Just before Christmas (on 22 December to be precise) EMA finally issued a revised Chapter 3.II: XEVPRM User Guidance. This was pretty late timing, since all resubmissions were supposed to be made by 31 December. It is highly unlikely that companies will be able to respond to this guidance immediately, but it may be of relevance for maintenance submissions, or in explaining how EMA may change the data submitted when they QC review the XEVPRMs submitted.
There are no great changes in the guidance - and many were expected, as they had been discussed with the Article 57(2) Implementation Working Group over the past months. The changes have been driven either by:
- the EEA countries formally adopting the Pharmacovigilance legislation
- clearer guidance given on the need to submit records for these countries and what languages to use
- problems identified during QC checking
- records must refer to the current QPPV (many records were received with out-of-date QPPVs)
- companies must undertake MedDRA coding at the most granular and comprehensive level (see below for further explanation as this could have significant implications for some companies/products)
- companies must submit any multi-constituent substances and their individual constituents as listed in the SmPC (e.g. lemon flavour and its constituents)
- a desire to tidy up a few items that may be causing minor problems, or are simply agreements that have already been made
- how to request additions/amendments of more than 5 substances (via Excel)
- how to support provision of supporting information for a renewal date (options provided)
- how to handle proposed dosage forms and routes of administration that are pending with EDQM (certain conditions need to be met if a Proposed term is to be provided)
- package description information can be in English
- what the latest version of MedDRA actually means (i.e. it is implemented within XEVMPD)
As mentioned above, the MedDRA coding has the greatest potential impact. It indicates EMA’s position and approach to correction of the coding already performed by companies. The applicability of MedDRA LLTs has been specified to a level of detail not previously seen. This clearly reflects the issues that EMA is having with the way companies have coded indications (compared to how EMA thinks they should be coded). Key points are:
- Coding should be performed at the most granular and comprehensive level
- The stage or type of the disease (where this is available in MedDRA) should be captured
- Coding of terms should be in line with any abbreviations used in the SmPC (For example COPD and Chronic obstructive pulmonary disease are different LLTs, but when the SmPC states Chronic obstructive pulmonary disease (COPD), then both are to be coded)
- An additional five examples are provided that cover how multiple LLTs should be defined for the terms used in the SmPC (Page 105/106)
This clarification indicates that EMA will probably redefine MedDRA codes already submitted to be in line with their interpretations. The examples will therefore be useful in the interpretation of reasons for the changes being implemented. For those companies that have not yet resubmitted their records, these new rules could still be implemented in the records (although this may be too short-term to be feasible). Updating of MedDRA coding rules for future new products should be considered.
About the same time, EMA published another two documents:
- An XEVMPD Fact Sheet. It has been known for some while, that EMA has been planning a communication via the NCAs to get to MAHs that do not routinely monitor the EMA website and announcements. This is available in all EU languages (link)
- A revised Quality control of medicinal-product data submitted as per the legal requirement introduced by Article 57(2) of Regulation (EC) No 726/2004 (9 December 2014). This has just an additional introductory statement (link)
It is recommended that MAHs review the revised Chapter 3.II guidance and determine how it might affect them.