Note: This article is not a commitment to features or capabilities of ACUTA products or services.
When ACUTA added the Registration module to to ARIM version 3.0 in 2017, our expectation was that IDMP (Identification of Medicinal Products, the ISO standards being implemented first in Europe) was imminent. Because of that, we expected it would replace XEVMPD (Extended EudraVigilance Medicinal Product Dictionary, the current EU standard for product registration) in a swift manner. On top of that, we knew that companies with established products must already be compliant with XEVMPD, so the value of adding XEVMPD to ARIM seemed small.
However, EU’s IDMP implementation has been slower than hoped. Because the initial plans for IDMP would not be able to completely replace XEVMPD, and expected delays due to Brexit and the complexities of implementation, it is likely that XEVMPD could still be in use through 2022.
That makes it a good time, to re-examine XEVMPD’s requirements, how it may impact ARIM development, and how to move from there to IDMP.
XEVMPD’s origins come from EU law: Article 57(2) of Regulation (EC) No. 726/2004 (usually just called ‘Article 57’) and establishes a requirement to electronically submit information on the registrations of all authorised medicines, so that there is a product dictionary to assist in safety signal detection and enforcement. This is essentially the same requirements as IDMP, and it would have been ideal if IDMP could have been how Europe implemented Article 57 in the 2012-2014 timeframe. However, the IDMP standards had just been approved by ISO in 2012, and implementation guides weren’t available.
The XEVMPD XML format was created nearly as a mirror of IDMP’s requirements. Some items were lopped off if they weren’t applicable to Europe (jurisdictional approvals designed for situations such as Quebec within Canada; dose form characteristics such as color and shape that carried over from the US Drug Listings; etc.). The initial XEVMPD specifications were deemed too complex, however, and by 2014, only months before enforcement began, the requirements were trimmed down significantly.
There are some things to like about XEVMPD compared to IDMP: Its XML is simpler and more concise, versus the very verbose Health Level 7 Clinical Document Architecture used in IDMP. It was also designed with the messaging to regulators in mind: each type of item (products, substances, organisations, controlled vocabulary items, etc.) has its own sub-records, with operations (Insert, Update, Nullify, etc.), that can be chained together in a single message. This permits you to say in one submission, “I have a new product, for a new company, with a new substance and a new dose form.” Comparatively, IDMP requires many of those items to be pre-registered in a separate message, before they can be included in a new product submission.
That approach does have its downside, though: in the initial submissions, a lot of duplicate substances were created, and it took some time to sort out the records. This meant that the agency changed company records, and did a fair amount of recoding in other areas such as indications coded in MedDRA. At least one Tier-1 pharma company has said that they maintain a separate set of registration data from the XEVMPD database, because they do not agree with the changes that were made.
Migrating to IDMP will present several challenges, in three major areas
- Re-coding: many of the controlled vocabularies will have either the same coding (MedDRA for indications, and ISO country and language codes, for instance), or one-to-one mapping. Others, however, will need to be re-coded and in some cases there may be multiple, more-specific codes needed than were used in XEVMPD. This may mean maintaining codes for each submission purpose – and other countries such as the US FDA Drug Listings mean additional coding for the same information. There is an intent in the IDMP standards to use only international vocabularies, but with Europe leading the charge to IDMP, the code lists may not be complete for all regions.
- Detail: Europe’s implementation of IDMP will be iterative. One of the first iteration’s primary goals is to minimize the expansion from XEVMPD, but other business objectives, such as the e-prescribing regulations, support for the Falsified Medicines Directive, and permitting some product variations to be filed as only an IDMP record, would require more data fields. This is still to be finalized, but may include such things as detail on indications for co-morbidity (e.g. an antibiotic for pneumonia in HIV patients), and the intended effect (treat symptoms, cure the disease, prevent the disease, etc.). These extensions of the data will likely require re-analysis of source documentation including the Summary of Product Characteristics (SmPC). There is a lot of effort being spent to automate that analysis, but there will likely be a lot of cases requiring human judgement.
- Packaging: This is the area where there is the most potential for expanded detail in the first iteration. The XEVMPD guidance states, “Mandatory provision of pack size information and the information on the product down to the pack size level have been deferred to until ISO IDMP standards implementation.” This left the package description as an optional field – only about 2/3 of the products even have it filled in. The biggest problem areas come from authorisations that include multiple pack sizes. While the Centralized Procedure has an authorisation number for each pack size – and thus a separate XEVMPD record – other procedures do not. This means that a package description might say, “Blister pack of 10, 20, or 40 tablets” if it says anything at all. The expected direction is that the information needed will be minimized, but there will likely be messy exceptions for kits with multiple pharmaceutical products (cream and suppository) or components (vials of powder and diluent).
There is a lot of discussion going on as to how migration should happen. Between the need for turning a single XEVMPD package description field into multiple detailed records, and possible changes to coding, some pharma companies would like to start from scratch with new submissions. However, that’s a big effort, and the European Medicines Agency is planning on providing a translation from XEVMPD to IDMP. Especially if existing company product registration databases include more detail than XEVMPD, it may be tricky to resolve which new records go where – regardless of whether the agency or the company creates the record.
The Registration module in ACUTA’s ARIM 3.0.1 is still evolving, and we welcome your feedback on how we can help you comply with the regulations for product registrations around the world. Please contact us or start a conversation in the comments here as to how you expect to move toward IDMP while continuing to support XEVMPD.