The Falsified Medicines Directive (FMD) was introduced to prevent falsified pharmaceuticals from entering the market. Part of this is a Track & Trace system that detects these counterfeits so they can be taken out of circulation. If a counterfeit drug does make it into the supply chain, the alerts are used to detect it so it can be taken off the market. The respective alerts were previously collected via the Melior portal and made available to the respective marketing authorization holder (MAH) for further processing. To simplify this process and speed up the handling of individual alerts, the European Medicines Verification Organization (EMVO) has developed a central Alert Management System (AMS).
However, not all incoming alerts relate to counterfeits. Often, they emerge from the Track & Trace directive itself and the resulting tightly meshed supply chain. Incoming alerts and the arising problems are usually caused by scanning errors, e.g. before medicine is handed to patients. Regardless of the type of alert, it is mandatory to follow up on it, identify the cause of the alert, and verify whether it is indeed a counterfeit or not. Now the best practice recommendations of the EMVO for handling alerts have been tightened even further. This is where the new Alert Management System Hub comes into place. How MAHs have to deal with notifications from EMVO’s AMS portal, in which timeframe these must be processed, and what marketing authorization holder have to pay attention to in the future, we discuss in this article.
EMVO’s AMS Portal
The EMVO has set out to advance the European Medicine Verification System (EMVS) in coordination with the FMD. For this purpose, the European AMS Hub has been developed. It facilitates the exchange of information between stakeholders and, as a result, patients’ safety. The AMS Hub is used for communication between MAHs, end users, the National Medicines Verification Organizations (NMVO) and the National Competent Authorities (NCA) regarding incoming alerts. Through an online platform, EMVO’s so-called AMS portal, onboarding Partners can access the AMS Hub. The portal simplifies the processing of alerts by allowing direct feedback on them to NMVOs. The go-live date of the AMS portal was February 09, 2023. NMVOs will be connected stepwise.
Differences of Alerts
If an alert arises, manufacturers must process and analyze it. Could an actual counterfeit get into circulation or has an error occurred? Errors that can occur are treated differently by the EMVO. Firstly, there is the question of whether the alert could be a suspected counterfeit, and secondly, whether it should be forwarded to the EU Hub.
|EMVO Alert Type||Description||Potential Suspect Falsification||Sent to European Hub|
|#A1||Product not found||Yes||No|
|#A2||Batch not found||Yes||Yes|
|#A3||Pack not found||Yes||Yes|
|#A7||Pack already in the requested state||Yes||Yes|
|#A24||Status change could not be performed||Yes||Yes|
|#A32||Duplicate serial number||Yes||No|
|#A52||Expiry date mismatch||Yes||Yes|
|#A54||Insufficient Randomization of Serial Numbers||No||Yes|
|#A68||Batch identifier mismatch||Yes||Yes|
Handling of alerts
If an error occurs, MAHs and the NMVOs must act and investigate the cause. A precise sequence of EMVO action steps describes the ideal course of action:
- Determine alert type & source
- MAH documents warning, no reporting required for A7, A24 and A68.
- Internal root cause investigation
- MAH takes corrective action & informs NMVO
- EU Hub investigation
- In case of an error message triggered by the Hub: MAH informs NMVO of the Hub issue
- MAH requests NMVO support
- NMVO feedback
- MAH requests a photo of the package
- If applicable, MAH confirms that there is no indication of falsification and informs NMVO
- MAH requests package
- Suspected falsification, MAH informs NMVO and NCA
The type of procedure also depends on the alert in question. Thus, depending on the alert message, the sequence of action steps may change. Here, the EMVO distinguishes between three groups of alerts:
A7, A24 and A68.
These types of alerts do not need to be further investigated. MAHs are usually not responsible here, as these are often errors caused by end users. However, there are four exceptions where MAHs need to take action:
- They are aware that the alert was caused by repeated decommissioning transactions while the packages are under their control;
- An end user contacts them about such an alert;
- NMVO contacts them about such an alert generated by an end user for which no cause can be determined by the end user;
- The NCA asks the NMVO to investigate the alert.
If any of the above apply, MAHs skip step 2 of the sequence of actions and immediately perform step 3.
A2, A3 and A52
For these alerts, the MAHs determine whether they themselves are at fault for the alert message. If they are informed of the alert by the NMVO or an end user, no further action by the MAHs is necessary and they simply perform step 2 of the sequence of actions. To the extent that the MAH does not specifically know that the alert is due to an error on the part of the end users, they should proceed with the step of investigating the cause internally, i.e., step 3.
All other alert types
For all other alerts, the sequence of action is followed as specified above.
The time period in which MAHs must process incoming alerts varies depending on the country of origin of the alert. A detailed list of EU countries can be found here:
- As early as possible: Denmark and Finland
- 1 day: Slovenia and Spain (Spain at the end of the stabilization period).
- 2 days: Iceland, Latvia, Luxembourg and Poland
- 3 days: Estonia, Austria, Croatia, Cyprus, Malta, Norway and Sweden
- 7 days: Germany and Romania
- 10 days: Slovakia
- 14 days: Czech Republic and Northern Ireland
- Not defined: Belgium, Bulgaria, Hungary, Ireland, Lithuania, Liechtenstein, the Netherlands and Portugal.
The alert management system of the EMVO also runs to a large extent through the individual NMVOs. Thus, it is also their responsibility to investigate incoming alerts. The go-live date of the country-specific NMVOs therefore varies but is constantly updated in the EMVO’s AMS portal.
Our Alert Management Service
Even a small number of alerts can complicate daily operations in pharmaceutical companies. This is especially noticeable in small and medium-sized companies with less personnel capacity. With our Alert Management Service, we take care of our customers and analyze the causes of the various alerts for them.[Disclaimer]
This information is only one possible interpretation of the regulations. They are also in a constant state of change, so the information in this article may be incomplete or out of date. The above article is expressly no legal advice. Please refer to the official documents for information before making any business decisions. (Status of information: April 2023)