the XSLT. 

2.4 - Access ePI via the API

The ePI application programming interface enables access to ePI data by consuming systems.

The API response does not contain QRD styles. If desired, users can convert the ePI data to HTML containing QRD styles using the XSLT. 

3 - How to style ePI

 3.1 - Escape characters 

To ensure ePIs are properly interpreted without breaking the XHTML/XML/JSON file structure, special symbols must be escaped. The required escape character sequences are shown in Table 1.

Table 1. Special symbols and required escape characters

3.2 - Section headings

Section headings in ePI are standard text, as defined in FHIR's string primitive datatype.

Section headings cannot contain HTML tags or style attributes.

Applicants are not required to add styles for section headings to their FHIR XML files.

QRD styles are managed by the style sheet as described in Table 2. 

Table 2. Section headings

3.3 - Section content

Section content is XHTML, as defined in FHIR's narrative xhtml type (https://www.hl7.org/fhir/narrative.html#xhtml).

Tags listed in Table 2 must be used for section content. Standard QRD styles will be applied by the QRD style sheet (see Table 2) and must not be added by the applicant.

Table 3. Section content

3.4 - Styles not included in QRD style sheet

⚠ Additional styling should only be added in the ePI when specifically required by the applicant/authority. 

Any unnecessary additional styling will reduce the portability and reusability of the ePI data. 

In case the applicant/authority requires specific styles in addition to the standard QRD styles applied by the style sheet, they must be added using one of the following options: 

1. Add an inline style to a whole paragraph using the style attribute in the paragraph element.

For example: <p style="color: red;">This whole paragraph is red using inline style.</p>

2. Add an inline style to a few words using the style attribute in a span element

For example: <p>This is <span style="color: red;">red text</span> using a span element with inline style.</p>

3.5 - Boxed warning

Boxed warning text must have a border applying the following inline styles to the whole paragraph:

• border: 1px solid black;

• padding: 5px;

• margin-bottom: 1em

Tables must not be used for boxed warnings.
​​​​​​

3.6 - Shaded text

Shaded text, used by applicants to highlight text which will not be printed, should have the following inline style applied using the style attribute and the span element, as follows:

<p><span style="background-color: silver;">Grey shaded text</span>and other text</p>

3.7 - Black triangle

The black triangle for medicinal products subject to additional monitoring should be entered using the Unicode character U+25BC.
Shapes must not be used for the black triangle.

3.8 - Tables with hidden borders

Tables with invisible/hidden borders, such as the table used in the list of local representatives of the Marketing Authorisation Holder in the Package Leaflet, should use:

<td style="border-style: hidden;"></td>
 

3.9 - Images

Recommended attributes for <img> tags include

• alt, specifies an alternative text for an image: include a brief but meaningful description of the image to facilitate accessibility features such as screen reading (required for WCAG AA compliance)

• height, in pixels, specifies the height of an image

• width, in pixels, specifies the width of an image

• src attribute, containing the reference to the Binary resource with the image.

Images larger than 600 pixels in width will be resized.

4 - Accessibility

ePI section content should comply with WCAG Level AA.

5 - Display ePI using the QRD CSS and XSLT

This guide is accompanied (see Related attachments, below) by:

• the QRD CSS (ema-epi-qrd.css), which is used to apply QRD styles to ePI 

• an XSLT (ema-epi-html-main.xslt), which is used to transform ePI to HTML format with QRD styles

These resources can be used to display ePI for quality control checks, to determine QRD styles applied by the regulator, for creation of web pages or for other display purposes, as follows:

1. Install your XSLT processor of choice.
2. Run the transformation in your terminal.
3. View the output in any browser.

Purpose and context

Quality Review of Documents template lists provide identifiers, term names, term translations in EU official languages, hierarchy and attributes to be used for creation of ePI compliant with QRD templates and the EU ePI Common Standard.

Currently QRD template version 10.4 is available.

• Link: https://epi.ema.europa.eu/qrdtemplate/