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Updated on: 05 February 2024

Purpose and Context

EMA is pleased to announce the web-based Human Variations electronic application form (eAF) for Centrally Authorised Products (CAPs) has gone live on 4^th November 2022, on the new Product Lifecycle Management (PLM) Portal. This is a big, first, milestone in the ongoing journey to improve the eAF and related processes. EMA has been collaborating with the UNICOM consortium to develop the human variation form and other new web-forms.

Following the release, users of the Human Variations eAF should expect continual work on improvements in the form of regular releases. These will be a mix of bug fixes, scheduled improvements, improvements based on user acceptance testing (UAT) feedback or that may be identified by users after the release and new features, such as additional structured data fields.

This document lists and briefly describes the new features and fixed issues included in the release of the PLM Portal FHIR XML only. For the Release notes related to the eAF, please visit the guidance on the PLM Portal.
The most recent release appears first.

About this Document

Component	Short Description
PLM Portal	This component relates to the website, the UI (user interface)
Human Variations eAF	The business process where MAH’s create and edit their variation eAF (electronic application form) on the PLM Portal
PDF	The PDF that is available for download after the completion of an application
FHIR XML	The FHIR xml file attached to exported PDF

Version: 2.0.0 (Announcement date: 31/01/2024 – Release date: 30/04/2024)

Version Goal

We are eager to announce the upgrade of the eAF human variation FHIR XML version 2.0.0 that includes the latest official FHIR version “Release #5 (5.0.0): http://hl7.org/fhir". This replaces the current version FHIR Release #5: Draft Ballot (4.6.0): http://hl7.org/fhir/2021May/, which will remain online for approximately 3 months to give consuming systems time to adapt to the change.

Version Content

The upgrade of the eAF XML to the current official Release #5 of FHIR is the first part of EMAs strategy to synchronize different projects on a stable FHIR version that will provide the necessary stability in the network to implement the new data exchange format on a larger scale.

Together with the upgrade to Release #5, we have reviewed and improved the eAF mappings in FHIR in order to provide the most stable version yet for consuming systems to start importing the eAF.

What this is not

This release note will enable consuming systems to read the message and extract the necessary data. It is not a documentation to create the message itself. The necessary Guide to create an eAF FHIR message is being worked on and will be published at a later stage.

How to read the release documentation?

To provide consumers of the FHIR XML message the easiest possible way to upgrade to the eAF XML 2.0.0.0 containing the new FHIR #5 resources or to start your implementation with the latest version, we have prepared^*:

A change log: 2024 01 30 Changelog eAF Variation FHIR 4.6 to 5.0.xlsx This contains an extensive list of all changes done in the new eAF XML version with links to the data requirements, 4.6 Paths, 5.0 Paths and the reason for change
A snapshot of the current eAF data requirements: 2024 01 30 AF Data Requirements.xlsx This contains all fields for variation and medicinal product being used now or in future versions of the PLM portal
All resources in v4.6 and v5.0 as XML for an easy comparison usable for permissive testing: MedicinalProduct Domain Resources - 4.6 and 5.0, Variation Domain Resources - 4.6 and 5.0 A complete list of examples for every resource in both versions to easily compare the changes and understand how the new structure looks like
As complete as possible examples of an invented variation message exported in 4.6 and 5.0 from the PLM portal: eAF human variation 4.6.0 - 1.2.0.8.xml, eAF human variation 5.0.0 - 2.0.0.0.xml An example was created of a complete bundle that was filled in with a focus on completeness rather than realistic data. This is to be used to understand how the different resources behave in the bundle.

*The documents can be found here.

Version: 1.2.0 (Release date 21/11/2023)

Version Goal: Implementation of FHIR XML
Date: 21/11/2023
Environment: production
Version content (testable functionalities/use cases)

Version content

Functionality/use case	Component	Description
Implementation of the FHIR XML	FHIR XML 1.2.0	Commercially Confidential Data not related to the application content/variation removed from the FHIR XML

Issues fixed in this version

Description

Comments

38300, 15895, 46485

Identify minimum set of fields required to export and update FHIR generation to exclude information not needed

Removing Product data that has not been changed in the FHIR XML

Only Resources that are needed for the PDF are also contained in the XML.
Confidential data is not included when not needed.

Paradigm
Rule Nr.1: If a resource has a change to 1 property the entire resource needs to be there.
Rule Nr.2: If a resource has a link to a resource that is not being changed, the link should stay, but the resource that is being linked should not be there. This is to be able to compare resources and confirm that something/nothing has changed.
Rule Nr.3: Resources pointed at by the Task should always be mandatory.

Mandatory resources (always included, irrespective if they are being changed):

Medicinal ProductDefinition
IngredientDefinition
- Reason: Substance Name
- implicit: Link to medicinal product (extension) - not Admin product link
- Role = Active
RegulatedAuthorization - for selected packages and med products (Type=Marketing Authorization)
PackagedProductDefinition - ONLY IF SELECTED
All Orphan Resources
Orphan RAs, GMP RAs, Paediatric RAs, Market Exclusivity and Market Protection RAs
Organization (type=MA Holder and Regulator - linked to the RegulatedAuthorization)
All parallel resources (MedicinalProductDefinition + RA)
Substances (role = active)
PaymentNotices
PractitionerRole and its organizations

Subtasks/Scopes, which are represented as FHIR Tasks, will no longer be contained resources, but flattened *
Previous implementation: "/f:Bundle/f:entry/f:resource/f:Task/f:contained/f:Task"
Adjustment: "/f:Bundle/f:entry/f:resource/f:Task"

Suggestion for consuming systems using XPATH
//Task[id/@value=substring-after($reference,'#')]|//Task[id/@value=substring-after($reference,'Task/')]

* See detailed picture below

Old paradigm(Task represented in orange and Scope represented in Yellow):

New Paradigm(Task represented in orange and Scope represented in Yellow):

Known Issues

ID	Component	Short description
n/a	n/a	n/a

Version: 1.1.2 (Release date 10/02/2023)

Version: 1.0.2 (Release date 16/11/2022)

Version: 1.0.0 (Release date 04/11/2022)

Keywords: eAF, FHIR, release notes

ID	Description	Comments
36110	ASMF, DUNS Nr, Telephone and Email changes	Change ASMF, DUNS Nr, Telephone and Email mapping in FHIR according to the changes in the eAF
24565	Free text field changes	Limit width of free text fields
30382/30383/30387	Various refactoring	Ingredient/Ingredient Strength/Ingredient Documentation FHIR refactoring
38537	Device Definition	Attach every DeviceDefinition to a Medicinal Product
38779	ATC Source ID	Add the Source ID to the ATC while keeping the ATC name as well
37124/38274	Device variation	Minor fixes to the Device variation as new edge-cases were tested

ID	Description	Comments
26295 – FHIR XML	The HTML Change Provenance (unstructured provenance) doesn't contain the HTML changes when the proposed value and the present value are the same	This issue resulted a missing present and proposed section in the FHIR XML and in the pdf export when same value was presented in both ‘present’ and ‘proposed’ fields e.g., if user had added ‘see details on separate annex’ in both fields, the present and proposed sections were not available in the XML and were hidden in the pdf.
26247 – FHIR XML	Impossible to use the same image twice in the text areas in a form

ID	Component	Short description
38300	FHIR XML	Commercially Confidential Data not related to the application content/variation present in the FHIR XML

ID	Component	Short description
Known limitation	FHIR XML	Commercially Confidential Data not related to the application content/variation present in the FHIR XML

eAF - FHIR XML - Release Notes